bluuebunny/crossref_metadata_2025 huggingface dataset:
Utilizing a tablet-based artificial intelligence system to assess movement disorders in a prospective study
Authors: Purk Maximilian , Fujarski Michael , Becker Marlon , Warnecke Tobias , Varghese Julian
Published: June 2023

Spiral drawings on paper are used as routine measures in hospitals to assess Parkinson’s Disease motor deficiencies. In the age of emerging mobile health tools and Artificial Intelligence a comprehensive digital setup enables granular biomarker analyses and improved differential diagnoses in movement disorders. This study aims to evaluate on discriminatory features among Parkison’s Disease patients, healthy subjects and diverse movement disorders. Overall, 24 Parkinson’s Disease patients, 27 healthy controls and 26 patients with similar differential diagnoses were assessed with a novel tablet-based system. It utilizes an integrative assessment by combining a structured symptoms questionnaire—the Parkinson’s Disease Non-Motor Scale—and 2-handed spiral drawing captured on a tablet device. Three different classification tasks were evaluated: Parkinson’s Disease patients versus healthy control group (Task 1), all Movement disorders versus healthy control group (Task 2) and Parkinson’s Disease patients versus diverse other movement disorder patients (Task 3). To systematically study feature importances of digital biomarkers a Machine Learning classifier is cross-validated and interpreted with SHapley Additive exPlanations (SHAP) values. The number of non-motor symptoms differed significantly for Tasks 1 and 2 but not for Task 3. The proposed drawing features partially differed significantly for all three tasks. The diagnostic accuracy was on average 94.0% in Task 1, 89.4% in Task 2, and 72% in Task 3. While the accuracy in Task 3 only using the symptom questionnaire was close to the baseline, it greatly improved when including the tablet-based features from 60 to 72%. The accuracies for all three tasks were significantly improved by integrating the two modalities. These results show that tablet-based drawing features can not only be captured by consumer grade devices, but also capture specific features to Parkinson’s Disease that significantly improve the diagnostic accuracy compared to the symptom questionnaire. Therefore, the proposed system provides an objective type of disease characterization of movement disorders, which could be utilized for home-based assessments as well.

Clinicaltrials.gov Study-ID: NCT03638479.
Sperm-fluid-cell interplays in the bovine oviduct: glycosaminoglycans modulate sperm binding to the isthmic reservoir
Authors: Mahé Coline , Pranomphon Thanya , Reynaud Karine , Laffont Ludivine , Meylheuc Thierry , Schoen Jennifer , Mermillod Pascal , Saint-Dizier Marie
Published: June 2023

When entering the oviduct for fertilisation, spermatozoa come into contact with the oviduct fluid (OF) and can bind to luminal epithelial cells in the isthmus to form a sperm reservoir. The objective of this study was to examine how the OF modulates sperm adhesion to the oviduct reservoir using an in vitro model of oviduct epithelial spheroids (OES). Bovine oviducts from a local slaughterhouse were used to collect OF and isthmic fragments for the in vitro incubation of OES. Compared to a non-capacitating control medium, the pre-ovulatory OF significantly decreased by 80–90% the density of spermatozoa bound to OES without affecting sperm motility, membrane integrity, or sperm-cilia interactions. This effect on sperm binding was reproduced with (1) OF from different cycle stages and anatomical regions of the oviduct; (2) OF fractions of more than 3 kDa; (3) modified OF in which proteins were denatured or digested and (4) heparan sulphate but not hyaluronic acid, two glycosaminoglycans present in the OF. In conclusion, the OF significantly decreased the number of spermatozoa that bind to oviduct epithelial cells without affecting sperm motility and this effect was due to macromolecules, including heparan sulphate.
Annealing temperature effects on the size and band gap of ZnS quantum dots fabricated by co-precipitation technique without capping agent
Authors: Alwany Abduelwhab. B. , Youssef G. M. , Samir O. M. , Algradee Mohammed A. , A.Yahya Nabil A. , Swillam Mohamed A. , Humaidi Syahrul , Abd‑Shukor R.
Published: June 2023

ZnS quantum dots (QDs) were fabricated using the co-precipitation technique with no capping agent. The effects of different annealing temperatures (non-annealed, 240 °C and 340 °C for 2 h) on the structural and optical characteristics of ZnS QDs are reported. The samples were examined by XRD, TEM, PL, FTIR, and UV–Vis. An increase in annealing temperature led to an increase in the dot size and a lowering of the energy band gap (EG). The average crystallite size, D of ZnS was between 4.4 and 5.6 nm. The ZnS QDs showed a band gap of 3.75, 3.74 and 3.72 eV for non-annealed, 240 °C, and 340 °C annealed samples. The reflection spectra increased in the visible light and decreased in UV region with an increase in annealing temperature. This work showed that the band gap and size of ZnS QDs could be tuned by varying the annealing temperature.
PEG-grafted arsenic trioxide-loaded mesoporous silica nanoparticles endowed with pH-triggered delivery for liver cancer therapy
Authors: Jiang Liangdi , Wang Xuerui , Raza Faisal , Zhong Hongyu , Su Jing , Yuan Wei-En , Qiu Mingfeng
Published: June 2023

A pH-responsive nanoplatform (PEG-MSN@ATO) was fabricated. It can accumulate more to the tumor and achieve pH-triggered ATO release in the tumor microenvironment, exerting the anti-liver cancer effect through multiple mechanisms of ATO.
Polymer/copper nanocomplex-induced lysosomal cell death promotes tumor lymphocyte infiltration and synergizes anti-PD-L1 immunotherapy for triple-negative breast cancer
Authors: Hu Xiangxiang , Wang Mingming , Shi Shanshan , Keerthi Raja Manikanda , Gupta Gourab , Chen Hexin , Xu Peisheng
Published: June 2023

The PDA-PEG/copper nanocomplex kills 4T1 cells by lysosomal cell death and exhibits a synergetic effect with the PD-L1 antibody through ICD-boosted T-cell infiltration.
Peroxomolybdate@MOFs as effective catalysts for oxidative desulfurization of fuels: correlation between MOF structure and catalytic activity
Authors: Gao Yan , Granadeiro Carlos M. , Cunha-Silva Luís , Zhao Jianshe , Balula Salete S.
Published: June 2023

The highly active peroxomolybdate, TBA3{PO4[MoO(O2)2]4}·3H2O was incorporated for the first time in various porous MOF support structures (MIL-101, MOF-808, and ZIF-8) to form heterogeneous catalysts with different structural properties.
Distinct effects of nano-polystyrene, erythromycin, and their mixtures on the composition and metabolic profile of intestinal microbiota in Nereis succinea
Authors: Wang Dali , Zhong Yuheng , Ding Qi , Han Xiaofeng , Chen Kai , Pan Bo , You Jing
Published: June 2023

Mixture effects of nano-polystyrene (PS) and erythromycin to N. succinea and its intestinal microbiota are complex depending on exposure concentrations, and PS dominated the effects.
Multi-dimensional deep learning drives efficient discovery of novel neuroprotective peptides from walnut protein isolates
Authors: Lin Like , Li Cong , Zhang Li , Zhang Yujiao , Gao Lu , Li Tingting , Jin Lihua , Shen Yehua , Ren Difeng
Published: June 2023

A deep learning model named MiCNN–LSTM was designed for the rapid screening of multifunctional neuroprotective peptides in this paper. 4 Novel multifunctional neuroprotective peptides were selected from walnut protein and validated by d-gal-induced mice.
Untargeted metabolomics revealed the regulatory effect of Maillard reaction products of ovalbumin with different degrees on the metabolism of colitis mice
Authors: Yang Qi , Shang Xiaomin , Li Ting , Lyu Siwen , Liu Xuanting , Du Zhiyang , Liu Jingbo , Zhang Ting
Published: June 2023

The Maillard reaction (MR) is inevitable in food processing and daily cooking, but whether the MR degree would affect the biological activity of the protein in vivo remains unknown.
Photocatalytic water oxidation over LaWO0.6N2.4 mesoporous single crystals under visible and near-infrared light illumination
Authors: Yang Lin , Duan Hui , Xu Xiaoxiang
Published: June 2023

LaWO0.6N2.4 mesoporous single crystals have been topotactically converted from BiLaWO6, which deliver an AQE as high as 0.13% at 800 ± 20 nm for water oxidation to O2.
Selective C–C coupling of two nitriles affording rare-earth diazametallacyclopentadienes: synthesis, cooperative reactivity and mechanistic studies
Authors: Zhu Miaomiao , Chai Zhengqi , Li Tianyu , Wei Junnian , Lv Ze-Jie , Zhang Wen-Xiong
Published: June 2023

Selective C–C coupling of two nitriles mediated by rare-earth metals gives the first rare-earth diazametallacyclopentadienes through the insertion–release–insertion sequence. The diazametallacyclopentadienes exhibit diverse insertion reactivity.
MOFs for long-term gas storage: exploiting kinetic trapping in ZIF-8 for on-demand and stimuli-controlled gas release
Authors: Heinz Karsten , Rogge Sven M. J. , Kalytta-Mewes Andreas , Volkmer Dirk , Bunzen Hana
Published: June 2023

Pores as high-pressure containers: MOFs with a flexible pore opening for long-term gas storage under ambient conditions in air.
Melamine–isatin tris Schiff base as an efficient corrosion inhibitor for mild steel in 0.5 molar hydrochloric acid solution: weight loss, electrochemical and surface studies
Authors: Arshad Ifzan , Qureshi Khizar , Saleemi Awais Siddique , Abdullah Ali , Bahajjaj Aboud Ahmed Awadh , Ali Shafaqat , Bokhari Awais
Published: June 2023

In the current study, 3,3′,3′′-((1,3,5-triazine-2,4,6-triyl)tris(azaneylylidene))tris(indolin-2-one) (MISB), which is the condensation product of melamine (triazine) and isatin, was investigated as a mild steel corrosion inhibitor in 0.5 M HCl.
Polydots, soft nanoparticles, at membrane interfaces
Authors: Wijesinghe Sidath , Junghans Christoph , Perahia Dvora , Grest Gary S.
Published: June 2023

Soft nanoparticles (NPs) are emerging candidates for nano medicine, particularly for intercellular imaging and targeted drug delivery.
Adsorption and desorption of flavonoids on activated carbon impregnated with different metal ions
Authors: Lu Li , Cao Shuang , Li Zhexuan , Huang Jingdan , Jiang Yukai , Deng Changyong , Liu Zhimei , Liu Ziwei
Published: June 2023

The application for the flavonoids seperation of the activated carbon impregnated with metal ions.
A heterologous expression platform in Aspergillus nidulans for the elucidation of cryptic secondary metabolism biosynthetic gene clusters: discovery of the Aspergillus fumigatus sartorypyrone biosynthetic pathway
Authors: Lin Shu-Yi , Oakley C. Elizabeth , Jenkinson Cory B. , Chiang Yi-Ming , Lee Ching-Kuo , Jones Christopher G. , Seidler Paul M. , Nelson Hosea M. , Todd Richard B. , Wang Clay C. C. , Oakley Berl R.
Published: June 2023

Secondary metabolites are important for the pathogenesis of the fungus Aspergillus fumigatus which causes lethal Aspergillosis. Expressing groups of A. fumigatus genes in the fungus Aspergillus nidulans reveals new A. fumigatus secondary metabolites.
The scale-free theory of stellar convection
Authors: Chiosi C. , Pasetto S. , Chiosi E. , Crnojević D.
Published: June 2023

Context. A new, self-consistent, scale-free theory of stellar convection was recently developed (SFCT) in which velocities, dimensions, and energy fluxes carried by the convective elements are defined in a rest frame co-moving with the convective element itself. As the dynamics of the problem is formulated in a different framework with respect to the mixing length theory (MLT), the SFCT equations are sufficient to determine all the properties of stellar convection in accordance with the physics of the environment alone, with no need for the mixing length parameter (MLP). Subsequently, the SFCT was improved by introducing suitable boundary conditions at the surface of the external convective zones of the stars, and the first stellar models and evolutionary tracks on the Hertzsprung–Russell diagram were calculated.

Aims. The SFCT received alternatively positive and negative attention that spurred us to reconsider the whole problem. In this work, we aim to re-examine the physical foundations and results of the SFCT, elucidate some misconceptions on its physical foundations, reply to reported criticisms, and present some recent improvements to the SFCT.

Methods. The analysis was done using the same formalism of the previous studies, but novel arguments and demonstrations are added to better justify the controversial points, in particular the relaxation of instantaneous hydrostatic equilibrium between a convective element and the surrounding medium.

Results. The main results include (i) a novel detailed discussion of the boundary conditions to ensure that the temperature gradients in the outermost regions of a star are adequate for analyses of stability or instability in asteroseismology; (ii) a quantitative comparison with the MLT; and, finally, (iii) the recovery of the MLT as a particular case of the SFCT, but also in this case with no need for the MLP.

Conclusions. In conclusion, the SFCT is a step forward with respect to the classical MLT.
Electrochromic properties of monosubstituted benzylboronic acid viologen
Authors: Tang Shengwei , Niu Junlong , Jia Chunyang
Published: June 2023

Synthesis of monosubstituted benzyl boronic acid viologen (mBBV) has been achieved. The boronic acid group in mBBV can form boronic ester bonds with the hydroxyl groups in polyvinyl alcohol (PVA), resulting in an all-in-one electrochromic gel. The immobilized viologen by boronic ester bonds can slow down the diffusion rate and effectively mitigate viologen dimerization, which may address the issues caused by dimerization. The optical contrasts of mBBV and mBBV-PVA reached 49.02% and 45.01%, respectively. The electrochemical and electrochromic properties obtained from the tests suggest the potential application of mBBV in the field of electrochromics.
Research on the Development of Sensor Tracking Technology under the Guidance of Artificial Intelligence
Authors: Ge Shan
Published: June 2023

The development and application of artificial intelligence from before heavy calculation to today's parallel processing, has a qualitative leap, for the experience of human experts can predict the conclusion, the integration of chip development has been artificial intelligence to create economic benefits of a big research topic, and combined with the analysis of all kinds of indicators to sensor data technology also more directional in artificial intelligence, modern research and development of all kinds of tracking equipment and drone equipment to a certain extent, integrated the sensor detection technology, and on the development of programming language, have the updated research field.
Research on Properties of Polypropylene/Flake Graphite Molded Composite Materials
Authors: Zhou Haijun , Zhou Mengmeng , Zhang Xiaolei , Bai Lu , Chen Xiaoqi , Zhang Fen , Li ChengYu , Li Yantao
Published: June 2023

PP/FG composite materials were prepared by compressing moulding under high temperature through high-speed mixer, mixing mill and vulcanization machine taking PP as the matrix resin, FG as the thermal conductive filler, and NDZ-201 as the coupling agent. Effects of PP proportion, FG content and particle size on the thermal conductivity and mechanical properties of composite materials were studied. Results showed that PP proportion has little effect on the thermal conductivity of PP/FG composite materials, but it greatly affects the mechanical properties of the composite materials. Overall, the quality ratio of PP230 to K-4038 at 50:50 is more suitable. With the increasing of FG content, the thermal conductivity increases, and a significant critical value appears when the FG content is 50 wt%; The strength of the composite material first decreases and then increases, with an increase in modulus and a decrease in strain. As the FG particle size increases, the thermal conductivity of the composite material increases and the mechanical properties decrease.
Finite Element Simulation Calculation and Optimal Design of Permanent Magnet Synchronous Motor
Authors: Yuan Peizhi
Published: June 2023

In order to promote the development of green energy applications, this paper selects a 4-pole 24-slot surface-mounted permanent magnet synchronous motor and performs finite element simulation and optimization design on it. Firstly, finite element analysis is carried out, and the performance of the motor is verified by finite element simulation. Then, the parameterized simulation and sensitivity analysis of cogging torque and three-phase current are performed by selecting the variables of permanent magnet thickness, stator inner diameter, slot width, and air gap. Finally, simulation experiments provide optimization for each variable for the motor.
Time Response and Natural Frequency Analysis for Structures with Interval Parameters
Authors: Feng Xingxing , Cao Chang , Liu Min
Published: June 2023

This paper deals with the evaluations of lower and upper bounds of dynamic responses and natural frequencies for structures with uncertain interval parameters. The structural physical parameters, geometric dimensions and initial conditions can be considered as interval parameters. The modified Chebyshev interval method (MCIM) is presented to handle the uncertainties. In comparison with the Chebyshev interval method (CIM), MICM provides with tighter bounds of the time responses and natural frequencies without a significant increase in computation time. Monte Carlo method is also used to provide with exact bounds. MICM, CIM and Monte Carlo method are applied for structures with interval parameters, and the efficiency and accuracy of CIM and MCIM are verified.
Research on Distance Measurement Method of field driving Test system
Authors: Yao Yao , Chao Han , Yang Wu , Jinzhou Dai , Peng Xu
Published: June 2023

The accuracy of driving test systems is very important. Aiming at the content and characteristics of the subject II examination items, we studied the distance measurement items and methods of the field driving test system, and test the distance examination items in the field driving test system. The results show that the measurement method studied in this paper can realize the accurate judgment of the field driving test system, providing technical support for the accuracy detection of the driving test system, and ensure the fairness and justice of the driving test.
Experimental study on the factors affecting the performance of wire-plate Biefeld-Brown thrust unit
Authors: Li Jinbao , Lai Lin
Published: June 2023

Biefeld-Brown effect (B-B effect for short) refers to the phenomenon that when a high voltage is applied to an asymmetric capacitor, the capacitor generates an additional force. In order to explore the influencing factors and series characteristics of the B-B effect of wire-plate asymmetric capacitors in atmospheric pressure, a set of experimental devices with adjustable parameters was designed. Based on this device, the effects of different wire-plate lengths, power supply types and electrode application modes on the thrust and efficiency of B-B effect are studied. At the same time, the optimal parameters are selected to study the series characteristics. The research shows that the thrust generated by B-B effect is directly proportional to the length of the wire plate. The thrust generated by applying positive emission voltage to the copper wire and grounding the aluminum plate is the largest, and the two-stage series connection can achieve multiple increase of the thrust, with better performance.
Chemical composition and identification of glass products based on generalized linear model
Authors: Pan Zhuo
Published: June 2023

Weathering will cause the proportion of chemical composition of ancient glass products to change, thereby affecting the classification judgment of glass type. In order to reasonably analyze the composition content of ancient glass products, this paper provides a reference for studying the content change trend of glass weathering by exploring whether the appearance of glass cultural relics affects the weathering trend and the weathering composition law. According to the relationship between glass surface weathering and ornamentation, color and glass type, a linear regression model is constructed, and in order to solve the problem of heteroscedasticity in the perturbation term, the OLS robust + standard error method is used to improve the model parameters. The results show that the ornaments are B and C and are more likely to weather, high potassium glass is easy to weather, the color is green is mostly unweathered glass, and the color is black There is a tendency to change to weathered glass. The lower the content of potassium oxide, iron oxide and alumina in high potassium, the easier it is to weather, the higher the silica content, the easier it is to weather, and the regularity of weathering and component content of lead barium compared with high potassium is not obvious.
Vibrational analysis of stiffened double-layered plate in vacuum
Authors: Wang Peng , Li Zhao , Zhang Hao , Chen Jiandong , Li Wei , Liu Min
Published: June 2023

Stiffened plate has widely application in engineering, stiffened double-layered plate is one typical structure. In this work, research object is the stiffened double-layered plate, modal and forced vibration responses are studied through experimental work and numerical simulation with FEM software, and comparative analysis is also conducted. Numerical results show that, experimental results match well with numerical simulation results, the maximum difference for first four modal frequencies are less than 5%, so numerical simulation is verified to be correct. Conclusions here will help to support the further design and application of stiffened double-layered plate in engineering area.
A Method for Monitoring Operation Status of Oil-immersed Transformer Based on the Baffle Angle Characteristic of Gas Relay
Authors: Bai Peixian , Xie Yiling , Dou Longjiang
Published: June 2023

A gas relay in the transformer, an important non-electricity protection equipment, only triggers the stem leaf spring for the serious gas alarm when the baffle rotates to a certain angle, which cannot judge the transformer fault in the event of heavy gas before running state and fault development process, this paper puts forward a kind of based on gas relay panel corner of transformer running state monitoring methods. The partial structure of the gas relay is improved, and the baffle corner signal is extracted by installing a Hall sensor on the back of the baffle. On this basis, this paper develops a test stand capable of simulating the baffle characteristics of gas relays at different fault energies. Subsequently, the baffle angle variation law under different fault energies is studied, and the influence of pipe pressure and pipe flow rate on the baffle angle is given. The results show that, based on this improved gas relay, the real-time baffle angle information can reflect the internal operating state of the transformer and provide an effective method for transformer operating condition monitoring.
Wechsel von intensivierter Insulintherapie auf eine Insulinpumpe
Authors: Schoppe Theresia
Published: June 2023

Oft beginnt eine Umstellung der Insulintherapie mit dem Wunsch der Patient*innen. In anderen Fällen geht die Initiative vom Diabetesteam aus. In jedem Fall ist die Transition von intensivierter Insulintherapie auf eine Insulinpumpe ein längerer Prozess. Im Folgenden werden die einzelnen Schritte und Überlegungen bzgl. Entscheidungsfindung, Verordnung und Prüfung durch den Medizinischen Dienst sowie Therapieumstellung und Insulinpumpen-Schulung beschrieben.
Adipositas als Krankheit und Barriere
Authors: Metzler Michael
Published: June 2023

Gesellschaftlich ist die Prävention der Adipositas relevant. Wichtig ist die Anerkennung der Adipositas als Krankheit und Barriere. Eine berufliche Neuorientierung zur Förderung der Teilhabe mit dauerhafter beruflicher Perspektive bei Adipositas ist aber nur erschwert über eine Qualifizierung in einem Berufsförderungswerk (BFW) zu erreichen. Wie eine berufliche Neuorientierung für Menschen mit Adipositas gelingend gestaltet werden kann, wurde in einer Literaturanalyse und Stichprobenerhebungen der Adipositas im BFW untersucht. Ergebnisse: Für Menschen mit Adipositas gestaltet es sich schwierig, an Leistungen zur Teilhabe (LTA) beteiligt zu werden. Für die Adipositas Grad 1 (WHO) ICD E 66.00 wurden hier in Stichproben im BFW Oberhausen unter etwa 1000 Teilnehmern 4 % dokumentiert. Für die weitere Dokumentation wurden gelistet: Adipositas Grad 2 (WHO) E 66.01 mit 5 %, Adipositas Grad 3 BMI 40–50 (WHO) ICD E66.06 mit 2,5 %, Adipositas Grad 3 BMI 50–60 (WHO) ICD E66.07 mit 0,4 % und für Adipositas Grad 3 BMI > 60 (WHO) ICD E66.08 mit 0,1 %. Im Profil der Rehabilitationsdiagnosen der LTA spielt die Adipositas mit Krankheitsbezug nur zu einem kleinen Prozentsatz eine Rolle. Die Diagnose Adipositas wird in der Regel nicht als rehabilitationsrelevante Hauptdiagnose geführt. Eine besser abgestimmte Interaktion der Akteure in Gesundheitssektoren könnten die berufliche Rehabilitation im Kontext der Adipositas mehr als bisher einbeziehen. Eine Verhaltens- und Verhältnisprävention hat eine große Bedeutung. Eine nach ICF ausgerichtete Analyse und Förderung von Kompetenzen ist ein wichtiges Instrument. Über einen kontrollierten Zeitraum von 24 Monaten lassen sich sowohl positive Effekte für die berufliche Qualifizierung als auch spätere Berufsausübung erwarten. Ein verbesserter Gesundheitsstatus mit positiven Auswirkungen auf den Stoffwechsel führt zu einer gesteigerten Handlungskompetenz und körperlichen Fitness. Dem Verbleib im Beruf, und nicht alleinig einer guten Qualifizierung, sollte in Anbetracht der demografischen Entwicklung und knappen Arbeitskraftressourcen für Menschen mit Adipositas eine größere Aufmerksamkeit zukommen. Investitionen in die Prävention und nichtmedikamentöse / nichtoperative Behandlung sollten in zukünftigen Gesundheitskonzeptionen überdacht werden (z. B. Personal, Schwimmbäder nicht nur als Kostenfaktor betrachtet).
Investing in nature can improve equity and economic returns
Authors: Johnson Justin Andrew , Baldos Uris Lantz , Corong Erwin , Hertel Thomas , Polasky Stephen , Cervigni Raffaello , Roxburgh Toby , Ruta Giovanni , Salemi Colette , Thakrar Sumil
Published: June 2023

Sustainable development requires jointly achieving economic development to raise standards of living and environmental sustainability to secure these gains for the long run. Here, we develop a local-to-global, and global-to-local, earth-economy model that integrates the Global Trade Analysis Project (GTAP)-computable general equilibrium model of the economy with the Integrated Valuation of Ecosystem Services and Tradeoffs (InVEST) model of fine-scale, spatially explicit ecosystem services. The integrated model, GTAP–InVEST, jointly determines land use, environmental conditions, ecosystem services, market prices, supply and demand across economic sectors, trade across regions, and aggregate performance metrics like GDP. We use the integrated model to analyze the contribution of investing in nature for economic prosperity, accounting for the impact of four important ecosystem services (pollination, timber provision, marine fisheries, and carbon sequestration). We show that investments in nature result in large improvements relative to a business-as-usual path, accruing annual gains of $100 to $350 billion (2014 USD) with the largest percentage gains in the lowest-income countries. Our estimates include only a small subset of ecosystem services and could be far higher with inclusion of more ecosystem services, incorporation of ecological tipping points, and reduction in substitutability that limits economic adjustments to declines in natural capital. Our analysis highlights the need for improved environmental–economic modeling and the vital importance of integrating environmental information firmly into economic analysis and policy. The benefits of doing so are potentially very large, with the greatest percentage benefits accruing to inhabitants of the poorest countries.
Curculio dieckmanni (Faust). [Distribution map].
Authors: CABI  , EPPO
Published: June 2023

A new distribution map is provided for Curculio dieckmanni (Faust). Coleoptera: Curculionidae. Hosts: Asian hazel (
Corylus heterophylla
) and Corylus mandshurica.
Curculio elephas (Gyllenhal). [Distribution map].
Authors: CABI  , EPPO
Published: June 2023

A new distribution map is provided for Curculio elephas (Gyllenhal). Coleoptera: Curculionidae. Hosts: chestnut (
Castanea sativa
) and oaks (
Quercus
spp.).
RF02 Using functional genomic techniques to help us understand the TYK2 pathway in psoriasis
Authors: Elyoussfi Sarah , Rane Shraddha , Eyre Stephen , Warren Richard
Published: June 2023

Genetic screens have identified around 126 genetic signals associated with psoriasis through genome-wide association studies (GWAS) and rare variant analyses (Tsoi LC, Stuart PE, Tian C et al. Large scale meta-analysis characterizes genetic architecture for common psoriasis associated variants. Nat Commun 2017; 8:15382). The aim of this study was to use genome-editing techniques to investigate and validate the effect of a psoriasis-associated genetic signal on the expression of TYK2. GWAS have linked TYK2 to psoriasis susceptibility through the association of a protein-changing, exonic variant where TYK2 impairment confers protection against the development of psoriasis and other autoimmune diseases. The vast majority of disease risk-associated variants are found outside gene-coding regions. Functional experimental techniques may help characterize the effect of these variants on gene expression. The development of genome editing technology, clustered regularly interspaced short-palindromic repeat-Cas9 (CRISPR-Cas9), has made it possible to edit cell genomes. We used CRISPR-Cas9 to validate functionally the psoriasis-associated single nucleotide polymorphism (SNP) rs892085 on TYK2 expression in immortal T-cell lines. In-house data from our centre revealed the presence of long-range physical interactions between rs892085 and TYK2. We are the first to investigate functionally this signal and characterize this physical connection. We used CRISPR-Cas9 systems to both activate and inhibit the region around rs892085 and then measured the consequence of this through informative functional readouts using quantitative reverse transcription polymerase chain reaction. This revealed consistent alteration of TYK2 expression upon inhibition and activation of rs892085. This supports previous observations, where this regulatory region harbouring GWAS-implicated variation operates through direct long-distance contact. Previously, the closest or most biologically relevant gene was often assigned to a GWAS variant. We have shown that this is unreliable, with DNA regions looping over large distances to control genes. This work provides the first functional validation of the psoriasis-associated SNP rs892085. TYK2 is a recognized drug target with one therapy, deucravacitinib, approved by the US Food and Drug Administration. Drugs entering the clinical development stage that have used human genetic data to select drug targets may be more likely to succeed. This work demonstrates the potential complexity of how risk alleles may work to dysregulate TYK2 signalling in disease, with both gene function and expression increasing the risk of disease. Ultimately, genetic risk scores, incorporating functional evidence from studies like this, may be generated to predict how patients with different genetically perturbed biology pathways may respond to therapy.
CPC03 Triad of generalized rash, peripheral eosinophilia and coexisting obstructive airway disease
Authors: Willsher Alex , Soriano Livia , Selim Salma , Fong Wei Chen , Fityan Adam
Published: June 2023

An 87-year-old woman was referred to the acute dermatology service with a 1-week history of a generalized painful rash. She was under the care of the medical team for treatment of pneumonia with symptoms of a cough, fevers and shortness of breath. Her past medical history included adult-onset asthma, hyponatraemia and hypertension. She had never smoked. On examination, she had erythematous smooth papules and plaques on her limbs and torso with palmoplantar involvement, alongside purple macules and patches where older lesions were present. There was no lymphadenopathy and no mucosal involvement. She had an oxygen requirement of 2 L per minute via nasal cannula. Initial blood tests showed eosinophils of 2.8 × 109 cells L−1 and a C-reactive protein (CRP) of 77 mg L−1. A chest radiograph showed bilateral ill-defined shadowing. Two skin punch biopsies were performed for histology and immunofluorescence. Vasculitis screen identified positive antinuclear antibodies (anti-Ro) and reduced complement C4 with negative antineutrophil cytoplasmic antibody (ANCA). The patient remained unwell with increasing CRP and peripheral eosinophilia (up to 9.2 × 109 cells L−1) with rash progressing to exhibit a reticular pattern. Alongside bilateral patchy ground glass opacification on chest computed tomography, a clinical diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA) was made. Differential diagnoses included viral exanthem, erythema multiforme and urticarial vasculitis. Screening for cardiac, renal and sinus involvement was undertaken. The patient improved clinically following the initiation of systemic steroids and the peripheral eosinophilia returned to baseline. Skin histology reinforced the clinical diagnosis of EGPA, demonstrating a dermal and perivascular eosinophilic infiltrate with focal extension into vessel walls. EGPA is a rare small- to medium-sized vessel vasculitis with an annual incidence of 0.9–2.4 per million and a median age at diagnosis of 49–59 years. The clinicopathological hallmarks, as in this case, are asthma with peripheral eosinophilia and pulmonary eosinophilic infiltrates. Median time from onset of asthma to presentation with EGPA is 5–9 years. EGPA remains a clinical diagnosis, reinforced by serological and histological findings, although ANCA is reported to be negative in 60–70% of cases. Systemic steroids are the first-line therapy, with a role for second-line immunosuppressants such as methotrexate and rituximab. The key learning points from this case are to keep an open mind in considering a systemic cause for cutaneous manifestations, especially when the patient does not fulfil the usual demographic picture.
CPC05 A case of extensive hypertrophic lupus erythematosus responsive to topical steroids
Authors: Diong Sophie , Woods Graham , Wynne Bairbre
Published: June 2023

Hypertrophic lupus erythematosus (HLE) is a rare variant of lupus erythematosus, occurring in 2% of cases of chronic cutaneous lupus erythematosus (CCLE). It is an exaggerated proliferative epithelial response manifesting as verrucous-appearing hypertrophic indurated lesions occurring on sun-exposed sites. We present a case of the development of extensive HLE in a patient with subacute cutaneous lupus erythematosus (SCLE) with underlying pulmonary malignancy. A 74-year-old woman with Sjögren syndrome presented to dermatology with a 2-month history of a rash affecting her face and décolletage. Laboratory studies illustrated elevated antinuclear and anti-Ro antibodies. Biopsy from her chest confirmed SCLE. Malignancy screening revealed T1aN0 pulmonary lepidic adenocarcinoma, which was successfully managed with a lower lobectomy. Hydroxychloroquine was initially trialled but required discontinuation following intolerable side-effects. Mepacrine was then initiated, which allowed clearance of the rash, alongside yellow discoloration of the skin. Six months later, she developed a raised pruritic rash on her arms, legs and buttocks, resistant to current management alongside a trial of mycophenolate mofetil. Examination revealed violaceous hypertrophic plaques affecting 40% of her body-­surface area. The differential included hypertrophic lichen planus, nodular prurigo and HLE. Repeat lesional biopsies highlighted a lichenoid inflammatory infiltrate with overlying scale, favouring HLE. Owing to patient choice, topical mometasone furoate 0.1% was used to manage cutaneous disease, with a reduction in lesion size. HLE is a distinct subset of CCLE, regarded as a separate entity to SCLE. Twenty per cent of patients with SCLE also exhibit other types of cutaneous lupus erythematosus (CLE) lesions. No cases in the literature describe progression from SCLE to CCLE, or HLE, in particular. Hallmarks of HLE include verrucous lesions, chronicity and treatment resistance. Early recognition and follow-up are essential as malignancy may arise in long-standing lesions. Lung adenocarcinomas and hypertrophic lupus are both associated with p53 mutations and decreased granzyme B expression. Mutated p53 results in constitutive cell proliferation and DNA damage can accumulate in cells. Granzyme B is a protease in cytotoxic T cells involved in immune-mediated cell lysis. Both processes result in the potential to produce exaggerated hyperproliferative lesions, such as those observed in HLE and the lepidic adenocarcinomas. HLE is a rare clinical entity that can be easily misdiagnosed clinically and histopathologically. Increased awareness of this condition is essential to highlight the variety of clinical presentations of uncommon variants of CLE, to ensure they are considered while approaching clinical diagnosis.
CPC09 New-onset agminated Spitz naevi following hypopigmented pityriasis lichenoides chronica
Authors: Adams Laura , Chohan Brinder , Bleiker Tanya
Published: June 2023

A 9-year-old girl presented to dermatology with erythematous scaly patches affecting her legs and arms, and hypo­pigmented patches affecting the trunk. She was otherwise fit and well, with no preceding illness or new medications. Treatment with mometasone 0.1% and an emollient was unsuccessful. Two years later, she had continued to develop new hypopigmented patches, as well as dark clustered naevi on the trunk. An incisional biopsy was taken from a hypopigmented patch of the right abdomen and one of the new naevi from the right hip. Incisional biopsy of the hypo­pigmented patch showed scattered necrotic keratinocytes in the epidermis with mild hydropic degeneration of basal cells and a mild superficial and perivascular lymphohistiocytic infiltrate in the dermis, consistent with pityriasis lichenoides chronica (PLC). Incisional biopsy of an eruptive naevus showed a junctional proliferation of melanocytes with overlying epidermal hyperplasia and hyperkeratosis and transepidermal elimination of melanin. Nests of epithelioid melanocytes were present at the rete tips, with no pagetoid spread and no atypia, consistent with an eruptive Spitz naevus. PLC is a benign lymphoproliferative disorder, typically presenting with erythematous scaly papules that relapse and remit. However, cases of PLC presenting with hypopigmentation alone have also been reported, as in this case, which can be part of a postinflammatory dyspigmentation or active disease (Elbendary A, Abdel-Halim MR, Youssef R et al. Hypopigmented lesions in pityriasis lichenoides chronica patients: are they only post-inflammatory hypopigmentation? Aust J Dermatol 2021; 63:68–73). The clustered pattern of Spitz naevi in this patient is termed agminated Spitz naevus. Eruptive disseminated and agminated Spitz naevi are much rarer than the solitary presentation. Triggers of eruptive Spitz naevi include pregnancy, blistering disorders and topical tacrolimus, and in one case following pityriasis lichenoides et varioliformis acuta (Mazzurco J, Menssen K, Schapiro B et al. Eruptive disseminated Spitz nevi in a 26-year-old African-American woman. Int J Dermatol 2012; 51:1270–1), while agminated Spitz naevi are reported to occur after radiotherapy and sunburn, and to arise in naevus spilus or congenitally hypo- or hyperpigmented patches. No cases of malignancy in agminated or eruptive disseminated Spitz naevi have been reported. In this case, the new onset of agminated Spitz naevi may have been triggered by the inflammatory process of PLC. As far as we can ascertain, there have not been previous cases of this published in the literature. Our patient’s hypopigmented areas have now started to self-resolve and we have planned for ongoing monitoring of the agminated Spitz naevi.
P08 Successful treatment of paediatric morphoea with tofacitinib
Authors: Tang Junchi , Zheng Wenyue , Yang Bin
Published: June 2023

Morphoea is a chronic autoimmune fibrosing condition causing inflammation, skin sclerosis and underlying soft tissue. The Janus kinase (JAK)-STAT pathway is considered to be the downstream mediator in the process of promoting fibrosis by transforming growth factor-β, interleukin-6 and other factors and plays a signal transduction role in the process of fibrosis. JAK inhibitors have been shown in preclinical studies to inhibit the fibrotic pathway in systemic sclerosis (Celada LJ, Kropski JA, Herazo-Maya JD et al. PD-1 up-regulation on CD4(+) T cells promotes pulmonary fibrosis through STAT3-mediated IL-17A and TGF-beta1 production. Sci Transl Med 2018; 10). Here, we report the successful use of tofacitinib in two paediatric patients. Case 1 was a 6-year-old girl with a 4-year history of morphoea; case 2 was a 13-year-old boy, also with a 4-year history of morphoea. In case 1, we initiated tofacitinib therapy 2.5 mg twice daily, reduced the dose after 2 months and stopped using it after 8 months. For case 2, the dose was 5 mg twice daily for 5 months, considering the patient’s height and weight. We have seen a significant improvement in the appearance and pathology of the lesions. The Localized Scleroderma Cutaneous Assessment Tool (LoSCAT) was used to assess the disease activity and damage, and the post-treatment scores for both cases were significantly lower than before treatment. Skin biopsy in both cases after tofacitinib therapy revealed that collagen bundles were decreased in size and number, with decreased lymphocytic infiltration in the peripheral tissue. Immunofluorescence staining for case 1 showed that activated α-smooth muscle actin and myofibroblasts were significantly decreased after treatment of tofacitinib, mostly in the dermal papillary layer. The two patients remain under follow-up; neither of them has so far relapsed. To our knowledge, these are the first two paediatric cases of morphoea treated with tofacitinib to be reported in the literature. Disease progression was found to have been inhibited clinically and pathologically. The traditional treatment of morphoea with methotrexate, cyclophosphamide or mycophenolate mofetil is not invariably effective in our experience, especially in antifibrosis (Zhao M, Wu J, Wu H et al. Clinical treatment options in scleroderma: recommendations and comprehensive review. Clin Rev Allergy Immunol 2022; 62:273–91). Our results provide the rationale for large prospective cohort studies of tofacitinib in morphoea and other fibrotic disorders.
P18 A novel presentation of glycogenic acanthosis of the lip
Authors: Cosgrave Niall , Clowry Julianne , Coady Laoise , McMenamin Mairin , Moran Benvon
Published: June 2023

Glycogenic acanthosis (GAc) is a benign epithelial disorder, commonly observed in the oesophagus during endoscopy as multiple raised nodules affecting otherwise normal oesophageal mucosae (Tsai SJ, Lin CC, Chang CW et al. Benign esophageal lesions: endoscopic and pathologic features. World J Gastroenterol 2015; 21:1091). Despite its indolent disease course, oesophageal GAc is a minor diagnostic criterion for Cowden syndrome (CS). Glycogenic acanthosis affecting tissues other than the oesophagus is extremely rare. There have only been six cases of oral GAc reported to date, with no confirmed reports of GAc affecting the lip. We present the case of a 65-year-old White man with a 6-month history of asymptomatic white papules on the left lower lip. He was a lifelong nonsmoker. His past medical history was notable for colorectal cancer, which was in remission posthemicolectomy. He had also undergone ablative treatment for nasal polyps. He had no history of gastro-oesophageal reflux disease, or of thyroid disease, benign or malignant. Prominent facial actinic damage was present, and a biopsy was performed to rule out dysplasia. Histology demonstrated thickened hyperplastic epidermis and cytoplasmic clearing in the superficial epidermis. Keratinocytes with enlarged cytoplasm were positive on periodic acid–Schiff staining, supporting a diagnosis of GAc. On review, 3 months later, a single residual white papule was observed on the left lower lip. There were no other cutaneous features suggestive of CS. CS is caused by mutations in PTEN and is part of a spectrum of disorders known as PTEN hamartoma tumour syndrome (PHTS). It is associated with increased risk of solid-organ malignancies. Of the prior six reported cases of oral GAc, only one (Nishizawa A, Satoh T, Watanabe R et al. Cowden syndrome: a novel mutation and overlooked glycogenic acanthosis in gingiva. Br J Dermatol 2009; 160:1116–18) had a confirmed association with CS. Our patient remains under endoscopic surveillance but does not currently meet the criteria for either diagnosis or further genetic evaluation of CS. Oral glycogenic acanthosis may be an under-recognized entity due to its subtle clinical presentation. Biopsy and full-skin examination are warranted in suspected cases, to identify any association with an underlying genodermatosis.