bluuebunny/crossref_metadata_2025 huggingface dataset:
Häufigkeit und Charakteristika von Einsätzen der Gemeindenotfallsanitäter bei Pflegebedürftigen
Authors: Klausen Andrea Diana , Günther Ulf , Schmiemann Guido , Hoffmann Falk , Seeger Insa
Published: December 2023

Hintergrund

Ziel der Arbeit war eine differenzierte Betrachtung der Rettungsdiensteinsätze von Gemeindenotfallsanitätern (G-NFS) bei älteren Pflegebedürftigen im Pflegeheim und in der Häuslichkeit.

Methodik

Retrospektive Auswertung aller G‑NFS-Einsatzprotokolle aus dem Jahr 2021 von älteren Patienten (≥65 Jahre), unterteilt nach den Einsatzorten Pflegeheim, häusliche Pflege und nichtpflegebedürftig. Es wurden Maßnahmen, Dringlichkeit, Transport und Empfehlung deskriptiv analysiert.

Ergebnisse

Von 5900 G‑NFS-Protokollen entfielen 43,0 % (n = 2410) auf ältere Patienten (Durchschnittsalter 80,8 Jahre, 49,7 % weiblich). Die Einsätze erfolgten mit 20,6 % (n = 496) bei Pflegeheimbewohnern, 38,4 % (n = 926) bei Pflegebedürftigen in häuslicher Versorgung und 41 % (n = 988) bei Nichtpflegebedürftigen. Eine Beratung erhielten 48,4 % der Pflegeheimbewohner, 82,1 % der Pflegebedürftigen in häuslicher Versorgung und 83,7 % der Nichtpflegebedürftigen. Etwa 60 % der Einsätze wurden bei allen Einsatzorten als nichtdringlich eingestuft. Auf Transporte wurde bei 63,1 % der Pflegeheimbewohner, 58,1 % der Pflegebedürftigen in häuslicher Versorgung und 60,6 % der Nichtpflegebedürftigen verzichtet. Ein Besuch der Notaufnahme wurde 29,4 % der Pflegeheimbewohner, 37,6 % der Pflegebedürftigen in häuslicher Versorgung und 33,6 % der Nichtpflegebedürftigen empfohlen. Dauerkatheter wurden häufiger im Pflegeheim (38,5 %) versorgt als in häuslicher Versorgung (15,1 %) und bei Nichtpflegebedürftigen (9,3 %).

Schlussfolgerungen

G‑NFS übernehmen primärversorgende Aufgaben und können zu einer Reduzierung unnötiger Transporte beitragen. Es muss jedoch diskutiert werden, inwieweit der Rettungsdienst für solche Einsätze zuständig ist und wie ältere Pflegebedürftige zukünftig bedarfsgerecht versorgt werden können.
Development of sourdough bread from roll-milled and stone-ground soft (Triticum aestivum) wheat flours milled to different extraction rates
Authors: Cardinali Federica , Garofalo Cristiana , Taccari Manuela , Osimani Andrea , Polverigiani Serena , Milanović Vesna , Rampanti Giorgia , Aquilanti Lucia
Published: December 2023

The aims of the present study are: (i) to verify the influence of different flour extraction rates and milling procedures on bread quality, (ii) to optimize the bread-making process by using different percentage and time of fermentation of three spontaneously developed type I sourdoughs. These latter were prepared with a whole-meal wheat flour blend (SA), a type 0 wheat flour blend (SB) both obtained by steel roll milling, and a type 2 wheat flour blend obtained by stone grinding (SC). The pH, total titratable acidity (TTA), and stability of the microbiota of the three sourdoughs were assessed before baking trials. TTA, specific volume, weight, crumb core moisture, texture, and global liking of sourdough bread, in comparison to control bread made with commercial baker’s yeast, were determined. Moisture, texture, and global liking of bread were also evaluated during 6 days of storage. SA was characterized by a significantly higher pH and TTA values than SB and SC. Differences in the LAB-to-yeast ratio were registered among the three sourdoughs although no differences were seen in terms of the dominant microbial community. Concerning breads, although the type 0 roll-milled wheat flour showed better dough rheological performance compared to whole-meal wheat flour and stone-ground wheat flour, sourdough fermentation positively affected the specific volume, texture, and global liking of bread manufactured with stone-ground wheat flour. Overall, for an efficient use of sourdough and bread quality improvement, optimal conditions need to be found by tailoring sourdough to the type of flour used.
The algebraic and geometric classification of nilpotent binary and mono Leibniz algebras
Authors: Abdurasulov Kobiljon , Kaygorodov Ivan , Khudoyberdiyev Abror
Published: December 2023

This paper is devoted to the complete algebraic and geometric classification of complex 5-dimensional nilpotent binary Leibniz and 4-dimensional nilpotent mono Leibniz algebras. As a corollary, we have the complete algebraic and geometric classification of complex 4-dimensional nilpotent algebras of nil-index 3.
A case of bullous pemphigoid and renal disease after dipeptidyl peptidase 4 inhibitor administration
Authors: Suenaga Atsuhiko , Sawa Naoki , Oba Yuki , Ikuma Daisuke , Sekine Akinari , Yamanouchi Masayuki , Hasegawa Eiko , Mizuno Hiroki , Suwabe Tatsuya , Hayashi Nobukazu , Kono Kei , Kinowaki Keiichi , Ohashi Kenichi , Miyazono Motoaki , Yamaguchi Yutaka , Ubara Yoshifumi
Published: December 2023

A 62-year-old man with type 2 diabetes was admitted because of a decrease in estimated glomerular filtration rate from 72 to 17.5 mL/min/1.73 m2 in 10 years and development of widespread bullous skin lesions. His hemoglobin A1c level had been maintained at 6.0–7.0% for 10 years with a dipeptidyl peptidase (DPP)-4 inhibitor. Skin biopsy showed typical bullous pemphigoid, and kidney biopsy showed tubulointerstitial nephritis with eosinophilic infiltration and glomerular endothelial cell proliferation. After discontinuing the DPP-4 inhibitor, skin lesions improved, and renal decline slowed. This case indicates that DPP-4 inhibitors can cause not only skin lesions but also renal disease.
Diagnostic Assessment of Autism in Children Using Telehealth in a Global Context: a Systematic Review
Authors: Katakis Panos , Estrin Georgia Lockwood , Wolstencroft Jeanne , Sayani Shermina , Buckley Ellie , Mirzaei Venus , Heys Michelle , Skuse David
Published: December 2023

Reflecting the significant delays in autism assessments globally, studies have explored whether autism assessments conducted via telehealth are feasible and accurate. This systematic review investigated the psychometric properties of autism assessment tools for children administered via telehealth and examined the diagnostic accuracy of telehealth assessment procedures compared to care-as-usual in-person assessments. Relevant databases (MEDLINE, Embase and PsycInfo) were searched for eligible studies (PROSPERO: CRD42022332500). In total, 18 studies were included, collectively assessing 1593 children for autism. Telehealth assessments for autism were largely comparable to in-person assessments, with a diagnostic agreement of 80–88.2%. Individual behavioral observation tools, diagnostic interviews, and clinician-administered screening tools demonstrated acceptable validity. For many children, diagnostic decision-making can be expedited without loss of validity using telehealth.
MSC-Based Cell Therapy for COVID-19-Associated ARDS and Classical ARDS: Comparative Perspectives
Authors: Weiss Daniel J. , Rolandsson Enes Sara
Published: December 2023

Purpose of Review

Despite no general conclusions regarding the therapeutic effect of MSCs on virus-induced acute lung injury in pre-clinical studies, a significant number of clinical trials using MSC-based treatment for COVID-19-associated ARDS were initiated during the global pandemic. Here, we aimed to discuss differences and similarities in clinical trials using MSC-based treatments for classical ARDS and COVID-19-associated ARDS and to raise some future perspectives.

Recent Findings

Several pre-clinical studies have demonstrated that MSC treatment may not be a good treatment option for virus infections because MSCs themselves are susceptible to the virus. However, MSCs lack expression of the angiotensin-converting enzyme 2 (ACE2) receptor, suggesting that MSCs are not likely to be infected by the COVID-19 virus. Interestingly, recent meta-analyses demonstrated that an improved survival rate in patients with COVID-19-associated ARDS treated with MSCs was obtained in 24 out of 26 completed clinical trials.

This review provides comparative perspectives on MSC-based therapy for COVID-19-associated ARDS and classical ARDS.
Data-Driven Circular Economy of Biowaste to Bioenergy with Conventional Prediction Modelling and Machine Learning
Authors: Matheri Anthony Njuguna , Sithole Zanele Blessed , Mohamed Belaid
Published: December 2023

Rapid population growth has not only increased energy demand, but waste generation that has increased and introduced emerging pollutants into waste streams, posing sanitary and environmental risks. The purpose of this research was to investigate waste to energy (anaerobic digestion-bioenergy process) on integrated waste management and digitalization of biomethane production as a data-driven circular economy model across the value chain of the carbon cycle (transition from take-make-dispose to use-make-return) through waste quantification, characterization, biomethane potential test (BMP) to prediction of the biomethane production. Anaerobic digestion experiment was conducted at a laboratory scale to analyze biomethane production from diverse substrates such as food waste, cow manure, sewage sludge, and chicken manure, with an average pH of 7.58. The experimental results obtained were then modelled and simulated with Modified Gompertz, Logistic, and Richards models and compared to machine learning simulation using Python with Gompertz, Logistics, and Richards models. Modified Logistic model was shown to be the best-fit curve, with a coefficient of determination (R2) > 0.9 validating the conventional mathematical modeling and simulation performance. During simulation with machine learning (Python), the experimental results obtained from the cow manure substrate provided the best fitting curve to the training curve compared to other substrates with the highest average of R2 as 1.0 for training, validation, and test data. Cow manure had the best validation performance at MSE (mean squared error) of 25.36 at epoch 1.

Graphical Abstract
MPPT techniques for photovoltaic systems: a systematic review in current trends and recent advances in artificial intelligence
Authors: Boubaker Olfa
Published: December 2023

Over the past decades, solar photovoltaic (PV) energy has been the most valuable green energy. It is renowned for its sustainability, environmentally friendly nature, and minimal maintenance costs. Several methods aiming to extract the highest photovoltaic energy are found in the vast literature. The aim of this systematic review is to focus on current trends and the most recent advances in the field. A “Scopus” bibliographic survey is conducted around survey and research articles published over the past three years (2019–2022). Over the selected works, different taxonomies of maximum power point tracking (MPPT) approaches are found. The list of associated performance criteria is also established, current trends, future directions and challenges in the field are well identified. This survey paper could be a useful reference for researchers and companies concerned by the sustainable development goals (GSD) for clean energy production and climate change.
A Quantum-Inspired Direct Learning Strategy for Positive and Unlabeled Data
Authors: Zhang Chenguang , Du Xuejiao , Zhang Yan
Published: December 2023

Learning from only positive and unlabeled (PU) data has broad applications in fields such as web data mining, product recommendations and medical diagnosis, which aims to train a binary classifier in the absence of negative labeled data. However, due to the lack of negative label information, prevailing PU learning methods usually rely on prior knowledge of unknown class distributions heavily. In fact, without additional constraints imposed by the prior knowledge, a direct learning strategy to coordinate the underlying clustering information in unlabeled data with the label information from positive training data is often considered challenging. To tackle this challenge, we propose a direct PU learning strategy using quantum formalization. By employing neural networks as backends, the samples are mapped into two-qubit composite systems, which should be understood here as mathematical entities encapsulating various classical distributions of two classical bits. Subsequently, the two qubits within the systems are trained to be as independent as possible from each other, capturing patterns of different classes. At the same time, their measurement results serving as the model outputs are encouraged to be maximally dissimilar. These characteristics enable effective training of classifiers on PU data. After formulating an appropriate discriminant rule, we introduce a quantum-inspired PU method named qPU using the direct learning strategy. This method not only has the potential to alleviate parameter sensitivity issues caused by prior estimation in other methods but is also straightforward to implement. Finally, experiments conducted on 13 classical datasets validate the effectiveness of qPU.
A longitudinal study of endoscopic naso-leakage negative pressure drainage for anastomotic leak after esophagectomy
Authors: Liu Xin-Yang , He Meng-Jiang , Liu Yan-Bo , Yin Hao , Tan Li-Jie , Zhou Ping-Hong , Lin Miao
Published: December 2023

Background and aims

Postoperative anastomotic leak is a threatening complication after esophagectomy. This study aims to evaluate the efficacy of endoscopic naso-leakage negative pressure drainage for anastomotic leak by longitudinal analyses, so as to focus on the intra-individual changes associated with the drainage in the disease course and to minimize the between-subject variations.

Methods

We conducted a retrospective longitudinal study. We hypothesize that maximum temperature (Tmax), maximum heart rate (HRmax), White blood cell count (WBC), and C reactive protein (CRP) had a two-piece linear spline growth curve with a notch at the time of drainage. Linear mixed-effects regressions were used to test the hypothesis of whether endoscopic naso-leakage negative pressure drainage changed the pattern of development of these clinical parameters with time.

Results

Thirty patients were included, among which 83.3% were male, with a median age of 77 years. The median postoperative time to drainage was 16.5 days (range 6-66). Observations for Tmax, HRmax, WBC, CRP and PCT were 1366, 1372, 394, 296 and 290, respectively. After adjusting for age, sex, and body mass index, Tmax, HRmax, WBC and CRP showed similar pattern. There was no significant change over time before naso-leakage negative pressure drainage, while the four parameters all decreased significantly over time after naso-leakage negative pressure drainage.

Conclusions

The slope over time of Tmax, HRmax, WBC and CRP changed significantly after naso-leakage negative pressure drainage. Naso-leakage negative pressure drainage brought gradual decrease of these inflammatory parameters and could serve as a promising management for postoperative anastomotic leak after esophagectomy.
Two-dimensional Janus drops in shear: deformation, rotation and their coupling
Authors: Zhang Chun-Yu , Chen Jia-Lei , Qian Li-Juan , Ding Hang
Published: December 2023

In this work, the dynamics of two-dimensional rotating Janus drops in shear flow is studied numerically using a ternary-fluid diffuse interface method. The rotation of Janus drops is found to be closely related to their deformation. A new deformation parameter

$D$

is proposed to assess the significance of the drop deformation. According to the maximum value of

$D$

(

$D_{max}$

), the deformation of rotating Janus drops can be classified into linear deformation (

$D_{max}\le 0.2$

) and nonlinear deformation (

$D_{max}> 0.2$

). In particular,

$D_{max}$

in the former depends linearly on the Reynolds and capillary numbers, which can be interpreted by a mass–spring model. Furthermore, the rotation period

$t_R$

of a Janus drop is found to be more sensitive to the drop deformation than to the aspect ratio of the drop at equilibrium. By introducing a corrected shear rate and an aspect ratio of drop deformation, a rotation model for Janus drops is established based on Jeffery's theory for rigid particles, and it agrees well with our numerical results.
Parliament and Revolution: Poland, Finland, and the End of Empire in the Early Twentieth Century
Authors: Marzec Wiktor , Turunen Risto
Published: December 2023

This article explores the political trajectories of the early twentieth-century Grand Duchy of Finland and the Kingdom of Poland in the context of the “global parliamentary moment,” when the constitutional script of revolution competed with the more daring script of social revolution. We scrutinize contrastive political choices of socialist parties in these two western borderlands of the Russian Empire. Finland and Poland emerged as independent parliamentary states in 1917–1918 but under manifestly different circumstances. The Finnish socialist party had enjoyed a stable foothold in the formally democratic but practically impotent national parliament since 1907, whereas the Polish socialists boycotted the Russian Duma and envisioned a democratic legislature as a guaranty of a Poland with true people’s power. The Finnish socialists later abandoned parliamentarism in favor of an armed revolution, in 1918, whereas most of their Polish counterparts used the parliamentary ideal of popular sovereignty to restrain the revolutionary upsurge. We argue that the socialist understandings of parliamentarism and revolution were of crucial importance at this juncture. We draw from a broad corpora of political press reports, handwritten newspapers, and leaflets to show how the diachronic sequence of events and synchronic power relations inside the Russian Empire made certain stances toward parliamentarism and revolution more likely at different points in time.
Auranofin attenuates Schistosoma mansoni egg-induced liver granuloma and fibrosis in mice
Authors: Atia A.F. , Abou-Hussien N.M. , Sweed D.M. , Sweed E. , Abo-khalil N.A.
Published: December 2023

Schistosomiasis is a serious tropical disease. Despite extensive research into the etiology of liver fibrosis, effective therapeutic options remain limited. This study aims to assess the effectiveness of auranofin in treating hepatic granuloma and fibrogenesis produced by Schistosoma (S.) mansoni eggs. Auranofin is a gold complex that contains thioglucose tetraacetate and triethylphosphine. Eighty BALB/c male mice were divided into four groups (n=20/group): negative control (GI), positive control (GII), and early (GIII) and late (GIV) treatment groups with oral auranofin according to beginning of treatment 4th week and 6th week post-infection. Mice were infected subcutaneously in a dose of 60±10 cercariae/mouse. Worm counts, egg loads, and oogram patterns were determined. Biochemical, histological, and immunostaining of interleukin-1β (IL-1β), Sirtuin 3 (SIRT3), and smooth muscle actin (SMA) were assessed. GIII showed a significant decrease in the total S. mansoni worm burden and ova/gram in liver tissue (with reduction percent of 63.07% and 78.26%, respectively). Schistosomal oogram patterns, immature and mature ova, also showed a significant decrease. The reduction in granuloma number and size was 40.63% and 48.66%, respectively, in GIII, whereas in GIV, the reduction percent was 76.63% and 67.08%. In addition, the degree of fibrosis was significantly diminished in both treated groups. GIV showed significant reduction in IL-1β and SMA expression and increase in SIRT3 expression. These findings reveal how auranofin suppresses the development of liver fibrosis. Therefore, it is crucial to take another look at auranofin as a prospective medication for the treatment of S. mansoni egg-induced hepatic granuloma and consequent fibrosis.
Neural networks need real-world behavior
Authors: Li Aedan Y. , Mur Marieke
Published: December 2023

Bowers et al. propose to use controlled behavioral experiments when evaluating deep neural networks as models of biological vision. We agree with the sentiment and draw parallels to the notion that “neuroscience needs behavior.” As a promising path forward, we suggest complementing image recognition tasks with increasingly realistic and well-controlled task environments that engage real-world object recognition behavior.
Using DNNs to understand the primate vision: A shortcut or a distraction?
Authors: Xu Yaoda , Vaziri-Pashkam Maryam
Published: December 2023

Bowers et al. bring forward critical issues in the current use of deep neural networks (DNNs) to model primate vision. Our own research further reveals fundamentally different algorithms utilized by DNNs for visual processing compared to the brain. It is time to reemphasize the value of basic vision research and put more resources and effort on understanding the primate brain itself.
Even deeper problems with neural network models of language
Authors: Bever Thomas G. , Chomsky Noam , Fong Sandiway , Piattelli-Palmarini Massimo
Published: December 2023

We recognize today's deep neural network (DNN) models of language behaviors as engineering achievements. However, what we know intuitively and scientifically about language shows that what DNNs are and how they are trained on bare texts, makes them poor models of mind and brain for language organization, as it interacts with infant biology, maturation, experience, unique principles, and natural law.
Perceptual learning in humans: An active, top-down-guided process
Authors: Slagter Heleen A.
Published: December 2023

Deep neural network (DNN) models of human-like vision are typically built by feeding blank slate DNN visual images as training data. However, the literature on human perception and perceptual learning suggests that developing DNNs that truly model human vision requires a shift in approach in which perception is not treated as a largely bottom-up process, but as an active, top-down-guided process.
Comprehensive assessment methods are key to progress in deep learning
Authors: Spratling Michael W.
Published: December 2023

Bowers et al. eloquently describe issues with current deep neural network (DNN) models of vision, claiming that there are deficits both with the methods of assessment, and with the models themselves. I am in agreement with both these claims, but propose a different recipe to the one outlined in the target article for overcoming these issues.
My pet pig won't fly and I want a refund
Authors: Tarr Michael J.
Published: December 2023

Pigs can't fly. Any person buying a pig should understand this – it would be absurd to be upset that they can't fly or play poker. But pigs are amazing creatures and can do many interesting and useful things.
Clarifying status of DNNs as models of human vision
Authors: Bowers Jeffrey S. , Malhotra Gaurav , Dujmović Marin , Montero Milton L. , Tsvetkov Christian , Biscione Valerio , Puebla Guillermo , Adolfi Federico , Hummel John E. , Heaton Rachel F. , Evans Benjamin D. , Mitchell Jeffrey , Blything Ryan
Published: December 2023

On several key issues we agree with the commentators. Perhaps most importantly, everyone seems to agree that psychology has an important role to play in building better models of human vision, and (most) everyone agrees (including us) that deep neural networks (DNNs) will play an important role in modelling human vision going forward. But there are also disagreements about what models are for, how DNN–human correspondences should be evaluated, the value of alternative modelling approaches, and impact of marketing hype in the literature. In our view, these latter issues are contributing to many unjustified claims regarding DNN–human correspondences in vision and other domains of cognition. We explore all these issues in this response.
The relevance of mechanisms and mechanistic knowledge for behavioural interventions: the case of household energy consumption
Authors: Grüne-Yanoff Till , Marchionni Caterina , Nuotio Tatu
Published: December 2023

We argue that behavioural public policies (BPP) should be categorized by the kind of mechanism through which they operate, not by the kind of treatment they implement. Reviewing the energy consumption BPP literature, we argue (i) that BPPs are currently categorized by treatment; (ii) that treatment-based categories are subject to mechanistic heterogeneity: there is substantial variation of mechanisms within each treatment type; and (iii) that they also display mechanistic overlap: there is substantial overlap between mechanisms across treatment types. Consequently, current categorizations of BPPs do not reveal the conditions of their efficacy and should be revised to better reflect mechanistic information.
ACCI could be a poor prognostic indicator for the in-hospital mortality of patients with SFTS
Authors: Gong Chen , Xiang Xinjian , Hong Baoyu , Shen Tingting , Zhang Meng , Shen Shichun , Ding Shenggang
Published: December 2023

This study aims to evaluate the predictive role of age-adjusted Charlson comorbidity index (ACCI) scores for in-hospital prognosis of severe fever in thrombocytopenia syndrome (SFTS) patients. A total of 192 patients diagnosed with SFTS were selected as the study subjects. Clinical data were retrospectively collected. Receiver operating characteristic curves were used to evaluate the diagnostic value of ACCI for the mortality of SFTS patients, and Cox regression models were used to assess the association between predictive factors and prognosis. The 192 SFTS patients were divided into two groups according to the clinical endpoints (survivors/non-survivors). The results showed that the mortality of the 192 hospitalized SFTS patients was 26.6%. The ACCI score of the survivor group was significantly lower than that of the non-survivor group. Multivariate Cox regression analysis showed that the increased ACCI score was a significant predictor of poor prognosis in SFTS. Kaplan–Meier survival analysis showed that SFTS patients with an ACCI >2.5 had shorter mean survival times, indicating a poor prognosis. Our findings suggest that ACCI, as an easy-to-use clinical indicator, may offer a simple and feasible approach for clinicians to determine the severity of SFTS.
Modeling Water Isotopes Using a Global Non‐Hydrostatic Model With an Explicit Convection: Comparison With Gridded Data Sets and Site Observations
Authors: Tanoue Masahiro , Yashiro Hisashi , Takano Yuki , Yoshimura Kei , Kodama Chihiro , Satoh Masaki
Published: December 2023

In this study, we developed a global cloud system‐resolving model (GCSRM) incorporating stable water isotopes (NICAM‐WISO). Using a single‐moment cloud microphysics scheme, we applied the new model to conduct a current climate simulation at a horizontal resolution of 56 km. NICAM‐WISO simulated the seasonal means of the atmospheric hydrological cycle, as well as water isotopic ratios of precipitation and vapor. The model captured the general features of precipitation isotope effects and its spatial correlations were comparable to those of other isotope‐incorporated global atmospheric models. The model showed better spatial correlation between simulated and observed values for a fine‐horizontal‐resolution (14 km) simulation compared to coarse‐horizontal‐resolution (56 km) simulation. However, the model had isotopic biases in tropical mid‐troposphere, ocean, and cold continental regions. A comparison of stable water isotopes between the simulation and observations offered clues for improving the model. For example, in the tropical mid‐troposphere, we found a negative bias in the mixing ratio and isotopic ratio of water vapor. Our analysis using satellite retrievals revealed that these underestimations were caused by weak mixing with the boundary layer vapor and low raindrop evaporation with a small evaporation fraction. The underestimations indicated weak shallow convective mixing in the model, inducing negative bias in the mixing ratio and isotopic ratio of the mid‐tropospheric vapor. These biases were also seen in the fine horizontal‐resolution simulation. Furthermore, we conducted several km‐scale atmospheric isotope circulation simulations using NICAM‐WISO. We expect that global‐scale fine‐horizontal‐resolution simulations using isotope‐incorporated GCSRMs will improve our understanding of the atmospheric hydrological cycle.
Numerical Prediction of Changes in Atmospheric Chemical Compositions During a Solar Energetic Particle Event on Mars
Authors: Nakamura Yuki , Leblanc François , Terada Naoki , Hiruba Sayano , Murata Isao , Nakagawa Hiromu , Sakai Shotaro , Aoki Shohei , Piccialli Arianna , Willame Yannick , Neary Lori , Vandaele Ann Carine , Murase Kiyoka , Kataoka Ryuho
Published: December 2023

Precipitation of solar energetic particles (SEPs) into planetary atmospheres causes changes in atmospheric chemical composition through ionization, dissociation, and excitation of atmospheric molecules. In contrast to the terrestrial atmosphere, where depletion of ozone in the polar mesosphere has been studied by observations and models for decades, there have been no studies on the effects of SEPs on the neutral chemical composition of Mars' present‐day atmosphere. This study provided the first estimate of the impacts of SEPs on neutral chemical composition in the present‐day Martian atmosphere coupling a Monte Carlo model and a one‐dimensional photochemical model. Our results showed that ozone density in the Martian atmosphere might decrease in the altitude range of 20–60 km with a factor 10 maximum enhancement occurring at 40 km during a Halloween‐class SEP event due to an enhanced concentration of HOx. The depletion of ozone occurred in the altitude range of 20–60 km, corresponding to the penetration of protons with an energy range of 4.6–46 MeV. Such ozone depletion should be detected by Trace Gas Orbiter/Nadir and Occultation for MArs Discovery during intense SEP event. A 75% depletion of the ozone density at 40 km can be expected during SEP events occurring once in every 1 year. Therefore, ozone concentration in the Martian atmosphere might sufficiently decrease during a SEP event as on Earth, but through different chemical pathways driven by CO2 ionization and CO recombination catalytic cycle.
Dental impact of anti-fibroblast growth factor 23 therapy in X-linked hypophosphatemia
Authors: Lira dos Santos Elis J. , Nakajima Kenta , Po Julien , Hanai Ayako , Zhukouskaya Volha , Biosse Duplan Martin , Linglart Agnès , Shimada Takashi , Chaussain Catherine , Bardet Claire
Published: December 2023

Elevated fibroblast growth factor 23 (FGF23) in X-linked hypophosphatemia (XLH) results in rickets and phosphate wasting, manifesting by severe bone and dental abnormalities. Burosumab, a FGF23-neutralizing antibody, an alternative to conventional treatment (phosphorus and active vitamin D analogs), showed significant improvement in the long bone phenotype. Here, we examined whether FGF23 antibody (FGF23-mAb) also improved the dentoalveolar features associated with XLH. Four-week-old male Hyp mice were injected weekly with 4 or 16 mg·kg−1 of FGF23-mAb for 2 months and compared to wild-type (WT) and vehicle (PBS) treated Hyp mice (n = 3–7 mice). Micro-CT analyses showed that both doses of FGF23-mAb restored dentin/cementum volume and corrected the enlarged pulp volume in Hyp mice, the higher concentration resulting in a rescue similar to WT levels. FGF23-mAb treatment also improved alveolar bone volume fraction and mineral density compared to vehicle-treated ones. Histology revealed improved mineralization of the dentoalveolar tissues, with a decreased amount of osteoid, predentin and cementoid. Better periodontal ligament attachment was also observed, evidenced by restoration of the acellular cementum. These preclinical data were consistent with the retrospective analysis of two patients with XLH showing that burosumab treatment improved oral features. Taken together, our data show that the dentoalveolar tissues are greatly improved by FGF23-mAb treatment, heralding its benefit in clinics for dental abnormalities.
Light People: Professor Lan Fu
Authors: Wang Hui , Yu Cun
Published: December 2023

Editorial

III-V semiconductors are compound semiconductor materials formed by combining group-III and group-V elements. With properties such as direct bandgap, high electron mobility, good homogeneity of large-size crystals and good lattice matching, they are widely used in micro- and opto-electronics, integrated circuits, laser communications, etc., and promise great potentials. Our Light People is someone who has long been engaged in the research of III-V semiconductor materials, structures and devices. She is Prof. Lan Fu from the Australian National University (ANU).

As an outstanding student of Prof. Chennupati Jagadish, President of the Australian Academy of Sciences, Prof. Fu is not only a leading researcher in her field, but also a scientist with an independent spirit. She is currently the Head of the Department of Electronic Materials Engineering, Research School of Physics, The Australian National University, where she leads a team in the research of III-V semiconductors.

A sincere and humble person, Prof. Fu focuses on nurturing professional attitude, critical thinking and problem solving skills in her students. In addition, she is actively involved in various professional activities, which allows her to integrate research and practice. She believes that integrity, passion, curiosity and perseverance are the key characters of a good scientific researcher and encourages her students to avoid being arrogant or rush but concentrate on good rigorous work.

For this issue of Light People, we will learn about Professor Lan Fu’s unique charisma as an academic and her fascinating life philosophy.
Microplastic induces mitochondrial pathway mediated cellular apoptosis in mussel (Mytilus galloprovincialis) via inhibition of the AKT and ERK signaling pathway
Authors: Mai Nhu Thi Quynh , Batjargal Ulziituya , Kim Won-Seok , Kim Ji-Hoon , Park Ji-Won , Kwak Ihn-Sil , Moon Byoung-San
Published: December 2023

Microplastics (MPs) is an escalating aquatic environmental crisis that poses significant threats to marine organisms, especially mussels. Here, we compare the cumulative toxic effects of the two most abundant morphotypes of MPs in the environment, microspheres, and microfibers, on the gill and digestive gland (DG) of Mytilus galloprovincialis in a dose-dependent (1, 10, and 100 mg/L) and time-dependent (1, 4, 7, 14, 21 days exposure) manner. DNA fragmentation assessment through TUNEL assay revealed consistency in the pattern of morphological disturbance degree and cell apoptosis proportions indicated by histopathological analysis. Upon the acute phase of exposure (day 1–4), gill and DG treated with low MPs concentration exhibited preserved morphology and low proportion of TUNEL+ cells. At higher concentrations, spherical and fibrous MP-induced structural impairments and DNA breakage occurred at distinct levels. 100 mg/L microfibers was lethal to all mussels on day 21, indicating the higher toxicity of the fibrous particles. During the chronic phase, both morphological abnormalities degree and DNA fragmentation level increased over time and with increasing concentration, but the differentials between the spherical and fibrous group was gradually reduced, particularly diminished in 10 and 100 mg/L in the last 2 weeks. Furthermore, analysis of transcriptional activities of key genes for apoptosis of 100 mg/L–day 14 groups revealed the upregulation of both intrinsic and extrinsic apoptotic induction pathway and increment in gene transcripts involving genotoxic stress and energy metabolism according to MP morphotypes. Overall, microfibers exert higher genotoxic effects on mussel. In response, mussels trigger more intense apoptotic responses together with enhanced energy metabolism to tolerate the adverse effects in a way related to the accumulation of stimuli.
Effect of thickness on the electrical properties of PEDOT:PSS/Tween 80 films
Authors: Carter Joseph L. , Kelly Catherine A. , Marshall Jean E. , Jenkins Mike J.
Published: December 2023

The lower material and manufacturing costs of conductive polymers, particularly PEDOT:PSS, compared to indium tin oxide have led to significant research into their use in optoelectric devices. In this study, improvements of the electrical properties of PEDOT:PSS and PEDOT:PSS/Tween 80 via the production of multilayered films were investigated. A single layer of pristine PEDOT:PSS was found to give a sheet resistance of 1639 Ω□–1. The application of an additional three layers reduced this value to 29 Ω□-1, corresponding to an increase in conductivity from 2.6 to 18.3 Scm–1. A similar trend was also found with formulations containing Tween 80. X-ray diffraction and Raman spectroscopy showed that the additional layers increased the crystalline order and induced a slight benzoid to quinoid shift. Surface profiling showed progressive increases in surface roughness with each additional layer of pristine PEDOT:PSS; however, this was mitigated by the presence of Tween 80 in the formulations.
T cell migration requires ion and water influx to regulate actin polymerization
Authors: de Boer Leonard L. , Vanes Lesley , Melgrati Serena , Biggs O’May Joshua , Hayward Darryl , Driscoll Paul C. , Day Jason , Griffiths Alexander , Magueta Renata , Morrell Alexander , MacRae James I. , Köchl Robert , Tybulewicz Victor L. J.
Published: December 2023

Migration of T cells is essential for their ability to mount immune responses. Chemokine-induced T cell migration requires WNK1, a kinase that regulates ion influx into the cell. However, it is not known why ion entry is necessary for T cell movement. Here we show that signaling from the chemokine receptor CCR7 leads to activation of WNK1 and its downstream pathway at the leading edge of migrating CD4+T cells, resulting in ion influx and water entry by osmosis. We propose that WNK1-induced water entry is required to swell the membrane at the leading edge, generating space into which actin filaments can polymerize, thereby facilitating forward movement of the cell. Given the broad expression of WNK1 pathway proteins, our study suggests that ion and water influx are likely to be essential for migration in many cell types, including leukocytes and metastatic tumor cells.
Docking for EP4R antagonists active against inflammatory pain
Authors: Gahbauer Stefan , DeLeon Chelsea , Braz Joao M. , Craik Veronica , Kang Hye Jin , Wan Xiaobo , Huang Xi-Ping , Billesbølle Christian B. , Liu Yongfeng , Che Tao , Deshpande Ishan , Jewell Madison , Fink Elissa A. , Kondratov Ivan S. , Moroz Yurii S. , Irwin John J. , Basbaum Allan I. , Roth Bryan L. , Shoichet Brian K.
Published: December 2023

The lipid prostaglandin E2 (PGE2) mediates inflammatory pain by activating G protein-coupled receptors, including the prostaglandin E2 receptor 4 (EP4R). Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce nociception by inhibiting prostaglandin synthesis, however, the disruption of upstream prostanoid biosynthesis can lead to pleiotropic effects including gastrointestinal bleeding and cardiac complications. In contrast, by acting downstream, EP4R antagonists may act specifically as anti-inflammatory agents and, to date, no selective EP4R antagonists have been approved for human use. In this work, seeking to diversify EP4R antagonist scaffolds, we computationally dock over 400 million compounds against an EP4R crystal structure and experimentally validate 71 highly ranked, de novo synthesized molecules. Further, we show how structure-based optimization of initial docking hits identifies a potent and selective antagonist with 16 nanomolar potency. Finally, we demonstrate favorable pharmacokinetics for the discovered compound as well as anti-allodynic and anti-inflammatory activity in several preclinical pain models in mice.
Design and structural validation of peptide–drug conjugate ligands of the kappa-opioid receptor
Authors: Muratspahić Edin , Deibler Kristine , Han Jianming , Tomašević Nataša , Jadhav Kirtikumar B. , Olivé-Marti Aina-Leonor , Hochrainer Nadine , Hellinger Roland , Koehbach Johannes , Fay Jonathan F. , Rahman Mohammad Homaidur , Hegazy Lamees , Craven Timothy W. , Varga Balazs R. , Bhardwaj Gaurav , Appourchaux Kevin , Majumdar Susruta , Muttenthaler Markus , Hosseinzadeh Parisa , Craik David J. , Spetea Mariana , Che Tao , Baker David , Gruber Christian W.
Published: December 2023

Despite the increasing number of GPCR structures and recent advances in peptide design, the development of efficient technologies allowing rational design of high-affinity peptide ligands for single GPCRs remains an unmet challenge. Here, we develop a computational approach for designing conjugates of lariat-shaped macrocyclized peptides and a small molecule opioid ligand. We demonstrate its feasibility by discovering chemical scaffolds for the kappa-opioid receptor (KOR) with desired pharmacological activities. The designed De Novo Cyclic Peptide (DNCP)-β-naloxamine (NalA) exhibit in vitro potent mixed KOR agonism/mu-opioid receptor (MOR) antagonism, nanomolar binding affinity, selectivity, and efficacy bias at KOR. Proof-of-concept in vivo efficacy studies demonstrate that DNCP-β-NalA(1) induces a potent KOR-mediated antinociception in male mice. The high-resolution cryo-EM structure (2.6 Å) of the DNCP-β-NalA–KOR–Gi1 complex and molecular dynamics simulations are harnessed to validate the computational design model. This reveals a network of residues in ECL2/3 and TM6/7 controlling the intrinsic efficacy of KOR. In general, our computational de novo platform overcomes extensive lead optimization encountered in ultra-large library docking and virtual small molecule screening campaigns and offers innovation for GPCR ligand discovery. This may drive the development of next-generation therapeutics for medical applications such as pain conditions.
A micro RNA mediates shoot control of root branching
Authors: Sexauer Moritz , Bhasin Hemal , Schön Maria , Roitsch Elena , Wall Caroline , Herzog Ulrike , Markmann Katharina
Published: December 2023

Plants extract mineral nutrients from the soil, or from interactions with mutualistic soil microbes via their root systems. Adapting root architecture to nutrient availability enables efficient resource utilization, particularly in patchy and dynamic environments. Root growth responses to soil nitrogen levels are shoot-mediated, but the identity of shoot-derived mobile signals regulating root growth responses has remained enigmatic. Here we show that a shoot-derived micro RNA, miR2111, systemically steers lateral root initiation and nitrogen responsiveness through its root target TML (TOO MUCH LOVE) in the legume Lotus japonicus, where miR2111 and TML were previously shown to regulate symbiotic infections with nitrogen fixing bacteria. Intriguingly, systemic control of lateral root initiation by miR2111 and TML/HOLT (HOMOLOGUE OF LEGUME TML) was conserved in the nonsymbiotic ruderal Arabidopsis thaliana, which follows a distinct ecological strategy. Thus, the miR2111-TML/HOLT regulon emerges as an essential, conserved factor in adaptive shoot control of root architecture in dicots.
Dung removal increases under higher dung beetle functional diversity regardless of grazing intensification
Authors: Noriega Jorge Ari , Hortal Joaquín , deCastro-Arrazola Indradatta , Alves-Martins Fernanda , Ortega Jean C. G. , Bini Luis Mauricio , Andrew Nigel R. , Arellano Lucrecia , Beynon Sarah , Davis Adrian L. V. , Favila Mario E. , Floate Kevin D. , Horgan Finbarr G. , Menéndez Rosa , Milotic Tanja , Nervo Beatrice , Palestrini Claudia , Rolando Antonio , Scholtz Clarke H. , Senyüz Yakup , Wassmer Thomas , Ádam Réka , Araújo Cristina de O. , Barragan-Ramírez José Luis , Boros Gergely , Camero-Rubio Edgar , Cruz Melvin , Cuesta Eva , Damborsky Miryam Pieri , Deschodt Christian M. , Rajan Priyadarsanan Dharma , D’hondt Bram , Díaz Rojas Alfonso , Dindar Kemal , Escobar Federico , Espinoza Verónica R. , Ferrer-Paris José Rafael , Gutiérrez Rojas Pablo Enrique , Hemmings Zac , Hernández Benjamín , Hill Sarah J. , Hoffmann Maurice , Jay-Robert Pierre , Lewis Kyle , Lewis Megan , Lozano Cecilia , Marín-Armijos Diego , de Farias Patrícia Menegaz , Murcia-Ordoñez Betselene , Karimbumkara Seena Narayanan , Navarrete-Heredia José Luis , Ortega-Echeverría Candelaria , Pablo-Cea José D. , Perrin William , Pessoa Marcelo Bruno , Radhakrishnan Anu , Rahimi Iraj , Raimundo Amalia Teresa , Ramos Diana Catalina , Rebolledo Ramón E. , Roggero Angela , Sánchez-Mercado Ada , Somay László , Stadler Jutta , Tahmasebi Pejman , Triana Céspedes José Darwin , Santos Ana M. C.
Published: December 2023

Dung removal by macrofauna such as dung beetles is an important process for nutrient cycling in pasturelands. Intensification of farming practices generally reduces species and functional diversity of terrestrial invertebrates, which may negatively affect ecosystem services. Here, we investigate the effects of cattle-grazing intensification on dung removal by dung beetles in field experiments replicated in 38 pastures around the world. Within each study site, we measured dung removal in pastures managed with low- and high-intensity regimes to assess between-regime differences in dung beetle diversity and dung removal, whilst also considering climate and regional variations. The impacts of intensification were heterogeneous, either diminishing or increasing dung beetle species richness, functional diversity, and dung removal rates. The effects of beetle diversity on dung removal were more variable across sites than within sites. Dung removal increased with species richness across sites, while functional diversity consistently enhanced dung removal within sites, independently of cattle grazing intensity or climate. Our findings indicate that, despite intensified cattle stocking rates, ecosystem services related to decomposition and nutrient cycling can be maintained when a functionally diverse dung beetle community inhabits the human-modified landscape.
Rare X-linked variants carry predominantly male risk in autism, Tourette syndrome, and ADHD
Authors: Wang Sheng , Wang Belinda , Drury Vanessa , Drake Sam , Sun Nawei , Alkhairo Hasan , Arbelaez Juan , Duhn Clif ,   Tourette International Collaborative Genetics (TIC Genetics), Bromberg Yana , Brown Lawrence W. , Cao Xiaolong , Cheon Keun-Ah , Cheong Kyungun , Choi Hannyung , Coffey Barbara J. , Deng Li , Fremer Carolin , Garcia-Delgar Blanca , Gilbert Donald L. , Glover Danea , Grice Dorothy E. , Hagstrøm Julie , Hedderly Tammy , Heyman Isobel , Hong Hyun Ju , Huyser Chaim , Kim Heejoo , Kim Young Key , Kim Eunjoo , Kim Young-Shin , King Robert A. , Koh Yun-Joo , Kook Sodahm , Kuperman Samuel , Lee Junghan , Leventhal Bennett L. , Madruga-Garrido Marcos , Mingbunjerdsuk Dararat , Mir Pablo , Morer Astrid , Murphy Tara L. , Müller-Vahl Kirsten , Münchau Alexander , Nasello Cara , Oh Dong Hun , Plessen Kerstin J. , Roessner Veit , Shin Eun-Young , Song Dong-Ho , Song Jungeun , Thackray Joshua K. , Visscher Frank , Zinner Samuel H. , Bal Vanessa H. , Langley Kate , Martin Joanna , Hoekstra Pieter J. , Dietrich Andrea , Xing Jinchuan , Heiman Gary A. , Tischfield Jay A. , Fernandez Thomas V. , Owen Michael J. , O’Donovan Michael C. , Thapar Anita , State Matthew W. , Willsey A. Jeremy
Published: December 2023

Autism spectrum disorder (ASD), Tourette syndrome (TS), and attention-deficit/hyperactivity disorder (ADHD) display strong male sex bias, due to a combination of genetic and biological factors, as well as selective ascertainment. While the hemizygous nature of chromosome X (Chr X) in males has long been postulated as a key point of “male vulnerability”, rare genetic variation on this chromosome has not been systematically characterized in large-scale whole exome sequencing studies of “idiopathic” ASD, TS, and ADHD. Here, we take advantage of informative recombinations in simplex ASD families to pinpoint risk-enriched regions on Chr X, within which rare maternally-inherited damaging variants carry substantial risk in males with ASD. We then apply a modified transmission disequilibrium test to 13,052 ASD probands and identify a novel high confidence ASD risk gene at exome-wide significance (MAGEC3). Finally, we observe that rare damaging variants within these risk regions carry similar effect sizes in males with TS or ADHD, further clarifying genetic mechanisms underlying male vulnerability in multiple neurodevelopmental disorders that can be exploited for systematic gene discovery.