bluuebunny/crossref_metadata_2025 huggingface dataset:
GhostKnockoff inference empowers identification of putative causal variants in genome-wide association studies
Authors: He Zihuai , Liu Linxi , Belloy Michael E. , Le Guen Yann , Sossin Aaron , Liu Xiaoxia , Qi Xinran , Ma Shiyang , Gyawali Prashnna K. , Wyss-Coray Tony , Tang Hua , Sabatti Chiara , Candès Emmanuel , Greicius Michael D. , Ionita-Laza Iuliana
Published: November 2022

Recent advances in genome sequencing and imputation technologies provide an exciting opportunity to comprehensively study the contribution of genetic variants to complex phenotypes. However, our ability to translate genetic discoveries into mechanistic insights remains limited at this point. In this paper, we propose an efficient knockoff-based method, GhostKnockoff, for genome-wide association studies (GWAS) that leads to improved power and ability to prioritize putative causal variants relative to conventional GWAS approaches. The method requires only Z-scores from conventional GWAS and hence can be easily applied to enhance existing and future studies. The method can also be applied to meta-analysis of multiple GWAS allowing for arbitrary sample overlap. We demonstrate its performance using empirical simulations and two applications: (1) a meta-analysis for Alzheimer’s disease comprising nine overlapping large-scale GWAS, whole-exome and whole-genome sequencing studies and (2) analysis of 1403 binary phenotypes from the UK Biobank data in 408,961 samples of European ancestry. Our results demonstrate that GhostKnockoff can identify putatively functional variants with weaker statistical effects that are missed by conventional association tests.
Highly potent natural fungicides identified in silico against the cereal killer fungus Magnaporthe oryzae
Authors: Khan Md. Arif , Al Mamun Khan Md. Abdullah , Mahfuz A. M. U. B. , Sanjana Jannatul Maowa , Ahsan Asif , Gupta Dipali Rani , Hoque M. Nazmul , Islam Tofazzal
Published: November 2022

Magnaporthe oryzae is one of the most notorious fungal pathogens that causes blast disease in cereals, and results in enormous loss of grain production. Many chemical fungicides are being used to control the pathogen but none of them are fully effective in controlling blast disease. Therefore, there is a demand for the discovery of a new natural biofungicide to manage the blast disease efficiently. A large number of new natural products showed inhibitory activities against M. oryzae in vitro. To find out effective biofungicides, we performed in silico molecular docking analysis of some of the potent natural compounds targeting four enzymes namely, scytalone dehydratase, SDH1 (PDB ID:1STD), trihydroxynaphthalene reductase, 3HNR (PDB ID:1YBV), trehalose-6-phosphate synthase, Tps1 (PDB ID:6JBI) and isocitrate lyase, ICL1 (PDB ID:5E9G) of M. oryzae fungus that regulate melanin biosynthesis and/or appresorium formation. Thirty-nine natural compounds that were previously reported to inhibit the growth of M. oryzae were subjected to rigid and flexible molecular docking against aforementioned enzymes followed by molecular dynamic simulation. The results of virtual screening showed that out of 39, eight compounds showed good binding energy with any one of the target enzymes as compared to reference commercial fungicides, azoxystrobin and strobilurin. Among the compounds, camptothecin, GKK1032A2 and chaetoviridin-A bind with more than one target enzymes of M. oryzae. All of the compounds except tricyclazole showed good bioactivity score. Taken together, our results suggest that all of the eight compounds have the potential to develop new fungicides, and remarkably, camptothecin, GKK1032A2 and chaetoviridin-A could act as multi-site mode of action fungicides against the blast fungus M. oryzae.
Deep neural network-based structural health monitoring technique for real-time crack detection and localization using strain gauge sensors
Authors: Yoon Jiyoung , Lee Junhyeong , Kim Giyoung , Ryu Seunghwa , Park Jinhyoung
Published: November 2022

Structural health monitoring (SHM) techniques often require a large number of sensors to evaluate and monitor the structural health. In this paper, we propose a deep neural network (DNN)-based SHM method for accurate crack detection and localization in real time using a small number of strain gauge sensors and confirm its feasibility based on experimental data. The proposed method combines a DNN model with principal component analysis (PCA) to predict the strain field based on the local strains measured by strain gauge sensors located rather sparsely. We demonstrate the potential of the proposed technique via a cyclic 4-point bending test performed on a composite material specimen without cracks and seven specimens with different lengths of cracks. A dataset containing local strains measured with 12 strain gauge sensors and strain field measured with a digital image correlation (DIC) device was prepared. The strain field dataset from DIC is converted to a smaller dimension latent space with a few eigen basis via PCA, and a DNN model is trained to predict principal component values of each image with 12 strain gauge sensor measurements as input. The proposed method turns out to accurately predict the strain field for all specimens considered in the study.
Polysaccharides from Pseudostellaria heterophylla modulate gut microbiota and alleviate syndrome of spleen deficiency in rats
Authors: Xiao Qing , Zhao Li , Jiang Chang , Zhu Yanjin , Zhang Jizhou , Hu Juan , Wang Guozeng
Published: November 2022

Pseudostellaria heterophylla, also called Tai-zi-shen (TZS) in Traditional Chinese Medicine (TCM), is always used clinically to treat spleen deficiency symptoms. Polysaccharides in TZS have various pharmacological activities, including anti-diabetic, immune regulation, and myocardial protection. However, the relationship between the spleen-invigorating effects of TZS or its polysaccharides and intestinal flora are not clear. This study investigated the effects of TZS decoction (PHD) and polysaccharide (PHP) on immune function and intestinal flora in a rat model of spleen deficiency syndrome (SDS) induced by a decoction of raw rhubarb (RRD). PHD and PHP increased immune organ index, alleviated inflammatory cell filtration, and reduced the levels of pro-inflammatory cytokines in rats with spleen deficiency syndrome. In addition, the production of butyric acid was promoted in PHD and PHP groups. Moreover, 16S rRNA gene sequencing showed that PHD and PHP reduced the relative abundance of Firmicutes while increasing the one of Bacteroidetes; significantly increased the abundance of Lactobacillus and decreased the abundance of Rombutsia; and PHP significantly increased the abundance of Alloprevotella. And there was a significant positive correlation between the alleviation of SDS and short-chain fatty acids (SCFAs)-producing bacteria. These findings suggested PHD and PHP, especially PHP, has a potential to relieve spleen deficiency by reducing intestinal inflammation, modulating structure and composition of gut microbiota, and promoting the production of butyric acid.
Photocatalytic enantioselective Minisci reaction of β-carbolines and application to natural product synthesis
Authors: Luo Mu-Peng , Gu Yi-Jie , Wang Shou-Guo
Published: November 2022

A highly efficient enantioselective direct C–H functionalization of β-carbolinesviaa Minisci-type radical process under a photo-redox and chiral phosphoric acid cooperative catalytic system has been disclosed.
Distributed cooperative formation of stochastic multi‐agent systems in finite horizon
Authors: Shi Jiantao , Chen Chuang , Shen Mouquan , Liu Dan
Published: November 2022

The paper addresses the distributed cooperative formation control problem for a class of general stochastic multi‐agent systems subject to time‐varying dynamics. A type of novel modified distributed state observer is constructed, whose estimation information is used to design the control scheme for guaranteeing the mean‐square formation maintenance in finite‐horizon. Furthermore, the observer and controller parameters are obtained iteratively through solving a set of constrained recursive matrix equations. Finally, the proposed scheme has been validated by a simulation study.
Two‐person games for uncertain random singular dynamic systems
Authors: Chen Xin , Zhu Yuanguo , Park Ju H.
Published: November 2022

A complex system exhibiting uncertainty as well as randomness may be portrayed by an uncertain random singular difference equation. This paper investigates two‐person nonzero‐sum and zero‐sum games based on uncertain random singular difference equations. First, an approach is proposed to translate the two‐person nonzero‐sum game into an equivalent game for a standard uncertain random dynamic system. The relevant recursive equations are developed to search the Nash equilibrium for the converted game. Solving the related recursive equations yields the solution to such a game. Following that, a Max‐Min Theorem is provided for finding the saddle‐point equilibrium of an uncertain random two‐person zero‐sum game. Finally, a numerical example is offered to demonstrate the validity of the findings.
Semi‐supervised learning dehazing algorithm based on the OSV model
Authors: Zhu Lijun , Wei Weibo , Pan Zhenkuan , Ji Lianshun , Song Jintao , Li Jinhan
Published: November 2022

Despite the great progress that has been made in the task of single image dehazing, the results of the existing models in restoring image edge and texture information are still challenging. Besides, most dehazing models are trained on synthetic data, resulting in poor generalization ability to real‐world images. To address the aforementioned problems, a semi‐supervised learning dehazing method based on the decomposition model of Osher, Solé, and Vese(The OSV model) is presented. Specifically, the OSV model is first applied to decompose the hazy image into the structure layer and texture layer, save the texture layer and dehaze for the structure layer to restore images with sharper texture and edge. Furthermore, the network adopts a semi‐supervised learning algorithm based on generative adversarial networks (GAN) to generalize better to real‐world images, which includes two branches: supervised learning and unsupervised learning. Extensive experiments indicate that the proposed method preserves the texture and edge information of images more accurately while dehazing better, and performs favourably against the advanced dehazing algorithms on both synthetic outdoor datasets and real‐world hazy images.
3D zebrafish tracking with topology association
Authors: Xu Yuan , Jin Yichao , Zhang Yang , Zhu Qunxiong , He Yanlin , Sheng Hao
Published: November 2022

Recently, zebrafish has received more and more attention due to its wide range of applications such as regeneration promoting therapeutics and drug discovery. Therefore, vision‐based trackers are utilized to record the swimming trajectory of zebrafish. In this paper, a re‐association method is introduced in the 3D reconstruction process to generate missed targets caused by occlusion. Since the variation of the overall tracking targets has the property of continuity and stability, a topology association model (TAM) is proposed by point group similarity into the tracking framework. TAM describes the movement of zebrafish from the macroscopic level and utilizes the changes of the point group structure for tracking. Experimental results show that the tracking framework enhances the overall performance and promotes the trajectory integrity. On the latest 3D‐ZeF20 benchmark, state‐of‐the‐art results are achieved. In addition, TAM tracking framework is applied to 2D general tracking to prove that the method is useful and have great advantage in other scenarios with relatively stable amount of targets as well.
Osteoprotektion beim nichtmetastasierten hormonsensitiven Prostatakarzinom (nmHSPC) unter androgendeprivativer Therapie (ADT): Aktuelle Daten aus Deutschland, vorgelegt von d-uo
Authors: Klier Jörg , König Frank , Schönfelder Robert , Eichenauer Rolf , Johannsen Manfred , Beuke Maike , Binder Manfred , Brenneis Horst , Burkert-Scholz Marcus , Fieseler Claus , Jaeger Andreas , Nitz Christian , Reese Stephan , Romagnolo Allesandro , Schröder Jörg , Hempel Elke , Doehn Christian
Published: November 2022

Einleitung Patienten mit einem Prostatakarzinom haben oftmals bereits eine verminderte Knochendichte. Wir haben die Versorgungssituation im Hinblick auf die Osteoprotektion zur Vermeidung eines Knochendichtverlusts bis hin zur sekundären Osteoporose bei Patienten mit einem nichtmetastasierten hormonsensitiven Prostatakarzinom (nmHSPC) unter androgendeprivativer Therapie (ADT) in urologischen Praxen in Deutschland untersucht.

Material und Methoden Es handelte sich um eine fragebogenbasierte
Untersuchung unter Mitgliedern von d-uo. Eingeschlossen wurden alle Patienten mit einem
histologisch gesicherten Prostatakarzinom, die zwischen 7/2019 und 6/2020 mindestens einmal in
der beteiligten Praxis gesehen wurden. Für die weitere Analyse wurden alle Patienten unter
einer Langzeit-ADT (definiert als > 12 Monate) hinsichtlich des Beginns, der Art und Dauer
der osteoprotektiven Therapie sowie der zusätzlichen Gabe von Kalzium und Vitamin D
betrachtet.

Ergebnisse Im o.g. Zeitraum wurden in 15 Praxen insgesamt 3.692 Patienten mit einem Prostatakarzinom gesehen. Hiervon erhielten 844 Patienten mit einem nmHSPC (22,9%) eine ADT. Eine osteoprotektive Therapie wurde bei 183/844 Patienten (21,7%) mit einem nmHSPC vorgenommen. Denosumab erhielten 73,2% dieser Patienten und ein Bisphosphonat 26,8%. Die Osteoprotektion wurde bei 32,8% der Patienten zeitgleich mit der ADT und bei 67,2% später begonnen. Bei 84,7% der Patienten wurde zusätzlich zur osteoprotektiven Therapie Kalzium und Vitamin D supplementiert. In 54,2% der Fälle war der Beginn zeitgleich mit der osteoprotektiven Therapie und in 45,8% der Fälle später.

Schlussfolgerung Eine medikamentöse Osteoprotektion wurde nur bei jedem fünften Patienten mit einem nmHSPC und ADT vorgenommen und nur bei jedem dritten Patienten zeitgleich mit der ADT begonnen. Zusammenfassend lässt sich daher feststellen, dass die medikamentöse osteoprotektive Therapie bei Patienten mit einem nmHSPC unter ADT eher die Ausnahme darstellt.
Hereditary Angioedema: The Clinical Picture of Excessive Contact Activation
Authors: Petersen Remy S. , Fijen Lauré M. , Levi Marcel , Cohn Danny M.
Published: November 2022

Hereditary angioedema is a rare, genetic disorder characterized by painful, debilitating and potentially life-threatening angioedema attacks in subcutaneous and submucosal tissue. While usually unpredictable, attacks can be provoked by a variety of triggers including physical injury and certain medication and are often preceded by prodromal symptoms. Hereditary angioedema has a profound influence on the patients' lives. The fundamental cause of hereditary angioedema in almost all patients is a mutation in the SERPING1 gene leading to a deficiency in C1-inhibitor. Subsequently, the contact activation cascade and kallikrein-kinin pathway are insufficiently inhibited, resulting in excessive bradykinin production triggering vascular leakage. While C1-inhibitor is an important regulator of the intrinsic coagulation pathway, fibrinolytic system and complement cascade, patients do not have an increased risk of coagulopathy, autoimmune conditions or immunodeficiency disorders. Hereditary angioedema is diagnosed based on C1-inhibitor level and function. Genetic analysis is only required in rare cases where hereditary angioedema with normal C1-inhibitor is found. In recent years, new, highly specific therapies have greatly improved disease control and angioedema-related quality of life. This article reviews the clinical picture of hereditary angioedema, the underlying pathophysiology, diagnostic process and currently available as well as investigational therapeutic options.
Vehicles fleet communications in data infrastructure unavailability situations
Authors: Savu T , Jugravu A B
Published: November 2022

The paper describes a solution for operating a fleet of AGVs or AMRs, when an appropriate communication infrastructure is not available, by using messages send from one vehicle to another. All vehicles are equipped with two-way radios and a server (fixed or placed on one vehicle) is managing the network messages and is storing the data about the position of each vehicle. A set of rules was defined for message management and the messages format was defined in detail. It was also defined an algorithm, running on the server, for defining the chain of vehicles to be used for sending one message in the network and for updating the data about the vehicles’ network structure. It was developed and tested the software to be implemented in the radio communication modules for managing the messages flow. Tests were performed for assessing the coverage area in a real environment and the results, proving the correct software implementation, are explained.
Gödel's Theorem: A Very Short Introduction
Authors: Moore A. W.
Published: November 2022

This book provides an introduction to Gödel’s theorem. Gödel’s theorem states that no axiomatization can determine the whole truth and nothing but the truth concerning arithmetic. The content of the theorem is elucidated and distinguished from that of other claims with which it is often confused. The significance of the theorem is also discussed. Particular emphasis is laid on the appeal of axiomatization and on attempts that were made, in the half century preceding Gödel’s proof, to provide the very thing that the theorem precludes. This includes discussion of Hilbert’s programme, part of which was to provide a consistent foundation for mathematics and to demonstrate its consistency by mathematical means. Two proofs of Gödel’s theorem are given. The second and more elaborate proof is also shown to yield Gödel’s second theorem: that no consistent axiomatization of arithmetic can be used to prove a statement corresponding to a statement of its own consistency. The final two chapters of the book explore the implications of Gödel’s results: for Hilbert’s programme; for the question whether the human mind, in its capacity to think beyond any given axiomatization of arithmetic, has powers beyond those of any possible computer; and for the nature of mathematics.
Anselm: A Very Short Introduction
Authors: Williams Thomas
Published: November 2022

Anselm of Canterbury (1033–1109) was the outstanding philosopher-theologian of the Latin West between Augustine and the thirteenth century. As a public figure, especially as Archbishop of Canterbury, he corresponded with kings and nobles, popes and bishops, in letters that reveal a fascinating personality and flesh out the practical dimensions of his theoretical philosophy. He wrote at a time when a renewed interest in logic encouraged careful and rigorous argumentation, but before the recovery of Aristotle filled the philosophical discourse with difficult technical jargon, making for writing that is unrivalled for its lucidity and accessibility. He offers the first clear account of what we nowadays call a libertarian view of free will, according to which free choices cannot be determined by the agent’s internal states or by external influences. His famous ‘ontological argument’ for the existence of God continues to generate discussion, debate, and puzzlement. His understanding of God is rightly regarded as one of the definitive expressions of classical theism or perfect-being theology, which remains influential in philosophy of religion and analytic theology. His account of the Atonement is one that every theologian to this day feels obligated to grapple with.
Investigation of the mechanical characteristics of the Cu/low-k BEOL under wire bonding process loading
Authors: Yuan Cadmus C A , Chang H M , Chiang K N
Published: November 2022

Wire bonding is a key integrated circuit (IC) interconnect technology, and it adheres metal wires to the IC pad and substrate by applying significant compression and energic loading. On the other hand, the Cu/low-k technology of the advanced IC industry is driven by the market demands of small size, and low resistance-capacitance delay applications. Because material properties of Cu/low-k back end of line (BEOL) exhibit significant differences from the conventional Al-based system, 3 new reliability failure modes are introduced after the wire bonding process, including the Al pad lift, Cu pad lift and the nanoscaled Cu diffusion barrier crack. To study the mechanical characteristics of the Cu/low-k BEOL under the wire bonding process loading, this research establishes a set of transient numerical models with mesh control and computation acceleration techniques. The mechanical characteristics of the wire bonding process and the differences between the conventional and Cu/low-k BEOLs are analyzed via the detailed analysis of the historical stress plots over the wire bonding process time. Moreover, the risks of wire bonding induced the failure modes against different Cu/low-k designs are studied by the proper mechanical indices, and optimized design trends are suggested.
The Expressivity of Quantified Group Announcements
Authors: Alechina Natasha , van Ditmarsch Hans , French Tim , Galimullin Rustam
Published: November 2022

Group announcement logic (GAL) and coalition announcement logic (CAL) allow us to reason about whether it is possible for groups and coalitions of agents to achieve their desired epistemic goals through truthful public communication. The difference between groups and coalitions in such a context is that the latter make their announcements in the presence of possible adversarial counter-announcements. As epistemic goals may involve some agents remaining ignorant, counter-announcements may preclude coalitions from reaching their goals. We study the relative expressivity of GAL and CAL and provide some results involving their more well-known sibling APAL. We also discuss how the presence of memory alters the relationship between groups and coalition.
The Taxonomy Dictionary. A tool for correct spelling of taxa.
Authors: Bagge Kristian
Published: November 2022

This article describes "The Taxonomy Dictionary". A tool that can enhance the spelling engine of a text editor like Word, so it correctly can spell every taxon described and enlisted in the largest taxonomy databases.
It contains 1.412.046 unique words, and once installed a wrongly spelled taxon will be marked by the spelling engine and it will suggest possibly correct spellings. Installation instructions can be found on the GitHub repository. The software is licensed with a GPL3 license.
Direct Cryo-ET observation of platelet deformation induced by SARS-CoV-2 Spike protein
Authors: Kuhn Christopher Cyrus , Basnet Nirakar , Bodakuntla Satish , Alvarez-Brecht Pelayo , Nichols Scott , Martinez-Sanchez Antonio , Agostini Lorenzo , Soh Young-Min , Takagi Junichi , Biertümpfel Christian , Mizuno Naoko
Published: November 2022

SARS-CoV-2 is a novel coronavirus responsible for the COVID-19 pandemic. Its high pathogenicity is due to SARS-CoV-2 spike protein (S protein) contacting host-cell receptors. A critical hallmark of COVID-19 is the occurrence of coagulopathies. Here, we report the direct observation of the interactions between S protein and platelets. Live imaging showed that the S protein triggers platelets to deform dynamically, in some cases, leading to their irreversible activation. Strikingly, cellular cryo-electron tomography revealed dense decorations of S protein on the platelet surface, inducing filopodia formation. Hypothesizing that S protein binds to filopodia-inducing integrin receptors, we tested the binding to RGD motif-recognizing platelet integrins and found that S protein recognizes integrin αvβ3. Our results infer that the stochastic activation of platelets is due to weak interactions of S protein with integrin, which can attribute to the pathogenesis of COVID-19 and the occurrence of rare but severe coagulopathies.
The prolactin receptor scaffolds Janus kinase 2 via co-structure formation with phosphoinositide-4,5-bisphosphate
Authors: Araya-Secchi Raul , Bugge Katrine , Seiffert Pernille , Petry Amalie , Haxholm Gitte W. , Lindorff-Larsen Kresten , Pedersen Stine F. , Arleth Lise , Kragelund Birthe B.
Published: November 2022

Class 1 cytokine receptors transmit signals through the membrane by a single transmembrane helix to an intrinsically disordered cytoplasmic domain that lacks kinase activity. While specific binding to phosphoinositides has been reported for the prolactin receptor (PRLR), the role of lipids in PRLR signalling is unclear. Using an integrative approach combining NMR spectroscopy, cellular signalling experiments, computational modelling and simulation, we demonstrate co-structure formation of the disordered intracellular domain of the human PRLR, the membrane constituent phosphoinositide-4,5-bisphosphate (PI(4,5)P2) and the FERM-SH2 domain of the Janus kinase 2 (JAK2). We find that the complex leads to accumulation of PI(4,5)P2at the transmembrane helix interface and that mutation of residues identified to interact specifically with PI(4,5)P2negatively affects PRLR-mediated activation of signal transducer and activator of transcription 5 (STAT5). Facilitated by co-structure formation, the membrane-proximal disordered region arranges into an extended structure. We suggest that the co-structure formed between PRLR, JAK2 and PI(4,5)P2locks the juxtamembrane disordered domain of the PRLR in an extended structure, enabling signal relay from the extracellular to the intracellular domain upon ligand binding. We find that the co-structure exists in different states which we speculate could be relevant for turning signalling on and off. Similar co-structures may be relevant for other non-receptor tyrosine kinases and their receptors.
Work–life balance: is an entrepreneurial career the solution?
Authors: Tahir Rizwan
Published: November 2022

Purpose

The present study, drawing on boundary theory, attempts to investigate entrepreneurs’ work–life balance (WLB) in terms of how they manage and construct the borders between their non-work and work lives.

Design/methodology/approach

The current qualitative study is grounded on in-depth interviews with 30 entrepreneurs currently living and working in the United Arab Emirates (UAE). When selecting the interviewees, the authors used purposeful sampling to ensure a diverse sample of interviewees with respect to nationality, age, gender and the nature of their business.

Findings

The findings suggest that most interviewees believe an entrepreneurial career can contribute positively to their lives. However, some individuals question whether it is possible to have some level of WLB while managing entrepreneurial businesses in the UAE’s competitive environment. Further, some entrepreneurs prioritize “work” over “family life,” indicating a love for their work and a lack of desire for any boundaries. Working long hours and managing a successful business over a longer period of time is also found to be negatively related to WLB.

Originality/value

Entrepreneurship has become a desirable career option, thus stimulating much research attention. However, little is known about entrepreneurs’ WLB challenges, especially regarding whether entrepreneurship improves individuals’ WLB. The present study uses boundary theory to understand how subjective insights regarding WLB and effective boundary management might address this gap.
Ustekinumab therapy for Netherton syndrome
Authors: Samuelov Liat , Shehadeh Waseem , Sarig Ofer , Gat Andrea , Matz Hagit , Sprecher Eli
Published: November 2022

Netherton syndrome (NS) is a rare disorder of cornification associated with high morbidity. It is caused by bi‐allelic mutations in SPINK5 encoding the serine protease inhibitor LEKTI. Previous studies have shown Th17 skewing with IL‐23 upregulation in NS, raising the possibility that targeting these inflammatory pathways may alleviate disease manifestations. We ascertained the therapeutic efficacy of six doses of ustekinumab administered to three patients with NS over a period of 13 months using the Ichthyosis Area and Severity Index (IASI), the Dermatology Life Quality Index (DLQI), a visual analogue scale (VAS) for itch and the peak‐pruritus numeric rating scale (PP‐NRS). Histopathology analysis including CD3, CD4, CD8 and interleukin 17 (IL‐17) immunostaining, was performed at baseline and 4 weeks following the last ustekinumab dose. Total IASI scores were reduced by 28% in two patients at week 16 with sustained response by week 56. No consistent improvement in DLQI, VAS for itch and PP‐NRS scores was observed. The inflammatory infiltrate and the degree of acanthosis were slightly reduced at week 56 as compared to baseline. No significant change in immunostaining of the various inflammatory markers was observed at week 56. In conclusion, this case series did not demonstrate a significant therapeutic effect of ustekinumab in NS.
Serum levels of C‐C motif chemokine ligand 2 and interleukin‐8 as possible biomarkers in patients with toxic epidermal necrolysis accompanied by acute respiratory distress syndrome
Authors: Watanabe Tomoya , Watanabe Yuko , Ikeda Noriko , Aihara Michiko , Yamaguchi Yukie
Published: November 2022

Toxic epidermal necrolysis (TEN) is a fatal cutaneous adverse reaction that occasionally affects multiple organs. Acute respiratory distress syndrome (ARDS) is a rare complication that can cause rapid and potentially fatal pulmonary dysfunction. However, the mechanisms underlying TEN‐induced ARDS remain unknown. This retrospective single‐center study aimed to identify potential biomarkers for predicting ARDS onset in TEN patients. Pre‐treatment serum samples were collected from 16 TEN patients and 16 healthy controls (HCs). The serum levels of cytokines/chemokines were determined using the Luminex Assay Human Premixed Multi‐analyte kit. The expression levels of cytokines and chemokines in the skin were examined via immunohistochemistry. The serum levels of C‐C motif chemokine ligand 2 (CCL2), interleukin (IL)‐6, and IL‐8 were significantly higher in TEN patients with ARDS than in those without ARDS and in HCs, whereas those of CCL2 and IL‐8 were not significantly different between TEN patients without ARDS and HCs. There was no significant difference in CCL2 and IL‐8 expression in the skin between TEN patients with and without ARDS. Interestingly, there were no significant differences in the cytokine/chemokine levels between TEN and other organ damage, other than ARDS and TEN without any organ damage. We further analyzed the changes in cytokine/chemokine levels before and after treatment in two TEN patients with ARDS. CCL2, IL‐6, and IL‐8 levels decreased after systemic treatment compared to their baseline levels before treatment at an early stage. These results suggest that IL‐8 and CCL2 may be involved in the pathogenesis of TEN‐induced ARDS and have potential application as predictive markers for ARDS onset.
Herbivory damage but not plant disease under experimental warming is dependent on weather for three subalpine grass species
Authors: Lynn Joshua S. , Abo‐Sido Nisreen , McCowen Ian W. , Villanueva Shermila B. , Harte John , Rudgers Jennifer A.
Published: November 2022

Both theory and prior studies predict that climate warming should increase attack rates by herbivores and pathogens on plants. However, past work has often assumed that variation in abiotic conditions other than temperature (e.g. precipitation) do not alter warming responses of plant damage by natural enemies. Studies over short time periods span low variation in weather, and studies over long time‐scales often neglect to account for fine‐scale weather conditions.

Here, we used a 20+ year warming experiment to investigate if warming affects on herbivory and pathogen disease are dependent on variation in ambient weather observed over 3 years. We studied three common grass species in a subalpine meadow in the Colorado Rocky Mountains, USA. We visually estimated herbivory and disease every 2 weeks during the growing season and evaluated weather conditions during the previous 2‐ or 4‐week time interval (2‐week average air temperature, 2‐ and 4‐week cumulative precipitation) as predictors of the probability and amount of damage.

Herbivore attack was 13% more likely and damage amount was 29% greater in warmed plots than controls across the focal species but warming treatment had little affect on plant disease. Herbivory presence and damage increased the most with experimental warming when preceded by wetter, rather than drier, fine‐scale weather, but preceding ambient temperature did not strongly interact with elevated warming to influence herbivory.

Disease presence and amount increased, on average, with warmer weather and more precipitation regardless of warming.

Synthesis. The effect of warming over reference climate on herbivore damage is dependent on and amplified by fine‐scale weather variation, suggesting more boom‐and‐bust damage dynamics with increasing climate variability. However, the mean effect of regional climate change is likely reduced monsoon rainfall, for which we predict a reduction in insect herbivore damage. Plant disease was generally unresponsive to warming, which may be a consequence of our coarse disease estimates that did not track specific pathogen species or guilds. The results point towards temperature as an important but not sufficient determinant and regulator of species interactions, where precipitation and other constraints may determine the affect of warming.
How rational are voters when expecting government parties to fulfil pledges? A cross‐national survey experiment
Authors: HEINISCH REINHARD , WERNER ANNIKA
Published: November 2022

That parties fulfil their pre‐election pledges once they are in government is a fundamental idea of many democracy models. This paper addresses the question of whether the government/opposition status of their party affects how much citizens want governments to fulfil their promises. We hypothesize that interest‐driven, rational voters are more likely to prefer their own party to keep its promises and investigate whether this rationale is impacted by public opinion and expert views. The analysis is based on a survey experiment conducted in Australia and Austria. It finds that voters broadly adhere to the democratic principle of expecting pledge fulfilment but, at the same time, some take a rational approach to government promises. The opinions of the public and experts mitigate but do not change this effect. Another key finding is the significant difference in the preference for promise keeping versus promise breaking between government and opposition voters in the Austrian case, the country with the more heterogeneous and polarized political system. This paper contributes to the literature on voters’ attitudes on democracy and pledge fulfilment by showing that voters are normatively driven but a significant number of voters deviate and instead follow the rational voter logic.
Silicicolous lichen communities of the Ukrainian Crystalline Shield
Authors: Khodosovtsev Alexander , Darmostuk Valerii , Prylutskyi Oleh , Kuzemko Anna
Published: November 2022

Questions

How many different silicicolous lichen syntaxa occur on the Ukrainian Crystalline Shield and what ecological factors are influencing their distribution?

Location

Ukrainian Crystalline Shield, Steppe and Forest–Steppe zones, Ukraine.

Methods

The field research was performed during 2013–2020. Analysis was done with the JUICE software using agglomerative hierarchical cluster analysis in the integrated PC‐Ord with data transformation, pseudospecies cut levels 0–5–25, distance measure – Jaccard, group linkage – Ward's method. For the ordination of the plots we used detrended correspondence analysis (DCA) and non‐metric multidimensional scaling (NMDS) with the “envfit” function, implemented in the R package vegan. As environmental variables we used mean indicator values obtained for each species from the ITALIC database. A generalized synoptic table, which combined both our own and literature data, was clustered using Euclidean distances and the Ward error sum of squares hierarchical clustering method with Ward's criterion.

Results

Seven clusters were obtained after JUICE analysis based on 197 relevés of lichen communities that included 119 lichen species. The main axis in both DCA and NMDS ordination is similar to the vector of substrate pH value. Communities on overhanging surfaces are acidophilous. Communities of water tracks are moderately basophilous to basophilous. Other communities included relevés on different granite characterized as mainly neutrophilous. Lichen communities on siliceous rocks of the Ukrainian Crystalline Shield are assigned to the classes Rhizocarpetea geographici, Leprarietea chlorinae, and Collematetea cristati. Two new alliances (Aspicilion intermutantis and Staurothelion frustulentae), four new associations and three subassociation are described.

Conclusion

Silicicolous lichen communities of the Ukrainian Crystalline Shield differ from the known units of Central Europe by species composition, where lichens with arid ecology are present. Their local distribution depends mainly on a combination of substrate pH, degree of eutrophication, protection from rain, and substrate moisture.
Moral courage and manager‐regret
Authors: Duckworth Craig
Published: November 2022

It has been suggested that moral courage in the workplace supports more robust application of regulatory principles. A workforce with the courage to act on moral imperative, it is argued, can bolster corporate governance and promote both more stable business organisations and greater economic stability at large. Research in the area investigates the bases of moral courage, a central implication being that businesses should invest in ethical training as a matter of public policy. It is standard to present moral courage as the strength of will to do the morally right thing. From a managerial perspective, however, this distorts the normative character of the kind of issues managers typically face. Doing the morally right thing commonly entails inflicting permissible harms. Such harms, though permissible, can be a source of moral concern to the conscientious manager. A difficulty for the standard account, then, is that moral courage may be expected in scenarios in which the moral implications of the manager's action have not been fully assessed. In this paper, an alternative account of moral evaluation is presented that incorporates the concern around permissible harms. The basis of such concern is found to be manager‐regret. Building on this foundation, we can establish a new definition of moral courage, that understands the right action to be that which entails defensible harms, and requires courage because those harms will likely have to be defended. It should be recognised in the academic literature that moral courage has this intellectual dimension. Furthermore, managerial training and practice should reflect this understanding of moral courage if its benefits to public policy, in particular corporate governance, are to be realised. The thesis takes a novel approach to the topic that draws, centrally, on the work of Bernard Williams, Martha Nussbaum and Søren Kierkegaard.
Interventions to promote development in the next 1000 days: A mapping review
Authors: Draper Catherine E. , Klingberg Sonja , Wrottesley Stephanie V. , Milner Kate , Fisher Jane , Lakes Kimberley D. , Yousafzai Aisha K.
Published: November 2022

The next 1000 days – the period from 2 to 5 years of age – has been highlighted as a key developmental stage in the life‐course. A mapping review was conducted to categorize existing literature on interventions in the next 1000 days that promote key developmental outcomes, including publications between 1990 and July 2020. A total of 805 intervention studies were included for data extraction in the review. The number of intervention studies has increased substantially from 2010. Most interventions were from high‐income countries, with few (5%) from low‐ and lower‐middle‐income countries. Interventions including typically developing children (n = 593, 74%) were mostly (80%) implemented in early childhood care and education (ECCE) settings, with 15% taking place in the home or with families and 5% in community or healthcare settings. Children's literacy and language outcomes were the target of 27% of these interventions, while 25% of interventions targeted early childhood development more holistically or targeted multiple developmental domains. Social–emotional development and social skills were the target of 15% of interventions, motor development 13%, numeracy 8% and cognitive development 8%. For children with any developmental delay, disability, disease or exposure (n = 212), interventions frequently targeted Autism Spectrum Disorder (24%), language or literacy delays (21%), developmental delays or disability more generally (20%); 16% targeted behavioral (or conduct) problems; and 5% targeted attention deficit hyperactivity disorder. Almost half (49%) took place in ECCE settings; 24% occurred in the home or with families, or in community (13%) and/or healthcare (14%) settings. This review highlights the need for more intervention research in low‐ and middle‐income countries and for interventions supporting development in the next 1000 days. While the evidence base for interventions to promote development in this age group continues to expand, the most vulnerable children are not benefiting from this evidence.
Effects of socio‐economic status on infant native and non‐native phoneme discrimination
Authors: Singh Leher , Cheng Qiqi , Yeung Wei‐Jun Jean
Published: November 2022

Infants undergo fundamental shifts in perception that are reported to be critical for language acquisition. In particular, infants’ perception of native and non‐native sounds begins to align with the properties of their native sound system. Thus far, empirical evidence for this transition – perceptual narrowing – has drawn from socio‐economically and linguistically narrow populations from limited world regions. In this study, infants were sampled across diverse socio‐economic strata and linguistic development in Singapore. One hundred and 16 infants were tested on their ability to discriminate both a native phonetic contrast (/ba/ versus /da/) and a non‐native Hindi contrast (/ta/ versus /ʈa). Infants ranged in age from 6 to 12 months. Associations between age and discrimination varied by contrast type. Results demonstrated that infants’ native sensitivities were positively predicted by family SES, whereas non‐native sensitivities were not. Maternal socio‐economic factors uniquely predicted native language sensitivity. Findings suggest that infants’ sensitivity to native sound contrasts is influenced by their family socio‐economic status.

Research Highlights

We investigated effects of socio‐economic status on infant speech perception.

Infants were tested on native and non‐native speech discrimination.

Socio‐economic status predicted native speech discrimination.

Maternal occupation was a key predictor of native speech discrimination.
Distintos tonos de gris más allá del blanco y negro. Efectos de la segmentación legal en la segmentación del mercado de trabajo en Europa
Authors: DINGELDEY Irene , GERLITZ Jean‐Yves
Published: November 2022

Se estudia el impacto de la legislación laboral en la segmentación de facto del mercado de trabajo en 22 países europeos de 1991 a 2014. Se distinguen tres funciones de la legislación laboral basadas en el concepto de segmentación legal —estandarización (protectora), constitución de privilegios e igualación— y se estudian sus efectos sobre el empleo global, típico y atípico, masculino y femenino mediante estadísticas descriptivas y multivariantes. Fuertes privilegios, combinados con un alto grado de estandarización, favorecen el empleo típico masculino y atípico femenino, mientras que la igualación en favor de las mujeres y demás grupos marginados aumenta el empleo atípico masculino.
Interpopulation variation in inbreeding is primarily driven by tolerance of mating with relatives in a spermcasting invertebrate
Authors: Olsen Kevin C. , Levitan Don R.
Published: November 2022

The degree to which individuals inbreed is a fundamental aspect of population biology shaped by both passive and active processes. Yet, the relative influences of random and non‐random mating on the overall magnitude of inbreeding are not well characterized for many taxa. We quantified variation in inbreeding among qualitatively accessible and isolated populations of a sessile marine invertebrate (the colonial ascidian Lissoclinum verrilli) in which hermaphroditic colonies cast sperm into the water column for subsequent uptake and internal fertilization. We compared estimates of inbreeding to simulations predicting random mating within sites to evaluate if levels of inbreeding were (1) less than expected because of active attempts to limit inbreeding, (2) as predicted by genetic subdivision and passive inbreeding tolerance, or (3) greater than simulations due to active attempts to promote inbreeding via self‐fertilization or a preference for related mates. We found evidence of restricted gene flow and significant differences in the genetic diversity of L. verrilli colonies among sites, indicating that on average colonies were weakly related in accessible locations, but their levels of relatedness matched that of first cousins or half‐siblings on isolated substrates. Irrespective of population size, progeny arrays revealed variation in the magnitude of inbreeding across sites that tracked with the mean relatedness of conspecifics. Biparental reproduction was confirmed in most offspring (86%) and estimates of total inbreeding largely overlapped with simulations of random mating, suggesting that interpopulation variation in mother–offspring resemblance was primarily due to genetic subdivision and passive tolerance of related mates. Our results highlight the influence of demographic isolation on the genetic composition of populations, and support theory predicting that tolerance of biparental inbreeding, even when mates are closely related, may be favoured under a broad set of ecological and evolutionary conditions.
Multiple Lugol‐unstained lesions predict higher cumulative risk of malignance in the esophagus
Authors: Qi Zifan , Liu Mengfei , Zhou Ren , Guo Chuanhai , Liu Anxiang , Yang Haijun , Li Fenglei , Duan Liping , Shen Lin , Wu Qi , Wu Nan , Liu Zhen , Pan Yaqi , Liu Fangfang , Liu Ying , Cai Hong , He Zhonghu , Ke Yang
Published: November 2022

Background and Aim

The impact of the presence of multiple Lugol‐unstained lesions (LULs) in the esophagus on the risk of having severe dysplasia and above (SDA) lesions among asymptomatic individuals is unknown.

Methods

We collected demographic factors, behavioral variables, and features of LULs from 1073 participants who were biopsied at baseline endoscopic screening in a population‐based screening trial, and these individuals were followed over a median time of 7 years. Outcome events were defined as SDA identified at screening, at reexamination, or during follow‐up. “Multiple LULs” were defined as ≥ 2 LULs found in the entirety of the esophagus. Multivariable logistic regression models were fitted to assess the effect of “multiple LULs” on the cumulative risk of SDA.

Results

There were 147 SDA cases in the current study. After adjustment for potential risk factors and endoscopic features of LULs, the presence of “multiple LULs” slightly increased the cumulative risk of having SDA with no statistical significance (adjusted odds ratio [OR] = 1.26; 95% confidence interval [CI] [0.85, 1.88]). Further stratified analysis showed that this association was strong among subjects with small LULs (≤ 5 mm) (adjusted OR = 3.29; 95% CI [1.39, 7.79]). However, no such association was observed in subjects with larger LULs (adjusted OR = 0.99; 95% CI [0.63, 1.55], P interaction = 0.022).

Conclusions

The presence of “multiple small LULs (≤ 5 mm)” in chromoendoscopy indicates a higher cumulative risk of having SDA in the esophagus. We recommend biopsies be taken and surveillance be maintained at a more active level in individuals with relatively small but multiple LULs.