bluuebunny/crossref_metadata_2025 huggingface dataset:
Palbociclib blocks neutrophilic phosphatidylinositol 3‐kinase activity to alleviate psoriasiform dermatitis
Authors: Chen Po‐Jen , Tseng Hsin‐Hui , Wang Yi‐Hsuan , Fang Shu‐Yen , Chen Shun‐Hua , Chen Chun‐Hong , Tsai Sheng‐Chieh , Chang Yu‐Chia , Tsai Yung‐Fong , Hwang Tsong‐Long
Published: March 2023

Background and Purpose

Neutrophilic inflammation is a critical pathogenic factor in psoriasis. The therapeutic applicability of palbociclib, a cyclin‐dependent kinase 4 and 6 (CDK4/6) inhibitor clinically used to treat cancer, in the treatment of neutrophil‐associated psoriasis remains undefined. In this study, we evaluated the therapeutic potential and pharmacological effect of palbociclib on neutrophil‐associated psoriasiform dermatitis.

Experimental Approach

The anti‐inflammatory effects of palbociclib were determined in activated human neutrophils. The therapeutic feasibility of palbociclib in psoriasis was demonstrated in a mouse model of imiquimod‐induced psoriasiform dermatitis. The in vitro enzymatic assays and in silico analyses were used to identify the underlying pharmacological mechanisms.

Key Results

This study found that palbociclib inhibited neutrophilic inflammation, including superoxide anion generation, reactive oxygen species (ROS) formation, elastase degranulation and chemotactic responses. The mechanistic studies identified that the anti‐inflammatory effects of palbociclib involved the targeting of phosphatidylinositol 3‐kinase (PI3K) but not CDK4/6 in human neutrophils. Palbociclib preferentially targeted the p110δ catalytic subunit of PI3K and thereby blocked signalling via the PI3K/protein kinase B (Akt) pathway. Furthermore, topical application of palbociclib significantly ameliorated imiquimod‐induced psoriasiform dermatitis in mice, including psoriatic symptoms, neutrophil infiltration, Akt activation and cytokine up‐regulation.

Conclusions and Implications

This is the first study to demonstrate that palbociclib can potentially be used to treat neutrophil‐associated psoriasiform dermatitis through the targeting of neutrophilic PI3K activity. Our findings prompt further research to explore the potential of palbociclib and PI3K in psoriasis and other inflammatory diseases.
Acanthopanax senticosus extract alleviates radiation‐induced learning and memory impairment based on neurotransmitter‐gut microbiota communication
Authors: Song Chen , Yin Yishu , Qin Yue , Li Tianzhu , Zeng Deyong , Ju Ting , Duan Fangyuan , Zhang Yingchun , Lu Weihong
Published: March 2023

Background

Acanthopanax senticosus (AS) is a medicinal and food plant with many physiological functions, especially nerve protection. Its extract has many functional components, including polysaccharides, flavonoids, saponins, and amino acids. Our previous study indicated that AS extract protected against nerve damage caused by radiation. However, little is known about the gut‐brain axis mechanism of AS and its impact on radiation‐induced learning and memory impairment.

Method

In 60Co‐γ ray‐irradiated mice, we investigated the changes in behavior, neurotransmitters and gut microbiota after different days of administration of AS extract as a dietary supplement.

Results

The AS extract improved learning and memory ability in mice, and the neurotransmitter levels in the hippocampus and colon started to change from the 7th day, which accompanied changes of the gut microbiota, a decreased abundance of Helicobacter on the 7th day and an increased abundance of Lactobacillus on the 28th day. Among the marker bacteria, Ruminococcus and Clostridiales were associated with 5‐HT synthesis, and Streptococcus were associated with 5‐HT and ACH synthesis. In addition, the AS extract increased the tight junction protein, inhibited inflammation levels in colon, and even increased the relative protein expression of BDNF and NF‐κB and decreased the relative protein expression of IκBα in the hippocampus of irradiated mice.

Conclusion

These results will lay the foundation for further study on the mechanism of the gut‐brain axis of AS in preventing radiation‐induced learning and memory impairment.
G9a promotes immune suppression by targeting the Fbxw7/Notch pathway in glioma stem cells
Authors: Cao Yufei , Liu Bin , Cai Lize , Li Yanyan , Huang Yulun , Zhou Youxin , Sun Xingjian , Yang Wei , Sun Ting
Published: March 2023

Aim

Immunotherapy for glioblastoma multiforme (GBM) is limited because of a strongly immunosuppressive tumor microenvironment (TME). Remodeling the immune TME is an effective strategy to eliminate GBM immunotherapy resistance. Glioma stem cells (GSCs) are inherently resistant to chemotherapy and radiotherapy and involved in immune evasion mechanism. This study aimed to investigate the effects of histone methyltransferases 2 (EHMT2 or G9a) on immunosuppressive TME and whether this effect was related to changes on cell stemness.

Methods

Tumor‐infiltrating immune cells were analyzed by flow cytometry and immunohistochemistry in orthotopic implanted glioma mice model. The gene expressions were measured by RT‐qPCR, western blot, immunofluorescence, and flow cytometry. Cell viability was detected by CCK‐8, and cell apoptosis and cytotoxicity were detected by flow cytometry. The interaction of G9a and F‐box and WD repeat domain containing 7 (Fbxw7) promotor was verified by dual‐luciferase reporter assay and chromatin immunoprecipitation.

Results

Downregulation of G9a retarded tumor growth and extended survival in an immunocompetent glioma mouse model, promoted the filtration of IFN‐γ + CD4+ and CD8+ T lymphocytes, and suppressed the filtration of PD‐1+ CD4+ and CD8+ T lymphocytes, myeloid‐derived suppressor cells (MDSCs) and M2‐like macrophages in TME. G9a inhibition decreased PD‐L1 and increased MHC‐I expressions by inactivating Notch pathway companying stemness decrease in GSCs. Mechanistically, G9a bound to Fbxw7, a Notch suppressor, to inhibit gene transcription through H3K9me2 of Fbxw7 promotor.

Conclusion

G9a promotes stemness characteristics through binding Fbxw7 promotor to inhibit Fbxw7 transcription in GSCs, forming an immunosuppressive TME, which provides novel treatment strategies for targeting GSCs in antitumor immunotherapy.
Discordance in cytomegalovirus viremia in kidney recipients from the same donor is associated with the worst outcomes
Authors: Zona Emily , Jorgenson Margaret , Dolma Sonam , Santos Angelie , Garg Neetika , Aziz Fahad , Mohamed Maha , Saddler Christopher M. , Smith Jeannina A. , Mandelbrot Didier , Parajuli Sandesh
Published: March 2023

Background

Cytomegalovirus (CMV) is a common viral infection in kidney transplant recipients (KTR) that has been associated with negative outcomes. The effect on outcomes of concordance versus discordance in CMV between two different recipients of kidneys from the same donor is largely unknown.

Methods

We reviewed all adult deceased donor kidney transplant recipients (DDKTs) for which both kidneys were transplanted to two different recipients at our center between 2014 and 2019. Recipient pairs from each donor were divided into groups based on concordance or discordance for the development of CMV viremia between the pair; concordant no CMV (cc‐no‐CMV) if neither KTR developed CMV, concordant CMV (cc‐CMV) if both KTRs developed CMV. The discordant group was then further divided based on the individual development of CMV (dc‐CMV) or lack of development of CMV (dc‐no‐CMV). Patient mortality and death‐censored graft failure (DCGF) were outcomes of interest.

Results

Of 578 KTRs, 67% were cc‐no‐CMV, 5% were cc‐CMV, 14% were dc‐no‐CMV, and 14% dc‐CMV. Some of the baseline characteristics differ among the groups including a higher prevalence of high‐risk serostatus (D+/R‐) in cc‐CMV (32%) and dc‐CMV (32%). In multivariate analysis, with reference to cc‐no‐CMV, dc‐CMV was associated with increased risk for DCGF (HR 3.13, 95% CI 1.58–6.19), and so was delayed graft function. Factors associated with increased risk of mortality were advanced recipient age and DGF. cc‐CMV was neither associated with mortality nor DCGF.

Conclusions

These findings support that in certain contexts, CMV viremia has adverse allograft outcomes, and this is highlighted when illustrated via discordance in CMV between pair kidneys from the same deceased donor.
Ability of grazing fish to generate particulate organic matter derived from autochthonous primary production
Authors: Abe Shin‐ichiro , Hoshino Daiki , Iguchi Kei’ichiro
Published: March 2023

Grazing fish play a role of controlling autochthonous primary production and converting it to secondary production by consuming benthic algae. Moreover, they will also provide autochthonous particulate organic matter (POM) for freshwater ecosystems by dislodging the benthic algal matrix while feeding. However, it has not been confirmed whether grazing fish induce POM production during their feeding on benthic algae. To verify this POM production during grazing by fish, short‐term (90 min) feeding experiments were conducted by introducing grazing fishPlecoglossus altivelisinto indoor aquaria with benthic algal mats. We found that the fish can generate POM by feeding on benthic algae. Although POM was generated in the aquaria where the fish had not grazed on the benthic algal mats at all, the concentration of POM in the aquaria increased with the frequency of the acts of scraping benthic algae by the fish. Furthermore, we observed that the fish egested faeces which corresponded to about 44% on average of the ingested benthic organic matter. In some cases, the fish generated POM that corresponded to 88% of the removed (dislodged and ingested) benthic organic matter through their feeding and defecation. This study suggested that grazing fish have a function of providing autochthonous POM to freshwater ecosystems both via dislodging benthic algae during feeding and through egestion of consumed benthic algae.
Long‐term outcomes of patients with paroxysmal nocturnal hemoglobinuria treated with eculizumab in a real‐world setting
Authors: Versmold Katharina , Alashkar Ferras , Raiser Carina , Ofori‐Asenso Richard , Xu Tao , Liu Yutong , Katz Pablo , Shang Aijing , Röth Alexander
Published: March 2023

Objective

Describe the real‐world clinical profile of eculizumab‐treated patients by characterizing their short‐ and long‐term clinical and laboratory outcomes.

Methods

This retrospective study used preexisting medical records of eculizumab‐treated patients with paroxysmal nocturnal hemoglobinuria (PNH) at the University Hospital Essen. Hematologic response, breakthrough hemolysis, transfusion dependence, and other outcomes were assessed.

Results

Of 85 patients with PNH, 76 received eculizumab for ≥24 weeks (mean follow‐up: 5.59 years; total: 425 person‐years). At 24 weeks (n = 57 patients with data), 7% and 9% had complete and major hematologic response, respectively. Breakthrough hemolysis occurred in 8%, and 38% required a blood transfusion. Over long‐term follow‐up (25–264 weeks), 70%–82% of patients did not achieve complete or major hematologic response in any 24‐week period. Breakthrough symptoms, breakthrough hemolysis, and transfusion dependence occurred in 63%, 43%, and 63% of patients, respectively, at any point during follow‐up. The majority (79%–89%) of patients did not achieve normalized hemoglobin, with 76%–93% having elevated bilirubin or absolute reticulocyte count in any 24‐week window. Mean percentage reduction in lactate dehydrogenase (baseline to end of follow‐up) was 80.3% (95% CI, 64.0–96.6).

Conclusions

A considerable proportion of patients with PNH receiving eculizumab did not achieve optimal clinical outcomes and had an ongoing disease burden.
Inhibition of neuronal peroxisome proliferator‐activated receptor‐γ attenuates motor function improvement after spinal cord injury in rats
Authors: Kim Youngkyung , Park Kyu‐won , Lee Eunji , Yoon Young Wook
Published: March 2023

Traumatic spinal cord injury (SCI) causes secondary damage in injured and adjacent regions due to temporal deprivation of oxygen and energy supply. Peroxisome proliferator‐activated receptor γ (PPARγ) is known to regulate cell survival mechanisms such as hypoxia, oxidative stress, inflammation and energy homeostasis in various tissues. Thus, PPARγ has the potential to show neuroprotective properties. However, the role of endogenous spinal PPARγ in SCI is not well established. In this study, under isoflurane inhalation, a 10‐g rod was freely dropped onto the exposed spinal cord after T10 laminectomy using a New York University impactor in male Sprague–Dawley rats. Cellular localization of spinal PPARγ, locomotor function and mRNA levels of various genes including NFκB‐targeted pro‐inflammatory mediators after intrathecal administration of PPARγ antagonists, agonists or vehicles in SCI rats were then analysed. In both sham and SCI rats, spinal PPARγ was presented in neurons but not in microglia or astrocytes. Inhibition of PPARγ induced IκB activation and increased mRNA levels of pro‐inflammatory mediators. It also suppressed recovery of locomotor function with myelin‐related gene expression in SCI rats. However, a PPARγ agonist showed no beneficial effects on the locomotor performances of SCI rats, although it further increased the protein expression of PPARγ. In conclusion, endogenous PPARγ has a role in anti‐inflammation after SCI. Inhibition of PPARγ might have a negative influence on motor function recovery through accelerated neuroinflammation. Nonetheless, exogenous PPARγ activation does not appear to effectively help with functional improvement after SCI.
Interplay between speech and gait variables in Parkinson's disease patients treated with subthalamic nucleus deep brain stimulation: A long‐term instrumental assessment
Authors: Cavallieri Francesco , Gessani Annalisa , Merlo Andrea , Campanini Isabella , Budriesi Carla , Fioravanti Valentina , Di Rauso Giulia , Feletti Alberto , Damiano Benedetta , Scaltriti Sara , Guagnano Noemi , Bardi Elisa , Corni Maria Giulia , Antonelli Francesca , Cavalleri Francesca , Molinari Maria Angela , Contardi Sara , Menozzi Elisa , Puzzolante Annette , Vannozzi Giuseppe , Bergamini Elena , Pavesi Giacomo , Fraix Valérie , Meoni Sara , Fraternali Alessandro , Versari Annibale , Lusuardi Mirco , Biagini Giuseppe , Pinto Serge , Moro Elena , Valzania Franco
Published: March 2023

Objective

To evaluate correlations between speech and gait parameters in the long term and under different medication and subthalamic nucleus deep brain stimulation (STN‐DBS) conditions in a cohort of advanced Parkinson's disease (PD) patients.

Methods

This observational study included consecutive PD patients treated with bilateral STN‐DBS. Axial symptoms were evaluated using a standardized clinical‐instrumental approach. Speech and gait were assessed by perceptual and acoustic analyses and by the instrumented Timed Up and Go (iTUG) test, respectively. Disease motor severity was evaluated with the total score and subscores of the Unified Parkinson's Disease Rating Scale (UPDRS) Part III. Different stimulation and drug treatment conditions were assessed: on‐stimulation/off‐medication, off‐stimulation/off‐medication, and on‐stimulation/on‐medication.

Results

Twenty‐five PD patients with a 5‐year median follow‐up after surgery (range 3–7 years) were included (18 males; disease duration at surgery: 10.44 [SD 4.62] years; age at surgery: 58.40 [SD 5.73] years). In the off‐stimulation/off‐medication and on‐stimulation/on‐medication conditions, patients who spoke louder had also the greater acceleration of the trunk during gait; whereas in the on‐stimulation/on‐medication condition only, patients with the poorer voice quality were also the worst to perform the sit to stand and gait phases of the iTUG. Conversely, patients with the higher speech rate performed well in the turning and walking phases of the iTUG.

Conclusions

This study underlines the presence of different correlations between treatment effects of speech and gait parameters in PD patients treated with bilateral STN‐DBS. This may allow us to better understand the common pathophysiological basis of these alterations and to develop a more specific and tailored rehabilitation approach for axial signs after surgery.
Characteristics of prescribing activity within primary care in Scotland 2013–2022 of general practitioners, nurse, pharmacist and allied health prescribers: A retrospective cross‐sectional study
Authors: MacVicar Sonya , Paterson Ruth E.
Published: March 2023

Background

Independent prescribing by nurses, pharmacists and allied health professionals is diversifying into a variety of healthcare settings as pressures mount on existing resources. Primary care was an early adopter of prescribing by non‐medical professionals with resulting improvements in accessibility and flexibility of services but also noted barriers. Exploring existing prescribing activity within primary care can support future initiatives that are cognisant of the needs of this specific population and targeted in the use of finite resources.

Aim

To explore the characteristics of prescribing activity of common drugs dispensed by community pharmacies in Scotland by prescribing groups of general practitioners, nurses, pharmacist and allied health professionals. Specifically, to compare overall drug prescribing frequency by prescriber group and identify emergent prescribing patterns of individual drugs.

Design

A cross‐sectional study.

Methods

The data from Public Health Scotland on frequency of the ten most common drugs prescribed and dispensed from community pharmacies between 2013 and 2022 by prescriber group were examined, applying descriptive statistics using secondary data analysis.

Results

Prescribing activity in non‐medical prescribing groups accounted for 2%–3% of overall prescribing activity in primary care. There is a growing interprofessional approach to prescribing in chronic disease. Proton pump inhibitors were the most commonly prescribed medication overall with a 4‐fold increase in nurse prescribing. The decline in prescribing frequency caused by COVID 19 restrictions has since returned to pre‐pandemic levels.

Conclusion

There is a growing contribution of nurse independent prescriber activity within primary care although still a relatively small proportion compared to medical practitioners. The pattern of increased prescribing of medications for long term and chronic conditions such as proton pump inhibitors by all prescribers is suggestive of multi‐disciplinary professionals supporting increased patient demand. This study provides a baseline to evaluate current service provision in further research and enable professional, service and policy development.
Extra‐pair paternity and sexual dimorphism in birds
Authors: Valcu Mihai , Valcu Cristina , Kempenaers Bart
Published: March 2023

Differences in the strength of sexual selection between males and females can lead to sexual dimorphism. Extra‐pair paternity (EPP) can increase the variance in male reproductive success and hence the opportunity for sexual selection. Previous research on birds suggests that EPP drives the evolution of dimorphism in plumage colour and in body size. Because EPP increases the intensity of sexual selection in males, it should lead to increased dimorphism in species with larger or more colourful males, but decreased dimorphism in species with larger or more colourful females. We explored the covariation between EPP and sexual dimorphism in wing length and plumage colouration in 401 bird species, while controlling for other, potentially confounding variables. Wing length dimorphism was associated positively with the frequency of EPP, but also with social polygamy, sex bias in parental behaviour and body size and negatively with migration distance. The frequency of EPP was the only predictor of plumage colour dimorphism. In support of our prediction, high EPP levels were associated with sexual dichromatism, positively in species in which males are more colourful and negatively in those in which females are more colourful. Contrary to our prediction, high EPP rates were associated with increased wing length dimorphism in species with both male‐ and female‐biased dimorphism. The results support a role for EPP in the evolution of both size and plumage colour dimorphism. The two forms of dimorphism were weakly correlated and predicted by different reproductive, social and life‐history traits, suggesting an independent evolution.
Selective adhesive luting: A novel technique for improving adhesion achieved by universal resin cements
Authors: Breschi Lorenzo , Josic Uros , Maravic Tatjana , Mancuso Edoardo , Del Bianco Federico , Baldissara Paolo , Mazzoni Annalisa , Mazzitelli Claudia
Published: March 2023

Objective

We aimed to introduce the concept of “Selective adhesive luting—SAL” which is explained through clinical steps and supported by preliminary laboratory evidence.

Clinical Considerations

Cementation with rubber dam is difficult to perform in case of short abutment teeth and/or subgingival crown margins. By means of universal resin cements/universal adhesive systems, which can be employed in self‐adhesive as well as adhesive luting procedures, this paper presents a novel technique allowing clinicians to perform reliable cementation where rubber dam isolation is difficult. The SAL technique entails the application of a universal adhesive system only on easily accessible abutment surfaces, enabling simultaneous adhesive and self‐adhesive luting in different portions of the abutment. The SAL clinical workflow is explained through prosthodontic rehabilitation of maxillary right central incisor affected by microdontia and restored with a lithium‐disilicate crown. Furthermore, our laboratory microshear bond strength study supports the rationale behind SAL application demonstrating higher bond strength even when the adhesive resin is placed only on one portion of the cementation substrate.

Clinical Significance

This article advocates the application of SAL technique in clinical situations where effective adhesive luting is uncertain, since it can improve the adhesion between the tooth and universal resin cements.
Clustering multivariate time series using energy distance
Authors: Davis Richard A. , Fernandes Leon , Fokianos Konstantinos
Published: March 2023

A novel methodology is proposed for clustering multivariate time series data using energy distance defined in Székely and Rizzo (2013). Specifically, a dissimilarity matrix is formed using the energy distance statistic to measure the separation between the finite‐dimensional distributions for the component time series. Once the pairwise dissimilarity matrix is calculated, a hierarchical clustering method is then applied to obtain the dendrogram. This procedure is completely nonparametric as the dissimilarities between stationary distributions are directly calculated without making any model assumptions. In order to justify this procedure, asymptotic properties of the energy distance estimates are derived for general stationary and ergodic time series. The method is illustrated in a simulation study for various component time series that are either linear or nonlinear. Finally, the methodology is applied to two examples; one involves the GDP of selected countries and the other is the population size of various states in the U.S.A. in the years 1900–1999.
Evaluation of the sensory properties of thickened and protein‐enhanced ice cream using check‐all‐that‐apply and temporal check‐all‐that‐apply
Authors: Moss Rachael , Gorman Mackenzie , LeBlanc Jeanne , Ritchie Christopher , McDowell Taylor K. , Lowe Judith , Ettinger Laurel , McSweeney Matthew B.
Published: March 2023

Ice cream formulations with varying amounts of added whey protein were created for those living with dysphagia in long‐term care facilities (LTCs) to improve protein and fluid intake. The samples of thickened ice cream included a control (0% whey protein [WP]) and formulations with 6% (6WP), 8% (8WP), 10% (10WP), 12% (12WP) and 14% (14WP) added whey protein by volume. The consistency of the samples was assessed using the International Dysphagia Diet Standardization Initiative (IDDSI) Spoon Tilt Test, a sensory trial (n = 102) using hedonic scales and check‐all‐that‐apply (CATA) and another sensory trial (n = 96) using temporal check‐all‐that‐apply (TCATA). The whey protein increased the acceptability of the thickened ice cream except for the 12WP and 14WP formulations. The formulations with higher amounts of whey protein were associated with bitterness, custard/eggy flavor, and mouthcoating. The TCATA identified that the addition of whey protein led to slippery, gritty, and grainy attributes being perceived in the thickened ice cream. The study identified that 10% whey protein by volume can be added to thickened ice cream without impacting its' acceptability and the 6WP, 8WP, and 10WP formulations were liked significantly more than the control (without whey protein).
A Post‐American Middle East? US Realities Vs. Chinese and Russian Alternatives
Authors: Colley Christopher K.
Published: March 2023

For the past 15 years, there have been increasing calls for the United States to reduce its overseas force structure and to bring troops home. Such discussion accelerated during the Trump administration, and perceptions of American retrenchment were heightened by President Joe Biden's decision to withdraw from Afghanistan. This article asks the key question: Is Washington really engaging in a systematic pullout from the Middle East? Based on publicly available evidence, I argue that, contrary to common perceptions, the American military is actually increasing its forward presence in the Arabian Peninsula and Gulf region. In addition, I contend that the two other states that have the potential to replace the United States in the Middle East, Russia and China, are for multiple reasons incapable of doing so. In addition to puncturing the myths, the article contributes to the ongoing policy debates and theoretical literatures regarding Middle East security and great‐power competition.
Inhibition of SlSKOR by SlCIPK23‐SlCBL1/9 uncovers CIPK‐CBL‐target network rewiring in land plants
Authors: Nieves‐Cordones Manuel , Amo Jesús , Hurtado‐Navarro Laura , Martínez‐Martínez Almudena , Martínez Vicente , Rubio Francisco
Published: March 2023

Transport of K+ to the xylem is a key process in the mineral nutrition of the shoots. Although CIPK‐CBL complexes have been widely shown to regulate K+ uptake transport systems, no information is available about the xylem ones. Here, we studied the physiological roles of the voltage‐gated K+ channel SlSKOR and its regulation by the SlCIPK23‐SlCBL1/9 complexes in tomato plants.

We phenotyped gene‐edited slskor and slcipk23 tomato knockout mutants and carried out two‐electrode voltage‐clamp (TEVC) and BiFC assays in Xenopus oocytes as key approaches.

SlSKOR was preferentially expressed in the root stele and was important not only for K+ transport to shoots but also, indirectly, for that of Ca2+, Mg2+, Na+, NO3−, and Cl−. Surprisingly, the SlCIPK23‐SlCBL1/9 complexes turned out to be negative regulators of SlSKOR. Inhibition of SlSKOR by SlCIPK23‐SlCBL1/9 was observed in Xenopus oocytes and tomato plants. Regulation of SKOR‐like channels by CIPK23‐CBL1 complexes was also present in Medicago, grapevine, and lettuce but not in Arabidopsis and saltwater cress.

Our results provide a molecular framework for coordinating root K+ uptake and its translocation to the shoot by SlCIPK23‐SlCBL1/9 in tomato plants. Moreover, they evidenced that CIPK‐CBL‐target networks have evolved differently in land plants.
Legalism without adversarialism?: Bureaucratic legalism and the politics of regulatory implementation in the European Union
Authors: Foster Chase
Published: March 2023

Many scholars predict that European integration will foster adversarial legalism in Europe. In this article, I empirically assess the Eurolegalism thesis by examining EU regulatory mandates in the competition and securities fields, two policy areas where adversarial legalism is seen as most likely to develop. I argue that the diffusion of adversarial legalism to Europe has faced significant political opposition in the EU policymaking process which has curtailed the use of private enforcement mandates in EU secondary legislation. European policymakers have relied more on administrative enforcement through public regulatory agencies, a mode of policy implementation closer to bureaucratic legalism. In practice, public authorities play the primary enforcement role and private litigation serves the narrower function of compensation following public enforcement actions. Drawing from institutionalist theory, I identify several factors that have encouraged the development of bureaucratic rather than adversarial styles of European legalism, especially member states' commitments to procedural subsidiarity, the negative feedback effects from the US experience with entrepreneurial litigation, and the stickiness of European legal and bureaucratic traditions.
Logistic or not Logistic?
Authors: Allison James S. , Ebner Bruno , Smuts Marius
Published: March 2023

We propose a new class of goodness‐of‐fit tests for the logistic distribution based on a characterization related to the density approach in the context of Stein's method. This characterization‐based test is a first of its kind for the logistic distribution. The asymptotic null distribution of the test statistic is derived and it is shown that the test is consistent against fixed alternatives. The finite sample power performance of the newly proposed class of tests is compared to various existing tests by means of a Monte Carlo study. It is found that this new class of tests are especially powerful when the alternative distributions are heavy tailed, like Student's t and Cauchy, or for skew alternatives such as the log‐normal, gamma and chi‐square distributions.
Hemostatics in patients with inhibited coagulation—A viscoelastic in‐vitro analysis
Authors: Lechner Raimund , Hanke Katharina , Schmid Anna , Mayer Benjamin , Helm Matthias , Kulla Martin , Hossfeld Björn
Published: March 2023

Background

The military has used topical hemostatic agents to successfully treat life‐threatening external bleeding for years. In contrast to the military environment, the general population are increasingly prescribed anticoagulants. There are only few comparative evaluations of topical hemostatic agents with anticoagulated human blood. It is important to understand the impact of these agents on those who take anticoagulants.

Study design and Methods

Citrated blood of patients treated with enoxaparin, heparin, and acetylsalicylic acid, apixaban or phenprocoumon was incubated with different hemostatic agents (QuikClot Gauze, Celox Granules, Celox Gauze, Chito SAM 100, WoundClot Trauma Gauze, QuikClot Gauze Moulage Trainer and Kerlix) and rotational thromboelastometry was performed with non‐activated thromboelastometry (NATEM reagent).

Results

All tested agents improved the onset of coagulation in all anticoagulants, mostly to a significant degree. Most significant improvements were produced by QuikClot Gauze and QuikClot Gauze Moulage Trainer, followed by the tested chitosans (Celox Granules, Celox Gauze, Chito SAM 100). Of the anticoagulant groups, the most significant improvements were seen in enoxaparin. This was followed in order by apixaban, heparin, and acetylsalicylic acid, and phenprocoumon.

Discussion

All the hemostatic agents tested were able to activate the clotting cascade earlier and initiate faster clot formation in anticoagulated blood. A definitive head‐to‐head comparison is not feasible, because of the limitations of an in‐vitro analysis. However, the sometimes‐presented hypothesis that kaolin‐based hemostatic agents are ineffective in anticoagulated blood is inaccurate according to our data. Hemostasis with hemostatic agents appears most challenging with phenprocoumon.
Cross-Cultural Adaptation and Validation of the Persian Version of the Functional Arm Scale for Throwers
Authors: Hessam Masumeh , Mousavi Mohammad Hossein , Saadat Maryam , Bliven Kellie C. Huxel
Published: March 2023

Background: The Functional Arm Scale for Throwers (FAST) is a reliable and valid region-specific tool designed to evaluate health-related quality of life in throwing athletes with upper-extremity injuries. The purpose of this study was to adapt, translate, and evaluate the psychometric properties of the Persian version of the Functional Arm Scale (FAST-Persian) for use in throwing athletes. Materials and Methods: The study was conducted based on 5 steps of cross-cultural adaptation including forward translation, synthesis, backward translation, expert committee review, and pretesting. The final Persian questionnaire, along with Persian versions of Disabilities of the Arm, Shoulder, and Hand and Kerlan-Jobe Orthopedic Clinic questionnaires, was completed by 177 throwing athletes for validity analysis. After 7 to 14 days, the FAST-Persian was reanswered by 80 throwers, who had no changes in this time interval. Internal consistency and test retest reliability were used to evaluate reliability of the questionnaire. Standard error of measurement and smallest detectable changes were also calculated. Construct validity was determined by correlational analysis with Disabilities of the Arm, Shoulder, and Hand and Kerlan-Jobe Orthopedic Clinic questionnaires. Dimensionality was evaluated with factor analysis. Result: Cronbachs alpha was .99, and the interclass correlation coefficient levels for total score and 5 subscales of the FAST-Persian ranged between .98 and .99. The standard error of measurement and smallest detectable changes were 3.17 and 8.80, respectively. The FAST-Persian had a high correlation with Disabilities of the Arm, Shoulder, and Hand (r = .98, P < .0001) and Kerlan-Jobe Orthopedic Clinic (r = .98, P < .0001) scores. Factor analysis revealed one factor with a total variance of 75.23%. Conclusion: The FAST-Persian is a reliable and valid measurement tool that can be used to evaluate health-related quality of life in overhead athletes and throwers.
Discovery and Characterization of Pneumococcal Serogroup 36 Capsule Subtypes, Serotypes 36A and 36B
Authors: Ganaie Feroze A. , Saad Jamil S. , Lo Stephanie W. , McGee Lesley , Bentley Stephen D. , van Tonder Andries J. , Hawkins Paulina , Keenan Jeremy D. , Calix Juan J. , Nahm Moon H.
Published: March 2023

Streptococcus pneumoniae
can produce a wide breadth of antigenically diverse capsule types, a fact that poses a looming threat to the success of vaccines that target pneumococcal polysaccharide (PS) capsule. Yet, many pneumococcal capsule types remain undiscovered and/or uncharacterized.
Direct Blockade of the Norovirus Histo-Blood Group Antigen Binding Pocket by Nanobodies
Authors: Kher Gargi , Sabin Charles , Lun Jennifer H. , Devant Jessica M. , Ruoff Kerstin , Koromyslova Anna D. , von Itzstein Mark , Pancera Marie , Hansman Grant S.
Published: March 2023

Human noroviruses are highly contagious and a major problem in closed institutions, such as schools, hospitals, and cruise ships. Reducing norovirus infections is challenging on multiple levels and includes the frequent emergence of antigenic variants, which complicates designing effective, broadly reactive capsid therapeutics.
Analysis of the Genomics and Mouse Virulence of an Emergent Clone of Streptococcus dysgalactiae Subspecies
equisimilis
Authors: Beres Stephen B. , Olsen Randall J. , Long S. Wesley , Eraso Jesus M. , Boukthir Sarrah , Faili Ahmad , Kayal Samer , Musser James M.
Published: March 2023

Our studies addressed a critical knowledge gap in understanding the genomics and virulence of the bacterial pathogen
Streptococcus dysgalactiae
subsp.
equisimilis
.
S. dysgalactiae
subsp.
equisimilis
strains are responsible for a recent increase in severe human infections in some countries. We determined that certain
S. dysgalactiae
subsp.
equisimilis
strains are genetically descended from a common ancestor and that these strains can cause severe infections in a mouse model of necrotizing myositis.
Continental crust delamination in a retreating subduction zone: A case study in the southern Alxa (Inner Mongolia, China), Central Asian Orogenic Belt
Authors: Zheng Rongguo , Zhang Jin , Xiao Wenjiao
Published: March 2023

Carboniferous-Permian igneous rocks in the southern Alxa (Inner Mongolia, China) of the southern Central Asian Orogenic Belt exhibit an oceanward migration trend, which provides an ideal area to reconstruct the process of crust-mantle material exchange within a retreating subduction zone. This study presents new geochronological and geochemical data for the Shouji plutons from the southern Alxa to address crust-mantle material exchange process. All these diorite, granodiorite, and K-feldspar granite samples from the Shouji batholith exhibit Early Permian zircon U-Pb ages (ca. 282−270 Ma). These diorite and granodiorite are characterized by high Sr contents as well as low Y, and Yb concentrations, coupled with distinctively high Sr/Y values. They exhibit fertile Nd-Hf isotopic compositions with negative whole-rock εNd(t) values, and zircon εHf(t) values, similar to those of continental crust-related adakites, which might originate from partial melting of lower crust, and followed by melt-mantle interactions. These K-feldspar granite samples display peraluminous and high-K calc-alkaline compositions, and negative zircon εHf(t) and whole-rock εNd(t) values, and originated from partial melting of Paleoproterozoic igneous rocks, with additions of mantle-derived melts in their sources, in low-temperature, low-pressure conditions. Previously published zircon U-Pb age data show that numerous mafic igneous rocks were mostly generated during the Early Permian, marking the onset of mafic volcanism in the southern Alxa. Moreover, compiled detrital zircon U-Pb age data for Late Carboniferous−Permian sedimentary succession imply a regional topographic uplift during the Early Permian. Both of these two lines of evidence suggest an Early Permian lower crustal delamination in the southern Alxa. These Shouji adakitic plutons were most likely to be generated during the lower crustal delamination. Furthermore, Sr-Nd isotope data of Carboniferous-Permian igneous rocks show that the continental crust was recycled back into the mantle during Early Permian within the southern Alxa by means of subduction erosion and lower crustal delamination.
Acoustic Metric and Planck Constants
Authors: Volovik G. E.
Published: March 2023

Based on Akama–Diakonov (AD) theory of emergent tetrads, it was suggested that one can introduce two Planck constants, $$\hbar $$ and $$\not h $$, which are the parameters of the corresponding components of Minkowski metric, $$g_{\text{Mink}}^{\mu \nu }=\text{diag}(-{{\hbar }^{2}},{{\not h }^{2}},{{\not h }^{2}},{{\not h }^{2}})$$. In the Akama–Diakonov theory, the interval $$ds$$ is dimensionless, as a result the metric elements and thus the Planck constants have nonzero dimensions. The Planck constant $$\hbar $$ has dimension of time, and the Planck constant $$\not h $$ has dimension of length. It is natural to compare $$\not h $$ with the Planck length $${{l}_{{\text{P}}}}$$. However, this connection remains an open question, because the microscopic (trans-Planckian) physics of the quantum vacuum is not known. Here we study this question using the effective gravity emerging for sound wave quanta (phonons) in superfluid Bose liquid, where the microscopic physics is known, and the elements of the effective acoustic metric are determined by the parameters of the Bose liquid. Since the acoustic interval is dimensionless, one may introduce the effective “acoustic Planck constants.” The acoustic Planck constant $${{\not h }_{\text{ac}}}$$ has dimension of length and is on the order of the interatomic distance. This supports the scenario in which $$\not h \sim {{l}_{\text{P}}}$$. We also use the acoustic metric for consideration of dependence of $$\hbar $$ on the Hubble parameter in expanding Universe.
Data driven background estimation in HEP using generative adversarial networks
Authors: Lohezic Victor , Sahin Mehmet Ozgur , Couderc Fabrice , Malcles Julie
Published: March 2023

Data-driven methods are widely used to overcome shortcomings of Monte Carlo simulations (lack of statistics, mismodeling of processes, etc.) in experimental high energy physics. A precise description of background processes is crucial to reach the optimal sensitivity for a measurement. However, the selection of the control region used to describe the background process in a region of interest biases the distribution of some physics observables, rendering the use of such observables impossible in a physics analysis. Rather than discarding these events and/or observables, we propose a novel method to generate physics objects compatible with the region of interest and properly describing the correlations with the rest of the event properties. We use a generative adversarial network (GAN) for this task, as GANs are among the best generator models for various applications. We illustrate the method by generating a new misidentified photon for the $$\gamma + \textrm{jets}$$

γ
+
jets

background of the $$\textrm{H}\rightarrow \gamma \gamma $$

H
→
γ
γ

analysis at the CERN LHC, and demonstrate that this GAN generator is able to produce a coherent object correlated with the different properties of the rest of the event.
Progress and R/D challenges for FCC-ee SRF
Authors: Venturini Delsolaro W. , Garlasche M. , Peauger F. , Rosaz G. , Karpov I. , Zhang L. , Valente Feliciano A. M. , Udongwo S. A. , Bianchi A. , Bellini G. , Ferrera L. M. A. , Pereira Carlos C. , Vega Cid L. , Leith S. , Proslier T. , Gorgi Zadeh S. , Timmins M. , Therasse M. , Koettig T. , Atieh S. , Brunner O. , Gerigk F.
Published: March 2023

The FCC-ee machines present a huge challenge for the RF systems, which need to be adapted to very diverse beam conditions going from moderate energy and high current for the Z machine to high energy and low beam current for the ttbar. This inverse scaling results naturally from a fixed budget for the synchrotron radiation, which the SRF cavities need to compensate. A global solution was elaborated for the FCC Conceptual Design Report (Abada in Eur Phys J Spec Top 228):261–623, 2019), and is referred here as the baseline. Recently, further studies have led to a new optimized baseline, still based on traditional elliptical cavities. In parallel, a novel concept, named the Slotted Waveguide ELLiptical (SWELL), was proposed with the potential of greatly simplified logistics and reduced costs. Under several aspects, all these changes call for enhanced performance of the RF systems. A vigorous R&D program has therefore continued since the publication of the CDR, with the aim of pushing the performance and demonstrating the feasibility of a more advanced baseline and, more recently, of the SWELL option. The progress and challenges of this ambitious program were presented in the dedicated SRF sessions at FCC week 2022 (FCC week 2022 website, 2022, https://indico.cern.ch/event/1064327/timetable/) and are summarized in this paper.
Delineation of heat transfer and flow analysis of Carreau nanofluid in microchannel using Buongiorno model
Authors: Almeida F. , Sindhu S. , Venkatesh P. , Gireesha B. J.
Published: March 2023

This paper reports the hydromagnetic mixed convective flow of Carreau nanofluid in the vertical microchannel with slip and convective mechanisms at the boundaries. The main objective of this work is to analyze the conduct of Carreau nanofluid under Buongiorno model as the nano-dimensions of the particle consequently encounters random motion. The novel impression is to retain the outcomes of the flow in regard of Brownian dispersion and thermophoresis. Parameters such as buoyancy ratio, Brownian motion and thermophoresis along with the effect of Weissenberg number are discussed on distribution of flow, temperature and concentration by using graphical demonstration. Surface drag coefficients, transport rates of mass and heat are portrayed by numeric esteems. Boundary layer approximations are made use to tackle nonlinear ordinary differential equations and solved by Runge–Kutta–Fehlberg 4-5th-order method. Results so obtained elaborate that velocity depletes with increased values of buoyancy ratio and viscosity ratio parameter along with power law index. Also, distinct behavior is noticed in the profile of velocity for varying Weissenberg number by boosting and diminishing depending on the power law index. On the other hand, temperature rises by augmentation of thermophoresis and Brownian motion parameter. Elevation in Brownian motion parameter accelerate the concentration panel of the fluid. Skin friction and Nusselt number are in direct proportion with buoyancy ratio parameter and Brownian motion parameter, respectively.
Effect of vacancy defects on the optoelectronic properties of 1T-TaS2 under torsional deformation
Authors: Bao Jinlin , Yang Lu , Jiang Sisong , Wang Yan
Published: March 2023

The effects of vacancy defects and torsion on the optoelectronic properties of single-layered 1[Formula: see text]-TaS2, including the band structure, electron density difference, defect formation energy and complex dielectric function, are systematically investigated using the first-principles method based on density functional theory (DFT). The results show that vacancy defects cause relaxation of surrounding atoms leading to local distortions in the structure and changes in bond length, and the formation energy of the V[Formula: see text] system is significantly lower than theV[Formula: see text] system, which is easier to achieve the single sulfur-atom vacancy in the experiment. The vacancies system successfully opens a narrow bandgap under torsion, where the V[Formula: see text] system shows a decreasing trend in the range of 2–8[Formula: see text], increasing after 10[Formula: see text], while V[Formula: see text] systems keep increasing. Meanwhile, we found that the optical properties of 1[Formula: see text]-TaS2 monolayer are closely related to defects and torsion. The results show that the static dielectric constant, the maximum of the imaginary part, initial absorption coefficient and reflectivity of 1[Formula: see text]-TaS2 monolayer gradually increases with torsion. The spectra of vacancy systems are all elevated in the low-frequency band, indicating that the vacancy defects have improved the properties of the visible region. The significant decrease after 5 eV indicates that the torsion substantially affects the properties in the UV region.
How to Run Surveys: A Guide to Creating Your Own Identifying Variation and Revealing the Invisible
Authors: Stantcheva Stefanie
Published: March 2023

Surveys are an essential approach for eliciting otherwise invisible factors such as perceptions, knowledge and beliefs, attitudes, and reasoning. These factors are critical determinants of social, economic, and political outcomes. Surveys are not merely a research tool. They are also not only a way of collecting data. Instead, they involve creating the process that will generate the data. This allows the researcher to create their own identifying and controlled variation. Thanks to the rise of mobile technologies and platforms, surveys offer valuable opportunities either to study broadly representative samples or to focus on specific groups. This article offers guidance on the complete survey process, from the design of the questions and experiments to the recruitment of respondents and the collection of data to the analysis of survey responses. It covers issues related to the sampling process, selection and attrition, attention and carelessness, survey question design and measurement, response biases, and survey experiments.