bluuebunny/crossref_metadata_2025 huggingface dataset:
A phase 1 study in healthy participants to characterize the safety and pharmacology of inclacumab, a fully human anti-P-selectin antibody, in development for treatment of sickle cell disease
Authors: Mayer Christina Lourdes , Koeck Kathleen , Hottmann Margot , Redfern Andrew , Davis Mark , Barth Aline , Geng Xin , Hoppe Carolyn , Yue Patrick
Published: July 2023

Purpose

We evaluated the safety, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of intravenous (IV) inclacumab, a fully human IgG4 anti–P-selectin monoclonal antibody in development for the treatment of sickle cell disease, at doses up to and exceeding those previously tested in healthy individuals.

Methods

In this phase 1, open-label, single-ascending-dose study, 15 healthy participants were enrolled into cohorts receiving 20 mg/kg (n = 6) or 40 mg/kg (n = 9) IV inclacumab and observed for up to 29 weeks post-dose. Safety, PK parameters, thrombin receptor-activating peptide (TRAP)-activated platelet-leukocyte aggregate (PLA) formation, P-selectin inhibition, plasma soluble P-selectin, and anti-drug antibodies were characterized.

Results

Two inclacumab-related treatment-emergent adverse events were reported in 1 participant; no dose-limiting toxicities were observed. Plasma PK parameters were generally dose-proportional, with a terminal half-life of 13 to 17 days. Mean TRAP-activated PLA formation decreased within 3 h from the start of infusion, and inhibition was sustained for ~ 23 weeks. Mean P-selectin inhibition > 90% was observed up to 12 weeks post-dose. The mean ratio of free to total soluble P-selectin decreased rapidly from pre-dose to end of infusion, then increased gradually to 78% of the baseline ratio by week 29. Treatment-emergent anti-drug antibodies were observed in 2 of 15 participants (13%), without apparent impact on safety, PK, or PD.

Conclusions

Inclacumab was well tolerated, with PK as expected for a monoclonal antibody against a membrane-bound target and a long duration of PD effects after both single IV doses, supporting a prolonged dosing interval.

Trial registration

ACTRN12620001156976; registered November 4, 2020.
The role of vaccines in the COVID-19 pandemic: what have we learned?
Authors: Krammer Florian
Published: July 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged late in 2019 and caused the coronavirus disease 2019 (COVID-19) pandemic that has so far claimed approximately 20 million lives. Vaccines were developed quickly, became available in the end of 2020, and had a tremendous impact on protection from SARS-CoV-2 mortality but with emerging variants the impact on morbidity was diminished. Here I review what we learned from COVID-19 from a vaccinologist’s perspective.
Gender differences in clinical and biochemical parameters among patients hospitalized for schizophrenia: towards precision medicine
Authors: Esposito Cecilia Maria , De Cagna Francesca , Caldiroli Alice , Capuzzi Enrico , Ceresa Alessandro , Di Paolo Martina , Auxilia Anna Maria , Capellazzi Martina , Tagliabue Ilaria , Cirella Luisa , Clerici Massimo , Brondino Natascia , Barkin Jennifer L. , Politi Pierluigi , Buoli Massimiliano
Published: July 2023

Background

The scientific literature shows some gender differences in the clinical course of schizophrenia. The aim of this study is to identify gender differences in clinical and biochemical parameters in subjects affected by schizophrenia. This would allow for the implementation of individualized treatment strategies.

Methods

We examined a large set of clinical and biochemical parameters. Data were obtained from clinical charts and blood analyses from a sample of 555 schizophrenia patients consecutively admitted for exacerbation of symptoms to the inpatient clinic of Fondazione IRCCS Policlinico (Milan) or ASST Monza in Italy from 2008 to 2021. Univariate analyses, binary logistic regression, and a final logistic regression model were performed with gender as dependent variable.

Results

The final logistic regression models showed that male patients (compared to females) were more prone to lifetime substance use disorders (p = 0.010). However, they also had higher GAF (global functioning) mean scores (p < 0.001) at the time of hospitalization. Univariate analyses showed that male patients (with respect to females) had an earlier age at onset (p < 0.001), a more frequent family history of multiple psychiatric disorders (p = 0.045), were more often smokers (p < 0.001), had a more frequent comorbidity with at least one psychiatric disorder (p = 0.001), and less often suffered from hypothyroidism (p = 0.011). In addition, men had higher levels of albumin (p < 0.001) and bilirubin (t = 2.139, p = 0.033), but lower levels of total cholesterol (t = 3.755, p < 0.001).

Conclusions

Our analyses indicate a less severe clinical profile in female patients. This is evident especially in the early years of the disorder, as suggested by less comorbidity with psychiatric disorders or later age at onset; this is consistent with the related literature. In contrast, female patients seem to be more vulnerable to metabolic alterations as demonstrated by more frequent hypercholesterolemia and thyroid dysfunction. Further studies are needed to confirm these results in the framework of precision medicine.
KCNE1 does not shift TMEM16A from a Ca2+ dependent to a voltage dependent Cl- channel and is not expressed in renal proximal tubule
Authors: Talbi Khaoula , Ousingsawat Jiraporn , Centeio Raquel , Schreiber Rainer , Kunzelmann Karl
Published: July 2023

The TMEM16A (ANO1) Cl- channel is activated by Ca2+ in a voltage-dependent manner. It is broadly expressed and was shown to be also present in renal proximal tubule (RPT). KCNQ1 is an entirely different K+ selective channel that forms the cardiac IKS potassium channel together with its ß-subunit KCNE1. Surprisingly, KCNE1 has been claimed to interact with TMEM16A, and to be required for activation of TMEM16A in mouse RPT. Interaction with KCNE1 was reported to switch TMEM16A from a Ca22+-dependent to a voltage-dependent ion channel. Here we demonstrate that KCNE1 is not expressed in mouse RPT. TMEM16A expressed in RPT is activated by angiotensin II and ATP in a KCNE1-independent manner. Coexpression of KCNE1 does not change TMEM16A to a voltage gated Cl- channel and Ca2+-dependent regulation of TMEM16A is fully maintained in the presence of KCNE1. While overexpressed KCNE1 slightly affects Ca2+-dependent regulation of TMEM16A, the data provide no evidence for KCNE1 being an auxiliary functional subunit for TMEM16A.
A contemporary assessment of total neoadjuvant therapy (TNT) protocols for locally advanced rectal cancer: adoption and expert perspectives at German Cancer Society (DKG)-certified colorectal cancer centers
Authors: Langheinrich Melanie , Paasch Christoph , Mantke René , Weber Klaus , Benz Stefan , Kersting Stephan
Published: July 2023

Purpose

The treatment paradigm for locally advanced rectal cancer (LARC) is shifting toward the total neoadjuvant therapy (TNT) concept, which administered systemic chemotherapy in the neoadjuvant setting, either before or after chemoradiotherapy (CRT) or short-course radiotherapy (SCRT). First results have shown higher pathologic complete response (pCR) rates and a favorable impact on disease-free survival (DFS). Our study aimed to evaluate the current clinical practice and expert opinion regarding TNT for locally advanced rectal cancer across DKG (German Cancer Society)-certified colorectal cancer centers.

Methods

A comprehensive online questionnaire, constituted of 14 TNT-focused queries targeting patients with locally advanced rectal cancer, was conducted among DKG-certified colorectal cancer centers registered within the database of the Addz (Arbeitsgemeinschaft Deutscher Darmzentren) between December 2022 and January 2023.

Results

A significant majority (68%) indicated that they treated between 0 and 10 patients using a TNT protocol. Only a third (36%) of these centers participated in patient enrollment for a TNT study. Despite this, 84% of centers reported treating patients in a manner analogous to a TNT study, with the RAPIDO regimen being the most prevalent approach, employed by 60% of the respondents. The decision to adopt a TNT approach was primarily influenced by factors, such as the lower third of the rectum (93% of centers), cT4 stage (86% of centers), and a positive circumferential resection margin (80% of centers). Regarding concerns, 65% of the survey respondents expressed no reservations about the TNT concept, while 35% had concerns. In particular, there appears to be disagreement and uncertainty in regard to a clinical complete response and the “Watch and Wait” approach. While some centers adopt the watch-and-wait approach (42%), others only utilize it when extirpation is otherwise necessary (39%), and a portion still proceeds with surgery as initially planned (19%). The survey also addressed unmet needs, which were elaborated in the free-text responses. Overall, there was high interest in participating in planned observational studies.

Conclusions

This study presents an overview of current clinical practice and unmet needs within DKG-certified German colorectal cancer centers. It is noteworthy that total neoadjuvant therapy (TNT) is predominantly performed outside of clinical trials. Moreover, across the centers, there is significant heterogeneity in handling clinical complete response and adopting the “watch and wait” approach. Further research is needed to establish standardization in the care of locally advanced rectal cancer.
Characterizing lithological, weathering, and hydrothermal alteration influences on volcanic rock properties via spectroscopy and laboratory testing: a case study of Mount Ruapehu volcano, New Zealand
Authors: Schaefer Lauren N. , Kereszturi Gabor , Kennedy Ben M. , Villeneuve Marlène
Published: July 2023

The geomechanical characterization of volcanic material has important implications for geothermal and mineral exploration, engineering design, geophysical signals of volcano unrest, and models of instability and mass flows. Chemical weathering and hydrothermal systems can alter the host rock, leading to changes in mechanical behavior and failure mode. Here, we compare the physical and mechanical properties of lava, autoclastic breccia, and pyroclastic (scoria) rocks from Mount Ruapehu volcano (Ruapehu) in New Zealand to mineralogical composition determined via infrared spectroscopy and scanning electron microscopy (SEM) with energy-dispersive X-ray spectroscopy (EDS). We use correlation matrices, principal component analysis, and parametric analysis to determine which parameters can be used to predict physical and mechanical properties and form the basis for transfer functions. Laboratory-based spectroscopy shows that the samples contain absorption features indicative of Al- and Mg-rich hydrous phyllosilicates (e.g., kaolinite, halloysite, montmorillonite), Fe- oxides (e.g., goethite), and sulfates attributed to surface weathering, supergene, and steam-heated alteration. We find that porosity and primary lithology are the predominant control on physical and mechanical properties, followed by the pervasiveness of weathering/alteration, and then mineralogical composition. Several properties, such as porosity, uniaxial compressive strength, P-wave seismic velocity, density, and Young’s modulus, show strong correlations with other properties, indicating the potential for transfer functions between these properties. Hydrothermally altered rocks near the vent complex (up to ~ 400 m depth beneath the crater lake) with high-intensity hydrothermal alteration do not follow typical physical and mechanical property trends due to high clay content, low permeability, and low strength. The presence of these rocks within the edifice at Ruapehu implies local barriers to fluid flow and subsequent pore pressure variations. Additionally, they may have less than half the strength than would be dictated by typical porosity-strength trends for surface rocks, increasing the likelihood of structural failure. Trends in the pervasiveness of weathering with physical and mechanical properties, along with shifts in the position of spectral absorption peaks as hydrothermal/weathering alteration increases, suggest that it may be possible to extrapolate properties from imaging spectroscopy.
A cohort follow-up study for diabetic retinopathy screening incidence in the North Denmark Region
Authors: Nissen Tobias P H , Vestergaard Peter , Vorum Henrik , Torp-Pedersen Christian , Aasbjerg Kristian
Published: July 2023

Aims

To evaluate diabetic retinopathy (DR) screening incidence in a universal healthcare system.

Methods

Registry-based cohort study based on a Danish regional population from 2009 to 2018. Individuals with diabetes were identified by medication. Screening attendance was estimated by surrogate measures using local and nationwide databases reported by cumulative incidence.

Results

18,832 patients were included. By the end of the first year, the cumulative incidence of screening for DR was 60.2% and by the end of the second year 74.2%. The cumulative incidence was 93.9% overall, 97.7% for patients with type 1 diabetes (T1D) and 93.4% for patients with type 2 diabetes. Screening proportions per 1, 2 and 5 years were calculated. Females, patients with T1D, and patients attending screening at hospitals had a higher Hazard Ratio of 1.084, 1.157, and 1.573, respectively. The Cochran–Armitage trend test indicated increased screening frequency from 2009 to 2018. Validation of DR screening was done at hospitals with a mean positive predictive value of 86.78%. Cumulative incidence curves showed a small right shift when censoring the first, second and third screening visits.

Conclusions

Nearly all patients were screened for DR over a 5-year timespan. Female patients with T1D who attended screening at hospitals were significantly more likely to be screened. Validation of screening visits at hospitals was reported with a high mean positive predictive value. Most other studies, to the best of our knowledge, only report screening attendance for patients already enrolled in a DR screening programme. This study describes the overall screening attendance for the total eligible diabetes population.
Access to device-aided therapies in advanced Parkinson’s disease: navigating clinician biases, patient preference, and prognostic uncertainty
Authors: Auffret Manon , Weiss Daniel , Stocchi Fabrizio , Vérin Marc , Jost Wolfgang H.
Published: July 2023

Device-aided therapies (DAT), which include deep brain stimulation and pump-based continuous dopaminergic stimulation with either levodopa or apomorphine, are among the major advances in the clinical management of Parkinson’s disease (PD). Although DAT are being increasingly offered earlier in the disease course, their classical indication remains advanced PD. Theoretically, every patient should be offered transition to DAT when faced with refractory motor and nonmotor fluctuations and functional decline. Worldwide clinical reality is far from these ideal, and, therefore, question the “real-world” equal opportunity of access to DAT for PD patients with advanced PD—even within a single health care system. Differences in access to care, referral pattern (timing and frequency), as well as physician biases (unconscious/implicit or conscious/explicit bias), and patients’ preferences or health-seeking behaviour are to be considered. Compared to DBS, little information is available concerning infusion therapies, as well as neurologists’ and patients’ attitudes towards them. This viewpoint aims to be thought-provoking and to assist clinicians in moving through the process of DAT selection, by including in their decision algorithm their own biases, patient perspective, ethical concerns as well as the current unknowns surrounding PD prognosis and DAT-related long-term side effects for a given patient.
Vapor phase-grown TiO2 and ZnO nanoparticles inside electrospun polymer fibers and their calcination-induced organization
Authors: Razouq Hasan , Berger Thomas , Hüsing Nicola , Diwald Oliver
Published: July 2023

The spatial organization of metal oxide nanoparticles represents an important factor in the chemical utilization of resulting structures. For the production of networks that are composed of metal oxide nanoparticle chains, we dispersed vapor phase-grown TiO2 and ZnO nanoparticles homogeneously in an aqueous polyvinyl alcohol solution. After electrospinning, we analyzed the sizes and diameters of the compositionally homogeneous electrospun fibers and discussed the size distribution and morphology of the nanoparticles inside. Calcination-induced polymer removal gives rise to self-supported nanoparticle-based nanofibers. Particle coarsening by a factor of ~ 2 for TiO2 and ~ 3 for ZnO nanoparticles is observed.

Graphical abstract
Authentication of two eighteenth century juniper-containing drug remains by HPLC–MS/MS and GC–MS
Authors: Nesměrák Karel , Lener Tomáš , Korban Anton , Štícha Martin
Published: July 2023

Two historical remains of juniper-containing drugs, dating from the eighteenth century, were analyzed using two separation techniques with mass detection (HPLC–MS/MS and GC–MS). As reference material, replicates of one of these analyzed historical remains, juniper preserve, were prepared according to period recipes. Although the HPLC–MS/MS method was suitable for authenticating the origin of a drug prepared from juniper berries (i.e., juniper preserve), it proved unsuitable for a drug containing only juniper wood. In contrast, GC–MS was able to demonstrate that this drug did indeed contain juniper wood. Thus both studied samples were verified to be juniper-containing drugs. A remarkable stability of some glycosides was observed in the samples analyzed. The presence of viridiflorin was demonstrated for the first time in the juniper plant, and a detailed ESI+-MSn fragmentation of this substance was proposed.

Graphical abstract
Utilization of zeolite catalysts in biomass exploitation: a minireview
Authors: Magyarová Zuzana , Králik Milan , Soták Tomáš
Published: July 2023

This minireview discusses the use of zeolites as catalysts in all stages of lignocellulose biomass (LCB) valorization process. A summary of some synthesis and characterization methods for zeolitic materials is provided. Utilization of various active sites of zeolites is explored with the focus on Brønsted and Lewis acid sites and the importance of hierarchical structures in the processes involving bulky biobased molecules. Zeolites modified by top-down methods, specifically desilication with various basic reagents, are good candidates for applications in LCB valorization. Some novelty methods such as a dry milling for incorporating metal nanoparticles into zeolite structure are mentioned. An overview of studies utilizing zeolites in processes such as catalytic pyrolysis of LCB, acid-catalyzed hydrolysis and reactions of platform molecules (ethanol, furans, glycerol, bio-hydrocarbons, lactic acid, succinic acid, levulinic acid, sorbitol, xylitol) is discussed. Special attention is dedicated to reactions of biomass-derived alcohols and value-added chemicals produced from them, e.g., esters. The most successful industrial zeolite application—fluid catalytic cracking—is also summarized for comparison. Challenges of zeolite stability in reactions carried out in liquid water conditions, as well as possibilities of catalyst stabilization, e.g., with extra-framework aluminum, or hydrophobization of the surface, are explored.

Graphical abstract
Development and validation of an assay for the quantification of glycosides using high-performance thin-layer chromatography (HPTLC)
Authors: Sultana Sharmin , Foster Kevin , Hossain Md Lokman , Lim Lee Yong , Locher Cornelia
Published: July 2023

This paper presents a simple and rapid approach to the quantification of various glycosides using high-performance thin-layer chromatography (HPTLC). Different classes of glycosides, represented by genistin and ononin (both monosaccharidic O-glycosides), rutin (a disaccharidic O-glycoside) and luteolin-6-C-glucoside (a monosaccharidic C-glycoside), were successfully separated using a mixture of ethyl acetate‒methanol‒glacial acetic acid‒formic acid (11:1:1:1, V/V) as the mobile phase followed by derivatisation with natural product–polyethylene glycol (NP–PEG) reagent. The method was validated for the quantification of these glycosides in accordance with the guidelines of the International Council for Harmonisation. The general applicability of the validated approach is demonstrated with the analysis of a large number of glycosides including two glycosides (i.e. rutin, naringin) in commercial products.
Rotor Position Estimation for Permanent Magnet Synchronous Machines using Electromotive Force and Anisotropy Using Extended-Kalman-Filter
Authors: Wilcken Nils , Grotjahn Martin
Published: July 2023

In this paper a new rotor position observer for permanent magnet synchronous machines (PMSM) based on an Extended-Kalman-Filter (EKF) is presented. With this method, just one single EKF is sufficent to evaluate the position information from electromotive force (EMF) and anisotropy. Thus, the PMSM can be controlled for the entire speed range without a position sensor and without the need to switch or synchronize between different observers. The approach covers online estimation of permanent magnetic field and mechanical load. The resulting EKF-based rotor position estimator is embedded in the existing cascaded control concept of the PMSM without need of additional angle trackers or signal filters. The experimental validation for the position sensorless control shows optimized dynamic behaviour.
Diffusion tensor imaging helps identify shunt-responsive normal pressure hydrocephalus patients among probable iNPH cohort
Authors: Sedlák Vojtěch , Bubeníková Adéla , Skalický Petr , Vlasák Aleš , Whitley Helen , Netuka David , Beneš Vladimír , Beneš Vladimír , Bradáč Ondřej
Published: July 2023

The aim of this study was to investigate whether white matter changes as measured by diffusion tensor imaging (DTI) can help differentiate shunt-responsive idiopathic normal pressure hydrocephalus (iNPH) patients from patients with other causes of gait disturbances and/or cognitive decline with ventriculomegaly whose clinical symptoms do not improve significantly after cerebrospinal fluid derivation (non-iNPH). Between 2017 and 2022, 85 patients with probable iNPH underwent prospective preoperative magnetic resonance imaging (MRI) and comprehensive clinical workup. Patients with clinical symptoms of iNPH, positive result on lumbar infusion test, and gait improvement after 120-h lumbar drainage were diagnosed with iNPH and underwent shunt-placement surgery. Fractional anisotropy (FA) and mean diffusivity (MD) values for individual regions of interest were extracted from preoperative MRI, using the TBSS pipeline of FSL toolkit. These FA and MD values were then compared to results of clinical workup and established diagnosis of iNPH. An identical MRI protocol was performed on 13 age- and sex-matched healthy volunteers. Statistically significant differences in FA values of several white matter structures were found not only between iNPH patients and healthy controls but also between iNPH and non-iNPH patients. ROI that showed best diagnostic ability when differentiating iNPH among probable iNPH cohort was uncinate fasciculus, with AUC of 0.74 (p < 0.001). DTI methods of white matter analysis using standardised methods of ROI extraction can help in differentiation of iNPH patients not only from healthy patients but also from patients with other causes of gait disturbances with cognitive decline and ventriculomegaly.
Small shrubby patches increase bird taxonomic and functional richness of wood-pastures
Authors: Lopes Paula C. , Palmeirim Jorge M. , Leal Ana I.
Published: July 2023

Wood-pastures are semi-natural systems that combine a grazed grassland with a tree layer. Shrubs are often controlled, mostly to improve grazing potential, resulting in a reduction of the available ecological niches. From a conservation perspective, it is thus important to identify management practices that counter this reduction. Our overall objective was to determine the value of small shrubby patches to increase the richness of wood-pasture bird communities. As study model we used Mediterranean oak wood-pastures in southern Portugal, locally known as montados. Birds and environmental variables were sampled in 50 m radius plots of wood-pasture with and without small shrubby patches (128–3748 m2, covering less than 0.5% of the study area), in winter (n = 54) and spring (n = 65). Species assemblages’ composition changed between seasons, but in both seasons the assemblages in plots with and without patches were statistically different. Seven species were statistically associated to the presence of patches, in winter and spring, increasing the richness of the respective assemblages. A comparison of the functional composition of communities of patches and matrix revealed that patches increased richness of landscapes by boosting the presence of species with functional traits uncommon in the ecologically simplified matrix. Their presence is promoted by resources added by the patches (e.g. nesting sites, protection, food), but the ranges of individual birds in general extended well beyond the patches. This study demonstrated that the presence of few and small shrubby patches can significantly enrich the bird communities of wood-pastures, both taxonomically and functionally, indicating that promoting them is a cost-effective management measure for these valuable systems.
Anammox with alternative electron acceptors: perspectives for nitrogen removal from wastewaters
Authors: Ponce-Jahen Sergio J. , Cercado Bibiana , Estrada-Arriaga Edson Baltazar , Rangel-Mendez J. Rene , Cervantes Francisco J.
Published: July 2023

In the context of the anaerobic ammonium oxidation process (anammox), great scientific advances have been made over the past two decades, making anammox a consolidated technology widely used worldwide for nitrogen removal from wastewaters. This review provides a detailed and comprehensive description of the anammox process, the microorganisms involved and their metabolism. In addition, recent research on the application of the anammox process with alternative electron acceptors is described, highlighting the biochemical reactions involved, its advantages and potential applications for specific wastewaters. An updated description is also given of studies reporting the ability of microorganisms to couple the anammox process to extracellular electron transfer to insoluble electron acceptors; particularly iron, carbon-based materials and electrodes in bioelectrochemical systems (BES). The latter, also referred to as anodic anammox, is a promising strategy to combine the ammonium removal from wastewater with bioelectricity production, which is discussed here in terms of its efficiency, economic feasibility, and energetic aspects. Therefore, the information provided in this review is relevant for future applications.
Molecular features of androgen-receptor low, estrogen receptor-negative breast cancers in the Carolina breast cancer study
Authors: Jinna Nikita D. , Van Alsten Sarah , Rida Padmashree , Seewaldt Victoria L. , Troester Melissa A.
Published: July 2023

Purpose

Androgen receptor (AR) expression is absent in 40–90% of estrogen receptor (ER)-negative breast cancers. The prognostic value of AR in ER-negative patients and therapeutic targets for patients absent in AR remains poorly explored.

Methods

We used an RNA-based multigene classifier to identify AR-low and AR-high ER-negative participants in the Carolina Breast Cancer Study (CBCS; N = 669) and The Cancer Genome Atlas (TCGA; N = 237). We compared AR-defined subgroups by demographics, tumor characteristics, and established molecular signatures [PAM50 risk of recurrence (ROR), homologous recombination deficiency (HRD), and immune response].

Results

AR-low tumors were more prevalent among younger (RFD =  + 10%, 95% CI = 4% to 16%) participants in CBCS and were associated with HER2 negativity (RFD = − 35%, 95% CI = − 44% to − 26%), higher grade (RFD =  + 17%, 95% CI = 8% to 26%), and higher risk of recurrence scores (RFD =  + 22%, 95% CI = 16.1% to 28%), with similar results in TCGA. The AR-low subgroup was strongly associated with HRD in CBCS (RFD =  + 33.3%, 95% CI = 23.8% to 43.2%) and TCGA (RFD =  + 41.5%, 95% CI = 34.0% to 48.6%). In CBCS, AR-low tumors had high adaptive immune marker expression.

Conclusion

Multigene, RNA-based low AR expression is associated with aggressive disease characteristics as well as DNA repair defects and immune phenotypes, suggesting plausible precision therapies for AR-low, ER-negative patients.
Racial and ethnic differences in tumor characteristics among endometrial cancer patients in an equal-access healthcare population
Authors: Desmond Daniel , Arter Zhaohui , Berenberg Jeffrey L. , Killeen Jeffrey L. , Bunch Kristen , Merritt Melissa A.
Published: July 2023

Purpose

There are racial and ethnic differences in endometrial cancer incidence and mortality rates; compared with Non-Hispanic White women, Black women have a similar incidence rate for endometrial cancer, but their mortality is higher. Pacific Islander women may also have worse outcomes compared to their White counterparts. We assessed tumor characteristics and adjuvant therapy by racial and ethnic group among endometrial cancer patients treated within the Military Health System, an equal access healthcare organization.

Methods

We retrospectively identified women diagnosed with invasive endometrial cancer among US Department of Defense beneficiaries reported in the Automated Central Tumor Registry database (year of diagnosis: 2001–2018). We compared tumor characteristics and receipt of adjuvant therapy across racial and ethnic groups using Chi-square or Fisher tests. Hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of all cause mortality were calculated using Cox proportional hazards regression models adjusting for age at diagnosis, adjuvant therapy, histology and stage.

Results

The study included 2574 endometrial cancer patients [1729 Non-Hispanic White, 318 Asian, 286 Black, 140 Pacific Islander and 101 Hispanic women]. Among all cases, a higher proportion of Black patients had non-endometrioid histology (46.5% versus ≤ 29.3% in other groups, P < 0.01) and grade 3–4 tumors (40.1% versus ≤ 29.3% in other groups, P < 0.01). In multivariable Cox models, compared with Non-Hispanic White cases, Black endometrial cancer patients had a higher mortality risk (HR 1.43, 95% CI, 1.13–1.83). There was no difference in mortality risk for other racial and ethnic groups.

Conclusion

Black patients with endometrial cancer presented with more aggressive tumor features and they had worse overall survival compared with patients in other racial and ethnic groups. Further study is needed to better direct preventive and therapeutic efforts in order to correct endometrial cancer disparities in the future.
Sparse optimization via vector k-norm and DC programming with an application to feature selection for support vector machines
Authors: Gaudioso Manlio , Giallombardo Giovanni , Miglionico Giovanna
Published: July 2023

Sparse optimization is about finding minimizers of functions characterized by a number of nonzero components as small as possible, such paradigm being of great practical relevance in Machine Learning, particularly in classification approaches based on support vector machines. By exploiting some properties of thek-norm of a vector, namely, of the sum of itsklargest absolute-value components, we formulate a sparse optimization problem as a mixed-integer nonlinear program, whose continuous relaxation is equivalent to the unconstrained minimization of a difference-of-convex function. The approach is applied to Feature Selection in the support vector machine framework, and tested on a set of benchmark instances. Numerical comparisons against both the standard$$\ell _1$$ℓ1-based support vector machine and a simple version of the Slope method are presented, that demonstrate the effectiveness of our approach in achieving high sparsity level of the solutions without impairing test-correctness.
Linking transport pathways and phosphorus distribution in a loamy soil: a case study from a North-Eastern German Stagnosol
Authors: Koch Stefan , Lederer Henrike , Kahle Petra , Lennartz Bernd
Published: July 2023

Heterogeneous flow pathways through the soil determine the transport of dissolved and particle-bound nutritional elements like phosphorus (P) to ground and surface waters. This study was designed to understand the spatial patterns of P in agriculturally used soils and the mechanisms causing P accumulation and depletion at the centimetre scale. We conducted dye tracer experiments using Brilliant Blue on a loamy Stagnosol in North-Eastern-Germany. The plant-available P was analysed using double lactate extraction (DL-P). The plant-available P content of the topsoil was significantly higher than that of the subsoil in all three replicates (p < 0.001). The topsoil’s stained areas showed significantly higher P contents than unstained areas (p < 0.05), while the opposite was found for the subsoil. The P content varied enormously across all observed soil profiles (4 to 112 mg P kg−1 soil) and different categories of flow patterns (matrix flow, flow fingers, macropore flow, and no visible transport pathways). The P contents of these transport pathways differed significantly and followed the order: Pmatrix flow > Pfinger flow > Pno visible transport pathways > Pmacropore flow. We conclude that P tends to accumulate along flow pathways in the topsoil in the observed fertilized and tilled mineral soil. In contrast, in the subsoil at a generally lower P level, P is depleted from the prominent macroporous flow domains.
Assessment of pixel-oriented k-NN machine learning algorithm performance for the interannual remote sensing monitoring of eelgrass beds at the mouth of the Romaine
Authors: Lemieux P. , Lalumière C. , Fugaru N. , Gilbert J.-P. , Tremblay A.
Published: July 2023

Eelgrass cover extent is among the most reliable indicators for measuring changes in coastal ecosystems. Eelgrass has colonized the mouth of the Romaine River and has become a part of environmental monitoring there since 2013. The presence of eelgrass in this area is an essential factor for the early detection of changes in the Romaine coastal ecosystem. This will act as a trigger for an appropriate environmental response to preserve ecosystem health. In this paper, a cost- and time-efficient workflow for such spatial monitoring is proposed using a pixel-oriented k-NN algorithm. It can then be applied to multiple modellers to efficiently map the eelgrass cover. Training data were collected to define key variables for segmentation and k-NN classification, providing greater edge detection for the presence of eelgrass. The study highlights that remote sensing and training data must be acquired under similar conditions, replicating methodologies for collecting data on the ground. Similar approaches must be used for the zonal statistic requirements of the monitoring area. This will allow a more accurate and reliable assessment of eelgrass beds over time. An overall accuracy of over 90% was achieved for eelgrass detection for each year of monitoring.
Exposure to silver and titanium dioxide nanoparticles at supra-environmental concentrations decreased sperm motility and affected spermatozoa subpopulations in gilthead seabream, Sparus aurata
Authors: Oliveira Catarina C.V. , Ferrão Leonor , Gallego Victor , Mieiro Cláudia , Oliveira Isabel B. , Carvalhais Ana , Pachedo Mário , Cabrita Elsa
Published: July 2023

Marine pollution by nanoparticles (NPs) can be reprotoxic for fish and disturb successful reproduction of wild populations. In gilthead seabream (Sparus aurata), a mild effect on sperm motility was observed after exposure to high concentrations of silver NPs. Considering the great heterogeneity traits within a sperm sample, it is possible that NPs affect spermatozoa accordingly, modulating subpopulation profile. Thus, this work aimed to analyse NP effects in sperm motility in general and considering spermatozoa population structure, using a subpopulation approach. Seabream sperm samples from mature males were exposed for 1 h to increasing concentrations of titanium dioxide (1, 10, 100, 1000 and 10,000 μg L−1) and silver (0.25, 25 and 250 μg L−1) NPs, including Ag NP and Ag+, dissolved in a non-activating medium (0.9 % NaCl). Concentrations chosen include realistic (10–100 and 0.25 μg L−1, respectively, for TiO2 and Ag) and supra-environmental values. The mean particle diameter was determined as 19.34 ± 6.72 and 21.50 ± 8.27 nm in the stock suspension, respectively, for titanium dioxide and silver. After the ex vivo exposure, sperm motility parameters were determined using computer-assisted sperm analysis, and sperm subpopulations were later identified using a two-step cluster analysis. Results revealed a significant reduction in total motility after exposure to the 2 highest concentrations of titanium dioxide NPs, while curvilinear and straight-line velocities were not altered. Exposure to silver NPs (Ag NP and Ag+) lowered significantly total and progressive motilities at all concentrations, while curvilinear and straight-line velocities were significantly lower only at the highest concentration. Sperm subpopulations were also affected by the exposure to both titanium dioxide and silver NPs. In both cases, the highest levels of NPs triggered a decrease in the percentage of fast sperm subpopulations (38.2% in TiO2 1000 μg L−1, 34.8.% in Ag NP 250 μg L−1, and 45.0% in Ag+ 250 μg L−1 vs 53.4% in the control), while an increase on slow sperm subpopulations. A reprotoxic effect was proven for both NPs, but only at supra-environmental concentrations.
Unwriting Brexit? Bridging Fictions and Liminal Aesthetics Within the UK’s Hostile Environment
Authors: Zander Laura A.
Published: July 2023

The article considers the various frictions and fissures in contemporary European politics. Contrary to its historical genesis, this politics often aims at division rather than community, a development epitomized by Brexit. The creation, reinforcement, and protection of borders seem to be a core aim of this policy, which can be observed in EU foreign policy in the narrower sense, but also in the central framing narratives that the EU pursues in the context of border politics and migration in order to fortify the ‘fortress Europe’, as does the UK with its Hostile Environment policy. Contrary to the supposed populist success of such policies, which were clearly demonstrated by the Brexit referendum vote, there is also widespread skepticism towards such disintegrating governance.

A vast body of literature, mostly so-called Brexlit, addresses the fractures created by Brexit but also the many pre-existing divisions that Brexit did not cause, but was a consequence of. Some of these works establish an antagonistic Leave or Remain dichotomy, perfectly understandable from the point of view of the losing side of the referendum, but perhaps not necessarily productive in terms of reducing the divisions in society or even generating compassion for the opposition. The article argues that there is, however, a body of literature that aims at the erasure of borders, that seeks to bridge the existing ruptures within society and to reconcile the divided camps. I would like to focus on two respective literary projects, the EFACIS Kaleidoscope series which features various writers and artists from Ireland and their respective views on Europe, and Ali Smith’s Seasonal Quartet and Companion Piece, five novels that negotiate contemporary UK politics post Brexit. While both projects perceptibly address contemporary borders and exclusions, they do not present them as inevitable. Rather, they offer alternative designs for overcoming the existing divisions by integrating them into their plots, but they also reflect this communal unity on the formal level of their works. In this respect, both projects seem particularly suited to create a welcoming climate of solidarity, in order to unwrite, if not Brexit itself, at least some of its consequences.
Duality of orthogonal and symplectic random tensor models: general invariants
Authors: Keppler Hannes , Muller Thomas
Published: July 2023

In Gurau and Keppler 2022 (arxiv:2207.01993), a relation between orthogonal and symplectic tensor models with quartic interactions was proven. In this paper, we provide an alternative proof that extends to polynomial interactions of arbitrary order. We consider tensor models of order D with no symmetry under permutation of the indices that transform in the tensor product of D fundamental representations of O(N) and Sp(N). We explicitly show that the models obey the N to $$-N$$

-
N

duality graph by graph in perturbation theory.
Teachers’ emotion regulation and related environmental, personal, instructional, and well-being factors: A meta-analysis
Authors: Wang Hui , Burić Irena , Chang Mei-Lin , Gross James J.
Published: July 2023

Teachers experience and express various emotions of different qualities and intensities. They also adopt emotion regulation strategies to increase teaching effectiveness and maintain professionalism. Previous reviews of teachers’ emotion regulation have focused on their emotional labor (i.e., deep and surface acting)—a subdimension of emotion regulation. The present review aims to incorporate multiple perspectives and conceptualizations, hence affording a more comprehensive understanding of teachers’ emotion regulation by examining antecedent- and response-focused strategies. The present meta-analysis included 87 articles investigating the relationships between teachers’ emotion regulation and seven related environmental, personal, instructional, and well-being factors (i.e., work-role interaction expectations, school context, classroom context, personal characteristics, motivation, teaching effectiveness, and teacher well-being). Antecedent-focused strategies demonstrated more adaptive associations with the related factors than response-focused strategies. More specifically, teachers who receive school support, have engaged and disciplined students, and possess favorable personal characteristics (e.g., conscientiousness) tend to adopt antecedent-focused emotion regulation; these teachers also have greater well-being. In contrast, teachers who work at unsupportive schools or who have relatively unfavorable personal characteristics (e.g., neuroticism) tend to use response-focused strategies; these teachers also have poor teaching effectiveness and well-being. Additional moderating analyses found differences concerning the conceptualizations of emotion regulation and cultural backgrounds.
Water level and vegetation type control carbon fluxes in a newly-constructed soft-sediment wetland
Authors: Tak Daniël B. Y. , Vroom Renske J. E. , Lexmond Robin , Lamers Leon P. M. , Robroek Bjorn J. M. , Temmink Ralph J. M.
Published: July 2023

Wetlands support unique biodiversity and play a key role in carbon cycles, but have dramatically declined in extent worldwide. Restoration is imperative yet often challenging to counteract loss of functions. Nature-based solutions such as the creation of novel ecosystems may be an alternative restoration approach. Targeted restoration strategies that account for the effects of vegetation on greenhouse gas (GHG) fluxes can accelerate the carbon sink function of such systems. We studied the relationships between vegetation, bare soil, and GHG dynamics on Marker Wadden in the Netherlands, a newly-created 700-ha freshwater wetland archipelago created for nature and recreation. We measured CO2 and CH4 fluxes, and soil microbial activity, in three-year-old soils on vegetated, with distinct species, and adjacent bare plots. Our results show that CH4 fluxes positively related to organic matter and interacted between organic matter and water table in bare soils, while CH4 fluxes positively related to plant cover in vegetated plots. Similarly, Reco in bare plots negatively related to water table, but only related positively to plant cover in vegetated plots, without differences between vegetation types. Soil microbial activity was higher in vegetated soils than bare ones, but was unaffected by substrate type. We conclude that GHG exchange of this newly-created wetland is controlled by water table and organic matter on bare soils, but the effect of vegetation is more important yet not species-specific. Our results highlight that the soil and its microbial community are still young and no functional differentiation has taken place yet and warrants longer-term monitoring.
Analysis by sex of safety and effectiveness of transvenous phrenic nerve stimulation
Authors: Samii Soraya , McKane Scott , Meyer Timothy E. , Shah Neomi
Published: July 2023

Purpose

Little is known about sex differences in the treatment of central sleep apnea (CSA). Our post hoc analysis of the remedē System Pivotal Trial aimed to determine sex-specific differences in the safety and effectiveness of treating moderate to severe CSA in adults with transvenous phrenic nerve stimulation (TPNS).

Methods

Men and women enrolled in the remedē System Pivotal Trial were included in this post hoc analysis of the effect of TPNS on polysomnographic measures, Epworth Sleepiness Scale, and patient global assessment for quality of life.

Results

Women (n = 16) experienced improvement in CSA metrics that were comparable to the benefits experienced by men (n = 135), with central apneas being practically eliminated post TPNS. Women experienced improvement in sleep quality and architecture that was comparable to men post TPNS. While women had lower baseline apnea hypopnea index than men, their quality of life was worse at baseline. Additionally, women reported a 25-percentage point greater improvement in quality of life compared to men after 12 months of TPNS therapy. TPNS was found to be safe in women, with no related serious adverse events through 12 months post-implant, while men had a low rate of 10%.

Conclusion

Although women had less prevalent and less severe CSA than men, they were more likely to report reduced quality of life. Transvenous phrenic nerve stimulation may be a safe and effective tool in the treatment of moderate to severe CSA in women. Larger studies of women with CSA are needed to confirm our findings.

Clinical trial registration

ClinicalTrials.gov NCT01816776; March 22, 2013.
New biofunctional effects of oleanane-type triterpene saponins
Authors: Matsuda Hisashi , Morikawa Toshio , Nakamura Seikou , Muraoka Osamu , Yoshikawa Masayuki
Published: July 2023

In the current review, we describe the novel biofunctional effects of oleanane-type triterpene saponins, including elatosides, momordins, senegasaponins, camelliasaponins, and escins, obtained from Aralia elata (bark, root cortex, young shoot), Kochia scoparia (fruit), Polygala senega var. latifolia (roots), Camellia japonica (seeds), and Aesculus hippocastanum (seeds), considering the following biofunctional activities: (1) inhibitory effects on elevated levels of blood alcohol and glucose in alcohol and glucose-loaded rats, respectively, (2) inhibitory effects on gastric emptying in rats and mice, (3) accelerative effects on gastrointestinal transit in mice, and (4) protective effects against gastric mucosal lesions in rats. In addition, we describe (5) suppressive effects of the extract and chakasaponins from Camellia sinensis (flower buds) on obesity based on inhibition of food intake in mice. The active saponins were classified into the following three types: (1) olean-12-en-28-oic acid 3-O-monodesmoside, (2) olean-12-ene 3,28-O-acylated bisdesmoside, and (3) acylated polyhydroxyolean-12-ene 3-O-monodesmoside. Furthermore, common modes of action, such as involvements of capsaicin-sensitive nerves, endogenous NO and PGs, and possibly sympathetic nerves, as well as common structural requirements, were observed. Based on our findings, a common mechanism of action might mediate the pharmacological effects of active saponins. It should be noted that the gastrointestinal tract is an important action site of saponins, and the role of the saponins in the gastrointestinal tract should be carefully considered.