bluuebunny/crossref_metadata_2025 huggingface dataset:
Long‐term outcomes in patients with chronic lymphocytic leukemia treated with ibrutinib: Focus on hypertension and cardiovascular toxicity
Authors: Gordon Max J. , Jones Jade E. , George Binsah , Peterson Christine , Burger Jan A. , Jain Nitin , Keating Michael , Wierda William G. , Durand Jean‐Bernard , Ferrajoli Alessandra
Published: April 2023

Background

Continuous ibrutinib administration is needed to maintain efficacy in patients with chronic lymphocytic leukemia (CLL) and, as such, long‐term toxicity is a concern. The authors report the 5‐year follow‐up of patients with CLL who received treatment with ibrutinib with a focus on hypertension and cardiovascular toxicities.

Methods

Patient characteristics were assessed, including blood pressure, cardiovascular disease, disease progression, and death. Univariate logistic regression analysis assessed the relation of patient characteristics and the development of new or worsened hypertension. The incidence of hypertensive outcomes was evaluated using competing risk. Survival was estimated using the Kaplan–Meier method.

Results

Three hundred patients with CLL who were treated with ibrutinib on clinical trials were included. The median patient age at study enrollment was 65 years (range, 29–83 years). Seventy percent of patients were men, and 88% were Caucasian. Sixty‐nine percent of patients had hypertension at baseline, and 47% were on antihypertensive medication. Eighty‐eight percent had relapsed or refractory CLL. New‐onset and worsening hypertension were common, occurring in 68.5% and 38% of patients, respectively. Systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥100 mm Hg was observed in 16.9% of patients. Hypertension was reversible after ibrutinib discontinuation. Older age, male sex, tobacco use, and chronic kidney disease were associated with ibrutinib‐related hypertension. Baseline hypertension was not associated with major adverse cardiovascular events in ibrutinib‐treated patients nor with event‐free or overall survival.

Conclusions

Hypertension is a common toxicity in patients with CLL who receive ibrutinib but is manageable in most patients. Other than chronic kidney disease, baseline cardiovascular disease did not affect ibrutinib‐related hypertension nor was hypertension associated with major adverse cardiovascular events or survival.

Plain Language Summary

Ibrutinib is an effective treatment for patients with chronic lymphocytic leukemia.

Ibrutinib is a well tolerated therapy, however hypertension can develop or worsen in patients receiving ibrutinib and other cardiovascular events are significant challenges to the use of this drug.

This may be particularly true in patients with heart disease.

Short‐term side effects may worsen heart disease, but the long‐term impact is unknown.

The long‐term results of ibrutinib on heart disease and hypertension are described.
Differential involvement of hippocampal subfields in the relationship between Alzheimer's pathology and memory interference in older adults
Authors: Adams Jenna N. , Márquez Freddie , Larson Myra S. , Janecek John T. , Miranda Blake A. , Noche Jessica A. , Taylor Lisa , Hollearn Martina K. , McMillan Liv , Keator David B. , Head Elizabeth , Rissman Robert A. , Yassa Michael A.
Published: April 2023

Introduction

We tested whether Alzheimer's disease (AD) pathology predicts memory deficits in non‐demented older adults through its effects on medial temporal lobe (MTL) subregional volume.

Methods

Thirty‐two, non‐demented older adults with cerebrospinal fluid (CSF) (amyloid‐beta [Aβ]42/Aβ40, phosphorylated tau [p‐tau]181, total tau [t‐tau]), positron emission tomography (PET; 18F‐florbetapir), high‐resolution structural magnetic resonance imaging (MRI), and neuropsychological assessment were analyzed. We examined relationships between biomarkers and a highly granular measure of memory consolidation, retroactive interference (RI).

Results

Biomarkers of AD pathology were related to RI. Dentate gyrus (DG) and CA3 volume were uniquely associated with RI, whereas CA1 and BA35 volume were related to both RI and overall memory recall. AD pathology was associated with reduced BA35, CA1, and subiculum volume. DG volume and Aβ were independently associated with RI, whereas CA1 volume mediated the relationship between AD pathology and RI.

Discussion

Integrity of distinct hippocampal subfields demonstrate differential relationships with pathology and memory function, indicating specificity in vulnerability and contribution to different memory processes.
Lower lip reconstruction using McGregor fan technique with or without depressor anguli oris chimeric flap. Is there a difference in function and aesthetic outcomes?
Authors: Al‐Aroomi Maged Ali , Al‐Worafi Naseem Ali , Zhou Wanhang , Telha Wael , Elayah Sadam Ahmed , Al‐Sharani Hesham Mohamed , Sun Changfu , Qi Zhongzheng
Published: April 2023

Background

Lower lip reconstruction aims to maintain facial subunit function and aesthetics. We present a minor modification of the McGregor flap technique, in which depressor anguli oris (DAO) muscle is separately elevated as a chimeric flap together to investigate the outcomes for reconstructing lower lip defects using various functional parameters.

Methods

The study included patients who underwent surgical repair of lower lip defects using a McGregor fan flap with or without DAO muscle chimeric flap between January 2018 and May 2021. The patients were divided into our modified technique with DAO chimeric flap (study group) and conventional McGregor (control group). The primary outcomes were functional evaluation of oral competency, speech intelligibility, and tactile sensation of reconstructed lip outcomes. The functional satisfaction and Patient and Observer Scar Assessment Scale (POSAS) were analyzed.

Results

A total of 20 patients were enrolled (10 patients for each group). Excellent oral competence was present in 12 patients, favorably significant in patients with DAO chimeric flap (n = 8/10, p = 0.018). All patients had intelligible speech with insignificant differences between the two groups. No patients demonstrated differences to light touch from baseline sensation at 1 year. Patients in the study group reported more lip function satisfaction (p = 0.049). The POSAS score indicates satisfaction with the appearance of all patients.

Conclusion

McGregor fan technique combined with DAO muscle chimeric flap offers a good choice by maintaining sensory and motor functions. Our minor modification can ensure the integrity of the oral sphincter, leading to improved lower lip function.
Acetylcholine‐sensitive control of long‐term synaptic potentiation in hippocampal CA3 neurons
Authors: Kassab Randa
Published: April 2023

A Hebbian form of long‐term potentiation (LTP) is believed to be the basis of memory storage at CA3 recurrent synapses. Abnormalities in CA3 intrinsic connectivity have been related to memory deficits in a variety of neurological disorders. Despite the promise of computational modeling for illuminating the pathogenic implication of connectivity changes, common Hebbian‐based models with preset structural topologies fall short in this regard. Here, I introduce a structure‐independent approach to modeling CA3 network focusing on how LTP shapes CA3 functional connectivity. Network simulations demonstrate that only a small fraction of the active synapses should be potentiated onto engram‐bearing cells for reaching CA3 optimal performance, and that this fraction should be actively regulated at the single‐cell level to maintain precise control over excitatory inputs to and from overlapping engram cells. In light of these findings, I develop a theory suggesting that synaptic potentiation is regulated through extrinsic and intrinsic cellular mechanisms involving the cholinergic modulation of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptors. The theory posits that the progressive increase of acetylcholine release during learning is commensurate with the rate of AMPA receptor trafficking during LTP development and that this dynamics is intended to conceal AMPA receptor potentiation and thereby to propel LTP progression until a target level of potentiation is attained at a restricted number of the active synapses. Functionally, this form of regulation allows encoding and retrieval dynamics to be dictated at the single‐cell level and thereby acts at the cell‐population level as a secondary mechanism complementing dentate gyrus‐mediated pattern separation or compensating for possible deficiencies. Conversely, when this regulation fails, the strength of AMPA receptors and their variability across synapses change over time and lead to pathological states.
A randomized double‐blind clinical trial evaluating comparative plaque and gingival health associated with commercially available stannous fluoride‐containing dentifrices as compared to a sodium fluoride control dentifrice
Authors: Geisinger Maria L. , Geurs Nicolaas C. , Novy Brian , Otomo‐Corgel Joan , Cobb Charles M. , Jacobsen Peter L. , Takesh Thair , Wilder‐Smith Petra
Published: April 2023

Background

Gingivitis is a non‐specific inflammatory lesion in response to the accumulation of oral biofilm and is a necessary precursor to periodontitis. Enhanced oral hygiene practices, including utilization of a dentifrice that could significantly improve plaque accumulation and gingival inflammation, is desirable to prevent and treat gingivitis and potentially prevent progression to periodontitis. This clinical study aimed to investigate the effect of a new stannous fluoride‐containing dentifrice with 2.6% ethylenediamine tetra acetic acid (EDTA) as an anti‐tartar agent to reduce plaque index and gingival index over a 3‐month study period compared to other commercially‐available fluoride‐containing dentifrices.

Methods

This double‐blind, randomized controlled clinical study evaluated plaque, gingival inflammation, and sulcular bleeding in patients using one of five commercially available fluoride‐containing dentifrices The dentifrices tested contained: 0.454% stannous fluoride and 2.6% EDTA (D1), 0.24% sodium fluoride (C), and 0.454% stannous fluoride (D2‐D4). One hundred fifty subjects participated over a 3‐month period. Co‐primary endpoints were improvements in plaque index (PI) and modified gingival index (mGI) from baseline values. No professional cleaning was performed during the study period.

Results

All subjects in the study demonstrated statistically significant improvements in all measures of oral hygiene over the 3‐month study period. Subjects using dentifrice 1 (D1) showed statistically significantly greater reductions in PI, mGI, and modified sulcular bleeding index (mSBI) compared with all other commercially‐available dentifrices tested (p < 0.00001).

Conclusions

A new dentifrice with 0.454% stannous fluoride and 2.6% EDTA demonstrated significant improvements in clinical parameters associated with gingivitis compared to other sodium and stannous fluoride containing dentifrices.
Characterization and Optimization of Injectable In Situ Crosslinked Chitosan‐Genipin Hydrogels
Authors: Priddy‐Arrington Tyler R. , Edwards Reagan E. , Colley Claire E. , Nguyen Marissa M. , Hamilton‐Adaire Tess , Caldorera‐Moore Mary E.
Published: April 2023

In recent years, there has been an increased interest in injectable, in situ crosslinking hydrogels due to their minimally invasive application and ability to conform to their environment. Current in situ crosslinking chitosan hydrogels are either mechanically robust with poor biocompatibility and limited biodegradation due to toxic crosslinking agents or the hydrogels are mechanically weak and undergo biodegradation too rapidly due to insufficient crosslinking. Herein, the authors developed and characterized a thermally‐driven, injectable chitosan‐genipin hydrogel capable of in situ crosslinking at 37 °C that is mechanically robust, biodegradable, and maintain high biocompatibility. The natural crosslinker genipin is utilized as a thermally‐driven, non‐toxic crosslinking agent. The chitosan‐genipin hydrogel's crosslinking kinetics, injectability, viscoelasticity, swelling and pH response, and biocompatibility against human keratinocyte cells are characterized. The developed chitosan‐genipin hydrogels are successfully crosslinked at 37 °C, demonstrating temperature sensitivity. The hydrogels maintained a high percentage of swelling over several weeks before degrading in biologically relevant environments, demonstrating mechanical stability while remaining biodegradable. Long‐term cell viability studies demonstrated that chitosan‐genipin hydrogels have excellent biocompatibility over 7 days, including during the hydrogel crosslinking phase. Overall, these findings support the development of an injectable, in situ crosslinking chitosan‐genipin hydrogel for minimally invasive biomedical applications.
Orthonormal discrete Legendre polynomials for nonlinear reaction‐diffusion equations with ABC fractional derivative and non‐local boundary conditions
Authors: Heydari Mohammad Hossein , Haji Shaabani Mahmood , Rasti Zahra
Published: April 2023

This paper introduces a fractional version of reaction‐diffusion equations with non‐local boundary conditions via a non‐singular fractional derivative defined by Atangana and Baleanu. The orthonormal discrete Legendre polynomials are introduced as suitable family of basis functions to find the solution of these equations. An operational matrix is derived for fractional derivative of these polynomials. A collocation method based on the expressed polynomials and their operational matrices is developed for solving such problems. The established method transforms solving the original problem under consideration into solving a system of algebraic equations. Some numerical examples are used to investigate the validity of the presented method.
Poultry red mite eradication potential of ivermectin and allicin combination treatment
Authors: Kang JeongWoo , Chae HyunYoung , Hossain Md Akil
Published: April 2023

Background

Existing treatments against poultry red mite (PRM; Dermanyssus gallinae) infestation have reduced efficacy or exhibit hazardous effects on chickens. Considering the economic importance of chickens, development of a safe and effective method for exterminating PRMs is necessary. Ivermectin and allicin are effective against some ectoparasites; however, their acaricidal efficacies against PRMs remain unknown.

Objective

To evaluate individual and combined efficacies of ivermectin and allicin in exterminating PRMs.

Methods

Different concentrations (0.10–1.0 mg/mL) of ivermectin (1 mL) were applied via dropping method in different insect culture dishes (ICDs), prior to transferring PRMs. For the spraying method, PRMs were transferred to ICDs, before spraying ivermectin (1 mg/mL) solution (1 mL). Further, the acaricidal effect of allicin on PRMs was evaluated by applying different concentrations (0.25–1.0 mg/mL) of allicin (1 mL). The combined acaricidal effects of ivermectin and allicin were analysed using four concentration combinations. PRM death rates were determined after 2 h, 24 h, 2 days, 5 days and 7 days of drug application.

Results

Ivermectin application (1 mg/mL) exterminated 64% and 100% of PRMs on 1 and 5 days, respectively, and prevented their revival. Further, 0.5 mg/mL ivermectin and 1 mg/mL allicin individually exterminated 98% and 44% of PRMs, respectively, within 7 days of treatment. In combination, 0.5 mg/mL ivermectin and 0.5 mg/mL allicin exterminated 100% of PRMs within 5 d of treatment. The most effective combination was 0.25 mg/mL ivermectin + 1.00 mg/mL allicin.

Conclusions

The efficacy of ivermectin–allicin combination in exterminating PRMs was demonstrated. This novel approach could be optimised for industrial applications.
Large N algebras and generalized entropy
Authors: Chandrasekaran Venkatesa , Penington Geoff , Witten Edward
Published: April 2023

Abstract

We construct a Type II∞ von Neumann algebra that describes the large N physics of single-trace operators in AdS/CFT in the microcanonical ensemble, where there is no need to include perturbative 1/N corrections. Using only the extrapolate dictionary, we show that the entropy of semiclassical states on this algebra is holographically dual to the generalized entropy of the black hole bifurcation surface. From a boundary perspective, this constitutes a derivation of a special case of the QES prescription without any use of Euclidean gravity or replicas; from a purely bulk perspective, it is a derivation of the quantum-corrected Bekenstein-Hawking formula as the entropy of an explicit algebra in the G → 0 limit of Lorentzian effective field theory quantum gravity. In a limit where a black hole is first allowed to equilibrate and then is later potentially re-excited, we show that the generalized second law is a direct consequence of the monotonicity of the entropy of algebras under trace-preserving inclusions. Finally, by considering excitations that are separated by more than a scrambling time we construct a “free product” von Neumann algebra that describes the semiclassical physics of long wormholes supported by shocks. We compute Rényi entropies for this algebra and show that they are equal to a sum over saddles associated to quantum extremal surfaces in the wormhole. Surprisingly, however, the saddles associated to “bulge” quantum extremal surfaces contribute with a negative sign.
Modeling elongational viscosity and brittle fracture of 10 polystyrene Pom-Poms by the hierarchical molecular stress function model
Authors: Hirschberg Valerian , Schußmann Max G. , Röpert Marie-Christin , Wilhelm Manfred , Wagner Manfred H.
Published: April 2023

A Pom-Pom polymer with qa side chains of molecular weight Mw,a at both ends of a backbone chain of molecular weight Mw,b is the simplest branched polymer topology. Ten nearly monodisperse polystyrene Pom-Pom systems synthesized via an optimized anionic polymerization and a grafting-onto method with Mw,b of 100 to 400 kg/mol, Mw,a of 9 to 50 kg/mol, and qa between 9 and 22 are considered. We analyze the elongational rheology of the Pom-Poms by use of the hierarchical multi-mode molecular stress function (HMMSF) model, which has been shown to predict the elongational viscosity of linear and long-chain branched (LCB) polymer melts based exclusively on the linear-viscoelastic characterization and a single material parameter, the so-called dilution modulus GD. For the Pom-Poms considered here, we show that GD can be identified with the plateau modulus $${G}_{N}^{0}={G}_{D}$$

G

N

0

=

G
D

, and the modeling of the elongational viscosity of the Pom-Poms does therefore not require any fitting parameter but is fully determined by the linear-viscoelastic characterization of the melts. Due to the high strain hardening of the Pom-Poms, brittle fracture is observed at higher strains and strain rates, which is well described by the entropic fracture criterion.

Graphical abstract
The decline of the ecosystem services generated by anadromous fish in the Iberian Peninsula
Authors: Almeida Pedro R. , Mateus Catarina S. , Alexandre Carlos M. , Pedro Sílvia , Boavida-Portugal Joana , Belo Ana F. , Pereira Esmeralda , Silva Sara , Oliveira Inês , Quintella Bernardo R.
Published: April 2023

This work aims to present an historical review of the ecosystem services provided by anadromous fish (i.e., species that migrate from the sea to the river to spawn) throughout Human time, as well as of the main related threats, focusing on the Iberian Peninsula region. Anadromous fish provide important provision, cultural, regulatory and supporting ecosystem services across their distribution range and have been extensively exploited by humans since prehistoric times. In the Iberian Peninsula, sea lamprey, allis and twaite shads, sea trout, Atlantic salmon and European sturgeon were once abundantly present in several river basins covering what is now Portuguese and Spanish territory. These species have suffered a severe decline across their distribution range, mainly due to habitat loss and overexploitation. Considered regal delicacies, these fishes were once a statement on the tables of the highest social classes, a much appreciated bounty for the poorer population and are still an important part of the local gastronomy and economy. Such high economic and cultural interest encouraged intensive fishing. Currently, management efforts are being implemented, pairing habitat rehabilitation (e.g., construction of fish passes in obstacles to migration such as weirs and dams) with sustainable fisheries. Considering the present climate change scenario, these species are bound to endure increased pressures, demanding novel management approaches to ensure population numbers that are able to secure their sustainable exploitation.
Addressing Post-Separation Parental Stalking: a Multimethod Qualitative Approach to Producing Knowledge of Stalking in Children’s Lives
Authors: Nikupeteri Anna , Laitinen Merja
Published: April 2023

Purpose

Based on our research, the purpose of this paper is to examine the production of knowledge about children’s exposure to parental stalking after their parents have separated. The paper addresses the following questions: (1) What dimensions of knowledge has the multimethod qualitative approach produced in our research? and (2) What methodological choices are conducive to conducting ethically sound research on parental stalking? The aim is to contribute to the methodological and ethical discussions in social science research on children exposed to stalking as a specific form of domestic violence and abuse.

Method

We utilized a multimethod qualitative approach in studying children’s exposure to parental stalking. The approach produced five dimensions of knowledge: (1) practice wisdom, (2) experiential knowledge, (3) contextual and situational knowledge, (4) socio-structural knowledge, and (5) norm-related knowledge, which all were important in studying children’s exposure to parental stalking.

Results

In conducting an ethically sound study, the central methodological choices were as follows: employing child-centered practice, respecting intergenerational dialogue, forming trusting relationships with professionals, and valuing different types of knowledge and realities by using a multivoice approach.

Conclusions

A multimethod qualitative approach enables rich dialogue through which knowledge of parental stalking can be constructed. We argue that the approach makes it possible to bring children’s marginalized voices into the academic and professional discussions on parental stalking and thereby to advance the realization of the rights of children who are subjected to a parent’s stalking behavior.
Quantifier Raising out of Mandarin relative clauses
Authors: Wang Huilei
Published: April 2023

Quantifier Raising usually exhibits finite-clause boundedness due to the syntactic and semantic constraints it is subject to (Fox 1995, 2000, Cecchetto 2004, a.o.). In this paper, I argue that QR out of a Mandarin prenominal pre-determiner RC is not only properly licensed, obeying both syntactic and semantic constraints, but also needed to account for the exceptional-scope effects observed across relative clause boundaries (Huang 1982, Aoun and Li 1993, a.o.). I further consider constructions where the exceptional-scope effects are not present, including relative clauses containing the focus-sensitive operatordouand full-sized subject RCs, and show that the absence of the exceptional-scope effects in these constructions follows directly from the proposed analysis.
Measuring Persistence in the US Equity Gender Diversity Index
Authors: Infante Juan , del Rio Marta , Gil-Alana Luis A.
Published: April 2023

An analysis of the SPDR SSGA Gender Diversity Index ETF using fractional integration or I(d) techniques and daily data from 8 March 2016 to 8 January 2021, reveals that the series is highly persistent with an order of integration smaller than, though very close to 1. However, when estimating d recursively across subsamples, two peaks can be observed. The first peak appears in the sample with 679 observations (ending at 26 December 2018) and the second one occurs in the sample with 974 observations and ending at 28 February 2020, which shows the most significant change in d, moving from values within the I(1) interval to values significantly above 1. The findings indicate that the Covid-19 pandemic has had a significant impact on the persistence of the SPDR SSGA Gender Diversity Index ETF, increasing its magnitude and thus the level of persistence.
The Relativistic Proton Spectrometer: A Review of Sensor Performance, Applications, and Science
Authors: Mazur J. E. , O’Brien T. P. , Looper M. D.
Published: April 2023

The Relativistic Proton Spectrometer (RPS) on the Van Allen Probes spacecraft was a particle spectrometer designed to measure the flux, angular distribution, and energy spectrum of protons from $\sim60~\text{MeV}$
∼
60

MeV
to $\sim2000~\text{MeV}$
∼
2000

MeV
. RPS provided new information about the inner Van Allen belt: a nearby region of space that had been relatively unexplored because of the difficulties of making charged particle measurements there and the associated hazards to satellite operations. We met the primary mission objective of providing accurate data for the AP9 radiation specification model at the high energies where there were little to no data prior to the Van Allen Probes mission. Along the way, we were able to demonstrate the long-term stability of parts of the Inner Belt by comparison with short-lived space science missions that operated decades prior to Van Allen Probes. The most significant surprises were the agreement between RPS and some of those historical measurements and the discovery of a trapped population of $>30~\text{MeV}$
>
30

MeV
leptons at the outer edge of the inner belt. This end-of-mission paper summarizes the instrument performance, calibration, data products, and specific science and engineering results, and includes suggestions for future investigations of intense radiation fields like those found within the inner belt.
Scientific progress, normative discussions, and the pragmatic account of definitions of life
Authors: Schoenmakers Ludo L.J.
Published: April 2023

Discussions on the status of definitions of life have long been dominated by a position known as definitional pessimism. Per the definitional pessimist, there is no point in trying to define life. This claim is defended in different ways, but one of the shared assumptions of all definitional pessimists is that our attempts to define life are attempts to provide a list of all necessary and sufficient conditions for something to count as alive. In other words, a definition of life is a strict, descriptive definition. Against this, several pragmatic alternatives have been put forward. On these pragmatic accounts, definitions of life are not strictly, but rather loosely descriptive. Their purpose is not to be true, but to be useful to scientists by guiding scientific practice. More recently, this position has come under attack for not being able to explain how our attempts to define life are connected to scientific progress within the biological sciences. Here, I argue to the contrary by showing how pragmatic definitions of life can be, and in fact are, conducive to scientific progress. Additionally, I show how the pragmatic account of definitions of life can be brought to bear upon our normative discussions involving definitions of life.
Characterization Frames Constructing Endoxa in Activists’ Discourse About the Public Controversy Surrounding Fashion Sustainability
Authors: Mercuri Chiara
Published: April 2023

This paper investigates the relationship between characterization frames and argumentation in activists’ discourse about the public controversy surrounding fashion sustainability. While previous studies proposing an argumentative approach to frames have acknowledged that frames are related to underlying implicit premises, how frames select certain implicit premises still needs to be systematically explained. Therefore, drawing on a theoretical framework combining Pragma dialectics (van Eemeren 2010) with the Argumentum Model of Topics an empirical analysis of a social media corpus has been performed in order to examine the connection between characterization frames and underlying implicit premises. This paper offers both a methodological and a theoretical contribution. From a methodological point of view, it offers linguistic-discursive tools for the analysis of characterization frames. From a theoretical perspective, it shows how characterization frames contribute to construct endoxa, i.e. underlying implicit premises, through argumentative patterns.
Optimizing Reservoir Water Management in a Changing Climate
Authors: Beça Pedro , Rodrigues António C. , Nunes João P. , Diogo Paulo , Mujtaba Babar
Published: April 2023

One of the UN agenda 2030 Sustainable Development goals is associated with water availability and its sustainable management. The present study intends to improve multipurpose reservoir management under climate change scenarios in water scarce regions such as the Mediterranean. Implemented methods include the sequential use of climate model results, hydrological modelling, and reservoir water balance simulation, which are used to estimate future water availability. This work focuses on developing an innovative reservoir management approach based on rule curves and a dynamic assessment of water needs, to improve the management of reservoirs that are dependent on a water transfer system. The proposed methods are implemented in two reservoirs located in a typical Mediterranean river basin and assessed under long-term climate change scenarios up to the year 2100. The results show that the proposed approach can ensure 100% of the urban water supply, improve the reliability of the irrigation supply from 75% to 86–91%, and provide 92–98% of the river ecological flow. It is also demonstrated that this management approach is beneficial, particularly in the case of multipurpose reservoirs in watersheds facing water scarcity risks, to optimize the balance between supply reliability, water transfer volumes, and costs.
Automated three-dimensional major white matter bundle segmentation using diffusion magnetic resonance imaging
Authors: Andica Christina , Kamagata Koji , Aoki Shigeki
Published: April 2023

White matter bundle segmentation using diffusion magnetic resonance imaging fiber tractography enables detailed evaluation of individual white matter tracts three-dimensionally, and plays a crucial role in studying human brain anatomy, function, development, and diseases. Manual extraction of streamlines utilizing a combination of the inclusion and exclusion of regions of interest can be considered the current gold standard for extracting white matter bundles from whole-brain tractograms. However, this is a time-consuming and operator-dependent process with limited reproducibility. Several automated approaches using different strategies to reconstruct the white matter tracts have been proposed to address the issues of time, labor, and reproducibility. In this review, we discuss few of the most well-validated approaches that automate white matter bundle segmentation with an end-to-end pipeline, including TRActs Constrained by UnderLying Anatomy (TRACULA), Automated Fiber Quantification, and TractSeg.
Flowers, Tractors, & Telegram: Who are the Protesters in Belarus?: A Survey Based Assessment of Anti-Lukashenka Protest Participants
Authors: Onuch Olga , Sasse Gwendolyn , Michiels Sébastien
Published: April 2023

Who are the people who, in the face of extreme repression, unexpectedly take to the streets en masse in an authoritarian state? This article aims to answer this question with reference to the case of the Belarusian anti-Lukashenka mass mobilization of 2020. It employs unique data from an original online protest survey among citizens of Belarus who were 18 or older and residing in the country at the time of the protests (Onuch et. al.; MOBILISE 2020 & 2021; n = 17,174), fielded August 18, 2020–January 29, 2021.2 This survey was designed to: (a) capture as many protesters as possible; and (b) capture a large enough sample of non-protesters as a comparative reference group enabling us to better understand how different anti-Lukashenka protesters (n = 11,719) were from non-protesters (n = 5,455). Guided by theoretical and empirical expectations of contentious politics scholarship, we first provide descriptive statistics about the socio-demographic characteristics of the protesters, self-reported protest grievances and claims, and median protester preferences on a range of attitudes and policies. This portrait of the protesters is followed up by regression analysis to test whether these patterns hold at a statistically significant level when comparing protesters and non-protesters.
Associations of food choice values and food literacy with overall diet quality: a nationwide cross-sectional study in Japanese adults
Authors: Murakami Kentaro , Shinozaki Nana , Livingstone M. Barbara E. , Yuan Xiaoyi , Tajima Ryoko , Matsumoto Mai , Masayasu Shizuko , Sasaki Satoshi
Published: April 2023

To date, a limited number of studies have examined aspects of food choice values and food literacy in relation to some aspects of dietary behaviours. The aim of this cross-sectional study was to comprehensively examine the associations of food choice values and food literacy with diet quality. In total, 2231 Japanese adults aged 19–80 years completed questionnaires asking about food choice values (accessibility, convenience, health/weight control, tradition, sensory appeal, organic, comfort and safety) and food literacy characterised by nutrition knowledge, cooking skills, food skills and eating behaviours (hunger, food responsiveness, emotional overeating, enjoyment of food, satiety responsiveness, emotional undereating, food fussiness and slowness in eating). As a measure of diet quality, the Healthy Eating Index-2015 (HEI-2015) was calculated using a brief-type diet history questionnaire (BDHQ) or a food combination questionnaire (FCQ). In males, after adjustment for potential confounding factors (including age, BMI and the ratio of reported energy intake to estimated energy requirement), the HEI-2015 derived from BDHQ and that derived from FCQ were associated significantly (P ≤ 0·02) and positively with the food choice values of organic and inversely with food fussiness. In females, the HEI-2015 showed positive associations with the food choice values of health/weight control, nutrition knowledge and cooking skills and an inverse association with food fussiness, irrespective of the dietary assessment questionnaire (P ≤ 0·03). In conclusion, this study suggests that several aspects of food choice values and food literacy were associated with diet quality, and the aspects related differed between males and females.
What do windsurfers and kitesurfers in Germany know about surfer's ear and how is it influenced by protective measures?
Authors: Wegener F , Wegner M , Weiss N M
Published: April 2023

Objective

This study investigated the frequency of ear canal protection use and looked at its influence on external auditory exostosis severity and knowledge about external auditory exostosis among windsurfers and kitesurfers on the German coast.

Method

This retrospective cross-sectional study interviewed 130 windsurfers and kitesurfers along the German coast on knowledge of external auditory exostosis, exposure time, use of neoprene hoods and earplugs, and otological complaints. Participants underwent bilateral video-otoscopic examination.

Results

Knowledge of external auditory exostosis was ‘good’ or ‘excellent’ in 78 of 130 (60 per cent) individuals and ‘poor’ or non-existent in 52 of 130 (40 per cent) individuals. Knowledge was positively correlated with hours of exposure, otological complaints and frequency of ear canal protection use. A significant negative influence of neoprene hood use on external auditory exostosis severity was shown.

Conclusion

The positive effect of external auditory exostosis knowledge on the frequency of ear canal protection and the reduction of external auditory exostosis risk implies a need for health education on this topic.
Directional serial verb constructions in Mandarin: A neo-constructionist approach
Authors: CHEN ZHISHUANG
Published: April 2023

This paper develops Ramchand’s first phase syntax theory by investigating the Mandarin directional serial verb construction. Specifically, the position of the theme argument in these constructions is investigated, and two major word order variants are identified: the VOV type and the VVO type. The former are argued to be accomplishments, whereas the latter are achievements. The analysis embraces Ramchand’s spirit that three sub-eventive projections (InitP, ProcP, and ResP) exist universally as the basic building blocks in the first-phase syntax, and it proposes that the surface word order alternation and situation type shift is the consequence of the occurrence/absence of the ResP and the different insertion position of the directional morphemes.
The second-order problem of other minds
Authors: Friedman Ori , Tasimi Arber
Published: April 2023

The target article proposes that people perceive social robots as depictions rather than as genuine social agents. We suggest that people might instead view social robots as social agents, albeit agents with more restricted capacities and moral rights than humans. We discuss why social robots, unlike other kinds of depictions, present a special challenge for testing the depiction hypothesis.
Virtual and real: Symbolic and natural experiences with social robots
Authors: Reeves Byron
Published: April 2023

Interactions with social robots are symbolic experiences guided by the pretense that robots depict real people. But they can also be natural experiences that are direct, automatic, and independent of any thoughtful mapping between what is real and depicted. Both experiences are important, both may apply within the same interaction, and they may vary within a person over time.
People treat social robots as real social agents
Authors: Eng Alexander , Chi Yam Kai , Gray Kurt
Published: April 2023

When people interact with social robots, they treat them as real social agents. How people depict robots is fun to consider, but when people are confronted with embodied entities that move and talk – whether humans or robots – they interact with them as authentic social agents with minds, and not as mere representations.
Social robots as social learning partners: Exploring children's early understanding and learning from social robots
Authors: Haber Amanda , Corriveau Kathleen H.
Published: April 2023

Clark and Fischer propose that people interpret social robots not as social agents, but as interactive depictions. Drawing on research focusing on how children selectively learn from social others, we argue that children do not view social robots as interactive toys but instead treat them as social learning partners and critical sources of information.
A more ecological perspective on human–robot interactions
Authors: Ravikumar Varun , Bowen Jonathan , Anderson Michael L.
Published: April 2023

Drawing from two strands of ecological psychology, we suggest that even if social robots are interactive depictions, people need not mentally represent them as such. Rather, people can engage with the opportunities for action or affordances that social robots offer to them. These affordances are constrained by the larger sociocultural settings within which human–robot interactions occur.
Anthropomorphism, not depiction, explains interaction with social robots
Authors: Petersen Dawson , Almor Amit
Published: April 2023

We question the role given to depiction in Clark and Fischer's account of interaction with social robots. Specifically, we argue that positing a unique cognitive process for handling depiction is evolutionarily implausible and empirically redundant because the phenomena it is intended to explain are not limited to depictive contexts and are better explained by reference to more general cognitive processes.
Dipolarization Fronts in the Jovian Magnetotail: Statistical Survey of Ion Intensity Variations Using Juno Observations
Authors: Blöcker A. , Kronberg E. A. , Grigorenko E. E. , Roussos E. , Clark G.
Published: April 2023

Energetic particle acceleration and energization in planetary magnetotails are often associated with dipolarization fronts characterized by a rapid increase of the meridional component of the magnetic field. Despite many studies of dipolarization events in Earth's magnetotail, Jupiter’s magnetotail provides an almost ideal environment to study high‐energetic ion acceleration by dipolarization fronts because of its large spatial scales and plasma composition of heavy and light ions. In this study, we focus on the response of different high‐energetic ion intensities (H, He, S, and O) to prominent magnetic dipolarization fronts inside the Jovian magnetotail. We investigate if ion energization and acceleration are present in the observations around the identified dipolarization fronts. Therefore, we present a statistical study of 87 dipolarization front signatures, which are identified in the magnetometer data of the Juno spacecraft from July 2016 to July 2021. For the ion intensity analysis, we use the energetic particle observations from the Jupiter Energetic Particle Detector Instrument. Our statistical study reveals that less than half of the identified events are accompanied by an increase of the ion intensities, while most of the other events show no significant change in the ion intensity dynamics. In about 40% of the events located in the dawn sector a significant decrease of the energy spectral index is detected indicating ion acceleration by the dipolarization fronts.
Ultra-high field imaging, plasma markers and autopsy data uncover a specific rostral locus coeruleus vulnerability to hyperphosphorylated tau
Authors: Van Egroo Maxime , Riphagen Joost M. , Ashton Nicholas J. , Janelidze Shorena , Sperling Reisa A. , Johnson Keith A. , Yang Hyun-Sik , Bennett David A. , Blennow Kaj , Hansson Oskar , Zetterberg Henrik , Jacobs Heidi I. L.
Published: April 2023

Autopsy data indicate that the locus coeruleus (LC) is one of the first sites in the brain to accumulate hyperphosphorylated tau pathology, with the rostral part possibly being more vulnerable in the earlier stages of the disease. Taking advantage of recent developments in ultra-high field (7 T) imaging, we investigated whether imaging measures of the LC also reveal a specific anatomic correlation with tau using novel plasma biomarkers of different species of hyperphosphorylated tau, how early in adulthood these associations can be detected and if are associated with worse cognitive performance. To validate the anatomic correlations, we tested if a rostro-caudal gradient in tau pathology is also detected at autopsy in data from the Rush Memory and Aging Project (MAP). We found that higher plasma measures of phosphorylated tau, in particular ptau231, correlated negatively with dorso-rostral LC integrity, whereas correlations for neurodegenerative plasma markers (neurofilament light, total tau) were scattered throughout the LC including middle to caudal sections. In contrast, the plasma Aβ42/40 ratio, associated with brain amyloidosis, did not correlate with LC integrity. These findings were specific to the rostral LC and not observed when using the entire LC or the hippocampus. Furthermore, in the MAP data, we observed higher rostral than caudal tangle density in the LC, independent of the disease stage. The in vivo LC-phosphorylated tau correlations became significant from midlife, with the earliest effect for ptau231, starting at about age 55. Finally, interactions between lower rostral LC integrity and higher ptau231 concentrations predicted lower cognitive performance. Together, these findings demonstrate a specific rostral vulnerability to early phosphorylated tau species that can be detected with dedicated magnetic resonance imaging measures, highlighting the promise of LC imaging as an early marker of AD-related processes.
Hypoxia switches TET1 from being tumor-suppressive to oncogenic
Authors: Yang Qi , Dang Hui , Liu Jiaxin , Wang Xingye , Wang Jingyuan , Lan Xinhui , Ji Meiju , Xing Mingzhao , Hou Peng
Published: April 2023

The classical oxidizing enzymatic activity of Ten Eleven Translocation 1 (TET1) and its tumor suppressor role are well known. Here, we find that high TET1 expression is associated with poor patient survival in solid cancers often having hypoxia, which is inconsistent with its tumor suppressor role. Through a series of in vitro and in vivo studies, using thyroid cancer as a model, we demonstrate that TET1 plays a tumor suppressor function in normoxia and, surprisingly, an oncogenic function in hypoxia. Mechanistically, TET1 mediates HIF1α-p300 interaction by acting as a co-activator of HIF1α to promote CK2B transcription under hypoxia, which is independent of its enzymatic activity; CK2 activates the AKT/GSK3β signaling pathway to promote oncogenesis. Activated AKT/GSK3β signaling in turn maintains HIF1α at elevated levels by preventing its K48-linked ubiquitination and degradation, creating a feedback loop to enhance the oncogenicity of TET1 in hypoxia. Thus, this study uncovers a novel oncogenic mechanism in which TET1 promotes oncogenesis and cancer progression through a non-enzymatic interaction between TET1 and HIF1α in hypoxia, providing novel therapeutic targeting implications for cancer.
Chronic hypoxia favours adoption to a castration-resistant cell state in prostate cancer
Authors: Cameron Sarina , Deblois Genevieve , Hawley James R. , Qamra Aditi , Zhou Stanley , Tonekaboni Seyed Ali Madani , Murison Alexander , Van Vliet Romy , Liu Juan , Locasale Jason W. , Lupien Mathieu
Published: April 2023

Predicting and treating recurrence in intermediate-risk prostate cancer patients remains a challenge despite having identified genomic instability [1] and hypoxia [2, 3] as risk factors. This underlies challenges in assigning the functional impact of these risk factors to mechanisms promoting prostate cancer progression. Here we show chronic hypoxia (CH), as observed in prostate tumours [4], leads to the adoption of an androgen-independent state in prostate cancer cells. Specifically, CH results in prostate cancer cells adopting transcriptional and metabolic alterations typical of castration-resistant prostate cancer cells. These changes include the increased expression of transmembrane transporters for the methionine cycle and related pathways leading to increased abundance of metabolites and expression of enzymes related to glycolysis. Targeting of the Glucose Transporter 1 (GLUT1) identified a dependency on glycolysis in androgen-independent cells. Overall, we identified a therapeutically targetable weakness in chronic hypoxia and androgen-independent prostate cancer. These findings may offer additional strategies for treatment development against hypoxic prostate cancer.