bluuebunny/crossref_metadata_2025 huggingface dataset:
Dysregulated Ca2+ signaling, fluid secretion, and mitochondrial function in a mouse model of early Sjogrens syndrome
Authors: Huang Kai-Ting , Wagner Larry E. , Takano Takahiro , Lin Xiao-Xuan , Bagavant Harini , Deshmukh Umesh , Yule David I
Published: March 2024

Saliva is essential for oral health. The molecular mechanisms leading to physiological fluid secretion are largely established, but factors that underlie secretory hypofunction, specifically related to the autoimmune disease Sjogrens syndrome (SS) are not fully understood. A major conundrum is the lack of association between the severity of inflammatory immune cell infiltration within the salivary glands and glandular hypofunction. In this study, we investigated in a mouse model system, mechanisms of glandular hypofunction caused by the activation of the stimulator of interferon genes (STING) pathway. Glandular hypofunction and SS-like disease were induced by treatment with 5,6-Dimethyl-9-oxo-9H-xanthene-4-acetic acid (DMXAA), a small molecule agonist of murine STING. Contrary to our expectations, despite a significant reduction in fluid secretion in DMXAA-treated mice, in vivo imaging demonstrated that neural stimulation resulted in greatly enhanced spatially averaged cytosolic Ca2+ levels. Notably, however, the spatiotemporal characteristics of the Ca2+ signals were altered to signals that propagated throughout the entire cytoplasm as opposed to largely apically confined Ca2+ rises observed without treatment. Despite the augmented Ca2+ signals, muscarinic stimulation resulted in reduced activation of TMEM16a, although there were no changes in channel abundance or absolute sensitivity to Ca2+. However, super-resolution microscopy revealed a disruption in the intimate colocalization of Inositol 1,4,5-trisphosphate receptor Ca2+ release channels in relation to TMEM16a. TMEM16a channel activation was also reduced when intracellular Ca2+ buffering was increased. These data are consistent with altered local coupling between the channels contributing to the reduced activation of TMEM16a. Appropriate Ca2+ signaling is also pivotal for mitochondrial morphology and bioenergetics and secretion is an energetically expensive process. Disrupted mitochondrial morphology, a depolarized mitochondrial membrane potential, and reduced oxygen consumption rate were observed in DMXAA-treated animals compared to control animals. We report that early in SS disease, dysregulated Ca2+ signals lead to decreased fluid secretion and disrupted mitochondrial function contributing to salivary gland hypofunction and likely the progression of SS disease.
The RNA-dependent interactions of phosphatidylinositol 4,5-bisphosphate with intrinsically disordered proteins contribute to nuclear compartmentalization
Authors: Sztacho Martin , Červenka Jakub , Šalovská Barbora , Antiga Ludovica , Hoboth Peter , Hozák Pavel
Published: March 2024

The RNA content is crucial for the formation of nuclear compartments, such as nuclear speckles and nucleoli. Phosphatidylinositol 4,5-bisphosphate (PIP2) is found in nuclear speckles, nucleoli and nuclear lipid islets and is involved in RNA polymerase I/II transcription. Intriguingly, the nuclear localization of PIP2 was also shown to be RNA-dependent. We therefore investigated whether PIP2 and RNA cooperate in the establishment of nuclear architecture. In this study, we unveiled the RNA-dependent PIP2-associated (RDPA) nuclear proteome in human cells by mass spectrometry. We found that intrinsically disordered regions (IDRs) with polybasic PIP2-binding K/R motifs are prevalent features of RDPA proteins. Moreover, these IDRs of RDPA proteins exhibit enrichment for phosphorylation, acetylation and ubiquitination sites. Our findings reveal that RDPA protein BRD4 associates with PIP2 in an RNA-dependent manner via electrostatic interactions, and that elevated PIP2 levels increase the number of BRD4 protein nuclear foci. Thus, we propose that PIP2 spatiotemporally orchestrates nuclear processes through association with RNA and RDPA proteins and affects their ability to phase separate. This suggests pivotal role of PIP2 for the establishment of a functional nuclear architecture competent for gene expression.
Replication efficiencies of human cytomegalovirus-infected epithelial cells are dependent on source of virus production
Authors: Mokry Rebekah L. , Monti Christopher E. , Rosas-Rogers Suzette , Schumacher Megan L. , Dash Ranjan K. , Terhune Scott S.
Published: March 2024

Human cytomegalovirus (HCMV) is a prevalent betaherpesvirus, and infection can lead to a range of symptomatology from mononucleosis to sepsis in immunocompromised individuals. HCMV is also the leading viral cause of congenital birth defects. Lytic replication is supported by many cell types with different kinetics and efficiencies leading to a plethora of pathologies. The goal of these studies was to elucidate HCMV replication efficiencies for viruses produced on different cell types upon infection of epithelial cells by combining experimental approaches with data-driven computational modeling. HCMV was generated from a common genetic background of TB40-BAC4, propagated on fibroblasts (TB40Fb) or epithelial cells (TB40Epi), and used to infect epithelial cells. We quantified cell-associated viral genomes (vDNA), protein levels (pUL44, pp28), and cell-free titers over time for each virus at different multiplicities of infection. We combined experimental quantification with data-driven simulations and determined that parameters describing vDNA synthesis were similar between sources. We found that pUL44 accumulation was higher in TB40Fbthan TB40Epi. In contrast, pp28 accumulation was higher in TB40Epiwhich coincided with a significant increase in titer for TB40Epiover TB40Fb. These differences were most evident during live-cell imaging, which revealed syncytia-like formation during infection by TB40Epi. Simulations of the late lytic replication cycle yielded a larger synthesis constant for pp28 in TB40Epialong with increase in virus output despite similar rates of genome synthesis. By combining experimental and computational modeling approaches, our studies demonstrate that the cellular source of propagated virus impacts viral replication efficiency in target cell types.

IMPORTANCE

Human cytomegalovirus (HCMV) is a ubiquitous pathogen that can cause serious disease under conditions of immunodeficiency and upon congenital infection. HCMV replicates in diverse cell types throughout the human body with tropism influenced by the source of the virus. Here, we investigated the contribution of viral sources to the kinetics of HCMV replication in epithelial cells using both experimental and mechanistic computational modeling approaches. These studies reveal that HCMV produced from epithelial cells exhibits a higher efficiency of replication despite similar viral DNA synthesis kinetics between viral sources. These differences likely involve a propensity of epithelial-derived virus to induce syncytia versus fibroblast-derived virus, and an accompanying higher synthesis rate of a late virion protein ultimately resulting in production of more extracellular infectious virus.
Molecular Mechanism of Condensin I Activation by KIF4A
Authors: Cutts Erin E. , Tetiker Damla , Kim Eugene , Aragon Luis
Published: March 2024

During mitosis, the condensin I and II complexes compact chromatin into chromosomes. Loss of the chromokinesin, KIF4A, results in reduced condensin I chromosome association. However, the molecular mechanism behind this phenotype is unknown. Here, we show that KIF4A binds directly to condensin I HAWK subunit, NCAPG, via a conserved disordered short linear motif (SLiM) found in its C-terminal tail. KIF4A binding directly competes with two auto-inhibitory interactions in condensin I, mediated by SLiMs found in the N-terminus of NCAPH and the C-terminus of NCAPD2, which bind sites that overlap with KIF4A binding on NCAPG. Addition of the KIF4A SLiM peptide alone is sufficient to stimulate condensin’s ATPase and DNA loop extrusion activity. We also identify SLiMs in known yeast condensin interactors, Sgo and Lrs4, that bind yeast Ycg1, the HAWK equivalent to NCAPG. Our findings, together with previous work on condensin II and cohesin, demonstrate that SLiMs binding to HAWK subunits is a conserved mechanism of regulation in SMC complexes.
Integrability, multifractality, and two-photon dynamics in disordered Tavis-Cummings models
Authors: Wierzchucka Agnieszka , Piazza Francesco , Claeys Pieter W.
Published: March 2024

The Tavis-Cummings model is a paradigmatic central-mode model in which a set of two-level quantum emitters (spins) are coupled to a collective cavity mode. Here we study the eigenstate spectrum, its localization properties, and the effect on dynamics, focusing on the two-excitation sector relevant for nonlinear photonics. These models admit two sources of disorder: in the coupling between the spins and the cavity, and in the energy shifts of the individual spins. While this model was known to be exactly solvable in the limit of a homogeneous coupling and inhomogeneous energy shifts, we establish here the solvability in the opposite limit of a homogeneous energy shift and inhomogeneous coupling, presenting the exact solution and corresponding conserved quantities. We identify three different classes of eigenstates, exhibiting different degrees of multifractality and semilocalization closely tied to the integrable points, and we study their stability to perturbations away from these solvable points. The dynamics of the cavity occupation number away from equilibrium, exhibiting boson bunching and a two-photon blockade, is explicitly related to the localization properties of the eigenstates, and it illustrates how these models support a collective spin description despite the presence of disorder.

Published by the American Physical Society
2024
Photonic quantum metrology with variational quantum optical nonlinearities
Authors: Muñoz de las Heras A. , Tabares C. , Schneider J. T. , Tagliacozzo L. , Porras D. , González-Tudela A.
Published: March 2024

Photonic quantum metrology harnesses quantum states of light, such as NOON or twin-Fock states, to measure unknown parameters beyond classical precision limits. Current protocols suffer from two severe limitations that preclude their scalability: the exponential decrease in fidelities (or probabilities) when generating states with large photon numbers due to gate errors and the increased sensitivity of such states to noise. Here, we develop a deterministic protocol combining quantum optical nonlinearities and variational quantum algorithms that provides a substantial improvement on both fronts. First, we show how the variational protocol can generate metrologically relevant states with a small number of operations which do not significantly depend on photon number, resulting in exponential improvements in fidelities when gate errors are considered. Second, we show that such states offer a better robustness to noise compared to other states in the literature. Since our protocol harnesses interactions already appearing in state-of-the-art setups, such as cavity QED, we expect that it will lead to more scalable photonic quantum metrology in the near future.

Published by the American Physical Society
2024
Controllable spontaneous emission spectrum in an artificial giant atom: Dark lines and bound states
Authors: Yan Yiying , Lü Zhiguo
Published: March 2024

We study the spontaneous emission spectra of a few-level giant atom strongly coupled to a one-dimensional waveguide by employing variational and analytical approaches, which are beyond the rotating-wave approximation and the Markovian approximation. We show that the interference effects due to the multiple coupling points result in dark lines in spontaneous emission spectra of either two-level or three-level giant atoms regardless of whether there is a bound state or not. We illustrate that the generation of dark lines depends on the distance between the coupling points and their number. In the absence of a bound state, the dark lines can be used to suppress emission at a certain frequency in the spectrum. In the presence of a bound state, the total intensity of the emission spectrum can be significantly suppressed. The present results offer the possibility of control over the spontaneous emission with the dark lines due to the destructive interference in giant atoms.

Published by the American Physical Society
2024
Clifford-Deformed Surface Codes
Authors: Dua Arpit , Kubica Aleksander , Jiang Liang , Flammia Steven T. , Gullans Michael J.
Published: March 2024

Various realizations of Kitaev’s surface code perform surprisingly well for biased Pauli noise. Attracted by these potential gains, we study the performance of Clifford-deformed surface codes (CDSCs) obtained from the surface code by the application of single-qubit Clifford operators. We first analyze CDSCs on the 3×3 square lattice and find that, depending on the noise bias, their logical error rates can differ by orders of magnitude. To explain the observed behavior, we introduce the effective distance d′, which reduces to the standard distance for unbiased noise. To study CDSC performance in the thermodynamic limit, we focus on random CDSCs. Using the statistical mechanical mapping for quantum codes, we uncover a phase diagram that describes random CDSC families with 50% threshold at infinite bias. In the high-threshold region, we further demonstrate that typical code realizations outperform the thresholds and subthreshold logical error rates, at finite bias, of the best-known translationally invariant codes. We demonstrate the practical relevance of these random CDSC families by constructing a translation-invariant CDSC belonging to a high-performance random CDSC family. We also show that our translation-invariant CDSC outperforms well-known translation-invariant CDSCs, such as the XZZX and XY codes.

Published by the American Physical Society
2024
4-Fluorobenzyl (Z)-2-(2-oxoindolin-3-ylidene)hydrazine-1-carbodithioate
Authors: Abdul Manan Mohd Abdul Fatah , Cordes David B. , McKay Aidan P.
Published: March 2024

The title compound, C16H12FN3OS, a fluorinated dithiocarbazate imine derivative, was synthesized by the one-pot, multi-component condensation reaction of hydrazine hydrate, carbon disulfide, 4-fluorobenzyl chloride and isatin. The compound demonstrates near-planarity across much of the molecule in the solid state and a Z configuration for the azomethine C=N bond. The Z form is further stabilized by the presence of an intramolecular N—H...O hydrogen bond. In the extended structure, molecules are linked into dimers by N—H...O hydrogen bonds and further connected into chains along either [2\overline{1}0] or [100] by weak C—H...S and C—H...F hydrogen bonds, which further link into corrugated sheets and in combination form the overall three-dimensional network.
Optimising project outcomes in complex environments: empirical insights on agile practices and stakeholder dynamics
Authors: Nguyen Tuan Son , Mohamed Sherif , Mostafa Sherif
Published: March 2024

Purpose

This study delves into the dynamics between Agile Response to Change (AR), Adaptive Scoping (AS), Stakeholder Engagement (SE) and Project Performance (PP), with a special focus on the moderating influence of Project Complexity (PC). The research, grounded in a thorough literature review, identifies critical gaps in these areas and examines the extent to which PC moderates the effects of AR, AS and SE on PP, offering new perspectives for managing complex projects.

Design/methodology/approach

The research develops a conceptual model based on a critical analysis of existing literature. A comprehensive questionnaire was designed, incorporating 28 items to measure AR, AS, SE, PP and PC. Data was collected from 136 project managers across various industries, and the responses were analysed using structural equation modelling (SEM) to explore the complex interplay between these variables.

Findings

The analysis revealed that internal AR (ARint) significantly enhances both quantitative (PPqt) and qualitative aspects of PP (PPql). AS and SE were found to positively influence PPql, but their impact on PPqt was not significant. Interestingly, PC was observed to negatively moderate the relationship between ARint and PPql, while its moderating effect on the relationship between ARint and PPql was not significant. The study also notes that PC does not significantly alter the positive correlations between AS, SE and PPql.

Originality/value

This research contributes to the existing body of knowledge by elucidating the relationships between ARint, AS, SE and different dimensions of PP. It uniquely explores the role of PC as a moderating variable in these relationships, offering valuable insights for practitioners and researchers in the field of complex project management.
Corporate diplomacy: the dimensional structure and outcomes
Authors: Jiang Sihan , Teng Wenbo , Huang Yuanyuan , Zhang Xiao
Published: March 2024

Purpose

Given the great upheaval in the international situation and the increasing operating risk in international business, research on corporate diplomacy is thriving. However, it still lacks clear conceptualization and operationalization. Based on social capital theory, our study conceptualizes corporate diplomacy as a three-dimensional construct and quantifies its distinct and combined impacts on multinational enterprises’ (MNE) subsidiary performance.

Design/methodology/approach

This research analyzes 134 responses collected from a questionnaire survey among key informants in Chinese MNEs using the regression method.

Findings

This research finds that corporate diplomacy is positively correlated with MNEs’ subsidiary performance. Specifically, compatriot-oriented diplomacy is the most effective, followed sequentially by host-partner-oriented and host-regulator-oriented diplomacy. In addition, compatriot-oriented diplomacy substitutes for host-partner-oriented diplomacy but complements host-regulator-oriented diplomacy in enhancing subsidiary performance.

Originality/value

Our research enriches the conceptualization and operationalization of corporate diplomacy and provides a nuanced view of its distinct and combined effects on MNEs’ subsidiary performance.
A critical discourse analysis of older women’s representation in housing and homelessness
Authors: Brown Taylah , Smedley Charlotte , Cameron Jacqui
Published: March 2024

Purpose

Despite a significant evidence base illustrating the issue of housing insecurity and homelessness experienced by women over the age of 55 in Australia [Pawson et al., 2018; Australian Institute of Health and Welfare (AIHW), 2021b; Mission Australia 2022; Per Capita 2022], there continues to be a knowledge gap in the representation of older women in current Federal and New South Wales (NSW) State Government housing and homelessness policies and initiatives. This paper aims to identify the extent and ways in which older women were represented (or not represented) in the Federal and NSW State housing and homelessness policies in 2022.

Design/methodology/approach

Of the total primary and supplementary Federal and NSW State policy and strategy documents, 16 were collected through a systematic review and then analysed using a Critical Discourse Analysis (CDA) framework and feminist lens to explore quotes, phrases, keywords and language choices which suggested prevalent themes, rhetorical devices and dominant discourses.

Findings

Three significant themes were identified by the analysis (1) “relinquished responsibility”, (2) “inconsistent rhetoric” and (3) “homogenising and ideological cherry picking”. These themes presented the authors with three main discussion points to inform policy reform which we have addressed in relation to policy implications, evidence-based policy decision-making and impacts on older women.

Originality/value

The combination of a systematic review with CDA provides a unique approach to exploring homelessness policy for older women.
Swirl-induced motion prediction with physics-guided machine learning utilizing spatiotemporal flow field structure
Authors: Zhou Ziming , Zhao Fengnian , Hung David
Published: March 2024

Purpose

Higher energy conversion efficiency of internal combustion engine can be achieved with optimal control of unsteady in-cylinder flow fields inside a direct-injection (DI) engine. However, it remains a daunting task to predict the nonlinear and transient in-cylinder flow motion because they are highly complex which change both in space and time. Recently, machine learning methods have demonstrated great promises to infer relatively simple temporal flow field development. This paper aims to feature a physics-guided machine learning approach to realize high accuracy and generalization prediction for complex swirl-induced flow field motions.

Design/methodology/approach

To achieve high-fidelity time-series prediction of unsteady engine flow fields, this work features an automated machine learning framework with the following objectives: (1) The spatiotemporal physical constraint of the flow field structure is transferred to machine learning structure. (2) The ML inputs and targets are efficiently designed that ensure high model convergence with limited sets of experiments. (3) The prediction results are optimized by ensemble learning mechanism within the automated machine learning framework.

Findings

The proposed data-driven framework is proven effective in different time periods and different extent of unsteadiness of the flow dynamics, and the predicted flow fields are highly similar to the target field under various complex flow patterns. Among the described framework designs, the utilization of spatial flow field structure is the featured improvement to the time-series flow field prediction process.

Originality/value

The proposed flow field prediction framework could be generalized to different crank angle periods, cycles and swirl ratio conditions, which could greatly promote real-time flow control and reduce experiments on in-cylinder flow field measurement and diagnostics.
The digital revolution in the tourism industry: role of anthropomorphic virtual agent in digitalized hotel service
Authors: Ben Saad Sihem
Published: March 2024

Purpose

In the tourism industry, immersive technologies become increasingly vital, amplifying traveler experiences and industry growth. By studying “e-booking” applications prevalent in hotels, this study aims to analyze the impact of integrating an anthropomorphic virtual agent (AVA) on user perceptions of humanness and service usage intent.

Design/methodology/approach

Two experiments were conducted to examine the effects of using an AVA and explain the psychological mechanism of how AVA’s attributes increase intention to use “e-booking” application.

Findings

The results highlight the positive influence of AVA on the intention to use. They illustrate the psychological mechanism of how AVA’s attributes (agency and emotionality) influence perceived humanness and intention to use. More specifically, the results indicate that perceived humanness mediated the effect of an AVA on intention to use.

Research limitations/implications

Further research should delve into additional capabilities related to humanness.

Practical implications

This study provides useful insights for hotels’ managers about incorporating AVAs in digital services to enhance the perceived humanness of AVAs. The findings suggest that such efforts could yield benefits, especially when they involve conveying that AVAs possess agency and emotionality.

Originality/value

To the best of the author’s knowledge, this study is the first to investigate how AVA impacts hotel human–computer interaction. It examines agency and emotionality features on humanness perception and behavioral intent. It also guides successful digitalized hotel service development and design, expanding existing research on human–virtual agent digital services, which mainly focuses on superficial traits like face and gender.
Principals' systems thinking and student outcomes: the intervening role of school structure
Authors: Nadav Nechama , Benoliel Pascale , Schechter Chen
Published: March 2024

Purpose

This study examines the relationship of principals’ systems thinking (PST) to student outcomes of academic achievement and school violence. The investigation relies on the contingency theory, according to which effective leadership is contingent on the nature of the situational influences to which managers are exposed. Specifically, the study investigates the influence of school structure – bureaucratic vs organic – on the relationship between PST and student outcomes of academic achievement and school violence after accounting for students’ socioeconomic backgrounds and principals' demographics.

Design/methodology/approach

A three-source survey design with self-reported and non-self-reported data was used, with a sample of 423 participants from 71 elementary schools in Israel. The sample included senior management team members and teachers. The data were aggregated at the school level of analysis.

Findings

Hierarchical regression analyses showed that organic school structure moderates the relationship between PST and student academic achievement, and bureaucratic school structure moderates the relationship between PST and school violence beyond the impact of students’ socioeconomic backgrounds.

Originality/value

This study provides important evidence for the benefits of aligning PST with school structure for improving student outcomes beyond the impact of students’ socioeconomic backgrounds. In addition, the study suggests principal system thinking leadership to achieve effective student outcomes that circumvent the effects of inequality on disadvantaged student groups.
Evolution of trade and productive integration in Latin America, 1995–2015: an input-output analysis
Authors: Vázquez-López Raúl
Published: March 2024

Purpose

The main goal of this paper is to examine the evolution of Latin American productive integration in terms of the regional value added incorporated in intra-regional exports of Argentina, Brazil, Chile, Colombia, Mexico and Peru. In addition, the study traces the trade and productive integration trajectories for each of these countries from 1995 to 2015.

Design/methodology/approach

Based on the use of OECD’s global ICIO input-output tables, this paper applies the methodological framework by Wang et al. (2018) for the analysis of trade flows at the bilateral level, which allows breaking down the value of gross exports of each sector-country, depending on the origin of the value added contained in exports, as well as their use.

Findings

The estimates show very low shares of value added from regional partners in the intra-regional exports of the countries studied. Conversely, the weight of the value added incorporated in these exports by countries outside the region has increased in tandem with China’s expanding involvement in Latin America. This development, along with the downward trend in domestic value added incorporated in exports, indicates a lack of a regional integration process of any depth.

Originality/value

This article addresses an economic problem of conventional importance from a global value chain perspective using a novel methodology based on the use of global input–output tables.
The educator’s role in democratic and multicultural societies: student perceptions at a teacher training college in Israel
Authors: Hisherik Michal , Paul-Binyamin Ilana
Published: March 2024

Purpose

Educators are recognized as key agents of social change, responsible for shaping future citizens. Beyond imparting knowledge, teachers are crucial in addressing societal challenges such as sustainability, democracy and social equality. This study aims to investigate the attitudes of Jewish and Arab students toward democratic values and how they perceive their role as educators in a multicultural society.

Design/methodology/approach

This study explores the attitudes of majority and minority group students in an Israeli teacher training college towards realizing democratic values and promoting shared citizenship. The sample included 382 Jewish and Arab students, who answered a questionnaire about attitudes regarding education for democracy and shared society, and their perception of their role in promoting this education.

Findings

The investigation delves into students’ civic perceptions, shedding light on the moderate and pluralistic stances held by both Jewish and Arab students. They advocate for cross-cultural exposure and interaction, with Jewish students demonstrating slightly more moderate views than the prevailing norms in Israeli society. Interestingly, Jewish students exhibited a willingness to engage in discussions on conflictual topics, whereas Arab students tended to avoid them.

Social implications

This study underscores the potential of teacher training colleges in shaping the upcoming generation of educators as advocates of tolerance, and democracy, and promoters of a shared society.

Originality/value

This research gains heightened relevance in a contemporary landscape where numerous nations, especially those comprising diverse cultures, grapple with surges of nationalism that threaten democratic values. Teacher training colleges hold the key to forging a more harmonious future by becoming beacons of transformative pedagogy. These institutions can shape a new generation of educators who are poised to catalyze authentic social change.
There's Something about Uvalde: American Patriarchy and the Slaughter of Innocents
Authors: Bates Carolyn M.
Published: March 2024

After every school shooting in the United States both a wish and a fear arise: Will this be the one? Will this be the tipping point for change in a nation so deeply divided over the meaning of “the right to bear arms?” Sandy Hook, Connecticut? No. Parkland, Florida? No. So, why might the killing of 19 children and 2 teachers in Uvalde, Texas, prove different? The American epidemic of mass school shootings betrays a country's willingness to let its children disappear, to sacrifice them on the altar of an archetypally violent ethos. While the internal experiences of alienation, resentment and contempt are often at play in the individuals who carry out such violence, the author suggests that the uniquely American glorification of “the lone wolf”, the “rugged individual” and the “misunderstood hero” fuels a supportive background for mass shooters in a nation that appears to be enamoured of ancient patriarchal attitudes as it doubles down on its valuing of weaponry. Such patriarchal attitudes, underscored by capitalism and the profits of the gun industry, are implicated in the territorial adhesion to American gun rights and in the high cost paid by the blood of innocents. Drawing on Vestergaard & Odde's (2021) concepts of socio‐analysis and sociality, this paper explores the dynamic process of “mass‐character” marked by “contagion, imitation, attraction and repulsion” that convolute cultural values of heritage and freedom into the perverse expression of mass violence.
My Silent Story: Conflicted Memories, Silences and Intergenerational Traumas1
Authors: Švara Manca , Virloget Katja Hrobat
Published: March 2024

This article aims to present the interdisciplinary project “My Story from Silence”, conceived in 2022. The project represents a pioneering effort in assembling individuals from diverse communities, characterized by varying ethnic, national, and migratory backgrounds, along a historically dynamic border. Its primary objective was to provide a platform for these participants to articulate and share narratives previously shrouded in silence, offering insights into their historical pasts. Emphasizing reciprocal dialogue for the first time, the initiative fostered an environment where participants engaged in the dual act of narrating their own experiences and attentively listening to the narratives of others. These memories were explored in group workshops on both sides of the border. By combining elements of cultural anthropology fieldwork and analytical psychology, the workshops attempted to address hitherto unaddressed traumas and silent personal memories linked to major traumatic historical events such as fascism and Istrian exodus through the narratives of individuals. Three vignettes will illustrate the workshop dynamic and our Jungian understanding of it.
Communicating diagnostic uncertainty reduces expectations of receiving antibiotics: Two online experiments with hypothetical patients
Authors: Sievert Elisabeth D. C. , Korn Lars , Gross Marina , Santana Ana Paula , Böhm Robert , Betsch Cornelia
Published: March 2024

The overprescription of antibiotics due to diagnostic uncertainty and inappropriate patient expectations influence antimicrobial resistance. This research assesses (i) whether communicating diagnostic uncertainty reduces expectations of receiving antibiotics and (ii) which communication strategies minimise unintended consequences of such communication. In two experimental online studies conducted in January and April 2023, participants read a vignette describing a doctor consultation for an ear infection and expressed their expectations of receiving antibiotics, trust in their doctor, rated the doctor's reputation and provided their intention to get a second doctor's opinion. Study 1 (N = 2213) investigated whether communicating diagnostic uncertainty and social externalities of antibiotic use (the negative social impacts of developing antibiotic resistance) decreases expectations for antibiotics and explores potential unintended consequences on the doctor–patient relationship. In Study 2 (N = 527), we aimed to replicate and extend the findings by adding specific treatment recommendations. Disclosing diagnostic uncertainty (vs. certainty) and communicating (vs. not communicating) the social externalities of antibiotic overuse reduced patients' expectations of receiving antibiotics. Yet, communicating uncertainty impaired trust in the doctor and the doctor's reputation. Combining the communication of uncertainty with specific treatment recommendations—particularly delayed antibiotic prescriptions—showed important to prevent these unintended consequences.
Exposure–efficacy and exposure–safety analyses of ropeginterferon alfa‐2b treatment in patients with polycythaemia vera
Authors: Qin Albert , Wu Daoxiang , Li Yaning , Zhang Jingjing , Wang Wei , Shen Weihong , Liao Jason , Lin Sheena , Chang Cynthia , Chen Haoqi , Cui Jie , Su Xia
Published: March 2024

Aims

To investigate the exposure–response (E‐R) relationship, including exposure–efficacy and exposure–safety, of ropeginterferon alfa‐2b treatment in patients with polycythaemia vera (PV).

Methods

Based on the results of the phase II trial A20‐202 regarding ropeginterferon alfa‐2b in patients with PV, E‐R analyses were performed to evaluate the efficacy and safety of the given dosing regimen. The E‐R analyses were based on logistic and linear regression and the relationship between exposure to ropeginterferon alfa‐2b and key efficacy and safety variables. The key efficacy variables included complete haematologic response (CHR) and reduction of the driver mutation JAK2V617F. The safety variable was treatment‐related adverse events (TRAEs).

Results

A clear relationship between the exposure to ropeginterferon alfa‐2b and CHR was observed, with an increase in drug exposure resulting in an increased probability of achieving CHR. Similar CHR probabilities were observed in the third and fourth quantiles of the average concentration at Week 24. The results from the exposure–JAK2V617F model indicated that the JAK2V617F allele burden decreased with increasing exposure to ropeginterferon alfa‐2b and baseline body surface area. Exposure–safety analysis revealed a risk of AEs associated with transaminase abnormalities, which were not associated with clinical significance.

Conclusions

Our analyses have shown that patients with PV treated with ropeginterferon alfa‐2b had an increased probability of achieving CHR and a molecular response with acceptable safety risks at the 250–350–500 μg titration dosing regimen. This study has provided the relevant data for the application of a biologics licence of ropeginterferon alfa‐2b for PV treatment in China.
Skeletons in the closet: How and when internal and external corporate social responsibility affect employees' internal whistleblowing behaviors
Authors: Wang Xu , Li Dandan , Meng Liang
Published: March 2024

The micro‐level corporate social responsibility (CSR) literature has underscored the economic benefits of an organization's CSR investments, such as bolstering employees' organizational commitment and improving work performance. Yet, research on the potential influence of CSR in fostering socially oriented outcomes among employees has been rather scarce. This study aims to investigate the influence of CSR on employees' internal whistleblowing behaviors and the underlying mechanisms. A three‐time‐point survey was distributed across the service, manufacturing, construction, and financial insurance industries in Chinese enterprises. The findings reveal that both internal and external CSR positively impact employees' internal whistleblowing behaviors through the mediating role of moral courage, with internal CSR demonstrating a stronger effect. Organizational loyalty positively moderates the mediating role of moral courage in the relationship between internal CSR/external CSR and internal whistleblowing behaviors. Theoretically, this study presents a pioneering endeavor in establishing the link between CSR and employees' internal whistleblowing behaviors, underscoring the significant role that employees' perceptions of CSR play in enhancing societal well‐being and ethical governance. Besides contributing to the micro‐level CSR literature, this study also provides practical insights for organizations seeking to leverage CSR as a tool for promoting employees' ethical conduct.
Clinical, radiological and molecular responses to combination chemotherapy with MAPK pathway inhibition in relapsed and refractory Langerhans cell histiocytosis
Authors: Karri Vivekanudeep , Lin Howard , Velazquez Jessica , Batajoo Akanksha , Parekh Deevyashali , Stanton Whitney , Abhyankar Harshal , El‐Mallawany Nader K. , Agrusa Jennifer , Eckstein Olive , Gulati Nitya , Schwartz Jeffrey , Woods‐Swafford Wendy , Boyd Jaime , Saha Anikit , Allen Carl E. , McClain Kenneth L.
Published: March 2024

Optimal therapeutic approaches for advanced Langerhans cell histiocytosis (LCH) are not known. We assessed the safety and efficacy of combined chemotherapy with MAPK pathway inhibition in 10 patients with refractory systemic disease and/or LCH‐associated neurodegeneration. Overall response rate was 9/10 (90%) for the entire cohort: 5/5 (100%) for patients with systemic disease and 6/7 (86%) for patients with central nervous system disease. BRAFV600E+ peripheral blood fraction decreased in 5/6 (83%). Toxicities included fever, skin rash, myalgias, neuropathy, cytopenias and hypocalcaemia. Prospective trials are required to optimize combination strategies, determine potential to achieve cure and compare outcomes to chemotherapy or MAPK inhibitor monotherapy.
Safety and efficacy of zandelisib plus zanubrutinib in previously treated follicular and mantle cell lymphomas
Authors: Soumerai Jacob D. , Diefenbach Catherine S. , Jagadeesh Deepa , Asch Adam , Kumar Abhijeet , Tsai Michaela L. , Jandl Thomas A. , Lossos Izidore S. , Kenkre Vaishalee P. , Awan Farrukh , Novotny William , Huang Jane , Miao Lu , Rajagopalan Prabhu , Ghalie Richard G. , Zelenetz Andrew D.
Published: March 2024

The combination of the phosphatidylinositol 3‐kinase delta (PI3Kδ) inhibitor zandelisib with the Bruton's tyrosine kinase (BTK) inhibitor zanubrutinib was hypothesized to be synergistic and prevent resistance to single‐agent therapy. This phase 1 study (NCT02914938) included a dose‐finding stage in patients with relapsed/refractory (R/R) B‐cell malignancies (n = 20) and disease‐specific expansion cohorts in follicular lymphoma (FL; n = 31) or mantle cell lymphoma (MCL; n = 19). The recommended phase 2 dose was zandelisib 60 mg on Days 1–7 plus zanubrutinib 80 mg twice daily continuously in 28‐day cycle. In the total population, the most common adverse events (AEs; all grades/grade 3–4) were neutropenia (35%/24%), diarrhoea (33%/2%), thrombocytopenia (32%/8%), anaemia (27%/8%), increased creatinine (25%/0%), contusion (21%/0%), fatigue (21%/2%), nausea (21%/2%) and increased aspartate aminotransferase (24%/6%). Three patients discontinued due to AEs. The overall response rate was 87% (complete response [CR] = 33%) for FL and 74% (CR = 47%) for MCL. The median duration of response and progression‐free survival (PFS) were not reached in either group. The estimated 1‐year PFS was 72.3% (95% confidence interval [CI], 51.9–85.1) for FL and 56.3% (95% CI, 28.9–76.7) for MCL (median follow‐up: 16.5 and 10.9 months respectively). Zandelisib plus zanubrutinib was associated with high response rates and no increased toxicity compared to either agent alone.
Protocol of the LATFIA trial (Laser Assisted Treatment of Fistula in Ano): a multicentre, prospective, randomized controlled trial comparing fistula‐tract laser closure (FiLaC™) with rectal advancement flap for high trans‐sphincteric fistulas
Authors: Gaillard Marie , Van den Broeck Sylvie , Op de Beeck Bart , Wouters Kristien , Stijns Jasper , Van de Putte Dirk , Gys Ben , Houben Bert , Van Dessel Els , Bislenghi Gabriele , Komen Niels
Published: March 2024

Aim

Anal fistula is one of the most common anal diseases, affecting between 1 and 3 per 10 000 people per year. Symptoms have a potentially severe effect on a patient's quality of life. Surgery is the mainstay of treatment, aiming to cure the fistula and preserve anal sphincter function. Rectal advancement flap (RAF) is currently the gold standard treatment but has recurrence rates varying between 20% and 50% and might lead to disturbance of continence. The aim of the trial described in this work is to discover if the minimally invasive fistula tract laser closure (FiLaC™) technique could achieve higher healing rates and a better functional outcome than RAF.

Method

We will perform a randomized prospective multicentre noninferiority study of the treatment of high trans‐sphincteric perianal fistulas, comparing FiLaC™ with RAF in terms of fistula healing, recurrence rate, functional outcome and quality of life. Primary and secondary fistula healing will be evaluated at 26 and 52 weeks’ follow‐up. Quality of life will be evaluated using the SF‐36 questionnaire, the Faecal Incontinence Quality of Life Scale questionnaire and the Vaizey score at 3, 6, 12 and 26 weeks postoperatively.

Conclusion

High trans‐sphincteric fistulas have a potentially severe effect on a patient's quality of life. Classical treatment with RAF is a time‐consuming invasive procedure. The LATFIA trial aims to compare FiLaC™ with the gold standard treatment with RAF. In case of noninferiority, FiLaC™ treatment could be standardized as a first line treatment for high trans‐sphincteric fistulas. Better conservation of the patient's anal sphincter function could possibly be obtained. Likewise, we will report on the postoperative quality of life when applying these two techniques.
A hybrid data fusion approach with twin CNN architecture for enhancing image source identification in IoT environment
Authors: Singh Surjeet , Sehgal Vivek Kumar
Published: March 2024

With the proliferation of digital devices in internet of things (IoT) environment featuring advanced visual capabilities, the task of Image Source Identification (ISI) has become increasingly vital for legal purposes, ensuring the verification of image authenticity and integrity, as well as identifying the device responsible for capturing the original scene. Over the past few decades, researchers have employed both traditional and machine‐learning methods to classify image sources. In the current landscape, data‐driven approaches leveraging deep learning models have emerged as powerful tools for achieving higher accuracy and precision in source prediction. The primary focus of this research is to address the complexities arising from diverse image sources and variable quality in IoT‐generated multimedia data. To achieve this, a Hybrid Data Fusion Approach is introduced, leveraging multiple sources of information to bolster the accuracy and robustness of ISI. This fusion methodology integrates diverse data streams from IoT devices, including metadata, sensor information, and contextual data, amalgamating them into a comprehensive data set for analysis. This study introduces an innovative approach to ISI through the implementation of a Twin Convolutional Neural Network Architecture (TCA) aimed at enhancing the efficacy of source classification. In TCA, the first CNN architecture, referred to as DnCNN, is employed to eliminate noise from the original data set, generating 256 × 256 patches for both training and testing. Subsequently, the second CNN architecture is employed to classify images based on features extracted from various convolutional layers using a 3 × 3 filter, thereby enhancing prediction efficiency. The proposed model demonstrates exceptional accuracy in effectively classifying image sources, showcasing its potential as a robust solution in the realm of ISI.
Habitat protection and removal of encroaching shrubs support the recovery of biodiversity and ecosystem functioning
Authors: Losapio Gianalberto , De Moraes Consuelo M. , Dirzo Rodolfo , Tscheulin Thomas , Zouros Nikos , Mescher Mark C.
Published: March 2024

Livestock overgrazing causes environmental degradation, species invasion, biodiversity loss, and productivity decline, with profound consequences for ecological sustainability and human livelihoods. Habitat protection can mitigate such impacts, but we know little about how the long‐term recovery of plant communities from livestock overgrazing depends on the presence of encroaching shrubs. Here, we explored how shrub encroachment mediates the effects of habitat protection (i.e., livestock exclusion and creation of UNESCO protected areas) on biodiversity recovery and ecosystem functioning (i.e., biomass productivity). We leveraged a long‐term (15–25 years) experiment of livestock exclusion and complemented it with the removal of an encroaching shrub species in pasture areas and protected areas. We reveal that habitat protection has positive effects on patterns of recovery. Yet, the effects of habitat protection are mediated by shrub encroachment. Encroaching shrubs have net positive effects on plant diversity in pasture areas but inhibit biodiversity recovery in protected areas. The combination of habitat protection and the removal of encroaching shrubs best enhances the recovery of plant diversity and biomass productivity. A potential underlying mechanism is the shift in plant interactions from facilitation for recruitment and associated resistance to competition for water. Understanding species interactions is key to guiding conservation and restoration actions which can turn degraded ecosystems back into functional, species‐rich communities.