bluuebunny/crossref_metadata_2025 huggingface dataset:
Generation of natural killer and myeloid cells in a 3D artificial marrow organoid system
Authors: Schell Bérénice , Zhao Lin-Pierre , Kergaravat Camille , Lereclus Emilie , Kalogeraki Maria , Fenaux Pierre , Ades Lionel , Toubert Antoine , Espeli Marion , Balabanian Karl , Clave Emmanuel , Dulphy Nicolas , Bisio Valeria
Published: January 2024

The human bone marrow (BM) microenvironment involves hematopoietic and non-hematopoietic cell subsets organized in a complex architecture. Tremendous efforts have been made to model it in order to analyse normal or pathological hematopoiesis and its stromal counterpart. Herein, we report an original, fully-humanin vitro3D model of the BM microenvironment dedicated to study interactions taking place between mesenchymal stromal cells (MSC) and hematopoietic stem and progenitor cells (HSPC) during the hematopoietic differentiation. This artificial marrow organoid (AMO) model is highly efficient to support NK cell development from the CD34+ HSPC to the terminally differentiated NKG2A-KIR2D+CD57+ NK subset. In addition, myeloid differentiation can also be recapitulated in this model. Moreover, mature NK cell phenotype showed significant differences in the AMO compared to a conventional 2D coculture model for the expression of adhesion molecules and immune checkpoint receptors, thus better reflecting the NK cell behaviour in the BM microenvironment. Lastly, we proved that our model is suitable for evaluating anti-leukemic NK cell function in presence of treatments. Overall, the AMO is a versatile, low cost and simple model able to efficiently recapitulate hematopoiesis and granting better drug response taking into account both immune and non-immune BM microenvironment interactions.

Graphical Abstract
MicroRNA-focused CRISPR/Cas9 Screen Identifies miR-142 as a Key Regulator of Epstein-Barr Virus Reactivation
Authors: Chen Yan , Kincaid Rodney P. , Bastin Kelley , Fachko Devin N. , Skalsky Rebecca L.
Published: January 2024

Reactivation from latency plays a significant role in maintaining persistent lifelong Epstein-Barr virus (EBV) infection. Mechanisms governing successful activation and progression of the EBV lytic phase are not fully understood. EBV expresses multiple viral microRNAs (miRNAs) and manipulates several cellular miRNAs to support viral infection. To gain insight into the host miRNAs regulating transitions from EBV latency into the lytic stage, we conducted a CRISPR/Cas9-based screen in EBV+ Burkitt lymphoma (BL) cells using anti-Ig antibodies to crosslink the B cell receptor (BCR) and induce reactivation. Using a gRNA library against >1500 annotated human miRNAs, we identified miR-142 as a key regulator of EBV reactivation. Genetic ablation of miR-142 enhanced levels of immediate early and early lytic gene products in infected BL cells. Ago2-PAR-CLIP experiments with reactivated cells revealed miR-142 targets related to Erk/MAPK signaling, including components directly downstream of the B cell receptor (BCR). Consistent with these findings, disruption of miR-142 enhanced SOS1 levels and Mek phosphorylation in response to surface Ig cross-linking. Effects could be rescued by inhibitors of Mek (cobimetinib) or Raf (dabrafenib). Taken together, these results show that miR-142 functionally regulates SOS1/Ras/Raf/Mek/Erk signaling initiated through the BCR and consequently, restricts EBV entry into the lytic cycle.
Translation initiation or elongation inhibition triggers contrasting effects onCaenorhabditis eleganssurvival during pathogen infection
Authors: Ghosh Annesha , Singh Jogender
Published: January 2024

Diverse microbial pathogens are known to attenuate host protein synthesis. Consequently, the host mounts a defense response against protein translation inhibition, leading to increased transcript levels of immune genes. The seemingly paradoxical upregulation of immune gene transcripts in response to blocked protein synthesis suggests that the defense mechanism against translation inhibition may not universally benefit host survival. However, a comprehensive assessment of host survival on pathogens upon blockage of different stages of protein synthesis is currently lacking. Here, we investigate the impact of knockdown of various translation initiation and elongation factors on the survival ofCaenorhabditis elegansexposed toPseudomonas aeruginosa. Intriguingly, we observe opposing effects onC. eleganssurvival depending on whether translation initiation or elongation is inhibited. While translation initiation inhibition enhances survival, elongation inhibition decreases it. Transcriptomic studies reveal that translation initiation inhibition activates a bZIP transcription factor ZIP-2-dependent innate immune response that protectsC. elegansfromP. aeruginosainfection. In contrast, inhibiting translation elongation triggers both ZIP-2-dependent and ZIP-2-independent immune responses that, while effective in clearing the infection, are detrimental to the host. Thus, our findings reveal the opposing roles of translation initiation and elongation inhibition inC. eleganssurvival duringP. aeruginosainfection, highlighting distinct transcriptional reprogramming that may underlie these differences.
Inferring the selective history of CNVs using a maximum likelihood model
Authors: Malekpour Seyed Amir , Kalirad Ata , Majidian Sina
Published: January 2024

Copy number variations (CNVs) – structural variations generated by deletion and/or duplication that result in change in DNA dosage – are prevalent in nature. CNVs can drastically affect the phenotype of an organism and have been shown to be both involved in genetic disorders and be used as raw material in adaptive evolution. Unlike single-nucleotide variations, the often large and varied effects of CNVs on phenotype hinders our ability to infer their selective advantage based on the population genetics data. Here, we present a likelihood-based approach, dubbed PoMoCNV, that estimates the evolutionary parameters of CNVs based on population genetics data. As a case study, we analyze the genomics data of 40 strains ofCaenorhabditis elegans, representing four different populations. We take advantage of the data on chromatin accessibility to interpret the evolutionary parameters of CNVs inferred by PoMoCNV. We further test the reliability of PoMoCNV by estimating the evolutionary parameters of CNVs for mutation-accumulation experiments inC. eleganswith varying levels of genetic drift.

Significance

Inferring the evolutionary parameters of copy number variations (CNVs) based on population genetics data is crucial to understand their role in evolution. However, given the diversity in the size and effects of CNVs, such inference poses a challenge. We developed a likelihood-based approach called PoMoCNV to address this issue.
Auranofin induces disulfide bond-mimicking S-Au-S bonds in protein thiol pairs
Authors: Quadros Barsé Laísa , Düchting Petra , Lupilov Natalie , Bandow Julia E. , Krämer Ute , Leichert Lars I.
Published: January 2024

Auranofin is an inhibitor of human thioredoxin reductase, clinically used in the treatment of rheumatoid arthritis. More recently, it has been shown to possess strong antibacterial activity. Despite the structural dissimilarity and the independent evolutionary origins of human thioredoxin reductase and its bacterial counterpart (TrxB), inhibition of bacterial thioredoxin reductase is often suggested to be a major factor in auranofin’s antibacterial mode of action. To test this hypothesis, we attempted to determine the mechanism of inhibition of auranofin for bacterial TrxB in the presence of thioredoxin, TrxB’s natural substrate. However, the data obtained in these experiments was not consistent with a specific and exclusive interaction between TrxB and auranofin. Instead, it suggested that auranofin directly interacts with the cysteine thiols in thioredoxin, TrxB’s substrate. Using the fluorescent redox protein roGFP2, we showed that auranofin does indeed directly interact with cysteine pairs in proteins, forming a thiol modification that is similar to, but clearly distinct from a disulfide bond. The Au:S stoichiometries of auranofin-treated roGFP2 and thioredoxin strongly suggest the presence of an S-Au-S bridge between two cysteines in those proteins. These S-Au-S bonds form independent of thioredoxin reductase at a rate that indicates their pertinence in auranofin’s antibacterial mode of action.
Combining RASG12C(ON) inhibitor with SHP2 inhibition sensitises immune excluded lung tumours to immune checkpoint blockade: a strategy for turning cold tumours hot
Authors: Anastasiou Panayiotis , Moore Christopher , Rana Sareena , de Castro Andrea , Tomaschko Mona , Boumelha Jesse , Mugarza Edurne , Blaj Cristina , de Carné Sophie , Goldstone Robert , Smith Jacqueline A.M. , Quintana Elsa , Molina-Arcas Miriam , Downward Julian
Published: January 2024

Mutant selective drugs targeting the inactive, GDP-bound form of KRASG12Chave been approved for use in lung cancer, but responses are short-lived due to rapid development of resistance. In this study we use a novel covalent tri-complex inhibitor, RMC-4998, that targets RASG12Cin its active, GTP-bound form to investigate treatment of KRAS mutant lung cancer in various immune competent mouse models. While this RASG12C(ON) inhibitor was more potent than the KRASG12C(OFF) inhibitor adagrasib, rapid pathway reactivation was still observed. This could be delayed using combined treatment with a SHP2 inhibitor, RMC-4550, which not only impacted RAS pathway signalling within the tumour cells but also remodelled the tumour microenvironment (TME) to be less immunosuppressive and promoted interferon responses. In an inflamed, “hot”, mouse model of lung cancer, RASG12C(ON) and SHP2 inhibitors in combination drive durable responses by suppressing tumour relapse and inducing development of immune memory, which can also be induced by combination of RASG12C(ON) and PD-1 inhibitors. In contrast, in an immune excluded, “cold”, mouse model of lung cancer, combined RASG12C(ON) and SHP2 inhibition does not cause durable responses, but does sensitise tumours to immune checkpoint blockade, enabling efficient tumour rejection, accompanied by significant TME reorganization, including depletion of immunosuppressive innate immune cells and recruitment and activation of T and NK cells. These preclinical results demonstrate the potential of the combination of RASG12C(ON) inhibitors with SHP2 inhibitors to sensitize anti-PD-1 refractory tumours to immune checkpoint blockade by stimulating anti-tumour immunity as well as by targeting KRAS-driven proliferation in tumour cells.
Lepton flavor violating dark photon
Authors: Zhevlakov Alexey S. , Kirpichnikov Dmitry V. , Lyubovitskij Valery E.
Published: January 2024

We study the possible impact of dark photons on lepton flavor phenomenology. We derive the constraints on nondiagonal dark photon couplings with leptons by analyzing corresponding contributions to lepton anomalous magnetic moments, rare lepton decays, and the prospects of fixed-target experiments aimed at searching for light dark matter based on missing energy/momentum techniques.

Published by the American Physical Society
2024
Fluctuations in the entropy of Hawking radiation
Authors: Bousso Raphael , Miyaji Masamichi
Published: January 2024

We use the gravitational path integral (GPI) to compute the fluctuations of the Hawking radiation entropy around the Page curve in a two-dimensional model introduced by Penington Before the Page time, we find that δS=e−S/2, where S is the black hole entropy. This result agrees with the Haar-averaged entropy fluctuations in a bipartite system. After the Page time, we find that δS∼e−S, up to a prefactor that depends logarithmically on the width of the microcanonical energy window. This is not symmetric under exchange of subsystem sizes and so does not agree with the Haar average for a subsystem of fixed Hilbert space dimension. The discrepancy can be attributed to the fact that the black hole Hilbert space dimension is not fixed by the state preparation: even in a microcanonical ensemble with a top-hat smearing function, the GPI yields an additive fluctuation in the number of black hole states. This result, and the fact that the Page curve computed by the GPI is smooth, all point towards an ensemble interpretation of the GPI.

Published by the American Physical Society
2024
Griffiths phase in a facilitated Rydberg gas at low temperatures
Authors: Brady Daniel , Bender Jana , Mischke Patrick , Ohler Simon , Niederprüm Thomas , Ott Herwig , Fleischhauer Michael
Published: January 2024

The spread of excitations by Rydberg facilitation bears many similarities to epidemics. Such systems can be modeled with Monte Carlo simulations of classical rate equations to great accuracy as a result of high dephasing. Motivated by experiments, we theoretically analyze the dynamics of a Rydberg many-body system in the facilitation regime in the limits of high and low temperatures. In the high-temperature limit, a homogeneous mean-field behavior is recovered, while characteristic effects of heterogeneity can be seen in a frozen gas. At high temperatures, the system displays an absorbing-state phase transition and, in the presence of an additional loss channel, self-organized criticality. In a frozen or low-temperature gas, excitations are constrained to a network resembling an Erdős-Rényi graph. We show that the absorbing-state phase transition is replaced with an extended Griffiths phase, which we accurately describe by a susceptible-infected-susceptible model on the Erdős-Rényi network taking into account Rydberg blockade.

Published by the American Physical Society
2024
Bianisotropic exceptional points in an isolated dielectric nanoparticle
Authors: Canós Valero Adrià , Bobrovs Vjaceslavs , Weiss Thomas , Gao Lei , Shalin Alexander S. , Kivshar Yuri
Published: January 2024

Exceptional points are spectral singularities of open systems, where several eigenvalues and eigenvectors coalesce. In photonics, they are associated to remarkable phenomena, such as unidirectional scattering, enhanced sensing or chiral mode conversion. In this work, we study scattering of electromagnetic waves by a single dielectric nanoparticle and observe the appearance of exceptional points in its eigenvalue spectrum. Their existence is linked to breaking the mirror symmetry of the particle. Remarkably, they mark the onset from weak to strong coupling of the resonant modes. We discuss in detail the example of the electric and magnetic dipole modes supported by a silicon nanoparticle. We argue that any two modes of a resonant dielectric nanoparticle can merge to create an exceptional point, provided their resonant frequencies cross as functions of a parameter such as, e.g., aspect ratio, and their field distributions have opposite signs after a reflection in the transverse plane of the structure. The strongly coupled modes radiate as a mixture of electric and magnetic dipoles resulting in an intense bianisotropic response, being easily controlled by symmetry-breaking perturbations. We also study the effect of a dielectric substrate and demonstrate that the latter provides an additional mechanism to tune the position of exceptional points in the parameter space. Finally, we discuss applications of bianisotropic EPs, including their use for refractive-index sensing.

Published by the American Physical Society
2024
Structural features of jammed-granulate metamaterials
Authors: Götz Holger , Pöschel Thorsten , D'Angelo Olfa
Published: January 2024

Granular media near jamming exhibit fascinating properties, which can be harnessed to create jammed-granulate metamaterials: materials whose characteristics arise not only from the shape and material properties of the particles at the microscale but also from the geometric features of the packing. For the case of a bending beam made from jammed-granulate metamaterial, we study the impact of the particles' properties on the metamaterial's macroscopic mechanical characteristics. We find that the metamaterial's stiffness emerges from its volume fraction, in turn originating from its creation protocol; its ultimate strength corresponds to yielding of the force network. In contrast to many traditional materials, we find that macroscopic deformation occurs mostly through affine motion within the packing, aided by stress relief through local plastic events, surprisingly homogeneously spread and persistent throughout bending.

Published by the American Physical Society
2024
Algorithmic Cluster Expansions for Quantum Problems
Authors: Mann Ryan L. , Minko Romy M.
Published: January 2024

We establish a general framework for developing approximation algorithms for a class of counting problems. Our framework is based on the cluster expansion of the abstract polymer model formalism of Kotecký and Preiss. We apply our framework to obtain efficient algorithms for (1) approximating probability amplitudes of a class of quantum circuits close to the identity, (2) approximating expectation values of a class of quantum circuits with operators close to the identity, (3) approximating partition functions of a class of quantum spin systems at high temperature, and (4) approximating thermal expectation values of a class of quantum spin systems at high temperature with positive-semidefinite operators. Further, we obtain hardness of approximation results for approximating probability amplitudes of quantum circuits and partition functions of quantum spin systems. This establishes a computational complexity transition for these problems and shows that our algorithmic conditions are optimal under complexity-theoretic assumptions. Finally, we show that our algorithmic condition is almost optimal for expectation values and optimal for thermal expectation values in the sense of zero freeness.

Published by the American Physical Society
2024
The impact of legal systems on CEO compensation and bank stability: a cross-country study
Authors: Jardak Maha Khemakhem , Sallemi Marwa , Ben Hamad Salah
Published: January 2024

Purpose

Remuneration policies may differ from country to country, and their effect on bank stability could be due to the legal framework. Therefore, this study aims to investigate how the legal system impacts the relationship between CEO compensation and bank stability across countries.

Design/methodology/approach

To test the study hypotheses, the authors use panel data of 74 banks operating in ten OECD countries during the period 2009–2016 and apply the generalized moments method regression model to better remediate the endogeneity problem.

Findings

The findings confirm that a country’s banking regulations significantly affect its bank stability. Common law countries have less bank stability than civil law countries. This result can be interpreted by the fact that, in common-law countries, banks’ CEO are strongly protected by the law, so they allocate a large part of bank assets to risky loans to improve their variable remuneration.

Practical implications

The research can help policymakers understand bank stability in one country. Any legal reform would require prior knowledge of how risk-taking may arise in executive compensation.

Originality/value

The contribution is to explain the controversial effect of executive compensation on bank stability in the framework of legal theory. The authors argue that regulators should monitor compensation structures and that the country’s legal origin of law shapes the CEO compensation structure and is a determinant of bank stability. To the best of the authors’ knowledge, there are no studies exploring this field. So, this study tries to shed more light on the dark side of CEOs’ behavior when undertaking risky projects to maximize their remuneration.
Perlmutter visited. Japanese international business strategic orientation transformation in India: progress made and forces against
Authors: Ashta Ashok
Published: January 2024

Purpose

Although Asia's rise in the global economy is increasingly recognized, international business (IB) interactions between Japan and India remain under-commented. These interactions are especially salient due to the United Nations Sustainable Development Goal 17 (UN SDG 17), which focuses on partnerships. This study updates and analyzes the strategic orientation of Japanese multinational enterprises (MNEs) in India.

Design/methodology/approach

Following a subjectivist approach, this study employs a constructivist epistemology. Utilizing mixed methods, it obtains primary data from interviews and informal conversations with senior personnel from Japan and India and secondary data from archives. These data then undergo manual organic thematic analysis.

Findings

The study reveals instances of Japanese MNEs diverging from traditional ethnocentric orientations, such as senior management's growing commitment to India. The findings also indicate that the transformation to a polycentric orientation remains incomplete.

Practical implications

The study uncovers themes impeding a polycentric transformation, offering insights for strengthening international partnerships and emphasizing the necessity of prioritizing local demands and cultural expectations.

Social implications

Clues to strengthening IB contribute to attain UN SDG 17, especially given the advanced-emerging characteristics of the Japan–India dyad.

Originality/value

This study’s research makes a novel contribution to the literature on international strategic orientations by providing insights into a rare dyad – namely, Japanese MNE expansion in India. It is also a valuable and timely addition consistent with current beyond-China business diversification trends.
Bi-objective optimization of a multi-mode, multi-site resource-constrained project scheduling problem
Authors: Hessami Shiba , Davari-Ardakani Hamed , Javid Youness , Ameli Mariam
Published: January 2024

Purpose

This study aims to deal with the multi-mode resource-constrained project scheduling problem (MRCPSP) with the ability to transport resources among multiple sites, aiming to minimize the total completion time and the total cost of the project simultaneously.

Design/methodology/approach

To deal with the problem under consideration, a bi-objective optimization model is developed. All activities are interconnected by finish-start precedence relations, and pre-emption is not allowed. Then, the ɛ-constraint optimization method is used to solve 24 different-sized instances, ranging from 5 to 120 activities, and report the makespan, total cost and CPU time. A set of Pareto-optimal solutions are determined for some instances, and sensitivity analyses are performed to find the impact of changing parameters on objective values.

Findings

Results highlight the importance of resource transportability assumption on project completion time and cost, providing useful insights for decision makers and practitioners.

Originality/value

A novel bi-objective optimization model is proposed to deal with the multi-site MRCPSP, considering both the cost and time of resource transportation between multiple sites. To the best of the authors’ knowledge, none of the studies in the project scheduling area has yet addressed this problem.
Innovations, strategic organizational actions, and sailing-ship effect: illustrated with an IT product
Authors: Kompella Lakshminarayana
Published: January 2024

Purpose

In socio-technical transition theory, resistance by existing technology and regime resistance plays a key role. The resistance is in the form of intentional improvements; eventually, the regime destabilizes and adopts the new technology, referred to as the sailing-ship effect. Researchers used a structural view and examined it as a strategic action and its relationship with new technology (competitive/symbiotic) in non-fast-changing sailing systems. This study uses a microlevel view and examines it in a fast-changing where products/services are developed by integrating existing technology with new product innovations; their success depends on addressing technical/market uncertainty. This study examines the sailing-ship effect in a fast-changing system and contributes to the socio-technical transition theory.

Design/methodology/approach

The authors need to examine the phenomena of the sailing-ship effect in its setting, and a case-study method is appropriate. The selected case provided diverse analytic and heuristic perspectives to examine the phenomena; therefore, it was a single case study.

Findings

In an IT scenario, the strategic actions decide and realize agility and competitive advantage by formulating appropriate goals with required budgets and coevolutionary changes to resources at product, process and organizational levels, addressing technical/market uncertainty. Moreover, the agility displayed by strategic actions determines the relationship with new technology, which is interspersed. Finally, it provided insights into struggle, navigation and negotiations, forming strategic actions to display the sailing-ship effect.

Research limitations/implications

The study selected a Banking Financial Services and Insurance product of an IT Services company. As start-ups exhibit inherent (emergent) agility, the authors can examine agility as a combination of emergent and strategic actions by selecting a start-up.

Practical implications

The study highlights the strategic actions specific to an IT services company. It developed its product and services by steering clear from IT innovations such as native cloud and continuous deployment. It improved its products/services with necessary organizational changes and achieved the desired agility and competitive advantage. Therefore, organizations devise appropriate strategic actions to combat the sailing-ship effect apart from setting goals and selecting IT innovations.

Originality/value

The study expands the socio-technical transition theory by selecting a fast-changing system. It provided insights into the relationship between existing and new technology and the strategic actions necessary to manage technical and market uncertainty and achieve the desired competitive advantage, or the sailing-ship effect.
How to engage and attract virtual influencers’ followers: a new non-human approach in the age of influencer marketing
Authors: Melnychuk Hanna-Anastasiia , Arasli Huseyin , Nevzat Raziye
Published: January 2024

Purpose

The purpose of this study is to identify the process of virtual influencer stickiness in the age of influencer marketing, which has received little attention in the literature. This is essential because the research creates a theoretical model of follower loyalty/stickiness to virtual influencer techniques from the standpoint of influencer marketing, which has a substantial effect on the evolution of the global marketing world.

Design/methodology/approach

In 2022, 302 people who currently follow an Instafamous virtual influencer took part in an Instagram self-administered online survey.

Findings

The findings show that both expertise and trustworthiness have a positive and significant influence on parasocial interaction, which in turn has a significant influence on virtual engagement and stickiness.

Originality/value

This research will specifically assist international readers in understanding how to harness and increase the efficiency and efficacy of interactive marketing strategies and methods to engage and retain followers of Instafamous virtual influencer. Moreover, the findings will be beneficial to opinion leaders, brand managers, company investors, entrepreneurs and service designers.

Highlights

The study pioneers a holistic virtual follower stickiness mechanism that comprises the role of source credibility, parasocial interaction, informational influence and virtual follower’s engagement and their interrelationship to each other.

This study is based on parasocial interaction theory and source credibility theory to understand the relationship between virtual followers and influencers stickiness process at social media platforms.

In addition, the study examined the subsequent effects of sources of credibility components on parasocial interaction; as well as, on virtual follower engagement and stickiness.

This study also categorized and examined the moderating effects exerted by the genres of informative influence of virtual influencer.
Evaluation of the inheritance and dominance of behavioral resistance to imidacloprid in the house fly (Musca domestica L.) (Diptera: Muscidae)
Authors: Hubbard Caleb B. , Murillo Amy C.
Published: January 2024

The house fly, Musca domestica, is a cosmopolitan species known for its pestiferous nature and potential to mechanically vector numerous human and animal pathogens. Control of adult house flies often relies on insecticides formulated into food baits. However, due to the overuse of these baits, insecticide resistance has developed to all insecticide classes currently registered for use in the United States. Field populations of house flies have developed resistance to imidacloprid, the most widely used neonicotinoid insecticide for fly control, through both physiological and behavioral resistance mechanisms. In the current study, we conducted a comprehensive analysis of the inheritance and dominance of behavioral resistance to imidacloprid in a lab‐selected behaviorally resistant house fly strain. Additionally, we conducted feeding preference assays to assess the feeding responses of genetic cross progeny to imidacloprid. Our results confirmed that behavioral resistance to imidacloprid is inherited as a polygenic trait, though it is inherited differently between male and female flies. We also demonstrated that feeding preference assays can be instrumental in future genetic inheritance studies as they provide direct insight into the behavior of different strains under controlled conditions that reveal, interactions between the organism and the insecticide. The findings of this study carry significant implications for pest management and underscore the need for integrated pest control approaches that consider genetic and ecological factors contributing to resistance.
Community Reinforcement and Family Training versus counselling for parents of treatment‐refusing young adults with hazardous substance use: A randomized controlled trial
Authors: Siljeholm Ola , Edvardsson Kerstin , Bergström Malin , Hammarberg Anders
Published: January 2024

Background and aims

Despite the high prevalence and negative effects of hazardous substance use, few young adults enter treatment. Community Reinforcement and Family Training (CRAFT), a support programme for concerned significant others of people with substance use disorders, has proved efficacious in promoting treatment entry. The aim of the current trial was to compare the efficacy of CRAFT with an active control for parents of young adults (aged 18–24 years) with hazardous substance use.

Design

This was a randomized controlled superiority trial comparing CRAFT (n = 58) with an active control group receiving manualized counselling (n = 55), with outcome assessments at 6, 12 and 24 weeks (primary end‐point). A sequential design with a stopping rule was added post recruitment commencement.

Setting

The study took place in two outpatient clinics for young adults in Stockholm, Sweden, and subsequently via video‐conference due to COVID‐19.

Participants

Between October 2018 and May 2021, 113 participants (92% female) who were parents of young adults (87% male) were recruited. Recruitment was discontinued when 70% of the planned sample had been recruited, following an interim analysis of the primary outcome showing no difference between conditions.

Intervention and comparator

Participants were randomized (ratio 1 : 1) to eight manual‐based individual CRAFT sessions or five individual manual‐based counselling sessions + one voluntary psychoeducative group session, delivered over maximum 14 weeks.

Measurements

The primary outcome measure was the rate of young adult entry in substance use treatment during the trial period (24 weeks).

Findings

At the 24 weeks follow‐up, 19 (33%) of CRAFT participants and 17 (31%) of counselling participants had reported young adult treatment entry, with no difference between conditions (odds ratio CRAFT versus counselling 0.84, 95% confidence interval = 0.35; 1.99, P = 0.700). Both conditions reported clinically relevant reductions in young adult substance use, but no change in participants’ levels of depression, anxiety or stress.

Conclusions

This trial showed no statistically significant evidence that Community Reinforcement and Family Training (CRAFT), a support programme for concerned significant others of people with substance use disorders, is more efficacious than manual‐based counselling regarding treatment entry for young adults.
Sperm selection by zona adhesion improves assisted reproductive treatment outcomes
Authors: Ganeva Rumiana , Parvanov Dimitar , Vidolova Nina , Handzhiyska Maria , Ruseva Margarita , Vasileva Magdaleva , Nikolova Kristina , Ivanova Ivka , Shaban Miray , Shabarkova Joanna , Hristova Rayna , Miladinova Milena , Stamenov Georgi
Published: January 2024

Background

Zona pellucida is one of the main selective barriers for the spermatozoa before reaching the oocyte. Using native zona in the sperm selection prior to Intracytoplasmic Sperm Injection (ICSI) has been proven effective but inconvenient approach in In Vitro Fertilisation (IVF) laboratory. The application of autologous solubilised zonae pellucidae in the sperm selection prior to ICSI has not been studied yet.

Objectives

To compare the assisted reproductive treatment (ART) outcomes (implantation, pregnancy, live birth, and miscarriage rates) after ICSI performed with spermatozoa selected on their ability to adhere to immobilised solubilised zonae pellucidae and conventionally selected spermatozoa.

Materials and methods

In total, 500 couples fulfilled the inclusion criteria and 368 of them were included in the study. After random allocation, 192 couples had spermatozoa selected by sperm–zona adhesion for ICSI (study group) and 176 patients underwent standard ICSI (control group).

In the study group, patients’ own zonae were acid solubilised and immobilised on petri dishes. The partner's motile spermatozoa were placed in the dishes and the adhered spermatozoa were used for ICSI. For the control group, the conventional sperm selection by morphological criteria was applied prior ICSI. All women underwent frozen ET with euploid embryos. Chi square test was used to compare the data.

Results

The sperm selection by zona adhesion resulted in significantly higher implantation rate (50.4% vs. 37.0%, p = 0.003), clinical pregnancy rate (43.8% vs. 33.3%, p = 0.018) and live birth rate (38.0% vs. 25.9%, p = 0.004) and significantly lower incidence of miscarriage (11.3% vs. 22.2%, p = 0.044) in comparison to the conventional method of the sperm selection.

Discussion and conclusion

The application of solubilised zonae pellucidae in the sperm selection for ICSI benefits ART outcomes in couples with unexplained infertility. Moreover, sperm–zona selection significantly reduces the risk of miscarriages.
New insights into sperm physiology regulation: Enlightenment from G‐protein‐coupled receptors
Authors: Dai Pengyuan , Chen Chen , Yu Jingyan , Ma Chaoye , Zhang Xiaoning
Published: January 2024

Background

G‐protein‐coupled receptors are critical in many physiological and pathological processes in various organs. Serving as the control panel for sensing extracellular stimuli, G‐protein‐coupled receptors recognise various ligands, including light, temperature, odours, pheromones, hormones, neurotransmitters, chemokines, etc. Most recently, G‐protein‐coupled receptors residing in spermatozoa have been found to be indispensable for sperm function.

Objective

Here, we have summarised cutting‐edge findings on the functional mechanisms of G‐protein‐coupled receptors that are known to be associated with sperm functions and the activation of their downstream effectors, providing new insights into the roles of G‐protein‐coupled receptors in sperm physiology.

Results

Emerging studies hint that alterations in G‐protein‐coupled receptors could affect sperm function, implicating their role in fertility, but solid evidence needs to be continuing excavated with various means. Several members of the G‐protein‐coupled receptor superfamily, including olfactory receptors, opsins, orphan G‐protein‐coupled receptors, CXC chemokine receptor 4, CC chemokine receptor 5 and CC chemokine receptor 6 as well as their downstream effector β‐arrestins, etc., were suggested to be essential for sperm motility, capacitation, thermotaxis, chemotaxis, Ca2+ influx through CatSper channel and fertilisation capacity.

Conclusion

The present review provides a comprehensive overview of studies describing G‐protein‐coupled receptors and their potential action in sperm function. We also present a critical discussion of these issues, and a possible framework for future investigations on the diverse ligands, biological functions and cell signalling of G‐protein‐coupled receptors in spermatozoa. Here, the G‐protein‐coupled receptors and their related G proteins that specifically were identified in spermatozoa were summarised, and provided references valuable for further illumination, despite the evidence that is not overwhelming in most cases.
Assessing the efficacy of a resilience training intervention for long‐term improvements in well‐being and resilience
Authors: Kreienkamp Martin , Wheatley Daniel , Ndobo André
Published: January 2024

This article has two aims: (1) to assess the impacts of a novel training intervention for individual well‐being and (2) to measure the trajectory of resilience over the training period dependent on reported significant life events. Using a randomised controlled trial with a diverse German sample with the majority drawn from a student population, we measure the effects of the intervention to provide insight into its impacts and act as a proof of concept for the training. We find that the training intervention boosts resilience and other related well‐being measures with a high effect size in comparison with a control group and compared with existing resilience training studies.
Enhancer‐activated RET confers protection against oxidative stress to KMT2A‐rearranged acute myeloid leukemia
Authors: Frett Brendan , Stephens Kimberly E. , Koss Brian , Melnyk Stepan , Farrar Jason , Saha Debasmita , Roy Choudhury Samrat
Published: January 2024

Ectopic activation of rearranged during transfection (RET) has been reported to facilitate lineage differentiation and cell proliferation in different cytogenetic subtypes of acute myeloid leukemia (AML). Herein, we demonstrate that RET is significantly (p < 0.01) upregulated in AML subtypes containing rearrangements of the lysine methyltransferase 2A gene (KMT2A), commonly referred to as KMT2A‐rearranged (KMT2A‐r) AML. Integrating multi‐epigenomics data, we show that the KMT2A‐MLLT3 fusion induces the development of CCCTC‐binding (CTCF)‐guided de novo extrusion enhancer loop to upregulate RET expression in KMT2A‐r AML. Based on the finding that RET expression is tightly correlated with the selective chromatin remodeler and mediator (MED) proteins, we used a small‐molecule inhibitor having dual inhibition against RET and MED12‐associated cyclin‐dependent kinase 8 (CDK8) in KMT2A‐r AML cells. Dual inhibition of RET and CDK8 restricted cell proliferation by producing multimodal oxidative stress responses in treated cells. Our data suggest that epigenetically enhanced RET protects KMT2A‐r AML cells from oxidative stresses, which could be exploited as a potential therapeutic strategy.
Assessment of plasma dexamethasone levels after 1‐mg dexamethasone suppression test in adults with obesity
Authors: Paopongpaiboon Pimonrat , Santisitthanon Prangareeya , Houngngam Natnicha , Snabboon Thiti , Boonchaya‐anant Patchaya
Published: January 2024

Background

The 1‐mg overnight dexamethasone suppression test is the most frequently used screening test for Cushing's syndrome. It has been proposed that people with obesity may have insufficient plasma dexamethasone levels for the test which may result in false positives. We sought to compare the plasma dexamethasone levels after 1‐mg dexamethasone suppression test in healthy obese participants and in optimal‐weight participants.

Methods

A total of 30 optimal‐weight participants (BMI ≤ 25 kg/m2) and 62 obese participants (BMI > 25 kg/m2) were enroled in the study. Obese participants were further divided into class 1 (25–29.9 kg/m2) and class 2 (>30 kg/m2). After a standard overnight 1‐mg dexamethasone suppression test, blood samples were obtained for serum cortisol and plasma dexamethasone levels. Plasma dexamethasone levels were quantified using liquid chromatography ‐ mass spectrometry (LC‐MS/MS).

Results

No significant difference in plasma dexamethasone levels were found between obese and optimal‐weight participants (3.31 ± 1.35 vs. 2.82 ± 1.11 nmol/L, mean ± SD; p = .09 respectively). There were also no correlations found between sex, BMI, body surface area and plasma dexamethasone levels. There was also no significant difference in the proportion of participants who achieved a plasma dexamethasone level >3.3 nmol/L in comparison between obesity class 1, obesity class 2, and optimal‐weight groups.

Conclusion

Our results suggest that obesity does not affect plasma dexamethasone levels. However, dexamethasone measurement may still be helpful in patients who are being investigated for Cushing's syndrome and suspected to have a false‐positive DST.
Functional characterization of inactivating ABCC8 variants causing congenital hyperinsulinism
Authors: Wang Ping , Liao Hong , Wang Quyou , Xie Hanbing , Xu Bocheng , Xiang Qinqin , Wang He , Yang Mei , Liu Shanling
Published: January 2024

Congenital hyperinsulinism (CHI; OMIM: 256450) is characterized by persistent insulin secretion despite severe hypoglycemia. The most common causes are variants in the ATP‐binding cassette subfamily C member 8(ABCC8) and potassium inwardly‐rectifying channel subfamily J member 11(KCNJ11) genes. These encode ATP‐sensitive potassium (KATP) channel subunit sulfonylurea receptor 1 (SUR1) and inwardly rectifying potassium channel (Kir6.2) proteins. A 7‐day‐old male infant presented with frequent hypoglycemic episodes and was clinically diagnosed with CHI, underwent trio‐whole‐exome sequencing, revealing compound heterozygous ABCC8 variants (c.307C>T, p.His103Tyr; and c.3313_3315del, p.Ile1105del) were identified. In human embryonic kidney 293 (HEK293) and rat insulinoma cells (INS‐1) transfected with wild‐type and variant plasmids, KATP channels formed by p.His103Tyr were delivered to the plasma membrane, whereas p.Ile1105del or double variants (p.His103Tyr coupled with p.Ile1105del) failed to be transported to the plasma membrane. Compared to wild‐type channels, the channels formed by the variants (p.His103Tyr; p.Ile1105del) had elevated basal [Ca2+]i, but did not respond to stimulation by glucose. Our results provide evidence that the two ABCC8 variants may be related to CHI owing to defective trafficking and dysfunction of KATP channels.
Long‐term results of a short‐term home‐based pre‐ and postoperative exercise intervention on physical recovery after colorectal cancer surgery (PHYSSURG‐C): a randomized clinical trial
Authors: Onerup Aron , Li Ying , Afshari Kevin , Angenete Eva , de la Croix Hanna , Ehrencrona Carolina , Wedin Anette , Haglind Eva
Published: January 2024

Aim

The aim of this work was to assess the effect of a short‐term, home‐based exercise intervention before and after colorectal cancer surgery on 12‐month physical recovery within a previously reported randomized control trial (RCT).

Method

PHYSSURG‐C is an RCT in six participating hospitals in Sweden. Patients aged ≥20 years planned for elective colorectal cancer surgery were eligible. The intervention consisted of unsupervised moderate‐intensity physical activity 2 weeks preoperatively and 4 weeks postoperatively. Usual care was control. The primary outcome measure in PHYSSURG‐C was self‐assessed physical recovery 4 weeks postoperatively. The predefined long‐term follow‐up outcomes included: self‐assessed physical recovery 12 months postoperatively and reoperations and readmissions 91–365 days postoperatively. The statistical models were adjusted with tumour site (colon or rectum), neoadjuvant therapy (none, radiotherapy or chemo/radiotherapy) and type of surgery (open or laparoscopic).

Results

A total of 616 participants were available for the 12‐month follow‐up. Groups were balanced at baseline regarding demographic and treatment variables. There was no effect from the intervention on self‐reported physical recovery [adjusted odds ratio (OR) 0.91, p = 0.60], the risk of reoperation (OR 0.97, p = 0.91) or readmission (OR 0.88, p = 0.58).

Conclusion

The pre‐ and postoperative unsupervised moderate‐intensity exercise intervention had no effect on long‐term physical recovery after elective colorectal cancer surgery. There is still not enough evidence to support clinical guidelines on preoperative exercise to improve outcome after colorectal cancer surgery.
Board co‐option and corporate environmental orientation: New insights from the waste management perspective
Authors: Gull Ammar Ali , Luong Hoa , Nadeem Muhammad
Published: January 2024

Research Question/Issue

We investigate the impact of board co‐option on corporate environmental orientation from the perspective of waste management. As waste presents damaging effects on the natural environment, climate change, and human health, businesses assume an ethical responsibility to conduct their operations in a sustainable and responsible manner.

Research Findings/Insights

Employing firm‐level waste production data, we document a significant negative relationship between board co‐option and waste generation, suggesting that co‐opted directors help firms reduce their waste—a finding that also carries economic significance. The cross‐sectional analyses reveal that the relationship only holds when a CEO does not chair the board and has a shorter tenure. Furthermore, we find that the board co‐option–waste management relationship is stronger in environmentally sensitive industries and is mainly driven by the manufacturing firms. We perform a battery of analyses to rule out endogeneity concerns and check for the robustness of our results. The channel test reveals that CEOs of firms with higher waste management face lower performance‐induced turnover, particularly when working with co‐opted boards. Finally, we also find that co‐option‐induced waste management initiatives ultimately increase firms' economic value.

Theoretical/Academic Implications

We document that co‐opted boards may enhance firms' waste management practices by reducing performance‐induced CEO turnover. Thus, we make important contributions to the corporate governance and environmentalism strands of the literature by highlighting the bright side of board co‐option for waste reduction initiatives.

Practitioner/Policy Implications

Our study provides vital policy implications for regulators and top management teams against the background of public outcry and social pressure to mitigate the damage to the environment and calls for ethical business practices.