bluuebunny/crossref_metadata_2025 huggingface dataset:
IL-4 downregulates BCL6 to promote memory B cell selection in germinal centers
Authors: Shehata Laila , Thouvenel Christopher D. , Hondowicz Brian D. , Pew Lucia A. , Rawlings David J. , Choi Jinyong , Pepper Marion
Published: January 2023

Germinal center (GC)-derived memory B cells (MBCs) are critical for humoral immunity as they differentiate into protective antibody-secreting cells during re-infection. GC formation and cellular interactions within the GC have been studied in detail, yet the exact signals that allow for the selection and exit of MBCs are not understood. Here, we show that IL-4 signaling in GC B cells directly downregulates BCL6 via negative autoregulation to release cells from the GC program and promote MBC formation. This selection event requires additional survival cues and can therefore result in either GC exit or death. We demonstrate that both increasing IL-4 bioavailability or limiting IL-4 signaling disrupt MBC selection stringency. In this way, IL-4 control of BCL6 expression serves as a tunable switch within the GC to tightly regulate MBC selection and affinity maturation.
A general force field by machine learning on experimental crystal structures. Calculations of intermolecular Gibbs energy withFlexCryst
Authors: Hofmann Detlef Walter Maria , Kuleshova Liudmila Nikolaevna
Published: January 2023

Machine learning was employed on the experimental crystal structures of the Cambridge Structural Database (CSD) to derive an intermolecular force field for all available types of atoms (general force field). The obtained pairwise interatomic potentials of the general force field allow for the fast and accurate calculation of intermolecular Gibbs energy. The approach is based on three postulates regarding Gibbs energy: the lattice energy must be below zero, the crystal structure must be a local minimum, and, if available, the experimental and the calculated lattice energy must coincide. The parametrized general force field was then validated regarding these three conditions. First, the experimental lattice energy was compared with the calculated energies. The observed errors were found to be in the order of experimental errors. Second, Gibbs lattice energy was calculated for all structures available in the CSD. Their energy values were found to be below zero in 99.86% of the cases. Finally, 500 random structures were minimized, and the change in density and energy was examined. The mean error in the case of density was below 4.06%, and for energy it was below 5.7%. The obtained general force field calculated Gibbs lattice energies of 259 041 known crystal structures within a few hours. Since Gibbs energy defines the reaction energy, the calculated energy can be used to predict chemical–physical properties of crystals, for instance, the formation of co-crystals, polymorph stability and solubility.
Scientometric, fuzzy NGT and DEMATEL analysis for determining sustainable business practices for entrepreneurial firms
Authors: Patra Bhairab Chandra , Lenka Usha
Published: January 2023

Purpose

The purpose of this article is to (1) map the most important topics in the domain of sustainable business practices for entrepreneurial firms in emerging countries, (2) identify important terms in the various dimensions of sustainability in business and (3) identify the important practices and prioritize the practices.

Design/methodology/approach

This study has adopted a unique methodology that combines state-of-art scientometric analysis with the fuzzy nominal group technique (NGT) and fuzzy decision-making trial and evaluation laboratory (DEMATEL). Results obtained from the co-occurrence analysis in scientometrics were further mapped through NGT to obtain the list of the most important topics in the domain. The factors affecting sustainable business practices obtained through topic mapping were analyzed through fuzzy DEMATEL to obtain the cause-and-effect relation of variables.

Findings

The scale of firms, leadership, uncertainty, gender, country/location, education and tourism were found to be the factors affecting the sustainable business practices of entrepreneurial firms. The sustainable business practices for entrepreneurial firms were (1) innovation, (2) resilience, (3) policy, (4) business ethics and virtue ethics, (5) business model, (6) upcycling and value creation, (7) collaboration and (8) triple bottom line.

Practical implications

Policymakers in entrepreneurial firms, as well as other organizations, can implement the identified sustainable business practices to obtain optimum results and smooth functioning of the companies. The research framework obtained can be tested using exploratory methods.

Originality/value

Very few researchers have used the technique of scientometric analysis to identify the sustainable business practices of entrepreneurial firms, and to the best of the knowledge of the authors, no earlier researcher has attempted to use the technique of topic mapping, fuzzy NGT and fuzzy DEMATEL in combination.
The dynamics of oil prices, uncertainty measures and unemployment: a time and frequency approach
Authors: Adeosun Opeoluwa Adeniyi , Olayeni Richard O. , Tabash Mosab I. , Anagreh Suhaib
Published: January 2023

Purpose

This study investigates the nexus between the returns on oil prices (OP) and unemployment (UR) while taking into account the influences of two of the most representative measures of uncertainty, the Baker et al. (2016) and Caldara and Iacovello (2021) indexes of economic policy uncertainty (EP) and geopolitical risks (GP), in the relationship.

Design/methodology/approach

The authors use data on the US, Canada, France, Italy, Germany and Japan from January 2000 to February 2022 and the UK from January 2000 to December 2021. The authors then apply the continuous wavelet transform (CWT), wavelet coherence (WC), partial wavelet coherence (PWC) and multiple wavelet coherence (MWC) to examine the returns within a time and frequency framework.

Findings

The CWT tracks the movement and evolution of individual return series with evidence of high variances and heterogenous tendencies across frequencies that also align with critical events such as the GFC and COVID-19 pandemic. The WC reveals the presence of a bidirectional relationship between OP and UR across economies, showing that the two variables affect each other. The authors’ findings establish the predictive influence of oil price on unemployment in line with theory and also show that the variation in UR can impact the economy and alter the dynamics of OP. The authors employ the PWC and MWC to capture the impact of uncertainty indexes in the co-movement of oil price and unemployment in line with the theory of “investment under uncertainty”. Taking into account the common effects of EP and GP, PWC finds that uncertainty measures significantly drive the co-movement of oil prices and unemployment. This result is robust when the authors control for the influence of economic activity (proxied by the GDP) in the co-movement. Furthermore, the MWC reveals the combined intensity, strength and significance of both oil prices and the uncertainty measures in predicting unemployment across countries.

Originality/value

This study investigates the relationship between oil prices, uncertainty measures and unemployment under a time and frequency approach.

Highlights

Wavelet approaches are used to examine the relationship between oil prices and unemployment in the G7.

We account for uncertainty measures in the dynamics of oil prices and unemployment.

We observe a bidirectional relationship between oil prices and unemployment.

Uncertainty measures significantly drive oil prices and unemployment co-movement.

Both oil prices and uncertainty measures significantly drive unemployment.
Worker resistance strategies and union action in platform work: the case of Uber in Spain
Authors: Riesgo Gómez Víctor
Published: January 2023

Purpose

The author analyses the strategies developed by workers and unions to obtain representation and the successes and limitations of the strategies, in a context of platform work such as Spanish dominated by labour relations of employee workers.

Design/methodology/approach

The empirical material is the result of a series of in-depth interviews conducted between August 2020 and September 2021 with 41 workers, 15 of them union delegates, in addition to 4 union members and a labour lawyer. From these interviews, the author obtains a detailed account of the working conditions and the different phases that unionism has gone through in its objective of obtaining representation in a completely new sector.

Findings

The author found that employment in the relationship does not solve all the problems of platform work, especially those related to algorithmic control, but employment in the relationship provides advantages such as the right to representation. Workers play an important role in union strategies.

Originality/value

This study is the first in Spain, where platform work in passenger transport includes the employment relationship as a legal contracting mechanism.
Antecedents and job outcomes from a self-efficacy perspective while working from home among professionals during the COVID-19 pandemic
Authors: Lathabhavan Remya , Griffiths Mark D.
Published: January 2023

Purpose

Working from home (WFH) was one of the major changes that occurred in many organizations during the COVID-19 pandemic. This also led to online training being conducted during this WFH period. The present study investigated the role of technology, manager support and peer support on self-efficacy and job outcomes (i.e. training transfer, work engagement and job satisfaction) of employees while WFH.

Design/methodology/approach

The study framework incorporated Bandura's self-efficacy theory. Data were collected from 852 employees in India, and structural equation modeling was used to analyze the data.

Findings

The study found positive relationships between ease of technology use, manager support and peer support on self-efficacy and a negative relationship between self-efficacy and technostress. The study also found significant positive relationships between self-efficacy and training transfer, work engagement and job satisfaction. Moreover, the study also identified the moderating effects of WFH and technical issues in the relationships of self-efficacy with training transfer, work engagement and job satisfaction.

Originality/value

The study is novel in that it extended self-efficacy theory regarding the WFH context with influencers such as technology, managers and peers as organizational factors. It also demonstrated the effectiveness of remote working and online training considering the potential antecedents while WFH. Moreover, the study highlighted the simultaneous role of technology and people (managers and peers) in enhancing job outcomes by increasing self-efficacy among employees.
Alternative certification system for supply chain sustainability: how stakeholder alignment affects institutionalization
Authors: Liu Chia-Yi
Published: January 2023

Purpose

This study expands the isomorphic logic on the participatory guarantee system (PGS) alternative certification method, which aims to level the supply chain sustainability field to determine how the alignment of disadvantaged agrifood stakeholders (e.g. small/applicant farmers, local organizations, consumers and volunteer auditors) might neutralize the negative effects of stakeholder heterogeneity (SH) on PGS recognition.

Design/methodology/approach

The sample comprised 113 multilateral matching questionnaires collected from disadvantaged agrifood stakeholders participating in the PGS activities of the Green Conservation Label managed by Taiwan's Tse-Xin Organic Agriculture Foundation (TOAF). This study adopted hierarchical regression to test the hypotheses.

Findings

Stakeholder alignment, external community (EC) constructs, similar backgrounds (SBs) and value congruence (VC) diminish the negative effects of SH on PGS recognition.

Social implications

PGS is an agrifood supply chain social movement designed to allow underprivileged actors to enact solutions collectively to address social inequities and ecological problems through fair procedures, collective assignments and collaborative intentionality. PGS members who leverage VC, SB and EC will have a greater chance of successfully overcoming their institutional disadvantages.

Originality/value

Based on the PGS activities initiated by disadvantaged agrifood stakeholders, this study transformed isomorphic logics, including coercive, mimetic and normative isomorphisms, into a mechanism with which individuals can build a governance structure that helps disadvantaged agrifood stakeholders develop alternative institutions by pooling their resources.
Compliance issues in arbitration proceedings – bribery, money laundering and other abuses
Authors: Teichmann Fabian , Boticiu Sonia Ruxandra , Sergi Bruno S.
Published: January 2023

Purpose

The purpose of this study is to provide a firsthand perspective on the challenges and risks that can arise in arbitration proceedings.

Design/methodology/approach

To investigate the concrete methods money launderers use, a qualitative study was conducted with 10 alleged money launderers and 18 prevention experts. The results were then tested quantitatively, and it was concluded that among money launderers, the highly regulated financial sector is less popular than other sectors.

Findings

Money launderers relocate to unregulated sectors or offshore banks to avoid being questioned by compliance officers. Therefore, it is necessary for arbitrators involved in commercial or investor–state arbitration to have the expertise to readily identify the issues raised by these criminal law concepts and provide answers.

Originality/value

This paper examines the intersection between the areas of international commercial arbitration and money laundering, bribery, as well as embezzlement. At the same time, it draws attention to the need to analyze compliance issues in arbitration proceedings.
The family business brand: cross-fertilization between fields
Authors: Aparicio Gloria , Maseda Amaia , Iturralde Txomin , Zorrilla Pilar
Published: January 2023

Purpose

Following a bibliometric approach, this study examines research on brand and branding in family businesses (FBs) to identify influential sources and main areas of knowledge, proposes an integrative framework that provides a holistic perspective of this field with an interdisciplinary cross-fertilization view and explores new avenues for future research and practice.

Design/methodology/approach

Based on 449 bibliographic references retrieved from the Web of Science database through a systematic process, the authors employed bibliographic coupling analysis to visualize the relationships among key works in the field and subsequently performed a literature review to deepen the analysis.

Findings

The bibliographic coupling analysis structured the existing research into six thematic clusters. Four of them follow an internal perspective and focus on FB identity and its influence on the construction of corporate brand identity, whereas the other two follow an external perspective that explores how FB brands are communicated and perceived by stakeholders and the influence of corporate brands and branding on FB image and reputation. Drawing from an in-depth review of the literature, this study offers a novel integrative framework, together with a set of proposals with managerial and theoretical implications.

Practical implications

The proposed framework aims to clarify the relationship between internal identity and management to build and communicate a FB brand. The study also shows the symbiosis that exists among family values, corporate reputation, brand equity and awareness in FBs. The existing interconnection between the family and business generates unique associations that are difficult to imitate.

Originality/value

This study is the first documented attempt at a bibliometric analysis of brands and branding in FBs, which serves to clarify the linkages between different research streams and connecting marketing, organization and FB literature to guide future research. Moreover, the integrative framework provides researchers and practitioners with a better understanding of its scope, highlighting the importance of corporate brand strategies beyond the boundaries of marketing departments.
Sandy seeds: Armour or invisibility cloak? Mucilage‐bound sand physically protects seeds from rodents and invertebrates
Authors: LoPresti Eric F. , Pan Vincent S. , Girvin Cecilia , Barber Gabhriel , Jaeger Sierra , Orrock John L.
Published: January 2023

Seeds represent a stage of a plant's life cycle that is extremely vulnerable to predation, which unlike most vegetative herbivory, is fatal to the individual. As such, understanding the distribution and abundance of plants may rely on understanding seed defences: characteristics that make seeds more difficult for granivores to locate, less beneficial for granivores to consume or both.

Seeds that produce mucilage are widespread, found across many families and species. Although short‐term (single day) studies indicate that mucilage may be a fundamental seed defence found throughout the plant kingdom, it is not clear to what extent mucilage provides long‐term benefits to seeds by reducing granivory. Moreover, it is not clear whether this long‐term defence occurs because mucilage reduces seed apparency as substrate‐coated seeds are more difficult to detect, whether substrate‐coated seeds are less valuable or both.

In the first field experiment, we factorially manipulated sand coatings, background sand colour and granivore community using feeding depots to test the mechanistic basis of mucilage‐bound sand as a seed defence against diverse granivores. We found that the sand coating significantly extended chances of seeds remaining over the 101‐day trial, during which rodents were the primary granivores, and our coloration manipulation suggests that the effect was almost entirely physical. We found that whether a seed's sand coating matched its background did not greatly affect chance of removal, leaving the crypsis mechanism unsupported.

We conducted a follow‐up field experiment to test the background‐matching hypothesis in more detail, using 20 sand colours and two colours of flax seeds. We again found no support for crypsis, corroborating the finding that mucilage‐bound sand provides a primarily physical defensive benefit.

Synthesis. The totality of the results from this and previous studies across granivore taxa and plant species suggests that seed mucilage is a widespread and highly effective physical defence employed by many plants against diverse granivores in many environments
Effects of hydrological change in fire‐prone wetland vegetation: An empirical simulation
Authors: Mason Tanya J. , Popovic Gordana C. , McGillycuddy Maeve , Keith David A.
Published: January 2023

Upland swamps are peat‐accumulating, groundwater‐dependent and fire‐prone wetland ecosystems. Drying caused by anthropogenic processes such as underground mining, ditching and climate change may disrupt surface and groundwater flows and result in bottom‐up controls on wetland expression. Fire is an endogenous, recurring disturbance that drives a top‐down consumptive force in many upland swamp systems. When compounded with drying, fire may facilitate permanent community transitions. A dearth of ecological data and temporal lags have hampered our ability to predict risks associated with multiple disturbances in wetland plant communities.

We collected intact wetland mesocosms from valley floors and lower slopes of four undisturbed swamp sites. We transferred the mesocosms to a glasshouse and established three different soil moisture availability levels to simulate wetland drainage. After 20 months of the hydrological treatment, we simulated a fire event by sequentially applying biomass removal (clipping), heat and smoke to half of the mesocosms. We monitored species biomass, richness and composition over a 3.5‐year time frame.

We found evidence of a temporal lag in biomass response to low water availability and synergistic hydrological and fire effects on species richness. In unburnt conditions, richness declined with low water availability but was maintained under high and medium water availability. After simulated fire under medium water availability, however, richness also declined and converged with depauperate low‐water mesocosm richness. Representation by many obligate swamp species declined in low compared with high water availability mesocosms over time, an effect that was amplified by the fire treatment.

Synthesis. Our evidence of lagged effects of hydrological change on wetland vegetation and compounding effects of fire should be considered in impact assessments, monitoring programs and ecosystem management to avoid irreversible wetland change in drying environments.
The differences between actions and desires: The role of religious congregations in national crises and disasters
Authors: Lundgren Linnea , Fransson Sara
Published: January 2023

During the last few decades in the handling of ongoing crises and preparing for future crises, governments and other public authorities increasingly emphasize the important role religious organizations can play in crises and disaster management. Considering this development, it is appropriate to ask whether the expectations by policymakers are mirrored by the religious organizations themselves? This article aims to answers this question by studying both the organizations' desired role in time of national crises and disasters and the actual role taken by local congregations in Sweden during the Covid‐19 pandemic. It also aims to study whether this differs in relation to organizational differences and religious affiliation. The study clearly shows that 8 out of 10 congregations believe they have an important role to play in the event of a disaster or crisis. However, despite the high level of willingness, the role congregations take may not always mirror the governments expectations. In terms of differences between congregations, although cross‐religious differences are noted, the size of the organization is the critical factor. The article concludes by discussing the disparity between policymakers' expectations and the willingness of organizations as well as the complexity of policymakers assuming that non‐profit organizations will help unequivocally.
Uterine‐preserving treatments or hysterectomy reintervention after myomectomy or uterine artery embolisation: A retrospective cohort study of long‐term outcomes
Authors: Amoah Alison , Quinn Stephen D.
Published: January 2023

Objective

To assess comparative rates of further uterine‐preserving procedures (UPP) or hysterectomy reintervention, after myomectomy or uterine artery embolisation (UAE).

Design

Population‐based, retrospective cohort study.

Setting

England.

Population

Women who underwent myomectomy or UAE between 2010 and 2015 under the NHS.

Methods

Data was abstracted from NHS Health Episode Statistics datasets. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using Cox proportional‐hazards regression.

Main Outcomes Measures

30‐day readmission, UPP and hysterectomy reintervention rates.

Results

9443 and 6224 women underwent elective myomectomy or UAE, respectively. After 118 136 total person‐years of follow‐up, the rate of hysterectomy was 8.34 and 20.98 per 1000 patient years for myomectomy or UAE, respectively. There was a 2.4‐fold increased risk of undergoing hysterectomy after UAE when compared with myomectomy in adjusted models (HR 2.38 [95% CI 2.10–2.66]) [adjusted for age, ethnicity, multiple deprivation index, geographical region and comorbidities]. The HR for undergoing a UPP reintervention was 1.44 (95% CI 1.29–1.60) in favour of myomectomy. The rate of hysterectomy was increased 22% following UAE compared with laparoscopic myomectomy (0.97–1.52). Age may influence reintervention rates, and there was variation in hysterectomy risk when stratified by geographical region.

Conclusions

After a median of 7 years of follow‐up, there is a 2.4‐fold increased rate of hysterectomy and 44% increased risk of UPPs as reintervention after UAE, relative to myomectomy. These findings will aid pre‐procedure counselling for women with fibroids. Future work should investigate the effect of other outcome modifiers, such as fertility intentions and fibroid anatomical characteristics.
Effects of rice protein, soy isolate protein, and whey concentrate protein on the digestibility and physicochemical properties of extruded rice starch
Authors: Bao Huiyi , Liu Qing , Yang Yueyue , Xu Lulian , Zhu Kunfu , Jin Zhengyu , Jiao Aiquan
Published: January 2023

Protein, as the second major component in starchy foods, is crucial for its influence on the physicochemical properties and digestibility of starch. However, the effect of different sources of protein on starch digestibility is still unclear. In this paper, the effects of different sources of proteins (rice protein: RP, soybean isolate protein: SPI, and whey concentrate protein: WPC) on structural features, digestibility, and enzyme activity of extruded rice starch were investigated. The addition of all three proteins reduced the starch digestibility of extrudates. Native SPI and WPC suppressed amyloglucosidase activity, and all three proteins exhibited stronger amyloglucosidase inhibition when hydrolyzed. The rheological properties and Fourier transform infrared spectroscopy results revealed the exogenous proteins and starch interacted through non‐covalent bonds and improved the ordered structures in the extrudates. The extrusion process also facilitated the formation of a V‐type structure. The sum of SDS and RS content of extrudates was negatively correlated with the content of leached amylose and positively correlated with the ratio of 1047/1022 cm−1. These findings suggest that the inclusion of exogenous proteins during extrusion can affect starch digestibility through mechanisms such as the interaction with starch molecules, as well as the inhibition of amylase activity.

Practical Application

This result indicated that the addition of protein during extrusion not only increased the nutritional value of the extrudate, but also decreased the starch digestibility. Extrusion technology can efficiently produce extruded products with protein, expanding further applications of protein in food and providing new healthy staple food options for special populations, such as diabetic and overweight people.
Influence of RNA‐Seq library construction, sampling methods, and tissue harvesting time on gene expression estimation
Authors: Chiari Ylenia , Howard Leif , Moreno Nickolas , Relyea Scott , Dunnigan James , Boyer Matthew C. , Kardos Marty , Glaberman Scott , Luikart Gordon
Published: January 2023

RNA sequencing (RNA‐Seq) is popular for measuring gene expression in non‐model organisms, including wild populations. While RNA‐Seq can detect gene expression variation among wild‐caught individuals and yield important insights into biological function, sampling methods can also affect gene expression estimates. We examined the influence of multiple technical variables on estimated gene expression in a non‐model fish, the westslope cutthroat trout (Oncorhynchus clarkii lewisi), using two RNA‐Seq library types: 3′ RNA‐Seq (QuantSeq) and whole mRNA‐Seq (NEB). We evaluated effects of dip netting versus electrofishing, and of harvesting tissue immediately versus 5 min after euthanasia on estimated gene expression in blood, gill, and muscle. We found no significant differences in gene expression between sampling methods or tissue collection times with either library type. When library types were compared using the same blood samples, 58% of genes detected by both NEB and QuantSeq showed significantly different expression between library types, and NEB detected 31% more genes than QuantSeq. Although the two library types recovered different numbers of genes and expression levels, results with NEB and QuantSeq were consistent in that neither library type showed differences in gene expression between sampling methods and tissue harvesting times. Our study suggests that researchers can safely rely on different fish sampling strategies in the field. In addition, while QuantSeq is more cost effective, NEB detects more expressed genes. Therefore, when it is crucial to detect as many genes as possible (especially low expressed genes), when alternative splicing is of interest, or when working with an organism lacking good genomic resources, whole mRNA‐Seq is more powerful.
aniMotum, an R package for animal movement data: Rapid quality control, behavioural estimation and simulation
Authors: Jonsen Ian D. , Grecian W. James , Phillips Lachlan , Carroll Gemma , McMahon Clive , Harcourt Robert G. , Hindell Mark A. , Patterson Toby A.
Published: January 2023

Animal tracking data are indispensable for understanding the ecology, behaviour and physiology of mobile or cryptic species. Meaningful signals in these data can be obscured by noise due to imperfect measurement technologies, requiring rigorous quality control as part of any comprehensive analysis.

State–space models are powerful tools that separate signal from noise. These tools are ideal for quality control of error‐prone location data and for inferring where animals are and what they are doing when they record or transmit other information. However, these statistical models can be challenging and time‐consuming to fit to diverse animal tracking data sets.

The R package aniMotum eases the tasks of conducting quality control on and inference of changes in movement from animal tracking data. This is achieved via: (1) a simple but extensible workflow that accommodates both novice and experienced users; (2) automated processes that alleviate complexity from data processing and model specification/fitting steps; (3) simple movement models coupled with a powerful numerical optimization approach for rapid and reliable model fitting.

We highlight aniMotum's capabilities through three applications to real animal tracking data. Full R code for these and additional applications is included as Supporting Information, so users can gain a deeper understanding of how to use aniMotum for their own analyses.
Dexmedetomidine for the prevention of delirium in adults admitted to the intensive care unit or post‐operative care unit: A systematic review of randomised clinical trials with meta‐analysis and Trial Sequential Analysis
Authors: Maagaard Mathias , Barbateskovic Marija , Andersen‐Ranberg Nina C. , Kronborg Jonas R. , Chen Ya‐Xin , Xi Huan‐Huan , Perner Anders , Wetterslev Jørn
Published: January 2023

Objectives

To assess any benefit or harm, we conducted a systematic review of randomised clinical trials (RCTs) allocating adults to dexmedetomidine versus placebo/no intervention for the prevention of delirium in intensive care or post‐operative care units.

Data Sources

We searched Medline, Embase, CENTRAL and other databases. The last search was 9 April 2022.

Data Extraction

Literature screening, data extraction and risk of bias volume 2 assessments were performed independently and in duplicate. Primary outcomes were occurrences of serious adverse events (SAEs), delirium and all‐cause mortality. We used meta‐analysis, Trial Sequential Analysis, and GRADE (Grading Recommendations Assessment, Development and Evaluation).

Data Synthesis

Eighty‐one RCTs (15,745 patients) provided data for our primary outcomes. Results from trials at low risk of bias showed that dexmedetomidine may reduce the occurrence of the most frequently reported SAEs (relative risk [RR] 0.69; 95% CI 0.43–1.09), cumulated SAEs (RR 0.70; 95% CI 0.52–0.95) and the occurrence of delirium (RR 0.62; 95% CI 0.43–0.89). The certainty of evidence was very low for delirium. Mortality was very low in trials at low risk of bias (0.4% in the dexmedetomidine groups and 1.0% in the control groups) and meta‐analysis did not provide conclusive evidence that dexmedetomidine may result in lower or higher all‐cause mortality (RR 0.47; 95% CI 0.18–1.21). There was a lack of information from trial results at low risk of bias for all primary outcomes.

Conclusions

Trial results at low risk of bias showed that dexmedetomidine might reduce occurrences of SAEs and delirium, while no conclusive evidence was found for effects on all‐cause mortality. The certainty of evidence ranged from very low for occurrence of delirium to low for the remaining outcomes.
Treatment with the senolytics dasatinib/quercetin reduces SARS‐CoV‐2‐related mortality in mice
Authors: Pastor‐Fernández Andrés , Bertos Antonio R. , Sierra‐Ramírez Arantzazu , del Moral‐Salmoral Javier , Merino Javier , de Ávila Ana I. , Olagüe Cristina , Villares Ricardo , González‐Aseguinolaza Gloria , Rodríguez María Ángeles , Fresno Manuel , Gironés Nuria , Bustos Matilde , Smerdou Cristian , Fernandez‐Marcos Pablo Jose , von Kobbe Cayetano
Published: January 2023

The enormous societal impact of the ongoing COVID‐19 pandemic has been particularly harsh for some social groups, such as the elderly. Recently, it has been suggested that senescent cells could play a central role in pathogenesis by exacerbating the pro‐inflammatory immune response against SARS‐CoV‐2. Therefore, the selective clearance of senescent cells by senolytic drugs may be useful as a therapy to ameliorate the symptoms of COVID‐19 in some cases. Using the established COVID‐19 murine model K18‐hACE2, we demonstrated that a combination of the senolytics dasatinib and quercetin (D/Q) significantly reduced SARS‐CoV‐2‐related mortality, delayed its onset, and reduced the number of other clinical symptoms. The increase in senescent markers that we detected in the lungs in response to SARS‐CoV‐2 may be related to the post‐COVID‐19 sequelae described to date. These results place senescent cells as central targets for the treatment of COVID‐19, and make D/Q a new and promising therapeutic tool.
The hard lives of trees in African savanna—Even without elephants
Authors: Coetsee Corli , Botha Judith , Case Madelon F. , Manganyi Adolf , Siebert Frances
Published: January 2023

The ongoing loss of large trees and densification of shrubs are two prevalent processes that take place in African savannas, with profound consequences for their structure and function. We evaluated herbivore impacts on savanna woody communities using a long‐term exclosure experiment in the Kruger National Park, South Africa, with three treatments: the exclusion of large mammals only (i.e. elephant and giraffe), exclusion of all herbivores larger than a hare, and areas open to all herbivores. We asked three questions: (1) How did variable exclusion of herbivores affect woody density and structure across the catena (i.e. riparian, sodic and crest vegetation)? (2) Did the exclusion of herbivores result in unique woody species composition? (3) Did herbivore exclusion result in a higher proportion of palatable species? After 17 years, we found that herbivores mainly affected the heights and densities of existing species, rather than leading to turnover of woody species assemblages. Although densities of individuals increased in the full exclosure (350 ha−1), the change was more moderate than expected. By contrast, mixed mega‐and meso‐herbivores decreased the number of trees and shrubs (decreases of 780 ha−1) via a variety of physical impacts. Meso‐herbivores alone, on the other hand, had less impact on individual density (i.e. no change), but limited average height growth and canopy dimensions in certain habitat types. Where elephants are present, they are effective at reducing the density of woody stems to the point of counteracting woody encroachment, but at the same time are actively preventing the persistence of large trees (>5 m) as well as preventing trees from recruiting to larger size classes. However, the lack of massive recruitment and woody cover increases with elephant exclusion, especially for more preferred species, suggests that factors beyond elephants, such as dispersal limitation, seed predation, and drought, are also acting upon species.
De‐occupation as planetary politics
Authors: Petryna Adriana
Published: January 2023

Russia's attempted occupation of Ukraine informs a concept of de‐occupation in an age of 21st‐century planetary wars. The tide of war crimes committed in Ukraine is beyond dispute, having been identified by legal scholars as genocidal attempts to condemn the very foundations of livelihood. I discuss the precedents that have allowed such crimes to occur and describe how Ukrainians are trying to counter these crimes, forming a particular kind of resistance that strikes against impunity. I locate impunity's persistence within post‐Soviet spheres, where solidarities among civilians who have been subject to Russian militarization complicate the view that the war in Ukraine is just another proxy war between superpowers. Given the dearth of architectures of peace and security to prevent genocide, de‐occupation emerges as a process in which de‐occupied people not only restore their territory but also play a central role in asserting less ruinous, more livable planetary futures.
Gestational weight gain adequacy and intrapartum oxytocin and cesarean section use: Observational population‐based study in France
Authors: Amyx Melissa , Zeitlin Jennifer , Blondel Béatrice , Le Ray Camille
Published: January 2023

Introduction

Research on maternal prepregnancy weight suggests adiposity is associated with dysfunctional labor, but knowledge about how gestational weight gain (GWG) affects labor is sparse. Our objective was to evaluate associations between GWG adequacy and intrapartum obstetric interventions (oxytocin administration; cesarean section) necessitated by labor dysfunction.

Material and methods

Using national, population‐based French National Perinatal Survey 2016 data, we included term cephalic singleton pregnancies involving trial of labor (n = 9724). For the intrapartum oxytocin administration analysis, we included only women with spontaneous labor (n = 7352). GWG was calculated as the difference between end of pregnancy and prepregnancy weight (both self‐reported) and categorized as insufficient, adequate (reference group), or excessive by prepregnancy body mass index (BMI; underweight <18.5, normal weight 18.5–24.9, overweight 25–29.9, obese ≥30 kg/m2) using the 2009 Institute of Medicine thresholds. Multilevel generalized estimating equation logistic regression models, unadjusted and adjusted for a priori confounders, evaluated intervention‐GWG adequacy associations within BMI categories (under/normal weight combined), stratified by parity (primiparas; multiparas).

Results

GWG adequacy was associated with oxytocin use among under/normal weight women (primiparas: insufficient 57.3%, adequate 60.8%, excessive 65.0%, p = 0.014; multiparas: insufficient 27.2%, adequate 29.1%, excessive 36.2%, p < 0.001) and overweight primiparas (insufficient 56.0%, adequate 58.7%, excessive 72.5%, p = 0.002). In unadjusted and adjusted models, trends of increased odds of oxytocin administration among women with excessive GWG were found regardless of parity and prepregnancy BMI. Similarly, among under/normal weight women, GWG adequacy was associated with intrapartum cesarean section (primiparas: insufficient 10.7%, adequate 12.7%, excessive 15.3%, p = 0.014; multiparas: insufficient 3.1%, adequate 3.5%, excessive 6.3%, p < 0.001) with increased cesarean section among multiparas with excessive GWG persisting in adjusted models (adjusted odds ratio 1.9, 95% confidence interval 1.3–2.7). However, intrapartum cesarean section was reduced among multiparas with overweight and obese prepregnancy BMI and excessive GWG.

Conclusions

Excessive GWG was associated with intrapartum oxytocin administration, regardless of parity or prepregnancy BMI, and cesarean section among women with under/normal weight prepregnancy BMI, providing evidence for benefits of healthy GWG for normal labor progression. Additional research is needed to verify our findings and understand differences by BMI.
A post‐marketing pharmacovigilance study of avapritinib: Adverse event data mining and analysis based on the United States Food and Drug Administration Adverse Event Reporting System database
Authors: Rong Li , Xie Mengyuan , Jiang Manxue , Qiu Hongyu , Kong Lingti
Published: January 2023

Aims

Avapritinib was first approved by the FDA in January 2020 and represents the first precision‐targeted drug for gastrointestinal stromal tumours. However, there is a lack of large‐scale data relating to adverse events (AEs) related to its use. We aimed to explore the avapritinib‐related AEs in real‐world practice based on the post‐marketing data.

Methods

We extracted all avapritinib‐related reports submitted to the FDA Adverse Event Reporting System (FAERS) by June 2022. Based on disproportionality analysis and Bayesian analysis, we then calculated the reporting odds ratio (ROR), proportional reporting ratio (PRR), information component (IC) and empirical Bayes geometric mean (EBGM) to evaluate whether there is a significant association between avapritinib and AEs. Gender, age and time to onset were comparable between haemorrhage/non‐haemorrhage, serious/non‐serious, death/non‐death AEs, respectively.

Results

In total, 3120 cases related to avapritinib were documented in the FAERS database, and 44% were reported within 30 days of commencing avapritinib. A total of 331 different AE signals were detected, and no significant differences between males and females was identified. Although the number of AEs associated with an abnormal skin texture and executive dysfunction was small, the signal intensity is high, suggesting that these events are strongly correlated with avapritinib. Subgroup analysis showed that elderly male patients were more likely to suffer from serious AEs compared to females (P < .01), but there was no significant difference between the haemorrhage group and the non‐haemorrhage group. Analysis of fatalities due to avapritinib‐related AEs indicated that sex, age and time‐to‐onset were all significantly related to death (P < .05).

Conclusion

Our study provides a more precise description of the incidence and characteristics of AEs after using avapritinib, clinicians should be particularly careful when prescribing avapritinib to elderly male patients, especially within the 30 days.
Why caregivers have no autonomy‐based reason to respect advance directives in dementia care
Authors: Lauridsen Sigurd , Folker Anna P. , Andersen Martin M.
Published: January 2023

Advance directives (ADs) have for some time been championed by ethicists and patient associations alike as a tool that people newly diagnosed with dementia, or prior to onset, may use to ensure that their future care and treatment are organized in accordance with their interests. The idea is that autonomous people, not yet neurologically affected by dementia, can design directives for their future care that caregivers are morally obligated to respect because they have been designed by autonomous individuals. In this paper, we first criticize the idea that ADs can retain moral authority in severe dementia by arguing that it is paradoxical. Second, we consider two arguments that initially seem to refute this critique of ADs, but we eventually dismiss them. The first argument states that ADs retain moral authority in severe dementia because autonomously formed interests, for example, ADs, can only be appropriately discarded by autonomous persons. This we term the historical autonomy argument. We dismiss it by demonstrating how we, in analog cases, are not obligated to continue to respect autonomously formed interests even though they have been discarded under nonappropriate conditions. The second argument is that ADs can be justified by what we term external interests. While we agree that people with severe dementia plausible can be said to have external interests, we show that ADs cannot express such interests and hence cannot be justified by them. We conclude that none of the discussed arguments support the use of ADs and because of this, the idea of ADs should be reassigned.
Pharmacokinetic and dose‐finding study of osimertinib in patients with impaired renal function and low body weight
Authors: Fujiwara Yutaka , Makihara Reiko , Hase Tetsunari , Hashimoto Naozumi , Naito Tomoyuki , Tsubata Yukari , Okuno Takae , Takahashi Toshiaki , Kobayashi Haruki , Shinno Yuki , Zenke Yoshitaka , Ikeda Takaya , Hosomi Yukio , Watanabe Kageaki , Kitazono Satoru , Sakiyama Naomi , Makino Yoshinori , Yamamoto Noboru
Published: January 2023

The safety of osimertinib is limited in patients with severe or moderate renal impairment, or low body weight. This study aimed to investigate the safety, pharmacokinetics (PK) and recommended dose (RD) of osimertinib in patients with epidermal growth factor receptor (EGFR)‐mutated non–small cell lung cancer (NSCLC) with impaired renal function and low body weight. Thirty‐one eligible patients were enrolled and allocated into four cohorts: A, normal renal function (estimated glomerular filtration rate [eGFR] ≥ 50 mL/min/1.73 m2) and normal body weight (≥45 kg); B, moderate renal impairment (eGFR = 30‐50 mL/min/1.73 m2); C, low body weight (<45 kg); and D, severe renal impairment (eGFR <30 mL/min/1.73 m2 or undergoing dialysis). PK parameters and safety were evaluated with a starting dose of 80 mg osimertinib administered orally once daily in cohorts A, B, and C and 40 mg once daily in cohort D. The PK parameters in cohorts A, B, and C were found to be similar. No dose‐limiting toxicity was observed, and the RD was determined to be 80 mg once daily in patients with moderate renal function and low body weight. Four serious adverse events, acneiform rash, diarrhea, QTc prolongation, and interstitial lung disease, were noted. Although the PK parameters of osimertinib were similar across all cohorts, toxicity occurred more frequently in patients with impaired renal function and low body weight. Clinicians should prescribe osimertinib with caution in NSCLC patients with impaired renal function and low body weight.
Considering the moral implications of psychiatric diagnosis for children
Authors: Isobel Sophie
Published: January 2023

Increasing numbers of children are meeting criteria for psychiatric disorders. While diagnoses may be of situational and individual benefit, they also have sustained and significant impacts on children's lives, including what they believe to be true, and how they understand themselves. Psychiatric diagnosis, therefore, has moral implications for children. This paper considers these moral implications, including uncertainty about the accuracy, treatment efficacy and long‐term effects of psychiatric diagnosis for children through a critical lens. Challenges of identifying, diagnosing and treating childhood mental illness are explored, including a discussion of the familial and societal contexts of adversity and understandings of accepted behaviour and responses. Emphasis is sustained on the importance of child agency and rights and how these may conflict with protective discourses about childhood, compounding epistemic injustices for children. The author proposes that there is a need to consider the child voice, while also being conscious of the boundaries of possibility of constructed reality, alongside the development of new ways of speaking about and understanding child distress. Achieving this requires questioning and critique of systems of psychiatric diagnosis applied to children and increased consideration of shared social and political responsibilities to prevent childhood adversity.