bluuebunny/crossref_metadata_2025 huggingface dataset:
The crowding-out effect of shareholder value-based CEO compensation on R&D investment in the European context: a new interpretation
Authors: Doruk Ömer Tuğsal
Published: October 2022

Purpose

In the present study, using a novel fractional logit model, the link between R&D (Research & Development) investment and shareholder value-based CEO (Chief Executive Officer) compensation has been examined within the non-financial sector in the Euro area economies using a firm-level dataset for 2002–2019.

Design/methodology/approach

The fractional logit model is utilized to examine the effects of corporate payment on R&D investment. The fractional logit model can be considered the empirical approach that takes into account R&D non-performer firms to avoid reducing the sample size. The fractional logit model is superior to the censored or truncated models, like Tobit, since the fractional logit model is useful to address the econometric limitations that are found in the censored and truncated models in the non-linear models.

Findings

The findings obtained in this study showed a significant and negative effect of short-term aim-based CEO payment on R&D expenditures in the Euro area economies using firm-level data. These findings are robust to different robustness checks and modeling alternatives.

Originality/value

To the author's knowledge, there is no study that examines the effects of short-term shareholder value maximization-based CEO compensation on R&D in the European context in the literature.
CEO characteristics, multinationality and downside risk: evidence from Chinese multinational corporations
Authors: Zhou Chao
Published: October 2022

Purpose

Real options theory posits that multinationality provides additional operating flexibility and helps firms reduce downside risk. This study aims to explore the effects of chief executive officer (CEO) characteristics on the downside risk implication of multinationality in Chinese multinational corporations (MNCs).

Design/methodology/approach

This study gathers a sample of Chinese MNCs from 2009 to 2020 and deploys a Tobit panel estimation model with fixed effects in the empirical analysis.

Findings

This study finds that multinationality has a significant negative effect on downside risk. The downside risk reduction effect of multinationality is stronger in firms led by older CEOs, women CEOs, CEOs with overseas experience or broader functional backgrounds or those with higher educational levels. Additionally, the above effects of CEO characteristics on the downside risk reduction effect of multinationality are more pronounced in firms with smaller top management team (TMT) sizes. Hence, the findings show that the multinational network constructed by Chinese MNCs could offer great operating flexibility, and CEO characteristics and the CEO–TMT interface play an important role in achieving real options flexibility from multinationality.

Originality/value

This study shows that multinationality could be an effective way for emerging market firms to reduce business risk. This study helps identify CEO characteristics that are associated with real option performance and emphasizes that CEO personal attitudes and abilities could influence the real options flexibility obtained from multinationality. This study also contributes to the understanding of micro foundations in international business by focusing on the role of CEO characteristics and the CEO–TMT interface in the downside risk implications of multinationality.
Second order slip flow of a conducting Jeffrey nanofluid in an inclined asymmetric porous conduit with heat and mass transfer
Authors: Ramamoorthy Meenakumari , Pallavarapu Lakshminarayana
Published: October 2022

Purpose

The present work explores the influence of Hall and Ohmic heating effects on the convective peristaltic flow of a conducting Jeffrey nanofluid in an inclined porous asymmetric channel with slip. Also, the authors investigated the impact of viscous dissipation, thermal radiation, heat generation/absorption and cross diffusion effects on the flow. Peristaltic flow has many industrial and physiological applications and most of the biofluids show the non-Newtonian fluid behaviour. Further, in a living body, several biofluids flow through different kinds of systems that are not symmetric, horizontal or vertical. The purpose of this paper is to address these issues.

Design/methodology/approach

The authors considered the flow of Jeffrey fluid which is generated by a sinusoidal wave propagating on the walls of an inclined asymmetric channel. The flow model is developed from the fixed frame to the wave frame. Finally, yield the nonlinear governing equations by applying the non-dimensional quantities with the assumptions of lengthy wave and negligible Reynolds number. The exact solution has been computed for the velocity and pressure gradient. The solutions for temperature and concentration are obtained by the regular perturbation technique.

Findings

Graphical analysis is made for the present results for different values of emerging parameters and explained clearly. It is noticed that the magnetic field enriches the temperature where it drops the fluid velocity. This work describes that the temperature field is decreasing due to the radiation but it is a rising function of temperature slip parameter. The temperature profile declines for growing values of the Hall parameter. The flow velocity diminishes for boosting values of the Darcy parameter. Further, the authors perceived that the concentration field reduces for large values of the chemical reaction parameter.

Originality/value

The authors validated and compared the results with the existing literature. This investigation will help to study some physiological systems, and heat transfer in peristaltic transport plays key role in medical treatments, so we ensure that these results are applicable in medical treatments like cancer therapy, drug delivery, etc.
Organizational practices as drivers of societal change: contextual spillover effects of environmental management on employees’ public sphere pro-environmental behavior
Authors: Jaich Hans , Jastram Sarah Margaretha , Blind Knut
Published: October 2022

Purpose

This study aims to draw on goal contagion theory to examine how organizations shape the pro-environmental behavior of their employees. It extends the scope of analysis beyond organizational boundaries and illustrates the external effects of organizational practices that support societal change. The fundamental research question is whether perceived environmental management practices strengthen employees’ public sphere pro-environmental behavior.

Design/methodology/approach

To test the research hypothesis, the authors combined survey and quasi-experimental evidence from two independent field studies. Both studies were carried out in the tourist industry in Germany. In the first study, the authors used a cross-sectional research design with data from 206 employees to examine whether perceived environmental management practices are positively associated with employees’ public sphere pro-environmental behavior. For causal inference, the authors conducted a second study involving a natural pretest-posttest quasi-experiment with a treatment and control group.

Findings

The results of the cross-sectional study revealed that perceived environmental management practices are positively associated with employees’ public sphere pro-environmental behavior. The findings of the natural quasi-experiment confirmed the hypothesized causation and minimized the probability of alternative explanations.

Practical implications

The study has important implications for policymakers, since the support and acceptance of public policies is a prerequisite for the realization of collective political action. By highlighting the potential of organizational practices to strengthen employees’ public sphere pro-environmental behavior, this research illustrates how rules and regulations that oblige firms to intensify their environmental protection practices might not only reduce the ecological footprint of organizations but also help cultivate societal acceptance of and support for environmental protection.

Social implications

This study illustrates how employees that align their normative goals in accordance with the implicit goals of organizational practices can become agents for corresponding societal changes. This perspective highlights the integration of structure and agency and underscores the idea that societal change works across macro-, meso- and micro-social levels.

Originality/value

To the best of the authors’ knowledge, the investigation is the first that examines the relationship between perceived environmental management practices and employees’ public sphere pro-environmental behavior. Herewith, it sheds light on a thus far overlooked mechanism for how organizations stimulate societal change.
Measuring green innovation through total quality management and corporate social responsibility within SMEs: green theory under the lens
Authors: Azam Tamoor , Songjiang Wang , Jamil Khalid , Naseem Sobia , Mohsin Muhammad
Published: October 2022

Purpose

In the modern business world, the main focus of the organizations is to improve the quality of the products and minimize the wastage of raw material. Keeping in view the green theory and improve the efficiency of the organization, the focus of the current study is to investigate the relationship between total quality management (TQM) and green innovation (GI), and examine how TQM practices can facilitate firms to achieve GI objectives. Corporate social responsibility (CSR) is also an important factor for organizations, and this study also focuses on the mediating role of CSR between the relationship of TQM and GI.

Design/methodology/approach

This is an empirical study. Data were gathered from the top management of 355 SMEs working in Pakistan through a questionnaire survey; the PLS-SEM approach was used to analyse the data.

Findings

Results of the study show that TQM has significant impacts on two aspects of GI namely green product innovation and green process innovation. Moreover, results also reveal that CSR partially mediates the relationship between TQM and GI.

Research limitations/implications

This study is limited to manufacturing SMEs and future research should test this model on non-manufacturing sector too. The findings of the study provide significant roadmap to the management of small and medium-sized manufacturing firms that how they can reduce wastage and improve the product and process innovation in their organizations through TQM and CSR.

Originality/value

This study contributes to bridging research gaps in the literature and advances how TQM, directly and indirectly, help firms improve green innovation via mediating roles of CSR.
Thermal analysis of concrete slabs with insulating materials using ANSYS
Authors: A. Parvathidevi , Ch Naga Satish Kumar
Published: October 2022

Purpose

This study aims to assess the efficacy of thermal analysis of concrete slabs by including different insulation materials using ANSYS. Regression equations were proposed to predict the thermal conductivity using concrete density. As these simulation and regression analyses are essential tools in designing the thermal insulation concretes with various densities, they sequentially reduce the associated time, effort and cost.

Design/methodology/approach

Two grades of concretes were taken for thermal analysis. They were designed by replacing the natural fine aggregates with thermal insulation aggregates: expanded polystyrene, exfoliated vermiculite and light expanded clay. Density, temperature difference, specific heat capacity, thermal conductivity and time were measured by conducting experiments. This data was used to simulate concrete slabs in ANSYS. Regression analysis was performed to obtain the relation between density and thermal conductivity. Finally, the quality of the predicted regression equations was assessed using root mean square error (RMSE), mean absolute error (MAE), integral absolute error (IAE) and normal efficiency (NE).

Findings

ANSYS analysis on concrete slabs accurately estimates the thermal behavior of concrete, with lesser error value ranges between 0.19 and 7.92%. Further, the developed regression equations proved accurate with lower values of RMSE (0.013 to 0.089), MAE (0.009 to 0.088); IAE (0.216 to 5.828%) and higher values of NE (94.16 to 99.97%).

Originality/value

The thermal analysis accurately simulates the experimental transfer of heat across the concrete slab. Obtained regression equations proved helpful while designing the thermal insulation concrete.
Heat it up to slow it down: Individual energetics reveal how warming reduces stream decomposition
Authors: Jochum Malte
Published: October 2022

Research Highlight: Réveillon, T., Rota, T., Chauvet, É., Lecerf, A., & Sentis, A. (2022). Energetic mismatch induced by warming decreases leaf litter decomposition by aquatic detritivores. Journal of Animal Ecology, https://doi.org/10.1111/1365‐2656.13710. Global change holds complex consequences for Earth's ecosystems, with global warming simultaneously affecting multiple aspects including individual physiology, population dynamics and ecosystem processes. In a recent study on stream decomposition under global warming, Réveillon, et al. (2022) combined individual‐level laboratory assessments of metabolic rates and leaf‐litter ingestion with experimentally parameterized consumer‐resource models, designed to reveal how stream‐detritivore populations respond to combined impacts of warming and declining body size. Their findings of reduced energetic efficiency, weakened detritivore populations and reduced decomposition in warmed streams expand our understanding of how global change mechanistically links changes from the individual to the ecosystem level.
Mothers, milk and mourning: The meanings of breast milk after loss of an infant
Authors: Waldby Catherine , Noble‐Carr Debbie , Carroll Katherine
Published: October 2022

Breast milk is a highly valued substance, immunologically and nutritionally, which also signifies maternal care and love for the infant. This intersection of biological and cultural qualities confers breast milk with complex meanings, which necessarily shape the experience of breastfeeding. Our research, investigating the experience of lactation after the loss of an infant, casts a novel light on these meanings. This article analyses the experience of 17 Australian bereaved mothers and 114 health professionals charged with their care. We find that while all the mothers found post‐loss lactation emotionally painful, many also found redemptive meaning in their milk‐production, as a bond with the lost child, as confirmation of their maternal competence and as a life giving substance that they could donate to other needy infants. These complex meanings and positive connotations were at odds with hospital cultures that regard post‐loss lactation as valueless and best dealt with through medical suppression, despite the more complex insights of individual health‐care professions.
Adaptation to climate change in small German municipalities: Sparse knowledge and weak adaptive capacities
Authors: Buschmann Daniel , Koziol Karin , Bausch Thomas , Reinhard Steurer
Published: October 2022

Understanding local adaptation to climate change is critical for the overall success of adaptation practices in Europe and around the world. Although it becomes more urgent by the day, existing literature does not adequately touch upon the topic of climate adaptation in small municipalities. This article addresses this gap. It explores whether adaptation measures in small municipalities are overlooked in research focused on other aspects of urban environment, or whether such measures are indeed inadequate. Based on a large quantitative survey among Bavarian municipalities (n = 401), we conducted 11 qualitative case studies to answer the following two questions. First, how active are small municipalities in Bavaria, Germany, in climate change adaptation? Second, why and how do municipal adaptation frontrunners implement adaptation measures and what lessons can we learn from their experience? Our findings confirm that small municipalities rarely adapt to climate change, and when they do, their actions usually target water‐related issues. Most often measures are responsive and pragmatic, instead of being preventive and transformative. The fact that the small municipality representatives that we have interviewed were not able to distinguish between adaptation and mitigation measures clearly illustrates the lack of local adaptation capacities. We conclude that national funding for municipal adaptation coordinators or networks is a promising way to improve local capacities.
Determinant factors associated with the use of evidence‐based dietetics practice among registered dietitian nutritionists
Authors: Van Horn Leslie Thompson , Wright Lauri , Arikawa Andrea Y. , Sealey‐Potts Claudia , Hamadi Hanadi
Published: October 2022

Aims

There is a lack of research assessing perceived and actual evidence‐based dietetics practice knowledge among registered dietitian nutritionists. This cross‐sectional research examined the association between determinant factors (i.e., education attainment) and objective knowledge (i.e., quiz items) of evidence‐based dietetics practices. Other determinant factors associated with perceived knowledge and skill, attitudes, behaviours and outcomes related to evidence‐based dietetics practice were also assessed. Perceived knowledge items were compared to objective knowledge items to evaluate the accuracy of self‐assessed evidence‐based dietetics practice knowledge among dietitians in the United States.

Methods

A modified and adapted evidence‐based practice survey was emailed to registered dietitian nutritionists in the United States via the Commission on Dietetic Registration database between November and December 2020. Analysis of variance assessed the relationship between highest degree held and actual knowledge of evidence‐based dietetics practices. Multiple linear regression and ordinal logistic regression determined participant‐level characteristics associated with survey subscales and survey items, respectively. Pearson's correlation coefficient evaluated the relationship between subjective and objective items.

Results

Four hundred and eighty‐two dietitians completed the survey. Each increase in degree type was associated with an increase in objective knowledge score (all comparisons p < 0.001). Other determinants included recency of degree completion and peer‐reviewed publications. Moderate positive associations (r = 0.35, p < 0.001) were found between subjective and objective measures.

Conclusion

Graduate‐level education, recency of degree completion and peer‐reviewed publications were supportive of evidence‐based dietetics practice‐related outcomes. Future research should evaluate the efficacy of training, particularly among those further from their highest completed degree.
Disentangling microstructure and environmental conditions in high‐altitude Andean microbialite systems (Catamarca, Argentine Puna)
Authors: Della Vedova Micaela , Villafañe Patricio G. , Cónsole‐Gonella Carlos , Bahniuk Rumbelsperger Anelize , Fadel Cury Leonardo , Horta Luis R. , Farías María E.
Published: October 2022

The study of microbialites development is a key tool to understand environmental pathways during deposition. We provide a detailed analysis of modern Central Andean microbialites from high‐altitude lakes. The stratigraphic record of Turquesa Lake shows a significant short‐term recolonization by microbialite‐producing microorganisms during environmental stress. Far from a crisis paradigm, the coasts and paleocoasts of Turquesa lake exhibit three microbialitic buildups formed along different stages, providing a good study case of biological resilience of these systems in harsh environments. The MI and MII microbialite buildups occupied two paleocoasts. Both are composed of oncoids with micritic to microsparitic textures. Morphological, textural and mineralogical similarities between the two buildups suggest that they were formed at different times, but under very similar environmental conditions. The microorganisms that produced the microbialitic buildup MIII are currently colonizing the coast of this lake. The previous oncoid morphology change to a parallel micritic–spartic lamination. This remarkable changes in the microstructure can be explained by an important environmental change caused by the isolation of the Peinado Lake, and a subsequently microorganism adaptation. This microbialite structures can be proposed as an interesting modern analogue for environmental changes along the geological record.
Protein tyrosine phosphatase PTPL1 suppresses lung cancer through Src/ERK/YAP1 signaling
Authors: Wang Jing , Li Shuanghui , Zhang Xiujuan , Zhu Ning , Yiminniyaze Ruzetuoheti , Dong Liang , Li Chengwei , Gulinuer Wumaier , Xia Jingwen , Li Jing , Zhou Daibing , Liu Xinning , Zhang Youzhi , Zhang Yuanyuan , Li Shengqing
Published: October 2022

Background

To reveal the function of protein tyrosine phosphatase‐L1 (PTPL1) in lung adenocarcinoma.

Methods

Lung cancer cell lines were transfected with short hairpin RNA against PTPL1 (shPTPL1 group) or negative control (shmock group). Quantitative real‐time polymerase chain reaction (qRT‐PCR) and western blotting were used to verify the transfection efficacy. Cell proliferation was analyzed by ethynyldeoxyuridine (EdU), Cell counting kit 8 (CCK8), and colony formation assay after PTPL1 or PTPL1 and yes‐associated protein (YAP1) knockdown. The effect of PTPL1 on tumor growth was examined in a xenograft lung cancer model.

Results

PTPL1 was downregulated in various types of lung cancer cell lines. The EdU, CCK8, colony formation assays and investigation using a xenograft lung cancer model indicated that PTPL1 knockdown increased the proliferation of lung cancer cells. Mechanistically, PTPL1 knockdown induced the activation of the Proto‐oncogene tyrosine‐protein kinase SRC (Src)/Extracellular regulated MAP kinase (ERK) pathway and thereby promoted yes‐associated protein (YAP1) nuclear translocation and activation.

Conclusions

In our study, PTPL1 played a crucial suppressive role in the pathogenesis of lung cancer potentially through counteracting the Src/ERK/YAP1 pathway.
Predictive value of early kinetics of ctDNA combined with cfDNA and serum CEA for EGFR‐TKI treatment in advanced non‐small cell lung cancer
Authors: Zheng Jie , Wang Yubo , Hu Chen , Zhu Mengxiao , Ii Jianghua , Lin Caiyu , Lu Conghua , Dou Yuanyao , Zhao Chenlong , Zhang Yimin , Wu Di , Li Li , Tang Huan , He Tingting , Pan Chunxiao , Han Rui , He Yong
Published: October 2022

Background

Circulating tumor DNA (ctDNA) has made a breakthrough as an early biomarker in operable early‐stage cancer patients. However, the function of ctDNA combined with cell‐free DNA (cfDNA) as a predictor in advanced non‐small cell lung cancer (NSCLC) remains unknown. Here, we explored its potential as a biomarker for predicting the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) in patients with advanced NSCLC.

Methods

A retrospective analysis was undertaken. Plasma collected from 51 patients with advanced NSCLC prior to and serially after starting treatment with EGFR‐TKIs was analyzed by next‐generation sequencing (NGS). The performance of ctDNA, cfDNA, and combining ctDNA with cfDNA were evaluated for their ability to predict survival outcomes.

Results

Patients with early undetectable ctDNA and increasing cfDNA had a markedly better progression‐free survival (PFS) (p < 0.001) and overall survival (OS) (p = 0.001) than those with early detectable ctDNA and decreasing cfDNA. Patients with early ctDNA clearance were more likely to have the ctDNA persistent clearance (p = 0.006). The early clearance rate of ctDNA in the normal carcinoembryonic antigen (CEA) group was significantly higher than in the low and high groups (p = 0.028). Patients with greater CEA decline had a higher early clearance rate of ctDNA than those with minor CEA change (p = 0.016).

Conclusions

We based this study on ctDNA and cfDNA, explored its prognostic predictive ability, and combined CEA to monitor EGFR‐TKI efficacy. This study may provide new perspectives and insights into the precise treatment strategies for NSCLC patients.
Clinicopathological analysis of a superior sulcus tumor treated by salvage surgery after concurrent definitive chemoradiotherapy followed by durvalumab: A case report
Authors: Funaki Soichiro , Ose Naoko , Kimura Toru , Kanou Takashi , Fukui Eriko , Shintani Yasushi
Published: October 2022

Surgical treatment of superior sulcus tumors (SSTs) is clinically challenging. Definitive chemoradiotherapy (CRT) is a standard treatment for SST. In operable cases, multimodal therapy (CRT followed by surgery) is another option, at least for experienced institutions. Immune checkpoint inhibitors (ICIs) have recently been developed, and several clinical trials have investigated definitive CRT followed by ICIs for consolidation or maintenance therapy of unresectable local advanced non‐small cell lung cancer (NSCLC), including SSTs. Clinical studies of salvage surgery after CRT followed by ICIs are also ongoing. However, the clinical outcomes of salvage surgery after multimodal therapies and histopathological analyses of surgical specimens after such treatments remain unclear. Here, we report the case of a patient with SST comprising squamous cell carcinoma with invasion of the second to third rib and vertebrae who underwent salvage surgery after concurrent definitive CRT followed by the ICI durvalumab, and show the results of clinicopathological analyses of the resected specimen.
Making and Mastering Violent Environments: Following the Infrastructures of Accumulation in Coastal Louisiana
Authors: Phillips Rachel , Soederberg Susanne
Published: October 2022

Louisiana’s coastal wetlands have been disappearing at an alarming rate over the past several decades, with the greatest harm experienced by vulnerable populations (poor and racialised residents). It was not until 2005 that the state legislature responded with a much‐lauded Master Plan tasked with integrating the construction of new flood control infrastructure with wetland restoration. Seeking to unsettle this initiative, we develop a historical‐geographical materialist approach to follow the entanglements between infrastructural production and capital accumulation in Louisiana over the past several hundred years. In so doing, we present a two‐fold argument: that the making and mastering infrastructural violence has always been part of the historical unfolding of the socio‐spatial dynamics of capitalism; and that infrastructural development has played an integral role in this duality at every historical turn. The capitalist state, at both the federal and state levels, has played a vital role in producing and controlling this violence.
The association between steatosis and liver damage in transfusion‐dependent beta thalassaemia patients
Authors: Padeniya Padmapani , Ediriweera Dileepa , De Silva Arjuna P. , Niriella Madunil , Premawardhena Anuja
Published: October 2022

Non‐alcoholic fatty liver disease (NAFLD) is a global health problem. Iron is the leading cause of liver damage in patients with transfusion‐dependent thalassaemia (TDT), and data on the contribution of NAFLD to liver damage in TDT is lacking. Forty‐five heavily transfused TDT patients who did not have biochemical or ultrasonic evidence of liver cirrhosis were evaluated for effects of iron overload, including the presence of diabetes mellitus, hypogonadism, serum ferritin, R2‐MRI‐liver, and liver enzymes alanine aminotransferase and aspartate aminotransferase. Liver fibrosis and steatosis were estimated using transient elastography (TE). Nine (20%) patients had significant steatosis (S1), and their body mass index (BMI) and liver fibrosis scores were higher than in patients without significant steatosis (S0) (p = 0.03 and p = 0.004, respectively). On regression analysis, the controlled attenuation parameter (CAP) score (i.e., degree of liver steatosis) was associated only with increasing BMI. The TE score (i.e., degree of liver fibrosis) was associated with increasing age, CAP score, male gender, and presence of diabetes. Neither liver steatosis nor fibrosis showed significant association with the liver iron concentration or iron‐related organ damage (hypogonadism). In this cohort of TDT patients, steatosis of the liver, which is associated with increasing BMI, appeared to increase the risk of liver fibrosis.
Matriarchy, Matricide and Mourning
Authors: Heller Serena
Published: October 2022

Matricide is suggested as an important counterpart to the traditional oedipal manifestations of patricide. This paper turns to The Oresteia to examine its murderous protagonists and the meaning of the drive to eliminate mothers. A daughter may enact unconscious matricidal wishes in order to separate from an ambivalent tie to her mother, by excising femininity and femaleness in herself. The author explores early bisexual pulls that can emanate from primal scene identifications. The capacity to relinquish the option to have all options is brought in as a ubiquitous and painful developmental move away from having and being all sexes. Father's role as crucial in the sexual development of daughters, including Freud's role in relation to his daughter Anna, is considered and mourning is linked to Klein's Depressive Position. The author includes clinical material of two children from the literature and draws on interviews conducted with trans men to reflect on these struggles. The paper explores early awareness of the difference between the sexes and argues that this can fuel a protest for daughters, sometimes manifesting as a ‘no‐mother’ or matricidal state of mind. If these wishes or phantasies remain unmourned, they can at times lead to a concrete flight from femininity.
Ribonucleoprotein transport in Negative Strand RNA viruses
Authors: Diot Cédric , Cosentino Gina , Rameix‐Welti Marie‐Anne
Published: October 2022

Negative‐sense, single‐stranded RNA (‐ssRNA) viruses comprise some of the deadliest human pathogens (Ebola, rabies, influenza A viruses etc.). Developing therapeutic tools relies on a better understanding of their multiplication cycle. For these viruses, the genome replication and transcription activities most‐often segregate in membrane‐less environments called inclusion bodies (IBs) or viral factories. These “organelles” usually locate far from the cell surface from where new virions are released, and ‐ssRNA viruses do not encode for transport factors. The efficient trafficking of the genome progeny toward the cell surface is most often ensured by mechanisms co‐opting the cellular machineries.

In this review, for each ‐ssRNA viral family, we cover the methods employed to characterize these host‐virus interactions, the strategies used by the viruses to promote the virus genome transport, and the current gaps in the literature. Finally, we highlight how Rab11 has emerged as a target of choice for the intracellular transport of ‐ssRNA virus genomes.
The utilization and safety of apixaban for therapeutic anticoagulation in heart transplant population requiring routine endomyocardial biopsies
Authors: Lindauer Kristen E. , Ingemi Amanda I. , McMahon Megan R. , Lichvar Alicia , Baran David A. , Cameron Chad , Badiye Amit , Sawey Edward J. , Old Wayne , Yao Andrew , Yehya Amin , Herre John M.
Published: October 2022

Purpose

Routine endomyocardial (EM) biopsies pose a challenge in the management of heart transplant recipients requiring anticoagulation. Apixaban is a direct‐acting oral anticoagulant (DOAC) with a short half‐life allowing for brief interruptions of anticoagulation for procedures. The study objective was to determine the safety and efficacy of apixaban in heart transplant patients undergoing EM biopsies.

Methods

This retrospective case series evaluated patients with a heart transplant from April 1, 2017 to July 30, 2020 who were treated with apixaban within 90 days post‐transplant. The primary outcome was the occurrence of a bleeding or thrombotic event.

Results

A total of 12 patients with >100 biopsies were included. The median age was 54 years (IQR 37–59) with a mean weight of 91 ± 20 kg. There were no bleeding or thrombotic events. During therapy, patients underwent an average of eight biopsies. The median time from transplant to initiation of apixaban was 39.5 days (range 9–77). Therapy was maintained without any need for reversal for a median of 276 days (IQR 45–245).

Conclusions

Apixaban is safe to use for anticoagulation of heart transplant recipients undergoing routine biopsies. Using apixaban allows for a short interruption of therapeutic anticoagulation to accommodate a biopsy without increased risk of bleeding.
Genetics of drug‐induced liver injury: Current knowledge and future prospects
Authors: Daly Ann K.
Published: October 2022

Idiosyncratic drug‐induced liver injury (DILI) remains an important clinical problem, both during drug development and the prescription of a range of licensed drugs. Although rare, the consequences are serious. Ongoing studies on genetic risk factors for DILI, especially genomewide association studies, have resulted in the identification of a number of genetic risk factors, including particular HLA alleles and a few non‐HLA genes, both immune‐related and metabolic. Some non‐HLA associations, such as N‐acetyltransferase 2 in isoniazid DILI and interferon regulatory factor 6 in interferon‐beta DILI are likely to be drug‐specific due to the role of the associated gene, but there is also evidence for polygenic susceptibility involving pathways such as oxidative and endoplasmic reticulum stress and mitochondrial function for DILI induced by multiple drugs. Increased knowledge of genetic risk factors should assist in better understanding underlying DILI mechanisms and help improve methods for identifying hepatotoxic drugs early in development. HLA allele‐specific T cell proliferation together with in silico prediction of drug binding to specific HLA proteins have confirmed genetic findings for certain common causes of DILI. However, studies in hepatocytes exposed to high drug concentrations suggest toxicity that is not dependent on genotype also occurs. It seems likely that susceptibility to DILI involves several genetic risk factors combining with other factors that affect drug levels. Despite recent progress in detecting genetic risk factors for DILI, low positive predictive values mean that general implementation of genotyping prior to prescription of potentially hepatotoxic drugs is not useful currently.
Reactive infectious mucocutaneous eruption due to COVID‐19 with erythema‐multiforme‐like lesions and myeloid cells
Authors: Ortiz Eduardo G. , Junkins‐Hopkins Jacqueline M.
Published: October 2022

Reactive infectious mucocutaneous eruption (RIME) is a recently described entity in which there is prominent mucositis, most commonly involving the oral and urogenital mucosa, secondary to a variety of pathogens. There is typically minimal cutaneous involvement in RIME. This contrasts with erythema multiforme (EM) in which characteristic targetoid lesions predominate, usually in isolation (EM minor), but in a subset of cases, with severe mucositis (EM major). While the histopathologic features of RIME have not been as well defined, those of EM are characterized by epidermal apoptosis and interface dermatitis with lymphocytes making up the predominant cell type. We report a unique case of RIME in a 16‐year‐old male with COVID‐19 characterized by significant mucositis involving the oral and genital mucosa, as well as numerous targetoid lesions on the trunk and extremities. Histopathologically, there was an inflammatory infiltrate obscuring and disrupting the epidermal interface, associated with epidermal necrosis, and blister formation. The infiltrate was composed of cells with irregular, non‐segmented and elongate nuclei, with myeloid and histiocytoid cytomorphology. The cells were positive for myeloperoxidase, CD68, and CD163 (subset) suggesting myeloid lineage. RIME is a rarely reported COVID‐19‐related eruption, and targetoid lesions and myeloid interface reactions have not been described with RIME.
Beliefs and attitudes of drug and alcohol clinicians when considering referral of Aboriginal clients to involuntary drug and alcohol treatment: A qualitative study
Authors: Lee K. S. Kylie , Bullen Lynette M. , Zheng Catherine , Dawson Angela , Munro Alice , Conigrave Katherine M.
Published: October 2022

Introduction

Involuntary drug and alcohol treatment occurs in many countries and its role is often controversial. This can be a particular concern in relation to First Nations or other culturally distinct populations. This study explores beliefs and attitudes of drug and alcohol clinicians when considering referral of Aboriginal Australians to involuntary drug and alcohol treatment in New South Wales (NSW), Australia.

Methods

The Involuntary Drug and Alcohol Treatment program (IDAT) is legislated by the NSW Drug and Alcohol Treatment Act 2007. There are two IDAT units—in urban (Sydney, four beds) and regional NSW (Orange, eight beds). NSW Health drug and alcohol clinicians who had referred clients to IDAT between 2016 and 2018 were invited to participate in a semi‐structured 1:1 interview. Eleven clinicians (n = 2, male) from six local health districts (urban through to remote) agreed to participate. A descriptive qualitative analysis of responses was conducted.

Results

Two key themes summarised the beliefs and attitudes that clinicians reported influencing them when considering referral of Aboriginal Australians to involuntary drug and alcohol treatment in NSW: (i) dilemma between saving someone's life and being culturally safe; and (ii) need for holistic wrap‐around care.

Discussion and Conclusions

Almost all clinicians were worried that being in IDAT would further erode their Aboriginal client's autonomy and be retraumatising. Strategies are needed to support the involvement of Aboriginal‐specific services in IDAT processes and ensure local support options for clients on discharge. Future research should examine the effectiveness, acceptability and feasibility of involuntary drug and alcohol treatment programs.
Differential response to climate change and human activities in three lineages of Sichuan snub‐nosed monkeys (Rhinopithecus roxellana)
Authors: Zhao Xumao , Li Xinrui , Zhang Zhixin , Garber Paul A. , Yu Min , Qiao Huijie , Li Ming
Published: October 2022

Aim

Determining the mechanisms by which climate change and human activities affect patterns of ecological specialization in different genetic units of the same species is crucial for developing local or regionally‐based conservation solutions. This study uses species distribution models and genetic analysis to (1) identify the evidence of intraspecific differences in the population size and distribution of the three extant lineages (Sichuan/Gansu (SG), Qinling (QL) and Shennongjia (SNJ)) of Sichuan snub‐nosed monkeys and (2) determine why some lineages have lower population numbers, a smaller geographical distribution, and are more threatened with extinction.

Location

China.

Methods

We used n‐dimensional hypervolume modelling and genotype‐environment association (GEA) models to compare the climatic niches of three snub‐nosed monkey lineages, SDMs to reconstruct the historical, current and future distributions of each lineage and SMC++ to calculate their effective population sizes.

Results

We found evidence of: (1) climatic niche differentiation among the SG, QL and SNJ lineages of Sichuan snub‐nosed monkeys; (2) geographical isolation combined with a decrease in population size during the LGM resulted in ecological specialization among these three lineages; and (3) a decline in climatic suitability and anthropogenically driven land conversion, combined with small population size and a narrow distributional range, indicates that the SNJ lineage is at a greater risk of extinction than the SG and QL lineages.

Main conclusions

We demonstrate that during the LGM a reduction in habitat suitability driven by climate change, in concert with decreasing population size, resulted in the geographical isolation of the three Sichuan snub‐nosed monkey subpopulations, leading to lineage differences in ecological specialization. GEA models and hypervolume models demonstrated that the three lineages occupy different ecological niches. Based on lineage‐level models, the SNJ and QL lineages should be the immediate focus of conservation efforts due to their small effective population size and expected future reductions in available suitable habitats. The modelling approach used here is robust and can be applied effectively to examine the biogeography, recent evolutionary history and effective population size of other endangered animal taxa.
Factors associated with successful weight loss after liraglutide treatment for obesity
Authors: Sannaa Wassel , Dilmaghani Saam , BouSaba Joelle , Maselli Daniel , Atieh Jessica , Eckert Deborah , Taylor Ann L. , Harmsen W. Scott , Acosta Andres , Camilleri Michael
Published: October 2022

Aim

To identify patient factors, including gastrointestinal functions, that are predictive or associated with weight loss in response to once‐daily 3 mg liraglutide administered subcutaneously (SQ) or placebo in obesity.

Methods

One hundred and thirty‐six obese adults (87% female) were randomized in a placebo‐controlled, 16‐week trial of liraglutide, escalated to 3 mg administered SQ daily. Gastrointestinal functions were measured at baseline and 16 weeks: gastric emptying of solids (GET1/2); fasting and postprandial gastric volumes; kcal ingested during ad libitum buffet meal and the nutrient drink test. GET1/2 was also measured at 5 weeks. A multiple variable regression model examined variables associated with weight loss of more than 4 kg at 16 weeks. A parsimonious model using backward selection identified the final model.

Results

Weight loss of more than 4 kg at 16 weeks occurred in 71% of liraglutide‐ and 16% of placebo‐treated patients. In all participants combined, parameters univariately associated with a weight loss of more than 4 kg were GET1/2 at 5 and 16 weeks, weight loss at 5 weeks and kcal intake during the buffet meal at 16 weeks. The final parsimonious model (area under the receiver operator characteristics [AUROC] curve = 0.832) identified that factors associated with more than 4‐kg weight loss were GET1/2 at 5 weeks (OR = 2.505; 95% CI: 1.57‐3.997) per 50 minutes and kcal intake during ad libitum meal at 16 weeks (OR = 0.721; 95% CI: 0.602‐0.864) per 100 kcal. Among only the 60 liraglutide‐treated subjects, kcal intake at 16 weeks was associated with 4‐kg weight loss (AUROC = 0.757).

Conclusions

Slower GET1/2 and weight loss at 5 weeks predicted a weight loss of more than 4 kg at 16 weeks in all participants. Among liraglutide‐treated adults, weight loss of more than 4 kg was associated with ad libitum meal kcal intake at 16 weeks.
Finerenone in patients across the spectrum of chronic kidney disease and type 2 diabetes by glucagon‐like peptide‐1 receptor agonist use
Authors: Rossing Peter , Agarwal Rajiv , Anker Stefan D. , Filippatos Gerasimos , Pitt Bertram , Ruilope Luis M. , Fonseca Vivian , Umpierrez Guillermo E. , Caramori Maria Luiza , Joseph Amer , Lambelet Marc , Lawatscheck Robert , Bakris George L. ,   the FIDELIO‐DKD and FIGARO‐DKD Investigators
Published: October 2022

Aims

To explore the modifying effect of glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) use on outcomes with finerenone across a wide spectrum of patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) in the pooled analysis of FIDELIO‐DKD and FIGARO‐DKD.

Materials and methods

Patients with T2D and CKD treated with optimized renin‐angiotensin system blockade were randomized to finerenone or placebo. Effects of finerenone on a cardiovascular composite outcome (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and a kidney composite outcome (kidney failure, sustained ≥57% estimated glomerular filtration rate [eGFR] decline, or renal death), change in urine albumin‐to‐creatinine ratio (UACR), and safety were analysed by GLP‐1RA use.

Results

Of 13 026 patients, 944 (7.2%) used GLP‐1RAs at baseline. Finerenone reduced the risk of the cardiovascular composite outcome (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.52–1.11 with GLP‐1RA; HR 0.87, 95% CI 0.79–0.96 without GLP‐1RA; P‐interaction = 0.63) and the kidney composite outcome (HR 0.82, 95% CI 0.45–1.48 with GLP‐1RA; HR 0.77, 95% CI 0.67–0.89 without GLP‐1RA; P‐interaction = 0.79) irrespective of baseline GLP‐1RA use. Reduction in UACR with finerenone at Month 4 was –38% in patients with baseline GLP‐1RA use compared with –31% in those without GLP‐1RA use (P‐interaction = 0.03). Overall safety and incidence of hyperkalaemia were similar, irrespective of GLP‐1RA use.

Conclusions

The cardiorenal benefits of finerenone on composite cardiovascular and kidney outcomes and UACR reduction in patients with CKD and T2D appear to be maintained, regardless of GLP‐1RA use. Subsequent studies are needed to investigate any potential benefit of this combination.
Comparing climatic suitability and niche distances to explain populations responses to extreme climatic events
Authors: Perez‐Navarro Maria A. , Broennimann Olivier , Esteve Miguel Angel , Bagaria Guillem , Guisan Antoine , Lloret Francisco
Published: October 2022

Habitat suitability calculated from species distribution models (SDMs) has been used to assess population performance, but empirical studies have provided weak or inconclusive support to this approach. Novel approaches measuring population distances to niche centroid and margin in environmental space have been recently proposed to explain population performance, particularly when populations experience exceptional environmental conditions that may place them outside of the species niche. Here, we use data of co‐occurring species' decay, gathered after an extreme drought event occurring in the southeast of the Iberian Peninsula which highly affected rich semiarid shrubland communities, to compare the relationship between population decay (mortality and remaining green canopy) and 1) distances between populations' location and species niche margin and centroid in the environmental space, and 2) climatic suitability estimated from frequently used SDMs (here MaxEnt) considering both the extreme climatic episode and the average reference climatic period before this. We found that both SDMs‐derived suitability and distances to species niche properly predict populations performance when considering the reference climatic period; but climatic suitability failed to predict performance considering the extreme climate period. In addition, while distance to niche margins accurately predict both mortality and remaining green canopy responses, centroid distances failed to explain mortality, suggesting that indexes containing information about the position to niche margin (inside or outside) are better to predict binary responses. We conclude that the location of populations in the environmental space is consistent with performance responses to extreme drought. Niche distances appear to be a more efficient approach than the use of climate suitability indices derived from more frequently used SDMs to explain population performance when dealing with environmental conditions that are located outside the species environmental niche. The use of this alternative metrics may be particularly useful when designing conservation measures to mitigate impacts of shifting environmental conditions.