bluuebunny/crossref_metadata_2025 huggingface dataset:
SUMOylation of the Cardiac Sodium Channel NaV1.5 Modifies Inward Current and Cardiac Excitability
Authors: Yoon Jin-Young , Greiner Alexander M. , Jacobs Julia S. , Kim Young-Rae , Kutschke William , Matasic Daniel S. , Vikram Ajit , Gaddam Ravinder R , Mehdi Haider , Irani Kaikobad , London Barry
Published: December 2022

Background

Decreased peak sodium current (INa) and increased late sodium current (INa,L), through the cardiac sodium channel NaV1.5 encoded bySCN5A, cause arrhythmias. Many NaV1.5 post-translational modifications have been reported by us and others. A recent report concluded that acute hypoxia increases INa,Lby increasing a Small Ubiquitin-like MOdifier (SUMOylation) at K442-NaV1.5.

Objective

To determine whether and by what mechanisms SUMOylation alters INa, INa,Land cardiac electrophysiology.

Methods

SUMOylation of NaV1.5 was detected by immunoprecipitation and immunoblotting. INawas measured by patch clamp with/without SUMO1 overexpression in HEK293 cells expressing wild type (WT) or K442R-NaV1.5 and in neonatal rat cardiac myocytes (NRCMs). SUMOylation effects were studiedin vivoby electrocardiograms and ambulatory telemetry using Scn5a heterozygous knockout (SCN5A+/-) mice and the de-SUMOylating protein SENP2 (AAV9-SENP2) or the SUMOylation inhibitor anacardic acid. NaV1.5 trafficking was detected by immunofluorescence.

Results

NaV1.5 was SUMOylated in HEK293 cells, NRCMs and human heart tissue. HyperSUMOylation at NaV1.5-K442 increased INain NRCMs and in HEK cells overexpressing WT but not K442R-Nav1.5. SUMOylation did not alter other channel properties including INa,L. AAV9-SENP2 or anacardic acid treatment of SCN5A+/-mice decreased INa, prolonged QRS duration, and produced heart block and ventricular arrhythmias. SUMO1 overexpression enhanced membrane localization of NaV1.5.

Conclusion

SUMOylation of K442-Nav1.5 increases peak INawithout changing INa,L, at least in part by altering membrane abundance. Our findings do not support SUMOylation as a mechanism for changes in INa,L. Nav1.5 SUMOylation may modify arrhythmic risk in disease states and represents a potential target for pharmacological manipulation.
Residential satisfaction and quality of urban life: examining diverse housing environments
Authors: Koçak Güngör Merve , Terzi Fatih
Published: December 2022

Purpose

As an important indicator of the quality of life of individuals, residential environments are continuing to evolve, due to the rapidly changing production–consumption relations. However, in this evolving process, the effect of the differentiated residential environments on the individuals' residential satisfaction remains unclear. This paper aims to measure the effects of the varying residential environments on the overall quality of urban life (QoUL) in Kayseri, one of the most developed cities in Central Anatolia.

Design/methodology/approach

It is based on empirical data on the quality of life in the different residential environments of Kayseri. The research method used stratified purposeful sampling, and the household survey data were analyzed using factor analysis, multiple regression and ANOVA statistical methods.

Findings

The most influential factors on the overall QoUL of individuals living in different Kayseri residential neighborhoods were satisfaction with neighborhood and city-level urban services, neighborhood relations and belonging factor groups. The critical finding obtained in this study is that residential satisfaction in low-rise and compact form housing areas in Kayseri is higher compared to residential satisfaction in high-rise neighborhoods. This result reveals that the high-rise building typology that is dominant in Turkey's big cities should be seriously questioned, and urban development policies should be re-evaluated.

Research limitations/implications

The study was designed to produce baseline data so that future changes in residential conditions as perceived by the residents of Kayseri could be monitored to support decisions for residential areas.

Originality/value

Comparative case studies, particularly on low-rise versus high-rise environments, are scarce. As a result, this research contributes to the field of comparative studies on residential environments.
Acceptance of in vitro meat and the role of food technology neophobia, dietary patterns and information – Empirical evidence for Germany
Authors: Heidmeier Anna Katharina , Teuber Ramona
Published: December 2022

Purpose

The present study addresses acceptance of in vitro meat (IVM) among a predominantly student sample in Germany. It is investigated to which extent food technology neophobia, the currently followed diet and information treatments impact acceptance of IVM measured via the construct willingness to buy (WTB).

Design/methodology/approach

A quantitative online-survey was conducted in August 2020 using a between-subject design with three different information treatments and one control group. Moreover, the Food Technology Neophobia (FTN) scale was employed, For the statistical analysis, the χ2 and Kruskal–Wallis test were used. Additionally, a binary logit model was specified and estimated in order to investigate the determinants of willingness to buy IVM accounting for the effects of gender, age, vegetarianism/veganism, FTN, prior knowledge, information treatments and potential interaction effects.

Findings

Participants following a vegan or vegetarian diet exhibit a lower likelihood of IVM acceptance in comparison to participants following an omnivore diet. However, a considerable share of vegan and vegetarian participants expressed a positive WTB. Moreover, an increasing FTN score (i.e. an increase in food technology neophobia) goes along with a reduced likelihood of acceptance, while all three information treatments increase acceptance in comparison to the control group. The largest effect on acceptance could be found for the environmental benefit treatment.

Practical implications

The findings show that especially among a young and highly educated sample the stressing of environmental benefits of IVM has a substantial impact on acceptance. This might be taken up in information and marketing campaigns once the product becomes available on the European market.

Originality/value

So far the empirical evidence on German consumers' acceptance of IVM is scarce. The present study addressed this research gap by focusing on a young sample with a high percentage of vegetarians and vegans and analyzing the role of food technology neophobia and different information treatments in a between-subject design.
Strength of HR signals and intent to stay: mediating role of psychological contract fulfillment
Authors: Bandyopadhyay Chiradip , Srivastava Kailash B.L.
Published: December 2022

Purpose

The study examined the relationship between human resource (HR) signals and intent to stay (ITS) in an attributional framework. It also investigated the mediating role of psychological contract fulfillment in the relationship between the strength of HR signal and ITS.

Design/methodology/approach

The data were collected from 460 managers in the manufacturing sector from eastern India using a structured questionnaire. The study adopted a mediated structural equation model to test the model fit and hypotheses.

Findings

The study confirmed the relationship between the strength of the H R signal and the ITS, and the mediating role of psychological contract fulfillment between the strengths of HR signals and ITS. The study indicates a positive role of the psychological contract fulfillment in strengthening the effect of HR signals on ITS.

Originality/value

The study adds to the body of knowledge by confirming a signaling role of HR practices within the firm having the attributional ability. It also indicates the role of psychological contract fulfillment in employee retention.
Gender diversity and SDG disclosure: the mediating role of the sustainability committee
Authors: Zampone Giovanni , Nicolò Giuseppe , Sannino Giuseppe , De Iorio Serena
Published: December 2022

Purpose

The study examines the association between board gender diversity and Sustainable Development Goal (SDG) disclosure from an international and longitudinal perspective. It also investigates the role of the Sustainability Committee (SC) as a possible factor that can mediate the relationship between board gender diversity and SDG disclosure.

Design/methodology/approach

The authors focused on the annual Communication on Progress (CoP) prepared annually by a sample of 526 companies from 39 countries and ten industry sectors along the 2017–2020 period to evaluate the SDG disclosure. Baron and Kenny's (1986) three-step model is estimated to test the impact of the presence of an SC on the SDG disclosure level and the mediating effect exerted by the SC on the relationship between board gender diversity and SDG disclosure.

Findings

Findings shed light on the usefulness of the CoP as an alternative reporting tool to communicate progress against SDGs achievement, especially regarding SDGs 13 and 8. This study evidences that board gender diversity positively influences SDG disclosure. The relationship between board gender diversity and SDG disclosure is not only direct but also mediated by the presence of an SC.

Research limitations/implications

Companies need to consider the role of women in enhancing the effectiveness of their governance mechanisms and their ability to meet stakeholder information needs. Establishing a specific SC represents a valid mechanism that ensures greater transparency about corporate actions tackled to contribute toward SDGs and enhances the relationship between board gender diversity and SDG disclosure among International companies.

Practical implications

The study's findings offer stimuli for policy-makers and regulators to reflect on the relevance of the CoP as a possible alternative communication tool to provide SDGs information and overcome the limitations of the Sustainability Reports.

Originality/value

This is the first study that examines companies' SDG disclosure practices focusing on CoPs. Further, to the best of the authors' knowledge, this is the first study that tests the relationship between gender diversity and SDG disclosure, considering the mediating effect of an SC committee.
Local infrastructure, rural households' resilience capacity and poverty: evidence from panel data for Southeast Asia
Authors: Hartwig Tim , Nguyen Trung Thanh
Published: December 2022

Purpose

The authors examine the association between infrastructure and a household's resilience capacity against shocks and the impacts of a household's resilience capacity on household consumption and poverty.

Design/methodology/approach

The authors use panel data (collected in 2010, 2013 and 2016) from 1,698 households in Thailand and 1,701 households in Vietnam and employ an instrumental variable approach.

Findings

The authors find that transportation and information and communication technology (ICT) infrastructure help improve households' absorptive capacity in coping with shocks. Furthermore, this capacity can prevent households from reducing consumption and falling into poverty.

Practical implications

Rural development policies should attend to transportation and ICT infrastructure.

Originality/value

The authors establish empirical evidence on the association between infrastructure and a household's resilience capacity and the impact of resilience capacity on poverty.
The link between workplace incivility, emotional exhaustion, and job embeddedness: examining the moderating role of power distance
Authors: Gustiawan Deni , Noermijati Noermijati , Aisjah Siti , Indrawati Nur Khusniyah , Hendryadi Hendryadi
Published: December 2022

Purpose

Integrating the conservation of resources theory, Hofstede's national culture theory and the cognitive-motivational-relational theory of emotions, the authors propose that power distance (as a moderator) and emotional exhaustion (as a mediator) play a role in the relationship between workplace incivility, emotional exhaustion and job embeddedness.

Design/methodology/approach

The data were collected in two stages using an online survey of 404 employees from three sectors, including hospitality, banking and manufacturing, in Indonesia. The authors tested a moderated mediation model using Hayes' macro PROCESS version 3.5.

Findings

Workplace incivility contributes to emotional exhaustion, which predicts job embeddedness. Emotional exhaustion also contributes to job embeddedness. In the moderation model, the authors found that the effect of workplace incivility on emotional exhaustion was more substantial for employees with high perceived power distance. Furthermore, power distance also played a moderating role in the relationship between emotional exhaustion and job embeddedness.

Practical implications

Since workplace incivility and job embeddedness differ across cultures, the results of this study contain practical management implications for Indonesian settings, especially the hospitality, manufacturing and banking sectors. The authors provide practical management implications for redesigning organizational culture to help employees avoid uncivil interactions in the workplace. The authors also provide implications concerning strategic managerial directions to improve communication and supervisors' skills at all levels of management.

Originality/value

This study is the first to introduce power distance as a complementary explanation for the relationship between workplace incivility, emotional exhaustion and job embeddedness while focusing on an Asian developing country.
Within‐host and external environments differentially shape β‐diversity across parasite life stages
Authors: Warburton Elizabeth M. , Budischak Sarah A. , Jolles Anna E. , Ezenwa Vanessa O.
Published: December 2022

Uncovering drivers of community assembly is a key aspect of learning how biological communities function. Drivers of community similarity can be especially useful in this task as they affect assemblage‐level changes that lead to differences in species diversity between habitats. Concepts of β‐diversity originally developed for use in free‐living communities have been widely applied to parasite communities to gain insight into how infection risk changes with local conditions by comparing parasite communities across abiotic and biotic gradients.

Factors shaping β‐diversity in communities of immature parasites, such as larvae, are largely unknown. This is a key knowledge gap as larvae are frequently the infective life‐stage and understanding variation in these larval communities is thus key for disease prevention. Our goal was to uncover links between β‐diversity of parasite communities at different life stages; therefore, we used gastrointestinal nematodes infecting African buffalo in Kruger National Park, South Africa, to investigate within‐host and extra‐host drivers of adult and larval parasite community similarity.

We employed a cross‐sectional approach using PERMANOVA that examined each worm community at a single time point to assess independent drivers of β‐diversity in larvae and adults as well as a longitudinal approach with path analysis where adult and larval communities from the same host were compared to better link drivers of β‐diversity between these two life stages.

Using the cross‐sectional approach, we generally found that intrinsic, within‐host traits had significant effects on β‐diversity of adult nematode communities, while extrinsic, extra‐host variables had significant effects on β‐diversity of larval nematode communities. However, the longitudinal approach provided evidence that intrinsic, within‐host factors affected the larval community indirectly via the adult community.

Our results provide key data for the comparison of community‐level processes where adult and immature stages inhabit vastly different habitats (i.e. within‐host vs. abiotic environment). In the context of parasitism, this helps elucidate host infection risk via larval stages and the drivers that shape persistence of adult parasite assemblages, both of which are useful for predicting and preventing infectious disease.
Changes in the rearing environment cause reorganization of molecular networks associated with DNA methylation
Authors: von Holdt Bridgett M. , Kartzinel Rebecca Y. , van Oers Kees , Verhoeven Koen J. F. , Ouyang Jenny Q.
Published: December 2022

Disentangling the interaction between the genetic basis and environmental context underlying phenotypic variation is critical for understanding organismal evolution. Environmental change, such as increased rates of urbanization, can induce shifts in phenotypic plasticity with some individuals adapting to city life while others are displaced.

A key trait that can facilitate adaptation is the degree at which animals respond to stressors. This stress response, which includes elevation of baseline circulating concentrations of glucocorticoids, has a heritable component and exhibits intra‐ and inter‐individual variation. However, the mechanisms behind this variability and whether they might be responsible for adaptation to different environments are not known. Variation in DNA methylation can be a potential mechanism that mediates environmental effects on the stress response, as early‐life stressors increase glucocorticoid concentrations and change adult phenotype.

We used an inter‐ and intra‐environmental cross‐foster experiment to analyse the contribution of DNA methylation to early‐life phenotypic variation. We found that at hatching, urban house wren (Troglodytes aedon) offspring had higher methylation frequencies compared with their rural counterparts.

We also observed age‐related patterns in offspring methylation, indicating the developmental effects of the rearing environment on methylation. At fledgling, differential methylation analyses showed that cellular respiration genes were differentially methylated in broods of different origins and behavioural and metabolism genes were differentially methylated in broods of different rearing environments. Lastly, hyper‐methylation of a single gene (CNTNAP2) is associated with decreased glucocorticoid levels and the rearing environment.

These differential methylation patterns linked to a specific physiological phenotype suggest that DNA methylation may be a mechanism by which individuals adjust to novel environments during their lifespan. Characterizing genetic and environmental influences on methylation is critical for understanding the role of epigenetic mechanisms in evolutionary adaptation.
Underexplored viral auxiliary metabolic genes in soil: Diversity and eco‐evolutionary significance
Authors: Sun Mingming , Yuan Shujian , Xia Rong , Ye Mao , Balcázar José Luis
Published: December 2022

Bacterial viruses are the most abundant biological entities in soil ecosystems. Owing to the advent of metagenomics and viromics approaches, an ever‐increasing diversity of virus‐encoded auxiliary metabolic genes (AMGs) have been identified in soils, including those involved in the transformation of carbon, phosphorus, and sulfur, degradation of organic pollutants, and antibiotic resistance, among other processes. These viral AMGs can alter soil biogeochemical processes and metabolic activities by interfering with bacterial host metabolism. It is recognized that viral AMGs compensate for host bacterial metabolism outputs by encoding accessory functional genes and are favourable for the hosts' adaptation to stressed soil environments. The eco‐evolutionary mechanisms behind this fascinating diversity of viral AMGs in soil microbiomes have begun to emerge, such as horizontal gene transfer, lytic‐lysogenic conversion, and single‐nucleotide polymorphisms. In this mini‐review, we summarize recent advances in the diversity and function of virus‐encoded AMGs in the soil environment, especially focusing on the evolutionary significance of AMGs involved in virus‐host interactions. This mini‐review also sheds light on the existing gaps and future perspectives that could have major significance for viral AMGs research in soils.
Debunking misinformation in times of crisis: Exploring misinformation correction strategies for effective internal crisis communication
Authors: Kim Young , Lim Hyunji (Dana)
Published: December 2022

This study aimed to explore misinformation correction strategies for effective internal crisis communication. Using an experimental study (N = 1196) with full‐time employees in the United States, this study found that a corrective strategy using more elaborated facts was effective in protecting internal reputation and that timely, proactive communication to debunk crisis misinformation was a significant factor influencing employees' cognitive reactance (counterarguing) and behavioural outcomes. This research can help crisis communicators better understand how to prevent negative outcomes that undermine the effectiveness of evidence‐based communication efforts. Specifically, the findings suggest the use of more proactive internal crisis communication to correct misinformation and to prevent damage caused by employees' misconceptions and related communication behaviours. Furthermore, the study theoretically extends the literature on debunking crisis‐misinformation by elucidating the cognitive and behavioural processes of crisis misinformation in internal crisis communication.
Standard Error Biases When Using Generated Regressors in Accounting Research
Authors: CHEN WEI , HRIBAR PAUL , MELESSA SAM
Published: December 2022

We analyze the standard error bias associated with the use of generated regressors—independent variables generated from first‐step regressions—in accounting research settings. Under general conditions, generated regressors do not affect the consistency of coefficient estimates. However, commonly used generated regressors can cause standard errors to be understated. Problematic generated regressors include predicted values, coefficient estimates, and measures derived from these estimates. Widely used generated regressors in accounting include measures of earnings persistence, normal accruals, litigation risk, and conditional conservatism. Using simple regression models and simulation, we demonstrate how generated regressors can produce understated standard errors in accounting research settings. We also demonstrate how the magnitude of the standard error bias is inversely related to the precision of the generated regressor. Finally, we discuss bootstrapping as a correction for the bias and demonstrate the pairs cluster bootstrap as a tool to improve inferences in common accounting settings involving generated regressors.
Blue economy, blue finance and ocean governance for achieving sustainable development goals
Authors: Sarangi Unmana
Published: December 2022

This research paper is an attempt to define and analyse the concept of the blue economy (BE) and its implications for achieving Sustainable Development Goals (SDGs). This study covers aspects such as building a blue economy to achieve SDGs, the importance of a healthy ocean for current and future generations, maintaining the momentum to save the ocean, achievements of the United Nations (UN) conference on the Sustainable Blue Economy, and the highlights of the UN World Water Development Report 2020. This study specifically analyses the health effects and threats to biodiversity, adaptation and mitigation, improved wastewater management, prioritizing water, accessing climate funds, water and climate change, and the relationship between the blue economy and UN SDGs as well as identification of key stakeholders. This is achieved through a detailed literature review on the blue economy that identifies global organizations working on creating a blue economy, elements of the blue economy and current development efforts, United Nations Convention on the Law of the Sea, sustainability and equity, ocean governance, international law and frameworks, and improvement in governance frameworks among other issues. The methodology used attempted to develop a macro, comprehensive, and systematic aggregate database at the country level on macro parameters, namely blue economy, blue finance, BE‐SDGs linkages, water development, marine sector, SDGs data on SDG‐14 (life underwater), SDG‐6 (access to safe drinking water and sanitation), SDG‐3 (good health and well‐being), and optimal management of water resources through scientific techniques, such as building several small reservoirs instead of mega projects, develop small catchment dams and protect wetlands, soil management, micro catchment development, recharging of underground aquifers thus reducing the need for large dams, which has encountered challenges due to data limitations. The results of this research study emphasize broader stakeholder consultations at the global level to resolve the issues relating to blue economy, blue finance, and ocean governance. The most important conclusion and policy implications of the study are that international organizations including the United Nations, the Asian Development Bank, and the World Bank are working towards achieving the SDGs in general, and the blue economy, blue finance, and ocean governance in particular.
The remote work revolution: Impact on real estate values and the urban environment: 2023 AREUEA Presidential Address
Authors: Van Nieuwerburgh Stijn
Published: December 2022

The covid‐19 pandemic induced a major shift in the prevalence of remote and hybrid work arrangements. This review article studies the effects of this remote work revolution for residential and commercial real estate values and for the future of cities. It also discusses consequences for productivity, innovation, local public finance, and the climate. The last part of the article discusses policy interventions.
Patterns of emergency department use in rural and metropolitan New South Wales by socioeconomic status: A population‐based study
Authors: Stephens Alexandre S , Dinh Michael M , Kinsman Leigh
Published: December 2022

Objective

To investigate the patterns of ED use in metropolitan and rural New South Wales (NSW) by socioeconomic status (SES).

Methods

We undertook a retrospective, population‐based study of de‐identified data from the NSW Emergency Department Data Collection (EDDC). The study population comprised of NSW residents who presented to an NSW public hospital ED in 2013–2019 and were registered in the NSW EDDC. Total ED presentations, negative binomial regression modelled annual changes in ED presentations over 2013–2019, and age‐ and sex‐standardised rates of ED presentations in 2019 were assessed.

Results

Overall, between 2013 and 2019, ED presentations increased in metropolitan and rural NSW, with mean annual percentage increases of 3.1% (95% confidence interval [CI] 2.8–3.5) and 2.5% (95% CI 2.0–2.9), respectively. This growth varied by SES, with larger increases observed in higher SES groups. The bulk of presentations in rural NSW were from individuals living in disadvantaged areas. Standardised rates of ED presentations were highest in the most disadvantaged quintiles (SES 1) and progressively decreased with increasing SES in both rural and metropolitan NSW (negative gradients). Rates were higher in rural NSW compared to metropolitan NSW across all SES quintiles for total, low acuity and non‐low acuity presentations.

Conclusions

Negative gradients in rates of ED presentations with increasing SES were observed in both metropolitan and rural NSW. At each SES quintile, rates of ED presentations were higher in rural compared to metropolitan areas. Further research exploring the underlying causal mechanisms leading to increased ED demand in rural NSW and socioeconomically disadvantaged populations is warranted.
Malaria and economic activity: Evidence from US agriculture
Authors: Malpede Maurizio
Published: December 2022

I conduct a disaggregated empirical analysis of the relationship between the reduction in malaria transmission and agricultural development in the United States. Exploiting exogenous geographic variations in malaria‐suitable weather conditions and using historical county data together with a robust quasi‐experimental approach, I show that the farm value per acre of arable land of more endemic counties increased by around eight percentage points after the eradication of the disease relative to less endemic counties. Using historical data on cropland distribution within the United States, I also find that arable land increased in high malaria‐risk areas. Finally, I shed light on the increased productivity of farmers as a potential channel. Robustness checks from geographic variations in malaria prevalence within neighboring counties and placebo treatments reinforce the positive effect of eradicating malaria on agricultural development in the United States.
Timing of migration dates and detection of first wintering sites for the Turtle Dove in Northwest Africa
Authors: Mansouri Ismail , Squalli Wafae , Nefla Aymen , Mounir Mohamed , Achiban Hamid , Abdelwahab Chedad , Hmidani Mohammed , El Ghadraoui Lahsen , Dakki Mohamed
Published: December 2022

The identification of migration dates and wintering zones for migratory birds are key elements for the understanding of the Afro‐Palearctic migration system. From 2015 to 2022, a large‐scale survey of Turtle Doves Streptopelia turtur, a vulnerable species, was established in Northwest Africa, including Morocco, Algeria, and Tunisia. We monitored migration dates and wintering individuals using the line‐transect method. We found that Turtle Doves arrived in the last week of March and left the North African region in mid‐October. Compared with Morocco, Doves arrived significantly earlier in Algeria and Tunisia. Moreover, Doves were discovered wintering on nine Northwest African sites, from October to February, where individuals feed in groups. We found that the occurrence probability of wintering Turtle Doves decreased significantly with increasing temperature and rainfall. Birds wintered most often close to wetlands since the overwintering probability decreased with the increasing distance from the recording area to the nearest water body. These are the first and only detailed findings on the migration phenology of the globally vulnerable Turtle Dove in north western Africa.
Immunotherapy in advanced cutaneous squamous cell carcinoma: Sydney west cancer network experience
Authors: Hasmat Shaheen , Howle Julie R. , Carlino Matteo S. , Sundaresan Puma , Veness Michael J.
Published: December 2022

Background

Cutaneous squamous cell carcinoma (CSCC) is the second most common malignancy in the Caucasian population. A minority of cases are inoperable at presentation, recur or develop metastatic disease with a historical 5‐year overall survival of ~10%. Treatment options in this setting are generally palliative. Immunotherapy has emerged as a new paradigm in managing these patients.

Methods

Patients presenting to Sydney West Cancer Network with locally advanced or metastatic CSCC treated with the anti‐PD1 agent cemiplimab were identified. Response to treatment was objectively assessed based on RECIST1.1 or PERCIST criteria. Primary end point was objective response rate (ORR). Secondary end points included progression‐free survival (PFS), overall survival (OS), therapy toxicity, and predictors of treatment response.

Results

A total of 19 patients were identified with a median age of 76 (range 56–94) and 4 immunosuppressed. The longest follow up duration was 28 months. ORR, complete response (CR), and partial response (PR) were 68% (13/19), 53% (10/19), and 16% (3/19), respectively. Median PFS was 12 months (95% CI 9–14) whilst median OS was not reached by end of study. Responders (CR or PR) had significantly superior OS compared to those with no response (P < 0.01). A primary site of head and neck cancer was significantly associated with ORR (P = 0.04). A single patient experienced Grade 3 toxicity with the rest being Grades 0–1.

Conclusion

This study confirms the clinical efficacy of cemiplimab in patients with advanced CSCC with many experiencing a durable response and an acceptable adverse effect profile.
Establishing a state‐wide pelvic exenteration multidisciplinary team meeting in South Australia
Authors: Fitzsimmons Tracy , Thomas Michelle , Tonkin Darren , Murphy Elizabeth , Hollington Paul , Solomon Michael , Sammour Tarik , Luck Andrew
Published: December 2022

Background

Pelvic exenteration surgery is complex, necessitating co‐ordinated multidisciplinary input and improved referral pathways. A state‐wide pelvic exenteration multidisciplinary team (MDT) meeting was established in SA and the outcomes of this were audited and compared with historical data.

Methods

All patients referred for discussion between August 2021 and July 2022 to the SA State‐wide Pelvic Exenteration MDT were included in this study. MDT discussion centred around disease resectability, risk versus benefit of surgery, and need for local or interstate referral. Prospective data collection included patient demographics and MDT recommendations of surgery, palliation, or referral. Patients referred for surgery locally or interstate were compared with a retrospective patient cohort treated previously between January and December 2020.

Results

Over 12 months, 91 patients were discussed (including nine multiple times), by a mean of 18 meeting participants each month. Forty‐eight patients (58.5%) had primary malignancy, 25 (30.5%) recurrent malignancy, and 9 (11.0%) had non‐malignant disease. Colorectal cancer was the most common presentation (56.1%), followed by gynaecological (30.5%) and urological (6.1%) malignancy. Pelvic exenteration surgery was recommended to be performed locally in 53.7% of patients and the remainder for non‐surgical treatment, palliation, or re‐discussion. During this time, 44 patients underwent surgery locally (versus 34 in 2020) and only 4 referred interstate (versus 8 in 2020).

Conclusion

The establishment of a dedicated state‐wide pelvic exenteration MDT has resulted in better coordination of care for patients with locally advanced pelvic malignancy in SA, and significantly reduced the need for interstate referral.
Longitudinal follow‐up on vascular morphology and function in children with kidney transplants
Authors: Bergdahl Ebba , Westphal Ladfors Susanne , Linnér Christina , Brandström Per , Hansson Sverker , Dangardt Frida
Published: December 2022

Aim

Our aim was to evaluate cardiovascular risk profile in 42 children with kidney transplants (KT) at the Queen Silvia Children's Hospital, Gothenburg Sweden.

Methods

Forty‐two children (7.1–18 years) with KT, time from transplantation 3.5 (0.9–13) years, were examined at inclusion and annually for three consecutive years. Eighteen matched controls were examined once. Cardiovascular phenotyping included ultra‐high‐frequency ultrasound (UHFUS), pulse wave velocity (PWV), and endothelial function.

Results

Children with KT had higher body mass index (BMI) z‐score and blood pressure (BP) z‐score than healthy controls (BMI z‐score: 0.4 ± 1.0 and − 0.2 ± 0.9, respectively, p = 0.02; SBP z‐score: 0.5 ± 0.9 and − 0.8 ± 0.7; DBP z‐score: 0.7 ± 0.7 and − 0.3 ± 0.5, respectively, p < 0.001). BP z‐score decreased significantly over 3 years; other vascular markers remained unchanged. PWV and carotid intima thickness (IT) were higher in children with KT compared to healthy controls. Children with pre‐emptive KT had lower radial IT and dorsal pedal media thickness (MT) compared to children with preceding dialysis.

Conclusion

Children with KT show increased cardiovascular risk parameters, not increasing over time. Children on dialysis before KT have more pronounced vascular changes than those with pre‐emptive KT, suggesting pre‐emptive transplantation more beneficial for cardiovascular health.
Stromal vascular fraction with platelet‐rich plasma injection during surgery is feasible and safe in treatment‐refractory perianal fistulising Crohn's disease: A pilot study
Authors: Arkenbosch Jeanine H. C. , van Ruler Oddeke , Dwarkasing Roy S. , Fuhler Gwenny M. , Schouten W. Rudolph , van Oud‐Alblas Marjolein Blussé , de Graaf Eelco J. R. , de Vries Annemarie C. , van der Woude C. Janneke
Published: December 2022

Background

An unmet need remains for improved management in perianal fistulising Crohn's disease (pCD). Recently, local administration of adipose‐derived cells has shown promising results.

Aims

To assess the safety and feasibility of injection of stromal vascular fraction (SVF) with platelet‐rich plasma (PRP) in patients with pCD.

Methods

Patients ≥ 18 years with pCD were included and underwent fistula curettage, SVF with PRP injection, and closure of the internal opening. The primary endpoint was safety at 12 months. The secondary outcomes were complete radiological healing at 3 months (absence of fluid‐containing tracts on MRI) and partial and complete clinical response at 3 and 12 months (closure of ≥1, respectively, all treated external opening(s)).

Results

Twenty‐five patients were included (35 [IQR 25–40] years; 14 [56%] female); median CD duration 4 [IQR 2–8] years. Twenty‐four (95%) patients had previously undergone fistula surgery. No adverse events were encountered at lipoharvesting sites. Two (8%) patients were readmitted to hospital and six (24%) underwent unplanned re‐interventions. Post‐operative MRI (n = 24) showed complete radiological healing in nine (37.5%) patients. Partial clinical response was present in 48% (12/25) at 3 months and in 68% (17/25) at 12 months, and complete clinical closure in five (20%) patients at 3 months and in 10 (40%) patients at 12 months.

Conclusion

Injection with autologous SVF with PRP is feasible and safe in patients with treatment‐refractory pCD. Early complete radiological healing was observed in more than one‐third of patients, and clinical response in two‐thirds of patients at 12 months.
Dissection of the autophagic route in oocytes from atretic follicles
Authors: Castro‐Cruz Abraham , Echeverría Olga M. , Sánchez‐Sánchez Luis , Muñoz‐Velasco Israel , Juárez‐Chavero Silvia , Torres‐Ramírez Nayeli , Vázquez‐Nin Gerardo H. , Escobar María Luisa
Published: December 2022

Background Information

Autophagy is a conserved process that functions as a cytoprotective mechanism; it may function as a cell death process called programmed cell death type II. There is considerable evidence for the presence of autophagic cell death during oocyte elimination in prepubertal rats. However, the mechanisms involved in this process have not been deciphered.

Results

Our observations revealed autophagic cell death in oocytes with increased labeling of the autophagic proteins Beclin 1, light chain 3 A (LC3 A), and lysosomal‐associated membrane protein 1 (Lamp1). Furthermore, mTOR and phosphorylated (p)‐mTOR (S2448) proteins were significantly decreased in oocytes with increased levels of autophagic proteins, indicating autophagic activation. Moreover, phosphorylated protein kinase B (p‐AKT) was not expressed by oocytes, but mitogen‐activated protein kinase/extracellular signalregulated kinase (MAPK/ERK) signaling was observed. Additionally, selective and elevated mitochondrial degradation was identified in altered oocytes.

Conclusions

All these results suggest that mTOR downregulation, which promotes autophagy, could be mediated by low energy levels and sustained starvation involving the phosphoinositide 3‐kinase (PI3K)/AKT/mTOR and MAPK/ERK pathways.

Significance

In this work, we analyzed the manner in which autophagy is carried out in oocytes undergoing autophagic cell death by studying the behavior of proteins involved in different steps of the autophagic pathway.
Single‐cell next‐generation sequencing of circulating tumor cells in patients with neuroblastoma
Authors: Kojima Masato , Harada Takanori , Fukazawa Takahiro , Kurihara Sho , Touge Ryo , Saeki Isamu , Takahashi Shinya , Hiyama Eiso
Published: December 2022

Circulating tumor cells (CTCs) derived from any tumor tissue could contribute to metastasis and resistance to cancer treatments. In this study, we performed single‐cell next‐generation sequencing of CTCs and evaluated their usefulness for characterizing tumor biology and the mechanisms of metastasis in neuroblastomas (NB). We aimed to isolate CTCs from 10 patients with NB at diagnosis before any treatments and four patients at relapse. GD2+CD90+CD45−CD235a−DAPI− cells were isolated as neuroblastoma CTCs using fluorescence‐activated cell sorting. In five patients with advanced stages (M stage), DNA and RNA sequencing of CTCs at single‐cell level were performed. NB CTCs were isolated from eight of the 10 patients at diagnosis and three of the four patients at relapse. More CTCs could be isolated from patients with advanced stages. In one patient, ALK mutation (p.F1174L), was identified in both tumor tissue and a CTC. In patients with MYCN amplification, this gene was amplified in 12 of 13 CTCs. Using single‐cell RNA sequencing, angiogenesis‐related and cell cycle‐related genes together with CCND1 and TUBA1A genes were found to be upregulated in CTCs. In one patient, CTCs were divided into two subgroups showing different gene expression profiles. In one subgroup, cell cycle‐related and proliferation‐related genes were differentially upregulated compared with the other group. In conclusion, next‐generation sequencing of CTCs at single‐cell level might help to characterize the tumor biology and the mechanisms of metastasis in NB.
High prevalence of coronary artery calcification and increased risk for coronary artery disease in patients with Sheehan syndrome—A case–control study
Authors: Laway Bashir Ahmad , Rasool Abid , Baba Mohammad Salem , Misgar Raiz Ahmad , Bashir Mir Iftikhar , Wani Arshad Iqbal , Choh Naseer , Shah Omair , Lone Ajaz , Shah Zaffar
Published: December 2022

Objective

Patients with Sheehan syndrome (SS) are predisposed to coronary artery disease (CAD) due to risk factors like abdominal obesity, dyslipidemia and chronic inflammation. In addition to estimate CAD risk enhancers like high sensitive C reactive protein (hsCRP), apolipoprotein B (ApoB) and lipoprotein A [Lp(a)], this study applies Framingham risk score (FRS) and coronary artery calcium (CAC) score to compute a 10‐year probability of cardiovascular (CV) events in SS patients.

Design

Case–control study Sixty‐three SS patients, on a stable hormonal replacement treatment except for growth hormone and 65 age, body mass index and parity‐matched controls.

Measurements

Measurement of serum hsCRP, ApoB and Lp(a) and estimation of CAC with 16‐row multislice computed tomography scanner.

Results

The concentrations of hsCRP, ApoB and Lp(a) were significantly higher in SS patients than in controls (p < .01). After calculating FRS, 95.2% of SS patients were classified as low risk, 4.8% as intermediate risk and all controls were classified as low risk for probable CV events. CAC was detected in 50.7% SS patients and 7.6% controls (p = .006). According to the CAC score, 26.9% SS patients were classified as at risk (CAC > 10) for incident CV events as against 1.6% controls. The mean Multi‐Ethnic Study of Atherosclerosis (MESA) score was significantly higher in patients with SS than controls. CAC corelated significantly with fasting blood glucose (r = .316), ApoB (r = .549), LP(a) (r = .310) and FRS (r = .294).

Conclusion

Significant number of asymptomatic SS patients have high coronary artery calcium score and are classified at risk for CAD.
Spectral‐domain optical coherence tomography biomarkers in vitreoretinal lymphoma
Authors: Guan Wenxue , Xiao Yuanyuan , Zhao Huiying , Hu Feng , Chen Chunli , Peng Xiaoyan
Published: December 2022

Background

Although early detection is critical, diagnosing vitreoretinal lymphoma (VRL) remains difficult. We sought to assess the potential diagnostic value of spectral‐domain optical coherence tomography (SD‐OCT) in VRL.

Methods

We reviewed the clinical records and pre‐treatment SD‐OCT images of biopsy‐confirmed VRL and uveitis patients, with primary involvement of the sub‐retinal pigment epithelium (RPE) and the outer retina, including acute syphilitic posterior placoid chorioretinitis (ASPPC), chronic stage sympathetic ophthalmitis (SO), and idiopathic multifocal choroiditis (MFC).

Results

We included 45 eyes of 45 VRL patients and 40 eyes of 40 uveitis patients (17 ASPPC eyes, eight chronic SO eyes, and 15 MFC eyes). On SD‐OCT, lymphoma cell infiltration was observed in various retinal layers, most commonly in the sub‐RPE (80%) and sub‐retinal space (62%). Highly sensitive features for VRL as compared to uveitis included vitreous cells (93%), focal hyper‐reflective sub‐retinal infiltration (51%), and diffuse RPE elevations (56%). The features strongly specific for VRL included preretinal deposits (92.5%), intra‐retinal infiltration (except the incomplete vertical hyper‐reflective type, 100%), banded hyper‐reflective sub‐retinal infiltration (90%), and confluent RPE detachments (100%). We identified an approach to VRL diagnosis based on these SD‐OCT findings: (1) two highly sensitive features plus one strongly specific feature; or (2) one highly sensitive feature plus two strongly specific features, demonstrated a sensitivity of 80% and specificity of 95% for VRL.

Conclusions

The SD‐OCT may enable the detection of detailed lymphoma infiltration characteristics and provide significant supplemental value for VRL diagnosis, particularly when combining highly sensitive and specific VRL‐associated SD‐OCT features.
Short‐ and long‐term outcomes following bridge to surgery and emergency resection in acute malignant large bowel obstruction
Authors: Arnarson Örvar , Axmarker Tobias , Syk Ingvar
Published: December 2022

Aim

Bridge to surgery (BtS) aims to decrease perioperative morbidity and mortality in emergency resection (ER) of the colon. Previous results are inconsistent, and long‐term comparisons are scarce. The aim of this study was to compare the short‐ and long‐term outcomes of BtS and ER.

Method

This retrospective study examined data from the Swedish Colorectal Cancer Registry for patients treated for acute malignant large bowel obstruction from 2007 to 2009. Patients were grouped by treatment strategy: BtS (using a self‐expanding metallic stent or diverting stoma) or ER. Medical records were scrutinized for all patients in the BtS group. The primary endpoints were 5‐year overall survival (OS) and 3‐year recurrence‐free survival (RFS). The secondary endpoints were postoperative mortality and morbidity rates and stoma permanence.

Results

Overall, 143 patients were treated using BtS versus 1302 patients treated with ER. The 5‐year OS was higher in the BtS group than in the ER group (53.8% vs. 37.4%; p < 0.05). No difference was noted in the 3‐year RFS (75.7% vs. 75.0%; p = 0.38). The postoperative mortality rate was lower in the BtS group than in the ER group (0.7% vs. 7.3%; p < 0.05). Complications occurred in 46.9% of patients in the BtS group (both procedures) versus 35.9% of patients in the ER group (p < 0.05); the rate of severe complications was 23.1% and 16.9%, respectively (p = 0.07).

Conclusion

This retrospective population‐based registry study showed higher long‐term survival and lower postoperative mortality rates among patients treated with BtS versus ER for acute malignant large bowel obstruction.