bluuebunny/crossref_metadata_2025 huggingface dataset:
Fabrication and characterization of model wireless biosensor-based electrochemical impedance spectroscopy (EIS) for detecting HER2 in plasma as therapeutics
Authors: Monajjemi Majid , Mollaamin Fatemeh
Published: July 2024

Purpose

Early prediction of any type of cancer is important for the treatment of this type of disease, therefore, our target to evaluate whether monitoring early changes in plasma human epidermal growth factor receptor 2 (HER2) levels (using EIS), could help in the treatment of breast cancer or not? Human epidermal growth factor receptor 2 (HER2) overexpression is an important biomarker for treatment selection in earlier stages of cancers. The combined detection of the HER2 gene in plasma for blood cancer provides an important reference index for the prognosis of metastasis to other tissues. For this purpose, the authors fabricated and characterized a model wireless biosensor-based electrochemical impedance spectroscopy (EIS) for detecting HER2 plasma as therapeutics.

Design/methodology/approach

Most sensors generally are fabricated based on a connection between component of the sensors and the external circuits through wires. Although these types of sensors provide suitable sensitivities and also quick responses, the connection wires can be limited to the sensing ability in various devices approximately. Therefore, the authors designed a wireless sensor, which can provide the advantages of in vivo sensing and also long-distance sensing, quickly.

Findings

The biosensor structure was designed for detection of HER2, HER3 and HER-4 from lab-on-chip approach with six units of screen-printed electrode (SPE), which is built of an electrochemical device of gold/silver, silver/silver or carbon electrodes. The results exhibited that the biosensor is completely selective at low concentrations of the plasma and HER2 detection via the standard addition approach has a linearity plot, therefore, by using this type of biosensors HER2 in plasma can be detected.

Originality/value

This is then followed by detecting HER2 in real plasma using standard way which proved to have great linearity (R2 = 0.991) proving that this technique can be used to detect HER2 solution in real patients.
Games, diversity and occupation: a bidimensional CSR perspective for adaptive organisations
Authors: Modarelli Giuseppe , Rainero Christian , Amelio Stefano
Published: July 2024

Purpose

The purpose of this study is to provide a bidimensional perspective to study the role that diversity and occupation play in corporate social responsibility (CSR).

Design/methodology/approach

Five big American companies were selected from a ranking carried out by a globally recognised website for finding flexible and inclusive jobs (www.flexjob.com). After a gap evaluation, content analysis and click analysis were carried out on the institutional websites.

Findings

This analysis provides insight into best practices for inducing employees to select inclusive and non-toxic working environments.

Research limitations/implications

Owing to its original application of game-based inclusiveness, the limited cases and exploratory research approach should be considered as limits of the study.

Practical implications

The research illustrates the internal relevance of sustainability and diversity, creating best practices for bidimensional CSR by matching the offer of and demand for social-inclusive recruitment and employment.

Originality/value

In pursuit of Sustainable Development Goal No.10, regarding reduction of inequalities, games as an inclusive practice could be used to avoid toxic work environments and promote well-being in the workplace.
The role of TNF‐α as a potential marker for acute cutaneous lupus erythematosus in patients with systemic lupus erythematosus
Authors: Jinshan Zhan , Yong Qu , Fangqi Chen , Juanmei Cao , Min Li , Changzheng Huang
Published: July 2024

Acute cutaneous lupus erythematosus (ACLE) is closely associated with systemic symptoms in systemic lupus erythematosus (SLE). This study aimed to identify potential biomarkers for ACLE and explore their association with SLE to enable early prediction of ACLE and identify potential treatment targets for the future. In total, 185 SLE‐diagnosed patients were enrolled and categorized into two groups: those with ACLE and those without cutaneous involvement. After conducting logistic regression analysis of the differentiating factors, we concluded that tumor necrosis factor‐alpha (TNF‐α) is an independent risk factor for ACLE. Analysis of the receiver operating characteristic revealed an area under the curve of 0.716 for TNF‐α. Additionally, both TNF‐α and ACLE are positively correlated with disease activity. TNF‐α shows promise as a biomarker for ACLE, and in SLE patients, ACLE may serve as a clear indicator of moderate‐to‐severe disease activity.
Virological characteristics of the SARS‐CoV‐2 Omicron EG.5.1 variant
Authors: Tsujino Shuhei , Deguchi Sayaka , Nomai Tomo , Padilla‐Blanco Miguel , Plianchaisuk Arnon , Wang Lei , Begum MST Monira , Uriu Keiya , Mizuma Keita , Nao Naganori , Kojima Isshu , Tsubo Tomoya , Li Jingshu , Matsumura Yasufumi , Nagao Miki , Oda Yoshitaka , Tsuda Masumi , Anraku Yuki , Kita Shunsuke , Yajima Hisano , Sasaki‐Tabata Kaori , Guo Ziyi , Hinay Alfredo A. , Yoshimatsu Kumiko , Yamamoto Yuki , Nagamoto Tetsuharu , Asakura Hiroyuki , Nagashima Mami , Sadamasu Kenji , Yoshimura Kazuhisa , Nasser Hesham , Jonathan Michael , Putri Olivia , Kim Yoonjin , Chen Luo , Suzuki Rigel , Tamura Tomokazu , Maenaka Katsumi , Irie Takashi , Matsuno Keita , Tanaka Shinya , Ito Jumpei , Ikeda Terumasa , Takayama Kazuo , Zahradnik Jiri , Hashiguchi Takao , Fukuhara Takasuke , Sato Kei ,   The Genotype to Phenotype Japan (G2P‐Japan) Consortium
Published: July 2024

In middle to late 2023, a sublineage of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) Omicron XBB, EG.5.1 (a progeny of XBB.1.9.2), is spreading rapidly around the world. We performed multiscale investigations, including phylogenetic analysis, epidemic dynamics modeling, infection experiments using pseudoviruses, clinical isolates, and recombinant viruses in cell cultures and experimental animals, and the use of human sera and antiviral compounds, to reveal the virological features of the newly emerging EG.5.1 variant. Our phylogenetic analysis and epidemic dynamics modeling suggested that two hallmark substitutions of EG.5.1, S:F456L and ORF9b:I5T are critical to its increased viral fitness. Experimental investigations on the growth kinetics, sensitivity to clinically available antivirals, fusogenicity, and pathogenicity of EG.5.1 suggested that the virological features of EG.5.1 are comparable to those of XBB.1.5. However, cryo‐electron microscopy revealed structural differences between the spike proteins of EG.5.1 and XBB.1.5. We further assessed the impact of ORF9b:I5T on viral features, but it was almost negligible in our experimental setup. Our multiscale investigations provide knowledge for understanding the evolutionary traits of newly emerging pathogenic viruses, including EG.5.1, in the human population.
Still No(,) More Bolam Please: McCulloch and others v Forth Valley Health Board
Authors: Hobson Clark
Published: July 2024

McCulloch v Forth Valley Health Board concerned an allegation of negligence, in failing to consider treating pericarditis with non‐steroidal anti‐inflammatory drugs as a reasonable alternative treatment and not discussing this option with the patient. Montgomery v Lanarkshire Health Board held that a medical professional must disclose to a patient material risks and any reasonable alternative treatments. The materiality of a risk is to be decided by reference to a reasonable person in the patient's position, or where the medical professional should be reasonably aware that the particular patient is likely to attach significance to that risk. However, Montgomery did not define the legal standard relating to the assessment of whether an alternative treatment is reasonable. McCulloch held the correct legal test to be applied as to whether an alternative treatment is reasonable is the professional‐practice test in Bolam v Friern Hospital Management Committee. There are practical, doctrinal and normative reasons to question whether Bolam is the correct legal test in respect of the assessment of reasonable alternative treatments. Additionally, the conceptualisation of Bolam in McCulloch is overly deferential. McCulloch fails to fully consider Montgomery’s emphasis that autonomy‐respecting principles are the values that risk disclosure practices are sensitive to.
Foraging trail traffic rules: a new study method of trajectories of the harvester ants
Authors: El Boukhrissi Abderrahmane , Taheri Ahmed , Bennas Nard , Belkhiri Abdelkhalek , El Ajjouri Bilal , Reyes‐López Joaquín L.
Published: July 2024

Harvester ants are one of the most extensively studied groups of ants, especially the group foraging ants, Messor barbarus (Linnaeus, 1767), which construct long‐lasting trunk trails. Limited laboratory investigations have delved into head‐on encounters along foraging trails involving workers moving in opposing directions, with fewer corresponding studies conducted in the natural environment. To address this gap, we devised an in‐field experimental design to induce lane segregation on the foraging trunk trail of M. barbarus. Using an image‐based tracking method, we analyzed the foraging behavior of this species to assess the costs associated with head‐on encounters and to figure out the natural coexistence of outgoing and returning workers on a bidirectional route. Our results consistently reveal heightened straightness and speed in unidirectional test lanes, accompanied by an elevated foraging rate compared to bidirectional lanes. This suggests a potential impact of head‐on collisions on foraging behavior, especially on foraging efficiency. Additionally, Kinematic analysis revealed distinct movement patterns between outbound and inbound flows, particularly low speed and sinuous trajectories of inbounding unladen workers. The study of encounter rates in two traffic systems hints at the plausible utilization of individual memory by workers within trails, underscoring the pivotal role of encounters in information exchange and load transfer.
Erythropoiesis‐stimulating agent hyporesponsiveness was associated with worse survival of hemodialysis patients independent of the serum ferritin level
Authors: Hanafusa Norio , Henn Lisa , Bieber Brian , Hasegawa Takeshi , Usui Tomoko , Robinson Bruce , Karaboyas Angelo , Nangaku Masaomi
Published: July 2024

Introduction

Ferritin level and erythropoiesis‐stimulating agent (ESA) responsiveness are each associated with hemodialysis patient survival. We assessed interrelationships between these two vs. survival.

Methods

Patients in the Japan Dialysis Outcomes and Practice Patterns Study Phases 4–6 (2009–2018) were included. All‐cause mortality associations were assessed with progressive adjustment to evaluate covariate influence.

Results

During follow‐up (median 2.6 years), 773 of 5154 patients died. After covariate adjustment, the mortality hazard ratio (HR) was 0.99 (95% CI: 0.81, 1.20) for low serum ferritin and 1.12 (CI: 0.89, 1.41) for high serum ferritin. By contrast, mortality risk with elevated ESA resistance index (ERI) persisted after covariate adjustment (HR 1.44, CI [1.17–1.78]). The serum ferritin and ERI interaction was not significant; p > 0.96 across all models.

Conclusions

Japanese hemodialysis patients with high ERI experienced worse survival independent of serum ferritin levels, highlighting the importance of identifying and mitigating ESA hyporesponsiveness among dialysis patients.
Continuous renal replacement therapy with vitamin E‐coated polysulfone hemofilter reduces inflammatory responses in a porcine lipopolysaccharide‐treated model
Authors: Horikawa Takumi , Yagi Kana , Ishikawa Chika , Atarashi Machi , Watanabe Atsushi , Kato Yoshihisa
Published: July 2024

Introduction

Biological invasions may promote the onset of systemic inflammatory response syndrome in patients eligible for continuous renal replacement therapy (CRRT), leading to poor prognosis. Hence, we aimed to examine the inflammatory reactions in circulation using vitamin E‐coated polysulfone hollow fiber membrane (ViLIFE).

Methods

Lipopolysaccharides were intravenously administered to pigs (2 μg/kg/30 min) to establish an acute inflammation model. Extracorporeal circulation was performed for 6 h in continuous venovenous hemodiafiltration mode using a hemofilter for CRRT filled with a polysulfone hollow fiber membrane or ViLIFE, and the differences in inflammatory reactions were evaluated.

Results

The ViLIFE group exhibited low platelet and cytokine levels (p < 0.05 vs. sham‐CRRT group). Additionally, the ViLIFE group had lower lactate and high mobility group box 1 levels than the other groups.

Conclusion

ViLIFE represents a promising CRRT modality that can inhibit the inflammatory response in circulation and inhibit further biological invasions.
You get what you test for: The killing effect of phage lysins is highly dependent on buffer tonicity and ionic strength
Authors: Vázquez Roberto , Gutiérrez Diana , Dezutter Zoë , Criel Bjorn , de Groote Philippe , Briers Yves
Published: July 2024

The phage lysin field has done nothing but grow in the last decades. As a result, many different research groups around the world are contributing to the field, often with certain methodological differences that pose a challenge to the interpretation and comparison of results. In this work, we present the case study of three Acinetobacter baumannii‐targeting phage lysins (wild‐type endolysin LysMK34 plus engineered lysins eLysMK34 and 1D10) plus one lysin with broad activity against Gram‐positive bacteria (PlySs2) to provide exemplary evidence on the risks of generalization when using one of the most common lysin evaluation assays: the killing assay with resting cells. To that end, we performed killing assays with the aforementioned lysins using hypo‐, iso‐ and hypertonic buffers plus human serum either as the reaction or the dilution medium in a systematic manner. Our findings stress the perils of creating hypotonic conditions or a hypotonic shock during a killing assay, suggesting that hypotonic buffers should be avoided as a test environment or as diluents before plating to avoid overestimation of the killing effect in the assayed conditions. As a conclusion, we suggest that the nature of both the incubation and the dilution buffers should be always clearly identified when reporting killing activity data, and that for experimental consistency the same incubation buffer should be used as a diluent for posterior serial dilution and plating unless explicitly required by the experimental design. In addition, the most appropriate buffer mimicking the final application must be chosen to obtain relevant results.
Rumen protozoa are a hub for diverse hydrogenotrophic functions
Authors: Toyber Ido , Kumar Raghawendra , Jami Elie
Published: July 2024

Ciliate protozoa are an integral part of the rumen microbial community involved in a variety of metabolic processes. These processes are thought to be in part the outcome of interactions with their associated prokaryotic community. For example, methane production is enhanced through interspecies hydrogen transfer between protozoa and archaea. We hypothesize that ciliate protozoa are host to a stable prokaryotic community dictated by specific functions they carry. Here, we modify the microbial community by varying the forage‐to‐concentrate ratios and show that, despite major changes in the prokaryotic community, several taxa remain stably associated with ciliate protozoa. By quantifying genes belonging to various known reduction pathways in the rumen, we find that the bacterial community associated with protozoa is enriched in genes belonging to hydrogen utilization pathways and that these genes correspond to the same taxonomic affiliations seen enriched in protozoa. Our results show that ciliate protozoa in the rumen may serve as a hub for various hydrogenotrophic functions and a better understanding of the processes driven by different protozoa may unveil the potential role of ciliates in shaping rumen metabolism.
Do dividends mitigate bad news hoarding, overinvestments, and stock price crash risk?
Authors: Kim Jeong‐Bon , Luo Le , Xie Hong
Published: July 2024

Using a large sample of US firms over the period of 1991–2015, we examine the economic benefits of paying dividends. We find that dividend payments mitigate stock price crash risk. We show that dividend payments reduce bad news hoarding (overinvestments) while bad news hoarding (overinvestments) is (are) positively associated with stock price crash risk, suggesting that curbing bad news hoarding and curtailing overinvestments are two channels through which dividends mitigate crash risk. Finally, our main results are robust to a battery of sensitivity checks including controls for potential endogeneity concerns.
Does corporate digitalisation moderate real earnings management?
Authors: Lou Zhukun , Li Mingran , Shan Yuan George , Ye Ailin
Published: July 2024

We investigate the association between corporate digitalisation and firms' real earnings management (REM). Using an archival data set of 11,806 firm‐year observations from the Shanghai and Shenzhen stock exchanges between 2011 and 2020, our results show a negative association between the degree of corporate digitalisation and the level of REM. Furthermore, we find that the association between corporate governance mechanisms – including power balance, board independence and audit quality – and REM is more pronounced in firms with a high degree of digitalisation. We also note that the reduction of REM resulting from corporate digitalisation has a positive effect on firms' operating efficiency.
Interrelated involvement of the endocannabinoid/endovanilloid (TRPV1) systems and epigenetic processes in anxiety‐ and working memory impairment‐related behavioural effects of nicotine as a stressor
Authors: Hayase Tamaki
Published: July 2024

The addictive use of nicotine contained in tobacco is associated with stressor‐like emotional and cognitive effects such as anxiety and working memory impairment, and the involvement of epigenetic mechanisms such as histone acetylation has recently been reported. Although the precise nature of behavioural plasticity remains unclear, both anxiogenic‐ and working memory impairment‐like effects were observed in the present experimental model of mice treated with repeated subcutaneous nicotine and/or immobilization stress, and these effects were commonly attenuated by the histone deacetylase (HDAC) inhibitors that induce histone acetylation. Such HDAC inhibitor‐induced resilience was mimicked by ligands for the endocannabinoid (ECB) system, a neurotransmitter system that is closely associated with nicotine‐induced addiction‐related behaviours: the anxiogenic‐like effects were mitigated by the cannabinoid type 1 (CB1) agonist arachidonylcyclopropylamide (ACPA), whereas the working memory impairment‐like effects were mitigated by the CB1 antagonist SR 141716A. Moreover, the effects of the HDAC inhibitors were also mimicked by ligands for the endovanilloid (transient receptor potential vanilloid 1 [TRPV1]) system, a system that shares common characteristics with the ECB system: the anxiogenic‐like effects were mitigated by the TRPV1 antagonist capsazepine, whereas the working memory impairment‐like effects were mitigated by the TRPV1 agonist olvanil. Notably, the HDAC inhibitor‐induced anxiolytic‐like effects were attenuated by SR 141716A, which were further counteracted by capsazepine, whereas the working memory improvement‐like effects were attenuated by capsazepine, which were further counteracted by SR 141716A. These results suggest the contribution of interrelated control of the ECB/TRPV1 systems and epigenetic processes such as histone acetylation to novel therapeutic approaches.
And the Oscar goes to… – Species‐specific ant behaviour related to predator defence in ant‐mimicking spiders
Authors: Perger Robert , Rubio Gonzalo D. , Baigorria Julián E.
Published: July 2024

Mimicry, the superficial resemblance between organisms of two or more species, is considered a textbook example for natural selection, for which it is assumed that predators are important selective agents. Ant mimicking spiders have received considerable attention in studies on mimicry because they include examples with remarkable, species‐specific morphological adaptations. Ant‐like behaviours such as erratic locomotory patterns, abdomen bobbing and vertical movements of the first or second pair of legs to imitate antennal movements, are assumed to have evolved before morphological mimicry and may be considered adaptations to general ant resemblance. Species‐specific behavioural ant mimicry (behaviour that is only observed in specific ants and imitated by their mimics) was very rarely documented and ant resembling behaviour that repels predator attacks has not been confirmed yet. In this study we report and discuss such species‐specific behaviour, a spray display (SD), in the castianeirine spiders Myrmecotypus iguazu (a morphologically accurate mimic of the carpenter ant Camponotus sericeiventris), and M. tahyinandu (a morphologically accurate mimic of C. crassus). The SD consisted of the raising of the cephalothorax and moving of the abdomen ventrally under the cephalothorax, pointing the apex forward, and holding the antennae (ant) or first pair of legs (spiders) at an angle of about 45°–120°. The morphological adaptations that are required to perform the SD and the lack of an alternative explanation for the purpose of this display suggest that the SD has evolved to enhance both general behavioural and morphologically accurate ant resemblance. The two observed Myrmecotypus species may be considered the behaviorally most accurate ant‐resembling spiders known to date, as the SD may provide protection against spider‐ and ant‐eating predators at a point in predator interactions where other myrmecomorph spiders may abandon their ant‐resembling behaviour.
Tree hollow decline in new forest reserves with a long history of logging
Authors: Gorrod Emma , Oliver Ian , Bedward Michael , McAllister Danielle , O'Kelly Tim , Lawrie Kristy
Published: July 2024

In many parts of the world, achieving a target of 30% of land managed for conservation under the Kunming‐Montreal Global Biodiversity Framework will require the protection of land with a long history of management for production. In newly protected forests, past logging practices will have impacted key aspects of stand structure, including hollow‐bearing trees that provide critical habitat for vertebrate fauna. The impacts of past silvicultural practices on hollow density, distribution, type and longevity may necessitate targeted ameliorative actions. We investigated tree hollows in the largest river red gum (Eucalyptus camaldulensis Denh.) forest in the world, which had undergone logging‐induced woody thickening prior to being converted to a conservation reserve in 2010. We recorded stem diameters and hollows in living and dead trees in 66 two‐hectare plots. Our sites sampled two productivity states and a wide range of total tree densities. On all sites, we found that hollow‐bearing tree densities were lower than reference values for unlogged stands and average density had halved relative to reference values. We found no relationship between the density of hollow‐bearing trees and total tree density, but we did find a weak positive relationship with site productivity. Larger trees had more hollows, bigger hollows and a greater diversity of hollow sizes. However, of the 1254 hollow‐bearing trees recorded, 43% were dead, 48% of the dead trees had been ringbarked. The proportion of hollow‐bearing trees that were dead was positively correlated with tree size, with 60% of trees in the largest quartile (>105 cm) recorded as dead. The prevalence of dead hollow‐bearing trees suggests that the density and diversity of hollows will continue to decline and ameliorative actions should be considered. These results highlight the need to consider the legacy of past silvicultural practices in the management of newly created conservation reserves.
Spatial variability in the contribution of termites to the decay of plant detritus
Authors: Wijas Baptiste J. , Letnic Mike , Cornwell William K.
Published: July 2024

Drylands are characterized by high spatial variability in resource availability due to sporadic rainfall, topography of the landscape and important effects of animals. Resource availability gradients may trigger patterns in decomposer population abundances and activity, which could affect ecosystem functions such as decomposition. Here, we examined the influence of resource availability gradients on the importance of termites in the decomposition of wood and grass litter. We placed wood blocks and grass litter baits in bags accessible and inaccessible to termites across wood and grass resource gradients as determined by the presence or absence of a top mammalian predator and across topographic gradients during a 9‐month period in arid Australia. We hypothesized that grass‐eating termite activity would track grass abundance and wood‐eating termite activity would track wood abundance. Termites were the predominant decomposition agent at these sites. Termites contributed to 99.5% of wood decomposition and 83.9% of grass decomposition during our study period. For wood, the termite effect was spatially variable and increased with habitat wood availability, which was greatest on dunes and where top predators were absent. However, the contribution of termites to grass litter decomposition did not track grass availability or termite abundance. The highest effects of termites on grass decomposition rates were found in habitats where the absence of top predators led to low grass availability. Our findings highlight how spatial variability in resources in addition to other factors that we do not document but are known to be influenced by the presence of top predators, such as insectivore predation rates, across the landscape could affect ecosystem functions such as decomposition.
Using bioindicators to inform effective predator management for threatened species protection
Authors: Adams C. A. , Van der Weyde L. K. , Tuft K. , Finlayson G. R. , Moseby K. E.
Published: July 2024

In Australia, most threatened species translocations conducted into areas where feral predators are present fail to establish viable, self‐sustaining populations despite intensive predator control. These translocations are occurring amidst a lack of understanding regarding the conditions required for native species to survive, including predator densities. This study investigated whether population trends of in situ common species could be used as bioindicators to determine the effectiveness of predator management for threatened species protection. We compared changes in capture rates of four small mammals and four reptile species inside and outside a predator‐proof reserve for 11 years after cat and fox removal to identify which species responded to cat and fox eradication at various time scales. We only used sites inside the reserve where threatened species had not yet been reintroduced to isolate the effects of cat and fox removal. The effectiveness of these bioindicators was then tested at an unfenced reserve where predators were controlled using baiting, trapping, and shooting. There was a significant increase in the abundance of native rodents (spinifex hopping mouse and Bolam's mouse) inside the fenced reserve compared to outside, however, these differences were not detected in the unfenced reserve possibly due to inadequate predator control or insufficient time for in situ species to recover with sustained predator control. Captures of the introduced house mouse were higher at sites inside the fenced reserve in some years, but the difference was not consistent. Native dunnarts and all four reptile species did not respond consistently over the 11‐year time frame at either reserve. Native rodent abundance was the best indicator of effective feral predator control and may provide a useful bioindicator for threatened species management, such as reintroductions.
Social norms, nutrition messaging, and demand for biofortified staple crops: Evidence from a discrete choice experiment in Ethiopia
Authors: Jada Kaleb Shiferaw , van den Berg Marrit
Published: July 2024

Biofortified maize offers a potential solution to combat micronutrient deficiencies in households, yet its adoption remains low. Realizing biofortification's benefits necessitates a shift in smallholder farmers' production and consumption behavior. Social norms can significantly influence societal behaviors and have the potential to trigger substantial changes. However, their role in promoting biofortification adoption remains underexplored. This study investigates the influence of nutrition information and social norm messaging on smallholder farmers' adoption of biofortified maize seeds in Ethiopia's highlands. We conducted an experiment with 2022 randomly selected households to evaluate the effectiveness of nutrition messages and social norm messaging on farmers' willingness to pay for biofortified maize seeds. Our results reveal that nutrition information alone significantly increases farmers' interest in purchasing biofortified maize seeds, highlighting the positive influence of information‐based interventions on biofortified crop adoption. Conversely, social norm messaging on its own has a limited effect on demand. However, a combined approach demonstrates a stronger positive influence, suggesting a synergistic relationship between these interventions. These results underscore the critical role of disseminating clear information about the nutritional benefits of biofortified crops in fostering their adoption among smallholder farmers. Additionally, our study suggests that integrating social norm messaging with information‐based interventions could be a highly effective strategy for promoting biofortified maize and similar nutrition‐focused initiatives. This research offers valuable insights for policymakers and organizations aiming to improve nutritional outcomes through food‐based approaches to agricultural development among smallholder farming communities.
Development of novel humanized CD19/BAFFR bicistronic chimeric antigen receptor T cells with potent antitumor activity against B‐cell lineage neoplasms
Authors: Wu Sungui , Luo Qian , Li Feiyu , Zhang Suwen , Zhang Cuiling , Liu Jianwei , Shao Bang , Hong Yang , Tan Taochao , Dong Xiaoqing , Chen Bing
Published: July 2024

Chimeric antigen receptor T cell (CAR‐T) therapy has shown remarkable efficacy in treating advanced B‐cell malignancies by targeting CD19, but antigen‐negative relapses and immune responses triggered by murine‐derived antibodies remain significant challenges, necessitating the development of novel humanized multitarget CAR‐T therapies. Here, we engineered a second‐generation 4‐1BB‐CD3ζ‐based CAR construct incorporating humanized CD19 single‐chain variable fragments (scFvs) and BAFFR single‐variable domains on heavy chains (VHHs), also known as nanobodies. The resultant CAR‐T cells, with different constructs, were functionally compared both in vitro and in vivo. We found that the optimal tandem and bicistronic (BI) structures retained respective antigen‐binding abilities, and both demonstrated specific activation when stimulated with target cells. At the same time, BI CAR‐T cells (BI CARs) exhibited stronger tumour‐killing ability and better secretion of interleukin‐2 and tumour necrosis factor‐alpha than single‐target CAR‐T cells. Additionally, BI CARs showed less exhaustion phenotype upon repeated antigen stimulation and demonstrated more potent and persistent antitumor effects in mouse xenograft models. Overall, we developed a novel humanized CD19/BAFFR bicistronic CAR (BI CAR) based on a combination of scFv and VHH, which showed potent and sustained antitumor ability both in vitro and in vivo, including against tumours with CD19 or BAFFR deficiencies.
Artificial intelligence for detection of prostate cancer in biopsies during active surveillance
Authors: Arvidsson Ida , Svanemur Edvard , Marginean Felicia , Simoulis Athanasios , Overgaard Niels Christian , Åström Kalle , Heyden Anders , Krzyzanowska Agnieszka , Bjartell Anders
Published: July 2024

Objectives

To evaluate a cancer detecting artificial intelligence (AI) algorithm on serial biopsies in patients with prostate cancer on active surveillance (AS).

Patients and methods

A total of 180 patients in the Prostate Cancer Research International Active Surveillance (PRIAS) cohort were prospectively monitored using pre‐defined criteria. Diagnostic and re‐biopsy slides from 2011 to 2020 (n = 4744) were scanned and analysed by an in‐house AI‐based cancer detection algorithm. The algorithm was analysed for sensitivity, specificity, and for accuracy to predict need for active treatment. Prognostic properties of cancer size, prostate‐specific antigen (PSA) level and PSA density at diagnosis were evaluated.

Results

The sensitivity and specificity of the AI algorithm was 0.96 and 0.73, respectively, for correct detection of cancer areas. Original pathology report diagnosis was used as the reference method. The area of cancer estimated by the pathologists correlated highly with the AI detected cancer size (r = 0.83). By using the AI algorithm, 63% of the slides would not need to be read by a pathologist as they were classed as benign, at the risk of missing 0.55% slides containing cancer. Biopsy cancer content and PSA density at diagnosis were found to be prognostic of whether the patient stayed on AS or was discontinued for active treatment.

Conclusion

The AI‐based biopsy cancer detection algorithm could be used to reduce the pathologists’ workload in an AS cohort. The detected cancer amount correlated well with the cancer length measured by the pathologist and the algorithm performed well in finding even small areas of cancer. To our knowledge, this is the first report on an AI‐based algorithm in digital pathology used to detect cancer in a cohort of patients on AS.
Insight into the regulatory mechanism of β‐arrestin2 and its emerging role in diseases
Authors: Qi Meng , Chen Ting‐Ting , Li Ling , Gao Ping‐Ping , Li Nan , Zhang Shi‐Hao , Wei Wei , Sun Wu‐Yi
Published: July 2024

β‐arrestin2, a member of the arrestin family, mediates the desensitization and internalization of most G protein‐coupled receptors (GPCRs) and functions as a scaffold protein in signalling pathways. Previous studies have demonstrated that β‐arrestin2 expression is dysregulated in malignant tumours, fibrotic diseases, cardiovascular diseases and metabolic diseases, suggesting its pathological roles. Transcription and post‐transcriptional modifications can affect the expression of β‐arrestin2. Furthermore, post‐translational modifications, such as phosphorylation, ubiquitination, SUMOylation and S‐nitrosylation affect the cellular localization of β‐arrestin2 and its interaction with downstream signalling molecules, which further regulate the activity of β‐arrestin2. This review summarizes the structure and function of β‐arrestin2 and reveals the mechanisms involved in the regulation of β‐arrestin2 at multiple levels. Additionally, recent studies on the role of β‐arrestin2 in some major diseases and its therapeutic prospects have been discussed to provide a reference for the development of drugs targeting β‐arrestin2.
A re‐assessment of the value of markers of corticosteroid contact allergy in the Spanish baseline series: Clobetasol propionate in the spotlight
Authors: Mercader‐García Pedro , Silvestre Juan Francisco , Navarro‐Triviño Francisco Jose , Giménez‐Arnau Ana María , Pastor‐Nieto María Antonia , Cordoba‐Guijarro Susana , Melé‐Ninot Gemma , Tous‐Romero Fátima , González‐Pérez Ricardo , Ruiz‐González Inmaculada , Sánchez‐Pérez Javier , Gática‐Ortega María Elena , Sánchez‐Pedreño Paloma , Miquel‐Miquel Javier , Ortiz‐Frutos Javier , Carrascosa Jose Manuel , Serra‐Baldrich Esther , Sanz‐Sánchez Tatiana , Soria‐Aledo Victoriano , Carrillo Andrés , Borrego Leopoldo ,   the REIDAC
Published: July 2024

Background

Budesonide and tixocortol pivalate as markers of contact allergy to corticosteroids have been questioned, as they are not able to detect a significant percentage of allergic patients.

Objectives

To investigate the potential role of clobetasol propionate in enhancing corticosteroid sensitisation detection.

Methods

Between January 2022 and December 2023, patients who attended centres involved in the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy were tested with an extended baseline series that included budesonide, tixocortol pivalate, clobetasol propionate 0.1% in ethanol and 1% in petrolatum.

Results

A total of 4338 patients were tested. Twenty‐four patients were allergic to budesonide (0.55%, 95% CI: 0.37–0.82); nine patients were allergic to tixocortol pivalate (0.21%, 95% CI: 0.11–0.39); and 23 patients were allergic to clobetasol (0.53%, 95% CI: 0.35–0.79). Only four of those patients allergic to clobetasol were detected by budesonide and one by tixocortol pivalate. No significant differences in the number of positive tests were found between clobetasol in petrolatum or ethanol.

Conclusions

In Spain budesonide remains the main corticosteroid allergy marker whereas the role of tixocortol pivalate is questionable. The addition of clobetasol propionate to the Spanish baseline series would improve the ability to detect patients allergic to corticosteroids.
Gradually increasing context‐sensitivity shapes the development of children's verb marking: A corpus study
Authors: Sawyer Hannah , Bannard Colin , Pine Julian
Published: July 2024

There is substantial evidence that children's apparent omission of grammatical morphemes in utterances such as “She play tennis” and “Mummy eating” is in fact errors of commission in which contextually licensed unmarked forms encountered in the input are reproduced in a context‐blind fashion. So how do children stop making such errors? In this study, we test the assumption that children's ability to recover from error is related to their developing sensitivity to longer‐range dependencies. We use a pre‐registered corpus analysis to explore the predictive value of different cues with regards to children's verb‐marking errors and observe a developmental pattern consistent with this account. We look at context‐independent cues (the identity of the specific verb being used) and at the relative value of context‐dependent cues (the identity of the specific subject+verb sequence being used). We find that the only consistent effect across a group of 2‐ to 3‐year‐olds and a group of 3‐ to 4‐year‐olds is the relative frequency of unmarked forms of specific subject+verb sequences being used. The relative frequency of unmarked forms of the verb alone is predictive only in the younger age group. This is consistent with an account in which children recover from making errors by becoming progressively more sensitive to context, at first the immediately preceding lexical contexts (e.g., the subject that precedes the verb) and eventually more distant grammatical markers (e.g., the fronted auxiliary that precedes the subject in questions).

Research Highlights

We provide a corpus analysis investigating input effects on young children's verb‐marking errors (e.g., Mummy go) across development (between 2 and 4 years of age).

We find evidence that these apparent errors of omission are in fact input‐driven errors of commission that persist into the third year of life.

We compare the relative effect on error rates of context‐independent (e.g., verb) and context‐dependent (e.g., subject+verb sequence) cues across developmental time.

Our findings support the proposal that children recover from making verb‐marking errors by becoming progressively more sensitive to preceding context.
The peer mental health stigmatization scale‐revised (PMHSS‐R): Psychometric properties and cross‐cultural factorial invariance in university students in Ireland and Argentina
Authors: Tisocco Franco , Nearchou Finiki , Hennessy Eilis , Fernández Liporace Mercedes
Published: July 2024

Introduction

The study aimed to assess the psychometric quality of the Peer Mental Health Stigmatization Scale – Revised (PMHSS‐R), by examining its factorial structure among young adults in Ireland and Argentina.

Method

A total of 429 participants aged between 18 and 25 years old were recruited (n = 187 Ireland, n = 242 Argentina). The PMHSS‐R was completed by Irish participants and was translated, pilot‐studied, and subsequently completed by Argentinian participants.

Results

A Confirmatory Factor Analysis demonstrated optimal factor loadings for an eight‐item solution and acceptable internal consistency for both scale dimensions in the Argentinian sample. Satisfactory levels of partial scalar invariance were achieved between countries, indicating that the scale measures mental health stigma consistently across cultures.

Discussion and Conclusions

Our findings highlight the PMHSS‐R as a cross‐culturally valid and reliable psychometric instrument to evaluate interventions targeting stigma. In conclusion, the PMHSS‐R can be used in cross‐cultural research to compare levels of mental health stigma and investigate the interplay between stigma and other psychologically relevant constructs between different countries and cultural contexts.
Deep abdominal breathing reduces heart rate and symptoms during orthostatic challenge in patients with postural orthostatic tachycardia syndrome
Authors: Stick Moritz , Leone Ariane , Fischer Fiona , Schulz Jörg B. , Maier Andrea
Published: July 2024

Background and purpose

This study investigated the effects of deep abdominal breathing on cardiovascular parameters and symptoms in patients with postural orthostatic tachycardia syndrome (POTS) during head‐up tilt‐table (HUT) challenge.

Methods

Thirty POTS patients completed two consecutive rounds of 10‐min HUT in a crossover design. One round was HUT without intervention, and one round combined the HUT with deep breathing at a rate of 6 breaths/min. Cardiovascular parameters, including mean blood pressure and maximum and mean heart rate (HR), were measured supine and standing. Symptoms were assessed using the Vanderbilt Orthostatic Symptom Score (VOSS).

Results

During the breathing technique, the mean HR increase was −7.35 bpm (95% confidence interval [CI] = −11.71 to −2.98), and the maximum HR increase was −6.27 bpm (95% CI = −11.85 to −0.68, p = 0.041), significantly lower compared to normal breathing. Additionally, improvements were observed in all absolute cardiovascular parameters during standing, with VOSS symptoms simultaneously and significantly decreasing by −5.38 (95% CI = −10.43 to −0.36).

Conclusions

Slow deep abdominal breathing can act as a simple technique to reduce the standing HR increase upon HUT in patients with POTS. This suggests that modulation of the cardiopulmonary neurocircuits and the respiratory pump may reduce HR increase and symptoms in patients with POTS. The findings of this study highlight the use of a safe, zero‐cost, and simple behavioral tool to suggest to POTS patients for symptom relief apart from standard treatment. The observed improvements in cardiovascular parameters and symptoms offer a promising therapeutic approach for patients in times of inadequate treatment options.
Drivers of sustainability reporting by local governments over time: A structured literature review
Authors: Mol André , van Schie Vera , Budding Tjerk
Published: July 2024

This paper provides an overview of the current state of the literature on sustainability reporting by local governments. It focuses on the reasons why municipalities use sustainability reporting and what contingency factors incentivize or disincentivize its implementation. The study is based on a structured literature review of 190 papers, published in journals on business, environment, and accountancy, covering a 35‐year period (1987–2021). We find that sustainability reporting by local governments can be explained from interrelated theoretical perspectives, mainly legitimacy, stakeholder, institutional, and accountability theory. The implementation of sustainability reporting is influenced by contextual factors; the main determinants are organizational and political variables. Based on the papers we reviewed, we provide policy recommendations to improve sustainability reporting in practice and make suggestions for future research.
Are there audit fee premiums for client portfolio management?
Authors: Taylor Stuart D.
Published: July 2024

Auditing is a credence good so its quality cannot be determined directly. The gain or loss of large clients is one publicly available signal that can used by other clients to ascertain the quality provided by audit firms. This paper examines whether this quality signal results in firms earning fee premiums and discounts. Empirical examination of a sample of 16,233 firm‐years of listed Australian companies for the period 2011–2021 shows that there is an association between offices and industry groups that gain and lose large clients, in both the current and previous periods, and economically significant fee premiums for both Big‐4 and non‐Big‐4 firms. These results suggest that clients can use auditor portfolio changes as quality signals and that they appear to reward firms that gain large clients and prune their portfolios of poor clients, particularly if these changes are in the same industry as the client.