bluuebunny/crossref_metadata_2025 huggingface dataset:
Mediterranean diet is associated with a lower probability of prodromal Parkinson's disease and risk for Parkinson's disease/dementia with Lewy bodies: A longitudinal study
Authors: Maraki Maria I. , Yannakoulia Mary , Xiromerisiou Georgia , Stefanis Leonidas , Charisis Sokratis , Giagkou Nikolaos , Kosmidis Mary H. , Dardiotis Efthimios , Hadjigeorgiou Georgios M. , Sakka Paraskevi , Scarmeas Nikolaos , Stamelou Maria
Published: January 2023

Background and purpose

Lifestyle factors have been implicated in the long‐lasting neurodegenerative process in prodromal Parkinson's disease (pPD). The aim was to investigate the associations between adherence to a Mediterranean diet (MeDi) and longitudinal changes of pPD probability and the development of Parkinson's disease (PD) or pPD in a Mediterranean older population.

Methods

Data from the Hellenic Longitudinal Investigation of Aging and Diet cohort (community‐dwelling individuals, aged ≥ 65 years) were used. A detailed food frequency questionnaire was used to evaluate dietary intake and calculate MeDi adherence score, ranging from 0 to 55, with higher scores indicating higher adherence. The probability of pPD was calculated according to the updated Movement Disorder Society research criteria.

Results

In all, 1047 non‐PD/dementia with Lewy bodies (DLB) participants were followed for 3 ± 1 years. MeDi adherence was associated with lower increase in pPD probability over time (b = −0.003, 95% confidence interval −0.006 to −0.001, p = 0.010). Forty‐nine participants had incident possible/probable pPD (i.e., pPD probability ≥ 30%). Compared to the participants in the lowest quartile of MeDi adherence, those in the higher quartiles had an approximately 60%–70% lower risk for possible/probable pPD (p for trend 0.003). MeDi–pPD associations were driven by both motor and non‐motor pPD markers and not from risk markers. Also, 21 participants were diagnosed with PD/DLB at follow‐up. For each unit increase in the MeDi score, there was a 9%–10% lower risk for PD/DLB (hazard ratio 0.906 [95% confidence interval 0.823–0.997], p = 0.044).

Conclusions

Mediterranean diet adherence is associated with lower increase in pPD probability over time and lower possible/probable pPD and PD/DLB incidence in older Mediterranean people. More studies are needed to confirm our results in other populations.
Observed associations between indicators of socioeconomic status and risk of multiple sclerosis in Sweden are explained by a few lifestyle‐related factors
Authors: Alfredsson Lars , Hillert Jan , Olsson Tomas , Hedström Anna Karin
Published: January 2023

Background and purpose

The association between socioeconomic status (SES) and the risk of multiple sclerosis (MS) is unclear. The aim was to study whether a potential association between indicators of SES and MS risk in Sweden is explained by lifestyle/environmental factors.

Methods

Using the Swedish MS registry and the Swedish patient registries, a register study was performed comprising all cases diagnosed with MS in Sweden between 1990 and 2018 (N = 24,729) and five randomly selected controls per case, matched by year and age at disease onset, sex and residential area at disease onset. Data from two matched case–control studies combined comprising data on environment/lifestyle factors (7193 cases, 9609 controls, inclusion period 2005–2018) were also utilized. For all participants, information regarding ancestry, formal education (available 1990–2018) and family income (available 1998–2018) was retrieved from the National Board of Health and Welfare.

Results

The registry study revealed no association between education and MS risk, whereas an income exceeding the upper quartile was associated with lower MS risk compared to having an income in the lowest quartile (odds ratio 0.86, 95% confidence interval 0.82–0.90). These findings were replicated in the crude analyses of the case–control study. However, after adjustment for confounding, no association was observed between income and risk of MS.

Conclusions

Education and income were not associated with occurrence of MS after adjustment for a few lifestyle‐related factors (smoking, alcohol consumption, body mass index and sun exposure habits), indicating that SES has no influence on MS risk besides its association with these lifestyle factors in the Swedish context.
Variegated forms of corporate capture: The state, MNCs, and the dark side of strategic coupling
Authors: Teixeira Tiago
Published: January 2023

Mainstream literature on global value chains (GVCs) and global production networks (GPNs) has increasingly demonstrated how the state and political conjunctures play a central role in strategic coupling. Nonetheless, scholarly attention still remains on the role of firms and their strategies. By focusing on firms, GVC and GPN scholars often underestimate the influence that non‐firm actors such as the state have on strategic coupling, especially concerning its negative development implicationsits “dark side”. To contribute to this literature, this article proposes an approach and research agenda to examine how processes of corporate capture evolve via strategic coupling. This approach is based on the interplay of three variables: the strategic selectivity of states; the strategic action of firms; and states' predominant mode of insertion into GPNs. I argue that corporate capture is much more common and variegated in capitalist states and consequently in strategic coupling than often assumed in mainstream literature.
Formal education and Blatant‐subtle prejudice: Intercultural education and contact theory in French educational system
Authors: Alessandro Bergamaschi , Catherine Blaya , Shekarforush Seyedafshin , Francesco Arcidiacono
Published: January 2023

According to the intercultural paradigm, prejudice reduction is a way of promoting positive interactions among people and preventing discriminatory behaviours. This paper focuses on the role of teacher interventions in reducing student prejudices. We carried out a quantitative survey, which was administered to middle and high school students in France, to identify the role played by individual, school and sociocultural variables on ‘flagrant’ and ‘subtle’ prejudices. The findings show that when students perceive that their teachers are discussing racism and discrimination during formal education, manifestations of both types of prejudice decline. In addition, this perceived engagement creates a multiplicative effect on intergroup contacts among students, and this is an important condition for decreasing prejudice. The study highlights the potential of formal education to deconstruct stereotypes and encourage interculturalism, even in a context which is quite hostile to any reference to cultural identities. It also underlines that intercultural practices can start at the micro level without any formal institutional support.
Evolution of female song and duetting in the chaffinch (Fringilla) species complex
Authors: Cooper Joseph E. J. , Garcia‐del‐Rey Eduardo , Lachlan Robert F.
Published: January 2023

Female song is ancestral to songbirds and shows considerable phylogenetic signal, but its presence also appears to be labile and correlated with life‐history and ecology. While previous studies have examined the evolution of female song across species‐rich families, here we studied female song in island populations of a recently diverged species‐complex, the chaffinches (genus Fringilla). We show this behaviour has recently evolved in these populations, and probably on two independent occasions. In F. teydea, female song is performed in loose duets with males, while in F. coelebs, female song is produced solo. Populations with singing females showed year‐round territoriality and were found in regions with low seasonality – both factors previously connected with high rates of female singing. To determine the relative saliency of female songs to conspecifics, and the degree to which they instigate territorial defence behaviours, we performed a series of speaker playback experiments. In F. c. canariensis, female song could induce comparable responses to male song, whilst duetting F. teydea playback produced similar responses to solo songs, and therefore may relate to within‐pair communication instead. Our results suggest female song can be a highly labile trait that can evolve over short evolutionary timescales.
Improving mathematics assessment readability: Do large language models help?
Authors: Patel Nirmal , Nagpal Pooja , Shah Tirth , Sharma Aditya , Malvi Shrey , Lomas Derek
Published: January 2023

Background

Readability metrics provide us with an objective and efficient way to assess the quality of educational texts. We can use the readability measures for finding assessment items that are difficult to read for a given grade level. Hard‐to‐read math word problems can put some students at a disadvantage if they are behind in their literacy learning. Despite their math abilities, these students can perform poorly on difficult‐to‐read word problems because of their poor reading skills. Less readable math tests can create equity issues for students who are relatively new to the language of assessment. Less readable test items can also affect the assessment's construct validity by partially measuring reading comprehension.

Objectives

This study shows how large language models help us improve the readability of math assessment items.

Methods

We analysed 250 test items from grades 3 to 5 of EngageNY, an open‐source curriculum. We used the GPT‐3 AI system to simplify the text of these math word problems. We used text prompts and the few‐shot learning method for the simplification task.

Results and Conclusions

On average, GPT‐3 AI produced output passages that showed improvements in readability metrics, but the outputs had a large amount of noise and were often unrelated to the input. We used thresholds over text similarity metrics and changes in readability measures to filter out the noise. We found meaningful simplifications that can be given to item authors as suggestions for improvement.

Takeaways

GPT‐3 AI is capable of simplifying hard‐to‐read math word problems. The model generates noisy simplifications using text prompts or few‐shot learning methods. The noise can be filtered using text similarity and readability measures. The meaningful simplifications AI produces are sound but not ready to be used as a direct replacement for the original items. To improve test quality, simplifications can be suggested to item authors at the time of digital question authoring.
Achieving success in English medium instruction using computer‐mediated terminology pretraining under the problem‐based learning pedagogy
Authors: Lee Yuan‐Hsuan
Published: January 2023

Background

Implementing English medium instruction (EMI) has become a proliferating measure in higher education to embrace globalization. Nevertheless, university students reported various challenges in taking EMI courses.

Objectives

This study investigated the effect of the computer‐mediated terminology pretraining on university students' EMI success, regarding their efficacy in taking EMI courses, self‐directed learning (SDL), and EMI performance.

Methods

Participants were 86 university students enrolled in two EMI educational psychology courses. Students in the experimental group were assigned computer‐mediated terminology pretraining tasks for 13 consecutive weeks, while those in the control group did not receive the pretraining assignment. Both groups were taught using the problem‐based learning (PBL) pedagogy with a computer‐mediated structured whiteboard.

Results and Conclusion

The study findings showed that the computer‐mediated terminology pretraining enhanced learners' response efficacy. Both groups increased their SDL under the PBL pedagogy. Besides, multigroup comparison results demonstrated that efficacy in EMI positively predicted SDL, which was related to better EMI performance in the experimental group but not in the control group. Notably, students conducting computer‐mediated terminology pretraining remitted the influence of English ability on their EMI performance.

Major Takeaways from the Study

Implications for instruction were made to use the combined strategy of the computer‐mediated terminology pretraining and PBL in EMI courses to facilitate university students' efficacy in taking EMI courses, self‐directed learning behaviours, and EMI performance.
Network meta‐analysis and systematic review comparing efficacy and safety between very high power short duration, high power short duration, and conventional radiofrequency ablation of atrial fibrillation
Authors: Tokavanich Nithi , Prasitlumkum Narut , Kewcharoen Jakrin , Chokesuwattanaskul Ronpichai , Phannajit Jeerath , Cheungpasitporn Wisit , Akoum Nazem , Ranjan Ravi , Bunch T. Jared , Navaravong Leenhapong
Published: January 2023

Background

High‐power short‐duration (HPSD) atrial fibrillation (AF) ablation with a power of 40–50 W was proved to be safe and effective. Very high‐power short‐duration (vHPSD) AF ablation is a novel method using >50 W to obtain more durable AF ablation. This study aimed to evaluate the efficacy and safety of vHPSD ablation compared with HPSD ablation and conventional power ablation.

Methods

A literature search for studies that reported AF ablation outcomes, including short‐term freedom from atrial arrhythmia, first‐pass isolation (FPI) rate, procedure time, and major complications, was conducted utilizing MEDLINE, EMBASE, and Cochrane databases. All relevant studies were included in this analysis. A random‐effects model of network meta‐analysis and surface under cumulative ranking curve (SUCRA) were used to rank the treatment for all outcomes.

Results

A total of 29 studies with 9721 patients were included in the analysis. According to the SUCRA analysis, HPSD ablation had the highest probability of maintaining sinus rhythm. Point estimation showed an odds ratio of 1.5 (95% confidence interval [CI]: 1.2–1.9) between HPSD ablation and conventional power ablation and an odds ratio of 1.3 (95% CI: 0.78–2.2) between vHPSD ablation and conventional power ablation. While the odds ratio of FPI between HPSD ablation and conventional power ablation was 3.6 (95% CI: 1.5–8.9), the odds ratio between vHPSD ablation and conventional power ablation was 2.2 (95% CI: 0.61–8.6). The procedure times of vHPSD and HPSD ablations were comparable and, therefore, shorter than that of conventional power ablation. Major complications were low in all techniques.

Conclusion

vHPSD ablation did not yield higher efficacy than HPSD ablation and conventional power ablation. With the safety concern, vHPSD ablation outcomes were comparable with those of other techniques.
Bivalent GAD autoantibody ELISA improves clinical utility and risk prediction for adult autoimmune diabetes
Authors: Kawasaki Eiji , Shimada Akira , Imagawa Akihisa , Abiru Norio , Awata Takuya , Oikawa Yoichi , Osawa Haruhiko , Kawabata Yumiko , Kozawa Junji , Kobayashi Tetsuro , Takahashi Kazuma , Chujo Daisuke , Fukui Tomoyasu , Miura Junnosuke , Yasuda Kazuki , Yasuda Hisafumi , Kajio Hiroshi , Hanafusa Toshiaki , Ikegami Hiroshi ,   the Committee of type 1 diabetes, Japan Diabetes Society
Published: January 2023

Aim/Introduction

To investigate the differences in the clinical significance and glutamic acid decarboxylase autoantibody (GADA) affinity between RIA (RIA‐GADA) and ELISA (ELISA‐GADA) in patients with type 1 diabetes.

Methods

A total of 415 patients with type 1 diabetes were enrolled, including 199 acute‐onset type 1 diabetes, 168 slowly progressive type 1 diabetes (SPIDDM), and 48 fulminant type 1 diabetes. GADA affinity was measured by a competitive binding experiment using unlabeled recombinant human GAD65 protein, and the diagnostic performance of both assays and the relationship between GADA affinity and the decline of fasting C‐peptide (F‐CPR) were examined.

Results

While the ELISA‐GADA displayed a higher sensitivity than the RIA method in diagnosing type 1 diabetes in acute‐onset patients, about 40% of SPIDDM patients with low‐titer RIA‐GADA were determined as negative by the ELISA method. Patients with type 1 diabetes with RIA‐GADA alone had an older age of onset, less diabetic ketoacidosis, a higher BMI, and a higher F‐CPR compared with patients positive for both RIA‐GADA and ELISA‐GADA. Additionally, 36% of RIA‐GADA‐positive patients had low‐affinity GADA (<1010 L/mol), which was significantly higher than in the ELISA‐GADA‐positive patients (4%, P < 0.0001). Furthermore, over a 3 year monitoring period, F‐CPR levels decreased in ELISA‐GADA‐positive SPIDDM, whereas it was maintained in patients with RIA‐GADA alone, regardless of GADA affinity.

Conclusions

These results suggest that bivalent ELISA for GADA is superior to the RIA method in diagnosing type 1 diabetes. Moreover, the diagnostic superiority of the ELISA‐GADA made possible the concurrent identification of SPIDDM patients at high‐risk of early progression, and allowed for more accurate clinical diagnosis and management.
Relationship between occlusal force and psychological frailty in Japanese community‐dwelling older adults: The Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians study
Authors: Akema Suzuna , Mameno Tomoaki , Nakagawa Takeshi , Inagaki Hiroki , Fukutake Motoyoshi , Hatta Kodai , Murotani Yuki , Tsujioka Yoshitaka , Hagino Hiromasa , Higashi Kotaro , Takahashi Toshihito , Wada Masahiro , Maeda Yoshinobu , Gondo Yasuyuki , Kamide Kei , Kabayama Mai , Ishizaki Tatsuro , Masui Yukie , Ogata Soshiro , Ikebe Kazunori
Published: January 2023

Background

Frailty increases the risk of negative health‐related events, such as falls, disability, hospitalizations, and death. Although the association between oral health and physical frailty is well established, the relationship between oral health and psychological frailty has not yet been investigated. Therefore, we conducted a cross‐sectional study to examine the association between maximal occlusal force and psychological frailty in Japanese community‐dwelling older adults.

Methods

Psychological frailty was defined as a World Health Organization‐5 scale (WHO‐5) score of <13, cognitive and functional status was defined as a Japanese version of the Montreal Cognitive Assessment (MoCA‐J) score of <23, and psychological robustness was defined as a WHO‐5 score of ≥13 and a MoCA‐J score of ≥23. We used a cross‐sectional study design to measure maximal occlusal force in 1810 participants, and examined the following factors relevant to psychological frailty: educational level, financial status, living situation, history of chronic diseases, handgrip strength, and instrumental activities of daily living. We used propensity score matching to match the psychological frailty and psychological robustness groups according to demographic and confounding factors. This process, resulted in 344 participants, of whom 172 were in the psychological frailty group and 172 were in the psychological robustness group. In the matched cohort, differences between groups with and without psychological frailty were compared using generalized estimating equations for maximal occlusal force after adjusting for the number of teeth.

Results

After controlling for potential confounding factors of frailty, the psychological frailty group showed lower maximal occlusal force compared with the psychological robustness group (unstandardized regression coefficients = −72.7, 95% confidence interval: −126.3 to −19.1).

Conclusions

Maximal occlusal force was associated with a reduced prevalence of psychological frailty among Japanese community‐dwelling older adults participating in our study.
Addressing multiscale microbial challenges using the Mesolens
Authors: Rooney Liam M. , Bottura Beatrice , Baxter Katherine , Amos William B. , Hoskisson Paul A. , McConnell Gail
Published: January 2023

We provide a brief review of the development and application of the Mesolens and its impact on microbiology. Microbial specimens such as infected tissue samples, colonies surfaces, and biofilms are routinely collected at the mesoscale. This means that they are relatively large multimillimetre‐sized samples which contain microscopic detail that must be observed to answer important questions across various sectors. The Mesolens presents the ideal imaging method to study these specimens as no other optical microscope can thanks to its unique combination of low magnification and high numerical aperture providing large field‐of‐view, high‐resolution imaging. We demonstrate the current applications of the Mesolens to microbial imaging and go on to outline the huge potential of the Mesolens to impact other key areas of microbiology.
Dental topographic proxies for ecological characteristics in carnivoran mammals
Authors: Waldman Emily , Gonzalez Yoly , Flynn John J. , Tseng Z. Jack
Published: January 2023

Form‐function relationships in mammalian feeding systems are active topics of research in evolutionary biology. This is due principally to their fundamental importance for understanding dietary adaptations in extinct taxa and macro‐evolutionary patterns of morphological transformations through changing environments. We hypothesize that three‐dimensional dental topographic metrics represent stronger predictors for dietary and other ecological variables than do linear measurements. To test this hypothesis, we measured three dental topographic metrics: Relief Index (RFI), Dirichlet Normal Energy (DNE), and Orientation Patch Count Rotated (OPCR) in 57 extant carnivoran species. Premolar and molar dental topographic indices were regressed against activity, diet breadth, habitat breadth, terrestriality, and trophic level variables within a phylogenetic framework. The results of this study showed significant correlations between RFI and the ecological variables diet breadth and trophic level. Weaker correlations are documented between OPCR and activity and between DNE and trophic level. Our results suggest that cusp height is strongly reflective of dietary ecology in carnivorans as a whole, and represents a proxy mainly for different degrees of hypercarnivory observed within this group of predatory mammals.
Masticatory performance in oral function assessment: Alternative methods
Authors: Imamura Yoshiki , Chebib Najla , Ohta Midori , Mojon Philippe , Schulte‐Eickhoff Regina Maria , Schimmel Martin , Graf Christophe , Sato Yuji , Müller Frauke
Published: January 2023

Background

Masticatory function declines with age or disease, implicating a poor chewing efficiency and an often‐unconscious change for a less healthy, yet easy to chew diet. Timely screening of masticatory function may foster an early‐onset diagnosis and potential treatment. The aim of this study was to compare alternative diagnostic tools for masticatory function to a Jelly‐scan test.

Materials and Methods

Patients aged 70 years and older who were hospitalised for rehabilitation were recruited for this study. A total of four different tests for masticatory function were administered. The Japanese Society of Gerodontology glucose extraction test (Jelly‐scan) was used as reference to compare a colour‐changing gum test (Gum1‐colour) as well as a mixing ability test with a visual (Gum2‐visual) and opto‐electronical (Gum2‐digital) analyses. Receiver operating characteristic (ROC) curves were used to establish the discriminative value, kappa‐values were used to estimate individual agreements and correlations were verified using Spearman's tests.

Results

Sixty‐one patients (Menn = 23, Womenn = 38) aged 82.4 ± 6.8 years participated in the experiments. The average number of natural teeth was 16.5 ± 10.5, 34.4% of the participants wore removable dentures. For all tests, the sum of sensitivity and specificity was >150%. All test correlated with Jelly‐scan (absolute Rho >0.5). With Jelly‐scan 51 participants (83.6%) were diagnosed with “masticatory hypofunction”. After reducing the cut‐off value of the test from 100 mg/dL to 65 mg/dL, only 33 participants (54%) fulfilled the diagnosis. This post‐hoc analysis increased the sensitivity of the Gum2‐tests and the agreement to kappa >0.5 for all three tests.

Conclusion

All three tests can be considered useful screening alternatives. In its original version, Jelly‐scan may tend to over‐diagnose masticatory hypofunction, hence a novel cut‐off with better agreement between tests is suggested.
Microbiological profile of peri‐implantitis: Analyses of microbiome within dental implants
Authors: Kensara Anmar , Saito Hanae , Mongodin Emmanuel F. , Masri Radi
Published: January 2023

Purpose

To characterize the microbiome composition within dental implants of peri‐implantitis subjects and healthy controls using 16S rRNA gene sequencing.

Materials and methods

Twenty‐three subjects with healthy (n = 11 implants) and diseased (peri‐implantitis, n = 21) implants were included in this controlled clinical cross‐sectional study. Samples were obtained from internal surfaces of dental implants using sterile paper points for microbiological analysis. DNA was extracted, and the16S rRNA gene was amplified using universal primers targeting the V3–V4 regions. The resulting 16S polymerize chain reaction amplicons were sequenced on Illumina MiSeq, and the sequences were processed using DADA2 and the Human Oral Microbiome Database (HOMD) as references. Alpha and Beta diversity, as well as core microbiome and differential abundance analyses were then performed using the MicrobiomeAnalyst workflow.

Results

A significant increase in microbial diversity was observed in the internal implant surface of healthy implants compared with the internal surfaces of peri‐implantitis (Shannon p = 0.02). Bacterial community structure was significantly different among groups (p = 0.012). High levels of Gram‐positive bacteria were detected inside implants with peri‐implantitis compared to healthy implants, especially Enterococci.

Conclusions

There is a shift in bacterial diversity inside implants with peri‐implantitis from the healthy control. The microbial colonization within that space might contribute to the etiology of peri‐implant disease.
Effect of culture conditions at lab‐scale on metabolite composition and antibacterial and antibiofilm activities of Dunaliella tertiolecta
Authors: Iglesias María José , Soengas Raquel , López‐Ortiz Fernando , Biondi Natascia , Tredici Mario R. , Gutiérrez‐del‐Río Ignacio , López‐Ibáñez Sara , Villar Claudio J. , Lombó Felipe , López Yuly , Gabasa Yaiza , Soto Sara
Published: January 2023

Dunaliella tertiolecta RCC6 was cultivated indoors in glass bubble column photobioreactors operated under batch and semi‐continuous regimens and using two different conditions of light and temperature. Biomass was harvested by centrifugation, frozen, and then lyophilized. The soluble material was obtained by sequential extraction of the lyophilized biomass with solvents with a gradient of polarity (hexane, ethyl acetate, and methanol) and its metabolic composition was investigated through nuclear magnetic resonance (NMR) spectroscopy. The effect of light on chlorophyll biosynthesis was clearly shown through the relative intensities of the 1H NMR signals due to pheophytins. The highest signal intensity was observed for the biomasses obtained at lower light intensity, resulting in a lower light availability per cell. Under high temperature and light conditions, the 1H NMR spectra of the hexane extracts showed an incipient accumulation of triacylglycerols. In these conditions and under semi‐continuous regimen, an enhancement of β‐carotene and sterols production was observed. The antibacterial and antibiofilm activities of the extracts were also tested. Antibacterial activity was not detected, regardless of culture conditions. In contrast, the minimal biofilm inhibitory concentrations (MBICs) against Escherichia coli for the hexane extract obtained under semi‐continuous regimen using high temperature and irradiance conditions was promising.
Association of cytochrome P450 2D15 (CYP2D15) nonsynonymous polymorphisms and exon 3 deleted RNA splice variant with CYP2D15 protein content and enzyme function in dog liver microsomes
Authors: Jimenez Tania Perez , Zhu Zhaohui , Court Michael H.
Published: January 2023

CYP2D15 is a major drug metabolizing P450 in canine liver. Like the human orthologue (CYP2D6), this enzyme is highly polymorphic with at least five common nonsynonymous variants reported that result in amino acid changes, including p.Ile109Val, p.Leu115Phe, p.Gly186Ser, p.Ile250Phe and p.Ile307Val. Furthermore, a mRNA splice variant of CYP2D15 has been found in canine liver that lacks the exon 3 gene region resulting in an inactive enzyme. The objective of this study was to evaluate whether any of these amino acid variants or the exon 3 deletion mRNA variant (exon3‐delta) was associated with differences in CYP2D15‐selective activities or protein content in a bank of canine livers. Livers were obtained from 25 Beagles and 34 dogs of various other breeds. CYP2D15‐selective activities measured included dextromethorphan o‐demethylation and tramadol o‐demethylation. Reverse transcription PCR showed that 76% of livers (44/58) expressed both exon3‐delta and normally spliced CYP2D15 RNA, while the remaining 24% (14/58) expressed only normally spliced RNA. The presence of exon3‐delta was not correlated with CYP2D15 activities or protein content. Compared with wild‐type livers, Beagle dog livers heterozygous for the p.Ile109Val and p.Gly186Ser variants showed from 40 to 50% reductions in median enzyme activities, while heterozygous p.Gly186Ser livers were associated with a 41% reduction in median CYP2D15 protein content (p < .05; Dunn's test). In the entire liver bank, livers homozygous for p.Ile109Val were also associated with a 40% reduction in median dextromethorphan O‐demethylation activities versus wild‐type livers (p < .05). These results identify several nonsynonymous CYP2D15 gene variants associated with variable CYP2D15 metabolism in canine liver.
A prophage‐encoded effector from “Candidatus Liberibacter asiaticus” targets ASCORBATE PEROXIDASE6 in citrus to facilitate bacterial infection
Authors: Du Jiao , Wang Qiying , Shi Hongwei , Zhou Changyong , He Jun , Wang Xuefeng
Published: January 2023

Citrus huanglongbing (HLB), associated with the unculturable phloem‐limited bacterium “Candidatus Liberibacter asiaticus” (CLas), is the most devastating disease in the citrus industry worldwide. However, the pathogenicity of CLas remains poorly understood. In this study, we show that AGH17488, a secreted protein encoded by the prophage region of the CLas genome, suppresses plant immunity via targeting the host ASCORBATE PEROXIDASE6 (APX6) protein in Nicotiana benthamiana and Citrus sinensis. The transient expression of AGH17488 reduced the chloroplast localization of APX6 and its enzyme activity, inhibited the accumulation of reactive oxygen species (H2O2 and O2−) and the lipid oxidation endproduct malondialdehyde in plants, and promoted the proliferation of Pseudomonas syringae pv. tomato DC3000 and Xanthomonas citri subsp. citri. This study reveals a novel mechanism underlying how CLas uses a prophage‐encoded effector, AGH17488, to target a reactive oxygen species accumulation‐related gene, APX6, in the host to facilitate its infection.
Faster surgery initiation in oral cancer patients during the COVID‐19 pandemic in Osaka, Japan
Authors: Koyama Shihoko , Morishima Toshitaka , Saito Mari Kajiwara , Ma Chaochen , Nishimura Nao , Aoki Kengo , Nishio Minako , Otsuka Tomoyuki , Tabuchi Takahiro , Ishibashi Miki , Miyashiro Isao
Published: January 2023

Background

We investigated the impact of the COVID‐19 pandemic on oral cancer (OC), comparing diagnosis and number of pre‐operative days in the diagnosis of OC in 2019 (pre‐COVID‐19) and that in 2020 (during the COVID‐19 pandemic).

Methods

Using data from a cancer registry‐based study on the impact of COVID‐19 on cancer care in Osaka (CanReCO), we collected details of sex, age, residential area, cancer site, date of diagnosis, clinical stage at first treatment and number of pre‐operative days in OC patients.

Results

A total of 1470 OC cases were registered. Incidence of OC before and during COVID‐19 was 814 and 656 cases, respectively. During the first wave of the pandemic (March to May 2020), incidence was about half that in the same period in 2019 (2019; n = 271, 2020; n = 145). Number of pre‐operative days (median number of days between the first hospital visit and surgery date) was significantly shorter during the COVID‐19 year (24.5 days) than in the pre‐COVID‐19 year (28 days, p = 0.0015).

Conclusions

Incidence of OC during the COVID‐19 pandemic was lower than in pre‐COVID‐19. Despite disruption in the healthcare system, the number of pre‐operative days for OC cases was shorter during the pandemic.
Vergence and accommodation responses in the control of intermittent exotropia
Authors: Mestre Clara , Neupane Sonisha , Manh Vivian , Tarczy‐Hornoch Kristina , Candy T. Rowan
Published: January 2023

Purpose

Individuals with different types of intermittent exotropia (IXT) may use neurally coupled accommodation and vergence responses differently from those without exotropia to achieve eye alignment. This study examined the relationship between simultaneously recorded accommodation and vergence responses in children and young adults with a range of types of IXT while aligned and deviated.

Methods

Responses of 29 participants with IXT (4–31 years) and 24 age‐matched controls were recorded using simultaneous eye‐tracking and eccentric photorefraction while they watched a movie in binocular or monocular viewing at varying viewing distances. Gradient response AC/A ratios and fusional vergence ranges were also assessed. Eight participants had divergence or pseudo‐divergence excess type IXT, 5 had convergence insufficiency and 16 had basic IXT.

Results

Control and IXT participants accommodated similarly both in monocular and binocular‐aligned conditions to visual targets at 80 and 33 cm. When deviated in binocular viewing, most participants with IXT exhibited changes in accommodation <0.5D relative to alignment. Gradient response AC/A ratios were similar for control [0.56 MA/D (IQR: 0.51 MA/D)] and IXT participants [0.42 MA/D (0.54 MA/D);p = 0.60]. IXT participants showed larger vergence to accommodation ratios with changes from distance to near fixation [1.19 MA/D (1.45 MA/D)] than control participants [0.78 MA/D (0.60 MA/D);p = 0.02], especially among IXT participants with divergence or pseudo‐divergence excess. Participants with IXT exhibited typical fusional divergence ranges beyond their dissociated position [8.86 Δ (7.10 Δ)] and typical fusional convergence ranges from alignment [18 Δ (15.75 Δ)].

Conclusions

This study suggests that control of IXT is typically neither driven by accommodative convergence alone nor associated with over‐accommodation secondary to fusional convergence efforts. These simultaneous measurements confirmed that proximal vergence contributed significantly to IXT control, particularly for divergence or pseudo‐divergence excess type IXT. For IXT participants in this study, achieving eye alignment did not conflict with having clear vision.
Perspectives on the nanocarriers with miRNAs for targeting melanoma stemness through epigenetic regulation
Authors: Liu Junqi , Zhang Jin , Beeraka Narasimha M. , Chen Kuo , Sinelnikov Mikhail Y. , Manogaran Prasath , Bannimath Gurupadayya , Nikolenko Vladimir N. , Fan Ruitai
Published: January 2023

Several research reports delineated the significant role of miRNAs in cancer proliferation, and their modulatory role in cancer mitigation, and drug resistance. Melanoma cells have been acquiring stemness to several chemotherapeutic agents through drug efflux proteins, epigenetic modulation, and DNA repair. miRNAs could be applied as novel therapeutic modalities for treating several kinds of cancers to modulate these mechanisms involved in stemness. Nanocarriers to carry these tumor‐targeting miRNAs to modulate stemness are a prominent strategy to overcome their low penetrability, minimal stability, and nonspecificity. We have searched several public databases such as PubMed, Medline, Google scholar, and NLM and obtained the information pertinent to the miRNA‐based nanocarrier systems to target stemness through epigenetic modulation in melanomas. This review delineates that various miRNAs can modulate the stemness in melanomas by specific intricate epigenetic signaling, and other cell‐based signaling mechanisms. Specific nanocarrier formulations with specific miRNAs are optimal methods to deliver these miRNAs in order to achieve significant entrapment efficiency, loading efficiency, and stability. Furthermore, the combinatorial regimen of FDA‐approved chemotherapeutic molecules with tumor‐targeting miRNAs and chemotherapy combined with nanocarriers can efficiently deliver the utmost therapeutic window by targeting tumor matrix, invasion, metastasis, and angiogenesis in melanomas. Substantial research should focus on the clinical application of this gene therapy in melanomas using these low immunogenic, highly degradable, and biocompatible combinatorial nanotherapeutic regimens.
T‐cell infiltrate intensity is associated with delayed response to treatment in late acute cellular rejection in pediatric liver transplant recipients
Authors: Peters Anna L. , Rogers Michael , Begum Gousia , Sun Qin , Fei Lin , Leino Daniel , Hildeman David , Woodle Ervin Steve
Published: January 2023

Background

Late acute cellular rejection (ACR) is associated with donor‐specific antibodies (DSA) development, chronic rejection, and allograft loss. However, accurate predictors of late ACR treatment response are lacking. ACR is primarily T‐cell mediated, yet B cells and plasma cells (PC) also infiltrate the portal areas during late ACR. To test the hypothesis that the inflammatory milieu is associated with delayed response (DR) to rejection therapy, we performed a single‐center retrospective case‐control study of pediatric late liver ACR using multiparameter immunofluorescence for CD4, CD8, CD68, CD20, and CD138 to identify immune cell subpopulations.

Methods

Pediatric liver transplant recipients transplanted at <17 years of age and treated for biopsy‐proven late ACR between January 2014 and 2019 were stratified into rapid response (RR) and DR based on alanine aminotransferase (ALT) normalization within 30 days of diagnosis. All patients received IV methylprednisolone as an initial rejection treatment. Immunofluorescence was performed on archived formalin‐fixed paraffin embedded (FFPE) liver biopsy tissue.

Results

Liver biopsies from 60 episodes of late ACR in 54 patients were included in the analysis, of which 33 were DR (55%). Anti‐thymocyte globulin was only required in the DR group. The frequency of liver‐infiltrating CD20+ and CD8+ lymphocytes and the prevalence of autoantibodies were higher in the DR group. In univariate logistic regression analysis, serum gamma‐glutamyl transpeptidase (GGT) level at diagnosis, but not ALT, Banff score or presence of DSA, predicted DR.

Conclusions

Higher serum GGT level, presence of autoantibodies, and increased CD8+ T‐cell infiltration portends DR in late ACR treatment in children.
Comparing Singlet Oxygen Generation of Schiff Base Substituted Novel Silicon Phthalocyanines by Sonophotochemical and Photochemical Applications
Authors: Ünlü Seda , Yaşa Atmaca Göknur , Tuncel Elmalı Fikriye , Erdoğmuş Ali
Published: January 2023

Although the sonophotodynamic method has an effective therapeutic outcome for anticancer treatment compared with the photodynamic method, there are not enough related studies in the literature and this study aims to contribute to the development of sonophotodynamic studies. For this purpose, the Schiff base substituted silicon phthalocyanines were designed and synthesized as effective sensitizer candidates and the photophysicochemical and sonophotochemical features of the phthalocyanines were examined to increase singlet oxygen efficiency. The calculated ΦΔ values indicate that the contribution of substituent groups improved the production of singlet oxygen compared with silicon (IV) phthalocyanine dichloride (SiPcCI2) and also the sonophotochemical applications increased the singlet oxygen yields. The ΦΔ values (ΦΔ = 0.76 for axially bis‐{4‐[(E)‐(pyridin‐3‐ylimino)methyl]phenol} substituted silicon (IV) phthalocyanine (2a), 0.68 for axially bis‐4‐[(E)‐{[(pyridin‐3‐yl)methyl]imino}methyl]phenol substituted silicon (IV) phthalocyanine (2b) in photochemical study) reached to ΦΔ = 0.98 for 2a, 0.94 for 2b in sonophotochemical study. This article will enrich the literature on increasing singlet oxygen yield.
β‐Aminobutyric acid induced phytotoxicity and effectiveness against nematode is stereomer‐specific and dose‐dependent in tomato
Authors: Singh Richard Raj , Ameye Maarten , Haesaert Geert , Deveux Melissa , Spanoghe Pieter , Audenaert Kris , Rabasse Jean‐Michel , Kyndt Tina
Published: January 2023

β‐Aminobutyric acid (BABA) induces resistance to a/biotic stress but is associated with phytotoxicity in some plant species. There are two enantiomers of BABA, the R and S enantiomers. We evaluated the phytotoxicity caused by the RS BABA (racemic mixture of R and S BABA), evaluating the dose–response effect and different modes of application on tomato. Results show that RS BABA‐induced phytotoxicity in tomato is dose‐dependent and stronger with foliar applications than with soil drench. We further evaluated the phytotoxicity of the two enantiomers separately and observed that BABA‐induced phytotoxicity is stereomer‐specific. In comparison with less phytotoxic effects induced by S BABA, R BABA induces dose‐dependent and systemic phytotoxic symptoms. To investigate the possible physiological causes of this phytotoxicity, we measured levels of oxidative stress and anthocyanins and validated the findings with gene expression analyses. Our results show that high doses of RS and R BABA induce hydrogen peroxide, lipid peroxidation, and anthocyanin accumulation in tomato leaves, while this response is milder and more transient upon S BABA application. Next, we evaluated BABA induced resistance against root‐knot nematode Meloidogyne incognita in tomato. BABA‐induced resistance was found to be stereomer‐specific and dependent on dose and mode of application. R or RS BABA multiple soil drench application at low doses induces resistance to nematodes with less phytotoxic effects. Taken together, our data provide useful knowledge on how BABA can be applied in crop production by enhancing stress tolerance and limiting phytotoxicity.
Quorum‐sensing interference in vibrios
Authors: Zhang Shanshan , Yang Qian , Eggermont Mieke , Defoirdt Tom
Published: January 2023

Vibrios belonging to the Harveyi clade and the Splendidus clade are important pathogens that cause high economic losses in aquaculture. To control bacterial diseases, antibiotics have been widely applied in aquaculture worldwide for many years, contributing to the development and spread of antibiotic resistance. To further limit the use of antibiotics without affecting the envisaged sustainable growth of the sector, novel therapies to control diseases are urgently needed. As the virulence of many bacterial pathogens is controlled by quorum sensing, quorum‐sensing interference has been the most intensively studied antivirulence therapy. It aims to disarm rather than kill the pathogens to prevent them from attacking their host. This strategy is believed to impose less selective pressure upon pathogens for resistance development when compared to antibiotics. In this review, we provide an overview of quorum‐sensing systems in vibrios belonging to the Harveyi clade and the Splendidus clade, as well as the virulence‐related phenotypes controlled by these systems. The major quorum‐sensing systems in these bacteria include three‐channel quorum‐sensing systems and indole signalling. Furthermore, we discuss different agents that interfere with quorum‐sensing systems and that protect aquatic animals from disease caused by Harveyi clade and Splendidus clade vibrios. These agents include small molecules (both natural and synthetic) that interfere with three‐channel quorum‐sensing systems or with indole signalling and signal molecule‐degrading bacteria. Finally, we identify knowledge gaps and propose some frontiers for further research in order to move this promising field forward.
Where to begin? A flexible framework to prioritize caribou habitat restoration
Authors: Dickie Melanie , Bampfylde Caroline , Habib Thomas J. , Cody Michael , Benesh Kendal , Kellner Mandy , McLellan Michelle , Boutin Stan , Serrouya Robert
Published: January 2023

Habitat loss is a leading threat to many species at risk, and as such, the need for habitat restoration is widespread. In the boreal forests of Western Canada, habitat restoration is a key habitat management action needed to achieve self‐sustaining populations of woodland caribou, a federally threatened species in decline. Hundreds of thousands of kilometers of linear features were created during the exploration or extraction of oil and gas that are no longer used, yet natural regeneration remains stagnated. Only a fraction of these linear features is restored each year, sparking the need for managers to prioritize efforts. We developed an algorithm to prioritize habitat restoration and demonstrate how it can be used to predict and monitor progress towards restoration goals. Our approach is based on the idea of maximizing the gain in unaltered caribou habitat per unit cost, while allowing for the inclusion of different goals, costs, and weighting criteria. Our algorithm ranked landscape units into five zones of restoration priority. The largest gain in unaltered habitat occurred following restoration of the highest priority zones, with diminishing returns as restoration proceeded. None of the caribou ranges reached habitat management targets when not considering restoration within energy project boundaries, even after all candidate linear features were restored. Our results highlight the need for ambitious, coordinated restoration, and the need for improved land‐use planning to minimize alteration within caribou range. We demonstrate the flexibility of our algorithm by applying the framework to a case study in a mountain ecosystem.
Programmatic action in Chinese health policy—The making and design of “Healthy China 2030”
Authors: Vogeler Colette S. , van den Dool Annemieke , Chen Meifang
Published: January 2023

The Programmatic Action Framework (PAF) is a powerful analytical perspective to advance our understanding of policy change by stressing the role of programmatic groups and how they promote their preferred policy programs. While the PAF has been applied successfully to European countries and the US, a considerable research gap remains regarding its explanatory power in other regions and political settings. To step into this research gap, we apply the PAF to authoritarian China through a qualitative case study of the making of “Healthy China 2030”, a national health policy program. We explore two research questions: firstly, to what extent can the PAF be operationalized in a nondemocracy to identify programmatic groups and evaluate policy design, and second, what are the limitations and challenges facing the application of the PAF to nondemocracies? Our empirical analysis shows that the design of this policy program involves actors from different policy areas, despite the top‐down political structure. With regards to the transfer of PAF hypotheses, we show that the framework is a helpful lens to identify programmatic groups and to evaluate policy programs' potential for success based on coherence, responsiveness, and program fit. Meanwhile, the research process of our study revealed the challenges of applying policy process theories to China, including hard‐to‐reach political actors for data collection, lack of transparency regarding collaboration processes between actors, and a lack of publicly available program‐related information.