bluuebunny/crossref_metadata_2025 huggingface dataset:
Brute Force (Anti) Federalism
Authors: Kisska‐Schulze Kathryn , Holden John T. , Ciocchetti Corey
Published: August 2023

States are engaging in brute force (anti) federalism, where both sides of the political spectrum push agendas that extend beyond the Founder's early ideal of balanced federalism, using popular support and special interest groups' interests as their springboard. These trial‐and‐error tactics increase vertical and interstate horizontal frictions, create political and economic challenges for businesses, and increase American polarization. However, they also allow states the opportunity to force an increasingly stalemated federal government into action. This article introduces the concept of brute force (anti) federalism by first examining the evolution of modern federalism. It then offers a sampling of state brute force efforts, analyzes the effect of popular momentum and special interest groups on state political activity, advances broad‐based perspectives surrounding brute force (anti) federalism, and poses additional questions to be considered.
Does it really matter that I do not remember my night? Consequences related to blacking out among college student drinkers
Authors: Richards Veronica L. , Glenn Shannon D. , Turrisi Robert J. , Altstaedter Alyssa , Mallett Kimberly A. , Russell Michael A.
Published: August 2023

Background

Alcohol‐induced blackouts (AIBs) are experienced frequently by college student drinkers and are more likely to occur on days with high‐intensity drinking (HID; 8+ for females/10+ for males) than non‐HID days. Research suggests that AIBs are associated with experiencing other alcohol‐related consequences (ARCs), including more serious ARCs (SARCs; e.g., legal and sexual consequences), but we do not know whether individuals experience more ARCs and more SARCs on occasions when they black out than when they do not black out. This study examines the associations between AIBs and the total number of both ARCs and SARCs.

Methods

Students (N = 462, 51.7% female, 87.7% White, Mage = 20.1) were assessed across 6 weekends via e‐surveys (80%–97% response rate). Multilevel models were used to test for main effects, controlling for drinking (HID or estimated blood alcohol concentration; eBAC) and sex.

Results

Drinking days when an AIB was experienced were associated with more total ARCs (b = 3.54, 95% CI: 3.10, 3.99) and more SARCs (b = 0.77, 95% CI: 0.60, 0.95) per day than non‐AIB days. The more frequently a person experienced an AIB, the more total ARCs (b = 5.33, 95% CI: 4.40, 6.25) and SARCs (1.05, 95% CI: 0.80, 1.30) they reported on average.

Conclusion

Alcohol‐induced blackout days were associated with higher levels of harm than non‐AIB days, even at the same levels of drinking. Interventions that focus on reducing the occurrence of AIBs and factors that contribute to them, in addition to reducing alcohol consumption, may help reduce total harm associated with drinking among college students.
Seedling growth and spinescence of three Vachellia species' populations in valleys formed by tectonic uplift
Authors: Scogings Peter F. , Mkhize Ntuthuko R.
Published: August 2023

The Southeastern Coastal Hinterland geomorphic province of South Africa is dissected by deep valleys created by tectonic uplift in the early Miocene and late Miocene/early Pliocene. We hypothesised that seedlings of Vachellia nilotica, V. tortilis and V. karroo grown from seeds from different valleys would differ in growth and spinescence because of geographical separation. Ninety seedlings (30 per species) were grown for 3 months in uniform conditions in a greenhouse. Mean height of V. nilotica and V. tortilis seedlings was greatest for the Phongolo populations and lowest for the Thukela populations. Maximum stem diameter of both species was attained by individuals from the Phongolo population. Mean spine dry mass of V. nilotica seedlings was greatest for the Phongolo population, suggesting a growth‐defence trade‐off, but did not differ for V. tortilis. Results suggested that Phongolo populations of V. nilotica and V. tortilis may be characterised by morphotypes clearly distinct from those in the other valleys. Unclear and inconsistent results for V. karroo in this study suggested subtly different morphotypes occur in each valley. We propose that distinct Phongolo morphotypes of V. nilotica and V. tortilis are explained as evolutionary adaptations to moderate fire and high browsing pressure compared to populations South of Phongolo.
Local Financial Agglomeration and Corporate Green Innovation*
Authors: He Yu , Chang Dianna , Wei Ran
Published: August 2023

Using a large sample of publicly listed firms in China, we examine the relation between local financial agglomeration and corporate green innovation. We document that local financial agglomeration positively affects corporate green innovation output. This positive effect is more pronounced when firms have better environmental performance, when the market‐level sentiment for corporate environmental responsibility is higher, or prior to the implementation of a green credit policy in China. Further analysis reveals that local financial agglomeration enhances corporate green investments and the quality of green innovation. Collectively, our findings reveal the real and environmental effects of local financial agglomeration.
Rural and urban exposures shape early life immune development in South African children with atopic dermatitis and nonallergic children
Authors: Lunjani Nonhlanhla , Ambikan Anoop T. , Hlela Carol , Levin Michael , Mankahla Avumile , Heldstab‐Kast Jeannette I. , Boonpiyathad Tadech , Tan Ge , Altunbulakli Can , Gray Clive , Nadeau Kari C. , Neogi Ujjwal , Akdis Cezmi A. , O'Mahony Liam
Published: August 2023

Background

Immunological traits and functions have been consistently associated with environmental exposures and are thought to shape allergic disease susceptibility and protection. In particular, specific exposures in early life may have more significant effects on the developing immune system, with potentially long‐term impacts.

Methods

We performed RNA‐Seq on peripheral blood mononuclear cells (PBMCs) from 150 children with atopic dermatitis and healthy nonallergic children in rural and urban settings from the same ethnolinguistic AmaXhosa background in South Africa. We measured environmental exposures using questionnaires.

Results

A distinct PBMC gene expression pattern was observed in those children with atopic dermatitis (132 differentially expressed genes [DEGs]). However, the predominant influences on the immune cell transcriptome were related to early life exposures including animals, time outdoors, and types of cooking and heating fuels. Sample clustering revealed two rural groups (Rural_1 and Rural_2) that separated from the urban group (3413 and 2647 DEGs, respectively). The most significantly regulated pathways in Rural_1 children were related to innate activation of the immune system (e.g., TLR and cytokine signaling), changes in lymphocyte polarization (e.g., TH17 cells), and immune cell metabolism (i.e., oxidative phosphorylation). The Rural_2 group displayed evidence for ongoing lymphocyte activation (e.g., T cell receptor signaling), with changes in immune cell survival and proliferation (e.g., mTOR signaling, insulin signaling).

Conclusions

This study highlights the importance of the exposome on immune development in early life and identifies potentially protective (e.g., animal) exposures and potentially detrimental (e.g., pollutant) exposures that impact key immunological pathways.
Cooperative employment in the regions of Spain (1999–2019): The convergence clubs
Authors: Barrios‐González María Candelaria , García‐Pérez Ana María , Yanes‐Estévez Vanessa
Published: August 2023

In times of crisis, the study of employment is of vital importance, especially that generated by cooperatives, which show great resilience. This paper analyzes the evolution of employment created by cooperatives in the different Spanish regions in relation to total employment between 1999 and 2019 with a pioneering approach. We analyze the existence of convergence clubs among the Spanish regions using the methodology developed by Phillips and Sul (2007, 2009). The results show the existence of four clubs that include the regions that converge in relative terms of cooperative employment over the 20 years analyzed. The lack of homogeneity in the behavior of employment in cooperatives in the different Spanish regions is demonstrated, with certain divergences among regions. These divergences make it difficult to establish a model of cooperative employment for the whole of Spain.
Efficient Algorithms for Building Representative Matched Pairs with Enhanced Generalizability
Authors: Zhang Bo
Published: August 2023

Many recent efforts center on assessing the ability of real-world evidence (RWE) generated from non-randomized, observational data to produce results compatible with those from randomized controlled trials (RCTs). One noticeable endeavor is the RCT DUPLICATE initiative. To better reconcile findings from an observational study and an RCT, or two observational studies based on different databases, it is desirable to eliminate differences between study populations. We outline an efficient, network-flow-based statistical matching algorithm that designs well-matched pairs from observational data that resemble the covariate distributions of a target population, for instance, the target-RCT-eligible population in the RCT DUPLICATE initiative studies or a generic population of scientific interest. We demonstrate the usefulness of the method by revisiting the inconsistency regarding a cardioprotective effect of the hormone replacement therapy (HRT) in the Women's Health Initiative (WHI) clinical trial and corresponding observational study. We found that the discrepancy between the trial and observational study persisted in a design that adjusted for the difference in study populations' cardiovascular risk profile, but seemed to disappear in a study design that further adjusted for the difference in HRT initiation age and previous estrogen-plus-progestin use. The proposed method is integrated into the R package match2C.
Neuropathological hallmarks in autopsied cases with mitochondrial diseases caused by the mitochondrial 3243A>G mutation
Authors: Miyahara Hiroaki , Tamai Chisato , Inoue Masanori , Sekiguchi Kazuhito , Tahara Daisuke , Tahara Nao , Takeda Kazuhiro , Arafuka Shusei , Moriyoshi Hideyuki , Koizumi Ryuichi , Akagi Akio , Riku Yuichi , Sone Jun , Yoshida Mari , Ihara Kenji , Iwasaki Yasushi
Published: August 2023

The mitochondrial (m.) 3243A>G mutation is known to be associated with various mitochondrial diseases including mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke‐like episodes (MELAS). Their clinical symptoms have been estimated to occur with an increased mitochondrial DNA (mtDNA) heteroplasmy and reduced activity of oxidative phosphorylation (OXPHOS) complexes, but their trends in the central nervous system remain unknown. Six autopsied mutant cases and three disease control cases without the mutation were enrolled in this study. The mutant cases had a disease duration of 1–27 years. Five of six mutant cases were compatible with MELAS. In the mutant cases, cortical lesions including a laminar necrosis were frequently observed in the parietal, lateral temporal, and occipital lobes; less frequently in the frontal lobe including precentral gyrus; and not at all in the medial temporal lobe. The mtDNA heteroplasmy in brain tissue samples of the mutant cases was strikingly high, ranging from 53.8% to 85.2%. The medial temporal lobe was preserved despite an inhospitable environment having high levels of mtDNA heteroplasmy and lactic acid. OXPHOS complex I was widely decreased in the mutant cases. The swelling of smooth muscle cells in the vessels on the leptomeninges, with immunoreactivity (IR) against mitochondria antibody, and a decreased nuclear/cytoplasmic ratio of choroidal epithelial cells were observed in all mutant cases but in none without the mutation. Common neuropathological findings such as cortical laminar necrosis and basal ganglia calcification were not always observed in the mutant cases. A high level of mtDNA heteroplasmy was observed throughout the brain in spite of heterogeneous cortical lesions. A lack of medial temporal lesion, mitochondrial vasculopathy in vessels on the leptomeninges, and an increased cytoplasmic size of epithelial cells in the choroid plexus could be neuropathological hallmarks helpful in the diagnosis of mitochondrial diseases.
Influence of Slco2b1‐knockout and SLCO2B1‐humanization on coproporphyrin I and III levels in rats
Authors: Kinzi Jonny , Hussner Janine , Schäfer Anima M. , Treyer Andrea , Seibert Isabell , Tillmann Annika , Mueller Vanessa , Gherardi Clarisse , Vonwyl Celina , Hamburger Matthias , Meyer zu Schwabedissen Henriette E.
Published: August 2023

Background and Purpose

Coproporphyrin (CP) I and III are byproducts of haem synthesis currently investigated as biomarkers for drug–drug interactions involving hepatic organic anion transporting polypeptide (OATP) 1B transporters. Another hepatically expressed OATP‐member is OATP2B1. The aim of this study was to test the impact of OATP2B1, which specifically transports CPIII, on CP serum levels, applying novel rat models.

Experimental Approach

CPIII transport kinetics and the interplay between OATP2B1 and multidrug resistance‐associated proteins (MRPs) were determined in vitro using the vTF7 expression system. Novel rSlco2b1−/− and SLCO2B1+/+ rat models were characterized for physiological parameters and for CP serum levels. Hepatic and renal expression of transporters involved in CP disposition were determined by real‐time qPCR, Western blot analysis, and immunohistochemistry.

Key Results

In vitro experiments revealed differences in transport kinetics comparing human and rat OATP2B1 and showed a consistent, species‐specific interplay with hMRP3/rMRP3. Deletion of rOATP2B1 was associated with a trend towards lower CPI serum levels compared with wildtype rats, while CPIII remained unchanged. Comparing SLCO2B1+/+ with knockout rats revealed an effect of sex: only in females the genetic modification influenced CP serum levels. Analysis of hepatic and renal transporters revealed marginal, but in part, statistically significant differences in rMRP2 abundance, which may contribute to the observed changes in CP serum levels.

Conclusion and Implications

Our findings support that factors other than OATP1B transporters are of relevance for basal CP levels. Only in female rats, humanization of SLCO2B1 affects basal CPI and CPIII serum levels, despite isomer selectivity of OATP2B1.
GPR84 in physiology—Many functions in many tissues
Authors: Aktar Rubina , Rondinelli Silvia , Peiris Madusha
Published: August 2023

Members of the GPCR superfamily have a wide variety of physiological roles and are therefore valuable targets for developing effective medicines. However, within this superfamily are receptors that are less well characterized and remain orphans, including GPR84. This receptor is stimulated by ligands derived from dietary nutrients, specifically medium chain fatty acids (C9–14), and novel synthetic agonists. There are data demonstrating the role of GPR84 in inflammatory pathways, in addition to emerging data suggesting a key role for GPR84 as a nutrient‐sensing GPCR involved in metabolism by sensing energy load via nutrient exposure and subsequent signalling leading to modulation of food intake. Exploring GPR84 pharmacology, its localization and what drives its expression has revealed multiple roles for this receptor. Here, we will reflect on these various roles of GRP84 demonstrated thus far, primarily by exploring data from pre‐clinical and clinical studies in various physiological systems, with a specific focus on the gastrointestinal tract.

LINKED ARTICLES

This article is part of a themed issue GPR84 Pharmacology. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.10/issuetoc
Cretaceous to Recent tectono‐sedimentary history and subsidence of the Barreirinhas, Ceará and Potiguar Basins, Brazilian Equatorial Margin
Authors: Basilone Luca , Roberts Gareth G. , Maia de Almeida Narelle , Fernandes Victoria M. , de Souza Ana Clara Braga , Alves Daniel P. V. , Jovane Luigi
Published: August 2023

Stratigraphy along the Brazilian Equatorial Margin is a crucial guide to the geodynamic history of rifting of Pangea and formation of the South Atlantic Ocean. Understanding the evolution of the Brazilian Equatorial Margin, which intersects the Saint Paul and Romanche Fracture Zones on the western margin of South Atlantic Ocean, is also key for reconstructing eustatic histories and natural resource exploration. In this study, we quantify the stratigraphic and subsidence histories of three sedimentary basins—Barreirinhas, Ceará, Potiguar—that sit within the margin. Stratigraphy was mapped using ca. 900‐line‐km of two‐dimensional seismic data. Biostratigraphic and check‐shot data from 23 wells drilled on the continental shelf, slope and in the distal parts of these basins were used to date and depth‐convert stratigraphy. Check‐shot data were also used to parameterise compaction. The mapped stratigraphy was backstripped to calculate subsidence histories for the basins. Subsidence curves were decompacted, water‐loaded and corrected for palaeo‐water depths using biostratigraphic data from well reports. The mapped stratigraphy of the Barreirinhas and Ceará Basins and theoretical subsidence curves indicate that stretching factors did not exceed 1.6. These values suggest that these basins can be regarded as failed rifts. In contrast, more distal stratigraphy mapped in the Potiguar Basin to the south indicates that it stretched by a factor of 5–6. Calculated subsidence histories indicate that this basin formed primarily because of Cretaceous rifting and Cretaceous to Recent post‐rift thermal sag, with amplitudes governed by the amount of initial stretching.
Radial and vertical variation of wood nutrients in Bornean tropical forest trees
Authors: Inagawa Takeshi , Riutta Terhi , Majalap‐Lee Noreen , Nilus Reuben , Josue James , Malhi Yadvinder
Published: August 2023

Nitrogen, phosphorus, potassium, calcium, and magnesium concentrations in woody tissue are poorly documented, but are necessary for understanding whole‐tree nutrient use and storage. Here, we report how wood macronutrient concentrations vary radially and along the length of a tree for 10 tropical tree species in Sabah, Malaysia. Bark nutrient concentrations were consistently high: 2.9–13.7 times greater than heartwood depending on the nutrient. In contrast, within the wood both the radial (sapwood vs. heartwood) and vertical (trunk bottom vs. trunk middle) variation was modest. Higher concentrations in sapwood relative to heartwood provide empirical support for wood nutrient resorption during sapwood senescence. Dipterocarp species showed resorption rates of 25.3 ± 7.1% (nitrogen), 62.7 ± 11.9% (phosphorus), and 56.2 ± 12.5% (potassium), respectively, while non‐dipterocarp species showed no evidence of nutrient resorption in wood. This suggests that while dipterocarps have lower wood nutrient concentrations, this family is able to compensate for this by using wood nutrient resorption as an efficient nutrient conservation mechanism. In contrast to other nutrients, calcium and magnesium tended to accumulate in heartwood. Wood density (WD) showed little vertical variation along the trunk. Across the species (WD range of 0.33 to 0.94 mg/cm3), WD was negatively correlated with wood P and K concentration and positively correlated with wood Ca concentration. As our study showed exceptionally high nutrient concentrations in the bark, debarking and leaving the bark of the harvested trees on site during logging operations could substantially contribute to maintaining nutrients within forest ecosystems.
A novel miRNA‐based signature as predictive tool of survival outcome of colorectal cancer patients
Authors: Zhao Bochao , Wang Weiqiang , Ye Haikun , Wang Jingchao , Meng Kewei , Yang Tao
Published: August 2023

It is great significance of identifying valuable biomarkers for early diagnosis and prognostic prediction of colorectal cancer (CRC) patients. This study aimed at developing and validating a miRNAs‐based signature as prognostic tool for CRC patients. The miRNA expression profile of 624 CRC samples (613 tumor tissues and 11 normal tissues) was analyzed, and 523 differentially expressed miRNAs (DEmiRNAs) were identified, in which 191 were downregulated and 332 were upregulated. All patients were randomly divided into a training cohort (N = 308) and an internal validation cohort (N = 200). Using the least absolute shrinkage and selection operator (LASSO) and Cox regression model, a prognostic signature of 10 miRNAs (hsa‐miR‐149‐5p, hsa‐miR‐193b‐5p, hsa‐miR‐193a‐3p, hsa‐miR‐3677‐3p, hsa‐miR‐29a‐3p, hsa‐miR‐200c‐5p, hsa‐miR‐200a‐5p, hsa‐miR‐6854‐5p, hsa‐miR‐216a‐5p and hsa‐miR‐891a‐5p) was developed in the training cohort. The risk score was calculated by the product of the expression level and the coefficients of each miRNA. The prognostic value of 10 miRNAs‐based signature for CRC patients was tested and validated. Survival analysis indicated that high‐risk patients (> 1.10) had a worse overall survival (OS) than low‐risk (≤ 1.10) patients (5‐year OS rate for training cohort: 59.3% vs. 78.9%, p < .001; validation cohort: 48.3% vs. 69.3%, p = .011). The miRNA‐based signature was an independent prognostic factor for CRC patients (HR for training cohort:2.476, 95% CI:1.202–5.098, p = .014; HR for validation cohort:2.050, 95% CI:1.087–3.869, p = .027). The AUC values for 3‐year and 5‐year OS prediction were 0.718 and 0.784 in the training cohort, 0.659 and 0.614 in the validation cohort, respectively. The 10 miRNAs‐based signature provided a proper prognostic stratification for CRC patients, and it might be a promising tool for survival prediction.
The roles of elevated temperature and carriers in the dyeing of polyester fibres using disperse dyes: Part 1 fundamental aspects
Authors: Burkinshaw Stephen M.
Published: August 2023

This review concerns the application of disperse dyes to poly(ethylene terephthalate) (PET) fibres using aqueous immersion dyeing processes and the roles of both elevated dyeing temperatures and carriers in such dyeing systems. This part of the paper presents a review of the fundamental properties and characteristics of PET fibres, disperse dyes and dyeing accelerants. In the next part of the paper, the various theories and concepts that have been proposed to explain the promotional effects imparted by elevated dyeing temperatures and carriers to disperse dye uptake on PET and other types of fibre, are reviewed and analysed, from the viewpoints of the essential physico‐chemical aspects of both the aqueous disperse dye/PET and disperse dye/carrier/PET systems. Later parts of the paper will present a mechanistic model of the disperse dye adsorption process based on dye solubility as well as a novel plasticisation model of dye diffusion.
A qualitative analysis of adolescents' perspectives on peer and influencer alcohol‐related posts on social media
Authors: Corcoran Erin , Doucette Hannah , Merrill Jennifer E. , Pielech Melissa , López Gabriela , Egbert Amy , Nelapati Shimei , Gabrielli Joy , Colby Suzanne M. , Jackson Kristina M.
Published: August 2023

Introduction

Adolescent exposure to alcohol‐related content on social media is common and associated with alcohol use and perceived norms; however, little is known about how exposure differs by the source of the content (e.g., peer or ‘influencer’). The purpose of this study was to utilise qualitative methods to compare adolescent perspectives on peer‐ versus influencer‐generated alcohol content on social media.

Methods

Nine virtual semi‐structured focus groups were conducted with adolescents (aged 15–19 years), following a general script aimed at ascertaining adolescent comparative perspectives on peer and influencer alcohol‐related media content and the contexts in which it occurs.

Results

Five main themes emerged: (i) although both influencers and peers post predominantly positively‐valenced alcohol content online, adolescents perceived some differences between these posts; (ii) adolescents perceived their peers to be more cautious and strategic when posting about alcohol than influencers are; (iii) the decision to engage with peer or influencer alcohol‐related posts is influenced by a number of factors; (iv) both peer and influencer posts were perceived to send the message that drinking is acceptable, normal or cool; and (v) adolescents believed they are more likely to be influenced by peers' alcohol posts than influencers' alcohol posts, with some exceptions.

Discussion and Conclusions

Future studies should aim to further understand the unique attributes and circumstances in which exposure to peer and influencer alcohol‐related posts impact adolescent alcohol‐related cognitions and behaviours. This knowledge will inform prevention and intervention efforts, such as media literacy training and media‐specific parenting practices.
Single‐cell RNA sequencing of a poorly metastatic melanoma cell line and its subclones with high lung and brain metastasis potential reveals gene expression signature of metastasis with prognostic implication
Authors: Kim Yoon‐Seob , Kim Dokyeong , Park Junseong , Chung Yeun‐Jun
Published: August 2023

The molecular mechanisms underlying melanoma metastasis remain poorly understood. In this study, we aimed to delineate the mechanisms underlying gene expression alterations during metastatic potential acquisition and characterize the metastatic subclones within primary cell lines. We performed single‐cell RNA sequencing of a poorly metastatic melanoma cell line (WM239A) and its subclones with high metastatic potential to the lung (113/6‐4L) and the brain (131/4‐5B1 and 131/4‐5B2). Unsupervised clustering of 8173 melanoma cells identified three distinct clusters according to cell type (‘Primary’, ‘Lung’ and ‘Brain’ clusters) with differential expression of MITF and AXL pathways and putative cancer and cell cycle drivers, with the lung cluster expressing intermediate but distinct gene profiles between primary and brain clusters. Principal component (PC) analysis revealed that PC2 (the second PC), which was positively associated with MITF expression and negatively with AXL pathways, primarily segregated cell types, in addition to PC1 of the cell cycle pathway. Pseudotime trajectory and RNA velocity analyses suggested the existence of cellular subsets with metastatic potential in the Primary cluster and an association between PC2 signature alteration and metastasis potential acquisition. Analysis of The Cancer Genome Atlas melanoma samples by clustering into PC2‐high and ‐low clusters by quartiles of PC2 signature expression revealed that the PC2‐high cluster was an independent significant factor for poor prognosis (p‐value = 0.003) with distinct genomic and transcriptomic characteristics, compared to the PC2‐low cluster. In conclusion, we identified signatures of melanoma metastasis with prognostic significance and putative pro‐metastatic subclones within a primary cell line.
The dynamics of circulating tumour DNA (ctDNA) during treatment reflects tumour response in advanced melanoma patients
Authors: Di Nardo Lucia , Del Regno Laura , Di Stefani Alessandro , Mannino Maria , Fossati Barbara , Catapano Silvia , Quattrini Laura , Pellegrini Cristina , Cortellini Alessio , Parisi Alessandro , Capoluongo Ettore , Autilio Chiara , Fargnoli Maria Concetta , Peris Ketty
Published: August 2023

Despite the introduction of targeted (BRAFi/MEKi) and immune checkpoint inhibitors (ICIs) has significantly reduced the recurrence rate and improved the overall survival (OS) of patients with Stage III and IV melanoma, only a percentage will benefit of durable disease control. The aim of this study was to examine whether the levels of circulating tumour DNA (ctDNA) in plasma of advanced melanoma patients undergoing BRAFi/MEKi or ICIs vary according to the patients' survival outcomes (i.e. progression‐free survival (PFS) and OS) and disease progression. Plasma samples of Stage III‐IV melanoma patients were collected at baseline (treatment initiation) and thereafter every 3 months. Circulating BRAFV600E/K and NRASQ61R/K mutations were analysed through droplet digital PCR (ddPCR, Bio‐Rad) in a total of 177 plasma samples from 48 melanoma patients (19 Stage III, 29 Stage IV). Baseline ctDNA concentration was significantly associated with OS (HR = 1.003, 95% CI = 1.000–1.006, p = 0.043) and PFS (HR = 1.004, 95% CI = 1.000–1.007, p = 0.029) independent of clinical‐prognostic confounders. For each unit increase in the ∆ctDNA (concentration difference between the last follow‐up and baseline) there was a 24% increased risk of disease progression, irrespective of treatment type and stage at diagnosis (OR = 1.24, 95% CI = 1.03–1.49, p = 0.020, AUC = 0.93). Patients with reduction of ctDNA level from baseline to the last follow‐up had longer OS (HR = 0.14; 95% CI = 0.05–0.44, p = 0.001) and PFS (HR = 0.08; 95% CI = 0.03–0.27, p < 0.0001) compared to patients with increased ctDNA, including adjustment for confounding factors. Our findings suggest that variation of ctDNA over time during melanoma treatment reflects the clinical outcome and tumour response to therapy and might be helpful in clinical monitoring.
Enhancing the qualitative and nutritional properties of strawberry juice through chitosan treatment
Authors: Heidarizadeh Fariba , Kolahi Maryam , Akhond Marziye
Published: August 2023

Strawberry (Fragaria x ananassa Duch.) belongs to the Rosaceae family. The fruit is very beneficial, with a delicious taste, attractive colour, and high vitamin and mineral content. The effect of chitosan on juice's transparency and phytochemical properties from the Camarosa cultivar was evaluated. Using chitosan as a clarifying agent for strawberry juice significantly reduced turbidity, phenolic content, flavonoids, protein and antioxidant properties. In contrast, the quantity of soluble solids, titratable acidity, pH, folate, vitamin C, anthocyanin and carbohydrates showed no significant changes. Changes were also observed in the colour‐related parameters of the juice. In order to assess potential contamination in strawberry fruit, the levels of heavy metals and pesticide residues were analysed separately using ICP and GC–MS techniques. There was a significant reduction in the levels of Cu, As, Co, Pb and Cd in strawberry juice after treatment with chitosan. Reducing heavy metals in fruit juice using chitosan helps improve the fruit juice's safety, nutritional properties and health benefits. It can be posited that chitosan affords the production of a more nutritious and healthier fruit juice as compared to natural strawberry fruit. Using chitosan as a clarifying agent produces a juice with extraordinary clarity, improves the safety, health benefits and nutritional value, and produces a consumer‐friendly product.
A review on development of plant‐based meat analogues as future sustainable food
Authors: Rout Srutee , S Sowmya R , Srivastav Prem Prakash
Published: August 2023

Consumers worldwide want to improve their diets by consuming nutritional and eco‐friendly products in their food. The demand for plant‐based meat analogues (PBMA) has increased due to the adverse effects on animals, people, and the environment. ‘Meat analogue’ means to use a substitute for meat as the primary element. The rising desire for ‘good for you’ and ‘good for the planet’ is driving the demand for plant‐based meat alternatives. This manuscript describes the methods and orientation used to create meat analogues that mimic meat. The term ‘bottom‐up approach’ describes putting together a structure from the ground up. By systematically structuring proteins through the assembly of individual structural pieces, bottom‐up processes can approach the design of the meat. The top‐down method is more efficient and scalable, but it can only generate the required shape at massive scales. Therefore, this review discussed various production methods and their processing consequences on PBMAs proposed for creating sustainable foods to enhance their structural and techno‐functionality.
A multicommodity pickup and delivery problem with time windows and handling time in the omni‐channel last‐mile delivery
Authors: Yang Jun , Li Yali
Published: August 2023

This paper investigates the vehicle routing problem faced by a third‐party logistics (3PL) provider that performs the last‐mile delivery service in omni‐channel retailing for a number of companies engaged in household appliances and furniture. In the problem, each company is associated with a set of warehouses, physical stores, and customers that provide or require various commodities. The request of a company is to transport commodities from the selected warehouses and stores to the customers. In addition, the pickup or delivery service at each location should be started in a predefined time window. Since the loading and unloading follow the last‐in‐first‐out fashion, the handling time incurred by additional operation is considered. The studied problem is formulated as a multicommodity pickup and delivery problem with time windows and handling time (MPDPTWH). MPDPTWH aims to satisfy the requests on the 3PL platform with the minimum total duration of the routes. We present a mixed integer programming formulation of the problem and propose a multirestart randomized tabu thresholding algorithm (MRTTA) as well as a memetic algorithm (MA) to solve this problem heuristically. Then, the performance of the mathematical model and the two heuristics is assessed over three sets of MPDPTWH instances. After this, we compare the proposed MRTTA and MA with algorithms from the literature on a related problem. Furthermore, we perform the sensitivity analysis in a case study by discussing the impact of picking cost and handling time on the solution, and give the managerial insights.
Mechanical tailoring of dislocations in ceramics at room temperature: A perspective
Authors: Fang Xufei
Published: August 2023

The potential of dislocations (line defects) in ceramics may have been greatly underrated until most recently. Promising proofs‐of‐concept have been demonstrated for dislocation‐tuned functional and mechanical properties, revealing a new research front for dislocations in ceramics for a wide range of potential applications. However, it is commonly known that ceramics are hard (difficult to deform) and brittle (easy to fracture), particularly at room temperature. It remains a great challenge to mechanically tailor dislocations in ceramics. To address this pressing bottleneck, this article discusses the mechanics‐based dislocation engineering in ceramics by examining the three fundamental factors of dislocation nucleation, multiplication, and motion. Successful experimental approaches to tune dislocation density and plastic zone size on single‐crystal strontium titanate are demonstrated. The dislocation‐based competition between plastic deformation and crack formation is discussed. The aspects of coupling external fields to manipulate dislocations are highlighted, which may hold the key to modulating the charged dislocation cores in ceramics and opening new routes for mechanical tailoring of dislocations at room temperature. Some open questions and challenges for engineering dislocations in ceramics are discussed.
SlGSTE8 in Spodoptera litura participated in the resistance to phoxim and chlorpyrifos
Authors: Xu Li , Liu Hongyu , He Chengshuai , Li Bo , Li Dongzhi , Song Genmiao , Liu Runqiang , Zhou Lin
Published: August 2023

Glutathione S‐transferases (GSTs) were reported to participate in insecticide resistance by metabolic and antioxidant activities. In our previous study, an ε class gene of GSTs, SlGSTe8 in Spodoptera litura, was screened out to be upregulated in a population resistant to pyrethroids and organophosphates. SlGSTe8 was highly expressed in the larvae stage, and the digestive tissue, foregut, midgut and hindgut, while the relative expression level was low in the pupae stage and other tissues. To further explore its role in the resistance to pyrethroids and organophosphates, the metabolic activity to insecticides by its recombinant protein was determined by Ultra Performance Liquid Chromatography, and its antioxidant enzyme activity was evaluated by disc diffusion assay. The recombinant protein showed significant metabolic activity to phoxim and chlorpyrifos, but not to fenvalerate, cyhalothrin or β‐cypermethrin. After incubation, the depletion rate of chlorpyrifos is 85.3%, higher than that of phoxim (17.5%). Also, the inhibition zone around filter discs decreased significantly after exposure to cumene hydroperoxide in recombinant plasmid than vector only, suggesting significant antioxidant activity of SlGSTE8. Further modelling and docking analysis indicated that the 3D structure of SlGSTE8 was well shaped for phoxim and chlorpyrifos, with the binding energy −5.58 and −5.15 kcal/mol, respectively. Our work provides evidence that SlGSTe8 in S. litura plays important roles in phoxim and chlorpyrifos resistance.
A deep reinforcement learning‐based maintenance optimization for vacuum packaging machines considering product quality degradation
Authors: Jiménez Hanser , Aribisala Adetoye , Cavalcante Cristiano , Do Phuc , Lee Chi‐Guhn
Published: August 2023

Vacuum loss in packaged meats can lead to product defects resulting in significant economic losses and negative public health issues. Therefore, it is crucial to study the degradation of components that are critical for the provision of vacuum and package sealing to enhance system availability and process safety. Accordingly, this article proposes a condition‐based maintenance policy that integrates quality information considering meat cuts that lack proper vacuum as defective items. A deep reinforcement learning algorithm is used to learn a set of adequate maintenance actions to be performed at each maintenance inspection while maximizing the system availability and/or minimizing the total maintenance cost including the cost of producing defectives items. A numerical case study and benchmarking were performed, demonstrating that the proposed model surpasses the corrective maintenance policy. It leads to a 2.2% increase in system reliability, a 91% reduction in maintenance costs, a 93% reduction in defects identified in production, and a 90% reduction in defects identified on supermarket shelves. Such results demonstrate that the model can (i) prescribe maintenance actions at each inspection according to critical degradation states; (ii) exploit maintenance opportunities that lead to economic savings; and (iii) reduce product reprocessing and propagation of defects to shelves.

Practical applications

A new machine learning‐based maintenance model promises to revolutionize the vacuum packaging industry by enhancing system reliability, reducing costs, and improving product quality. The model enables managers to make dynamic decisions based on the system state, avoiding inefficient maintenance planning and ensuring maximum productivity. By predicting quality performance through vacuum condition, the model allows for timely decision‐making and reduces the need for costly laboratory analysis. The free‐model's estimation of structural and economic relations of components enables managers to retrain and adapt maintenance policies for optimal system performance. With improved system reliability and reduced production of non‐conforming items, the industry can reduce reprocessing costs, contamination risks, and protect brand image by ensuring better control over meat hygiene. This new approach to maintenance optimization has significant implications for process safety, efficiency of operations, and profits of the vacuum packaging industry, making it a potential game‐changer in the field.
Improving light microscopy training routines with evidence‐based education
Authors: Imreh Gabriela , Hu Jianjiang , Le Guyader Sylvie
Published: August 2023

The low reproducibility of scientific data published in articles has recently become a cause of concern in many scientific fields. Data involving light microscopy is no exception. The low awareness of researchers of the technologies they use in their research has been identified as one of the main causes of the problem. Potential solutions have hinted at the need to improve technological and methodological education within research.

Despite the pivotal role of microscopy core facilities in the education of researchers being well documented, facility staff (FS) often learn their trade on the job, without receiving themselves any structured education about the technology they teach others to use. Additionally, despite endorsing an important role at the highest level of education, most FS never receive any training in pedagogy, the field of research on teaching and learning methods.

In this article, we argue that the low level of awareness that researchers have of microscopy stems from a knowledge gap formed between them and microscopy FS during training routines. On the one hand, FS consider that their teaching task is to explain what is needed to produce reliable data. On the other, despite understanding what is being taught, researchers fail to learn the most challenging aspects of microscopy, those involving their judgement and reasoning. We suggest that the misunderstanding between FS and researchers is due to FS not being educated in pedagogy and thus often confusing understanding and learning.

To bridge this knowledge gap and improve the quality of the microscopy education available to researchers, we propose a paradigm shift where training staff at technological core facilities be acknowledged as full‐fledged teachers and offered structured education not only in the technology they teach but also in pedagogy. We then suggest that training routines at facilities be upgraded to follow the principles of the Constructive Alignment pedagogical method. We give an example of how this can be applied to existing microscopy training routines. We also describe a model to define where the responsibility of FS in training researchers begins and ends.

This involves a major structural change where university staff involved in teaching research technologies themselves receive appropriate education. For this to be achieved, we advocate that funding agencies, universities, microscopy and core facility organisations mobilise resources of time and funding. Such changes may involve funding the creation and development of ‘Train‐the‐trainer’ type of courses and giving incentives for FS to upgrade their technological and pedagogical knowledge, for example by including them in career paths. We believe that this paradigm shift is necessary to improve the level of microscopy education and ultimately the reproducibility of published data.
Goodness‐of‐fit tests for the multivariate Student‐tdistribution based on i.i.d. data, and for GARCH observations
Authors: Meintanis Simos , Milošević Bojana , Obradović Marko , Veljović Mirjana
Published: August 2023

We consider goodness‐of‐fit tests for the multivariate Student'st‐distribution with i.i.d. data and for the innovation distribution in a generalized autoregressive conditional heteroskedasticity model. The methods are based on the empirical characteristic function and are relatively easy to implement, invariant under linear transformations, and globally consistent. Asymptotic properties of the proposed procedures are investigated, while the finite‐sample properties are illustrated by means of a Monte Carlo study. The procedures are also applied to real data from the financial markets.
Customized planning of the visible maxillary arch width in harmony with interparopia width and smile width for female facial aesthetics
Authors: Yang Xianrui , Justus Roberto , Li Bin , Xue Chaoran , Lee I‐Ting (David) , Guo Yongwen , Bai Ding , Han Xianglong , Xu Hui
Published: August 2023

Background

The visible maxillary arch width (VAW) is an important aesthetic‐determining feature. To date, there is no well‐established methodology to determine the aesthetically optimal VAW in customized treatment planning.

Methods

In this study, the common traits of the dentofacial configuration were investigated in most attractive Asian and Caucasian female smiles. The smiling photo of a subject was digitally modified based on combined variations of VAW, smile width (SW), transverse facial dimensions (TFD), and vertical facial dimensions. These modified photos were assessed for aesthetics. The aesthetically essential parameters were identified, and their mathematic correlations and reference ranges were determined for different vertical facial patterns. Using the obtained results, a mathematic guidance was constructed for customized smile designing. The applicability of this guidance was tested in Asian females.

Results

The most attractive Asian and Caucasian female smiles have intraracial and interracial commonalities in the VAW‐to‐TFD ratios. The interparopia width (IPD) predominated over facial widths in determining well‐matched VAW and SW. For optimal smile aesthetics, the VAW and SW were correlated as simulated by the formula 1.92 IPD ≤ VAW + 2.3 SW ≤ 2.17 IPD, plus the VAW‐to‐IPD ratio within 0.54 to 0.62 and the SW‐to‐IPD ratio within 0.61 to 0.71, ranges tailored to vertical facial patterns. This constitutes a mathematic guidance for customized planning of the aesthetically optimal VAW. This guidance was preliminarily validated to be applicable to Asian females.

Conclusions

The VAW‐to‐TFD ratios were essential for Caucasian and Asian female smile aesthetics. The mathematic guidance could serve as a reference for customized smile designs for Asian females.
Analysis of the Ability of a Distal Tibial Anatomical Locking Plate to Capture the Distal Tibial Fragments in Patients with Pilon Fractures
Authors: Liu Jun‐Hong , Zhang Qiang , Wei Guo‐Hua , Liu Liang , Mu Xin , Li Mao‐Lin , Wu Zong‐De
Published: August 2023

Objective

Although pilon fractures are rare in clinical practice, they are difficult to treat because of their complexity. Effective fixation of the fracture fragment is the key to the treatment of pilon fractures. Plate osteosynthesis is common clinically, but there are many types of plates and the evaluation of the effect of fixation plates is not comprehensive.

This study attempted to compare the capture effect of different fixation plates on the fracture fragments based on 3D modeling and fine distinctions of fracture fragments.

Methods

The computed tomography (CT) images before treatment of 127 patients with pilon fractures from January 2019 to December 2021 were retrospectively collected. The fracture lines were mapped and digitally displayed as 3D images using MIMICS 21 software. APLUS distal tibia anatomical locking plate (Plate A) and ZIMMER distal tibia anatomical plate (Plate B) were placed on a pseudo‐bone model and CT scans were used to determine the number of screws in the major and minor fragments of pilon fractures. The frequency of the two plates capturing the fracture fragments was recorded.

Results

Under Assumption 1 or 2, Plate A performed significantly better than Plate B in capturing the major, Chaput, Volkmann, medial malleolus, and die‐punch fracture fragments. Plate A captured markedly more minor fragments than Plate B under Assumption 2 but was not significantly different from Plate B under Assumption 1. Plate A or Plate B showed no obvious difference between major and minor capture rates under the same assumption, and A1 or B1 showed a markedly higher capture rate compared with A2 or B2. In addition, there was a significant positive correlation between the major capture rate and the major fragments in B1, and a significant negative correlation between the minor capture rate and the minor fragments in Plates A and B. However, there was no correlation between the major capture rate of Plate A and the major fragments.

Conclusion

The APLUS distal tibial anatomical locking plate is superior to the ZIMMER distal tibia anatomical plate in the ability to capture distal tibial fragments in pilon fracture cases.