bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inversin‐deficient (inv) mice do not establish a polarized duct system in the liver and pancreas
Authors: Fujisawa Hiromu , Ota Noriaki , Shiojiri Nobuyoshi 
Published: November 2023

AbstractInversin‐deficient (inv) mice have anomalies in liver and pancreatic development in addition to an inverted left–right axis of the body. The present study was undertaken to unveil mechanisms of bile and pancreatic duct development from immunohistochemical analyses of anomalies in inv mice. Intrahepatic bile ducts having proximodistal polarity in size and the height of their epithelia, and ductules were formed in livers of wild‐type neonates. By contrast, in inv mice, ductal plates, precursor structures of intrahepatic bile ducts and ductules, persisted without the proximodistal polarity. Their epithelial cells did not acquire planar cell polarity (PCP) in terms of expression of tight junction proteins although they expressed bile duct markers, HNF1β and SOX9. They had an apicobasal polarity from expression of basal laminar components. Enlargement of the hepatic artery and poor connective tissue development, including the abnormal deposition of the extracellular matrices, were also noted in inv mice, suggesting that bile duct development was coupled to that of the hepatic artery and portal vein. In pancreata of inv neonates, neither the main pancreatic duct was formed, nor dilated duct‐like structures had the morphological polarity from the connecting point with the common bile duct. Lumina of acini was dilated, and centroacinar cells changed their position in the acini to their neck region. Immunohistochemical analyses of tight junction proteins suggested that epithelial cells of the duct‐like structures did not have a PCP. Thus, Invs may be required for the establishment of the PCP of the whole duct system in the liver and pancreas.
Impact assessment of metabolite instability in the development and validation of LC–MS/MS bioanalytical assays for measurement of rosuvastatin in human plasma and urine samples
Authors: Cui Yuxiang , Kowalski Kevin , Van Parys Michael , Miller Dennis , Hansen Patricia , Liang Xiaorong , Dean Brian , Chen Liuxi 
Published: November 2023

AbstractDuring bioanalytical assay development and validation, maintaining the stability of the parent drug and metabolites of interest is critical. While stability of the parent drug has been thoroughly investigated, the stability of unanalyzed metabolites is often overlooked. When an unstable metabolite is known or suspected to interfere with measurement of the parent drug or other metabolites of interest through back‐conversion or other routes, additional tests with these unstable metabolites should be conducted. Here, the development and validation of two assays for quantification of rosuvastatin, one in human plasma and one in human urine, was reported. To this end, additional sets of quality control samples were added during assay validation to ensure the reliability of the assays. Acid treatment of samples is shown to be necessary for rosuvastatin quantification. In this regard, stability issues caused by the metabolite, rosuvastatin lactone, may have been overlooked if assay development and validation had only considered the parent drug, rosuvastatin. These assays represent a case study for how to develop and validate assays with unstable metabolites. Taken together, unstable metabolites should be included in all applicable stability tests.
A network study to differentiate suicide attempt risk profiles in male and female patients with major depressive disorder
Authors: Sarti Pierfrancesco , Colliva Chiara , Varrasi Simone , Guerrera Claudia Savia , Platania Giuseppe Alessio , Boccaccio Francesco Maria , Castellano Sabrina , Pirrone Concetta , Pani Luca , Tascedda Fabio , di Nuovo Santo , Caraci Filippo , Blom Johanna M. C. 
Published: November 2023

AbstractSuicide attempts are a possible consequence of Major Depressive Disorder (MDD), although their prevalence varies across different epidemiological studies. Suicide attempt is a significant predictor of death by suicide, highlighting its importance in understanding and preventing tragic outcomes. Researchers are increasingly recognizing the need to study the differences between males and females, as several distinctions emerge in terms of the characteristics, types and motivations of suicide attempts. These differences emphasize the importance of considering gender‐specific factors in the study of suicide attempts and developing tailored prevention strategies. We conducted a network analysis to represent and investigate which among multiple neurocognitive, psychosocial, demographic and affective variables may prove to be a reliable predictor for identifying the ‘suicide attempt risk’ (SAR) in a sample of 81 adults who met DSM‐5 criteria for MDD. Network analysis resulted in differences between males and females regarding the variables that were going to interact and predict the SAR; in particular, for males, there is a stronger link toward psychosocial aspects, while for females, the neurocognitive domain is more relevant in its mnestic subcomponents. Network analysis allowed us to describe otherwise less obvious differences in the risk profiles of males and females that attempted to take their own lives. Different neurocognitive and psychosocial variables and different interactions between them predict the probability of suicide attempt unique to male and female patients.
Business accountability in the Anthropocene
Authors: Grabs Janina 
Published: November 2023

AbstractThe arrival of the Anthropocene requires a profound rethinking of business accountability. A central challenge in this age is the possibility of pushing past planetary boundaries, which may irreversibly propel the Earth system into a new equilibrium that is less hospitable for human civilization. Businesses drive many of the processes contributing to such boundaries, and are powerful political actors who may shape or obstruct the necessary transformations to our socio‐economic systems. We therefore need to reconsider their accountability, focused on the following guiding question: Who (in business) should be accountable to whom for what? The answer to this question has important implications for environmental policy and governance. Drawing on a range of recent conceptual and policy developments, I present four major lines of thinking for reconsidering business accountability in the Anthropocene context: to rethink the purpose of business; to acknowledge companies' expanded but shared accountability for productive activities; to heighten collective and individual liability for past and future actions linked to overshooting planetary boundaries; and to recognize business accountability for influencing political and societal processes. Each of these lines of thinking imply policy changes related to, inter alia, corporate governance, due diligence, liability, and lobbying laws. I further call on businesses to actively participate in the large‐scale transformation necessary to keep within planetary boundaries by changing not only their production processes, but also product portfolios, business models, legal forms, and political and societal engagement; and highlight avenues for future research.
Walnut fruit diaphragm ethanol extract ameliorates damage due to Triton WR‐1339‐induced hyperlipidemia in rats
Authors: Palabiyik Esra , Sulumer Ayse Nurseli , Uguz Handan , Avci Bahri , Askin Seda , Askin Hakan 
Published: November 2023

AbstractThe walnut fruit diaphragm (WFD) is an economically and ecologically important by‐product of the Juglandaceae family. Components in the ethanolic extract of WFD (E‐WFD) were identified by gas chromatography‐mass spectroscopy (GC‐MS). In our study, the lipid‐lowering effect, antioxidant potential, and anti‐inflammatory properties of E‐WFD in the blood, heart, and liver tissues of rats (♂, Wistar) with hyperlipidemia caused by Triton WR‐1339 were determined using biochemical, histopathological, and molecular techniques. Experimental animals for analysis are as follows: K1: healthy control group, K2: E‐WFD (150 mg, o.d.), K3: E‐WFD (300 mg, o.d.), K4: HL (hyperlipidemic group) (400 mg kg–1 Triton WR‐1339, i.p.), K5: HL + E‐WFD (300 mg) grouped as (n = 6). After the application, anti‐hyperlipidemic analysis (TC, TG, LDL‐C, HDL‐C, ALT, and AST), oxidative stress (MDA, SOD, and CAT) parameters measurement, histopathological examinations, and inflammatory biomarker genes (Tnf‐α, Il‐6, Il‐1β, Mmp‐2, Mmp‐9, Lxr‐α and Srebp‐1c) expression stability were determined by q‐RT PCR. With the E‐WFD application, there was a decrease in TC and TG levels and an increase in HDL‐C. Oxidative stress decreased by changing MDA, SOD, and CAT levels. Histopathological deterioration in the tissues changed positively. In addition, E‐WFD showed significant inhibitory properties on Tnf‐α, Il‐6, Il‐1β, Mmp‐2, Mmp‐9, Lxr‐α, and Srebp‐1c genes.Practical Applications: It is known that hyperlipidemia causes a wide range of diseases. In this study, the effect of walnut fruit diaphragm (WFD) ethanol extract was compared against the effect of Triton WR‐1339‐induced hyperlipidemia on rats. With the use of WFD, the damages caused by hyperlipidemia were significantly ameliorated. Accordingly, it is expected to contribute to the pharmacology, food and cosmetic industries as a very valuable alternative product.]
Ligand Combination Approach in Pd‐Catalyzed Direct C−H Arylation of Benzothiazole and Benzoxazole
Authors: Bakare Sneha Prasad , Patil Mahendra 
Published: November 2023

AbstractThe use of ligand combination approach in the Pd catalyzed direct C−H arylation of benzothiazole and benzoxazole is demonstrated. The combination of two ligands phenanthroline monohydrate (Phen.H2O) and triphenylphosphine (PPh3) with Pd‐catalyst have offered the best catalytic properties in the C−H bond arylation reactions than either of two ligands employed separately in the reactions. This protocol exhibits a wide substrate scope affording C2 arylated benzothiazole and benzoxazole derivatives in excellent yields. Mechanistic studies including kinetic isotope effect (KIE), H/D exchange and competition experiments show that the C−H bond activation of benzothiazole and benzoxazole is very facile under reaction conditions. Furthermore, different mechanistic pathways originated from the catalytically active species such as Pd(η2‐dba)L (dba=dibenzylidene acetone) and Pd(PPh3)2 were investigated using computational methods. The computational results suggest that the generation of catalytically active species from Pd2(dba)3 is endoergic process and Phen ligand can initiate this step. On the other hand, the presence of PPh3 could be crucial for the oxidative addition of aryl halides which is the rate‐determining step of the reaction.
Extrapolating Metal (Cu, Ni, Zn) Toxicity from Individuals to Populations Across Daphnia Species Using Mechanistic Models: The Roles of Uncertainty Propagation and Combined Physiological Modes of Action
Authors: Hansul Simon , Fettweis Andreas , Smolders Erik , Schamphelaere Karel De 
Published: November 2023

Abstract
Mechanistic effect modeling is a promising tool to improve the ecological realism of environmental risk assessment. An open question for the mechanistic modeling of metal toxicity is whether the same physiological mode of action (PMoA) could be assumed for closely related species. The implications of various modeling choices, such as the use of parameter point estimates and assumption of simplistic toxicodynamic models, are largely unexplored. We conducted life-table experiments with Daphnia longispina, Daphnia magna, and Daphnia pulex exposed to the single metals Cu, Ni, and Zn, and calibrated toxicokinetic–toxicodynamic (TKTD) models based on dynamic energy budget theory. We developed TKTD models with single and combined PMoAs to compare their goodness-of-fit and predicted population-level sensitivity. We identified the PMoA reproduction efficiency as most probable in all species for Ni and Zn, but not for Cu, and found that combined-PMoA models predicted higher population-level sensitivity than single-PMoA models, which was related to the predicted individual-level sensitivity, rather than to mechanistic differences between models. Using point estimates of parameters, instead of sampling from the probability distributions of parameters, could also lead to differences in the predicted population-level sensitivity. According to model predictions, apical chronic endpoints (cumulative reproduction, survival) are conservative for single-metal population effects across metals and species. We conclude that the assumption of an identical PMoA for different species of Daphnia could be justified for Ni and Zn, but not for Cu. Single-PMoA models are more appropriate than combined-PMoA models from a model selection perspective, but propagation of the associated uncertainty should be considered. More accurate predictions of effects at low concentrations may nevertheless motivate the use of combined-PMoA models. Environ Toxicol Chem 2024;43:338–358. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Responsibility boundaries and the governance of global value chains: The interplay of efficiency, ethical, and institutional pressures in global strategy
Authors: DeBerge Thomas 
Published: November 2023

AbstractResearch SummaryI explore the relationship of firm global strategy and global value chain (GVC) governance, within a context of expanding responsibility boundaries for unethical practices in the value chain. Specifically, focusing on the tantalum supply chain within the digital electronics GVC, I conduct a case‐based process study that contextualizes the different strategic responses of three manufacturers of tantalum capacitors when faced with similar efficiency, ethical, and institutional pressures. Integrating the GVC and global strategy literatures, I find that structural inertia in GVCs limits the efficacy of strategies that preserve, rather than alter, the governance structure, instead requiring a strategic restructuring carried out by individual firms, whose internalization of responsibility boundaries is encouraged by the institutionalization of these boundaries through public policy.Managerial SummaryUnethical practices within global value chains are increasingly becoming the responsibility of firms with no direct control over such practices, leading to growing pressures for firms to alter their global strategies to meet social and institutional demands. Research has focused on strategies that preserve the structure of the value chain, despite questions about the efficacy of these approaches. By looking at the case of “conflict minerals” within the digital electronics value chain, this study finds that inherent flaws in value chain structures, which managers can identify, require individual firms to implement strategies that change the structure of the value chain, specifically by increasing ownership and control over the linkages where unethical practices occur and encouraging public policies that add value to these strategies.
Going the extra mile? General practitioners' upcoding of fees for home visits
Authors: O’Halloran Jamie , Oxholm Anne Sophie , Pedersen Line Bjørnskov , Gyrd‐Hansen Dorte 
Published: November 2023

AbstractGeneral practitioners' (GPs') income often relies on self‐reported activities and performances. They can therefore ‘game the system’ to maximize their remuneration. We investigate whether Danish GPs game their travel fees for home visits. Combining administrative and geographical data, we measure the difference between GPs' traveled and billed distances. We exploit a rise in the fees for home visits. If there is a link between the rise in fees and upcoding, we interpret this finding as indicative of gaming behavior. We find that upcoding occurs slightly more often than downcoding (16% vs. 13% of visits) for visits that can be both upcoded and downcoded. Using linear probability models with GP fixed effects, we find that the fee rise is associated with a reduction in upcoding of 0.6% of home visits (2.8% for visits where upcoding is feasible) and no change in downcoding. Importantly, we find no statistically significant differences in the reduction in upcoding across distance bands despite large differences in their fee rises. We therefore conclude that there is no causal evidence of GPs gaming their fees.
Evaluation of an acute trust Domestic Abuse Coordinator role: Impact findings and a budget impact model
Authors: Melendez‐Torres G. J. , Crathorne Louise , Hepworth Eleanor , Sloane Vanessa , Jackson Sally , Nicholas Rachel , Cohen Charlotte E. 
Published: November 2023

AbstractDomestic Abuse Coordinators (DACs) work strategically across National Health Service (NHS) hospital and other off‐site clinical settings to support clinical staff in domestic abuse enquiry and response, and to co‐lead the development and implementation of effective clinical policies and procedures for the management of domestic abuse and the support of survivors. Drawing on data from a large NHS acute trust in central London, we analyse the impact of the DAC role in increasing the rate of referrals of high‐risk domestic abuse cases, and generate plausible estimates of the budget impact of the DAC role in respect of costs accrued to NHS trusts. Using eight quarters of clinical data and an interrupted time series design, we find that evidence that implementation of a DAC role is linked with an increase in the rate of high‐risk referrals of between 18% and 21% per quarter, indicating improved responses to victim‐survivors at highest risk of imminent harm. Under a range of reasonable assumptions, initiation of the DAC role is shown to be cost‐saving to an employing acute trust. Future work should seek to quantify the direct impacts to survivor health and wellbeing of the implementation of the DAC role.
1,25(OH)2D3 inhibits Lewis lung cancer cell migration via NHE1‐sensitive metabolic reprograming
Authors: Chen Hong , Zhu Mei‐zhen , Wang Xi‐ting , Ai Min , Li Shuang‐shuang , Wan Ming‐yu , Wang Pei‐yao , Cai Wei‐wei , Hou Bao , Xu Fei , Lang Florian , Qiu Li‐ying , Zhou Yue‐tao 
Published: November 2023

AbstractHigh prevalence and metastasis rates are characteristics of lung cancer. Glycolysis provides energy for the development and metastasis of cancer cells. The 1,25‐dihydroxy vitamin D3 (1,25(OH)2D3) has been linked to reducing cancer risk and regulates various physiological functions. We hypothesized that 1,25(OH)2D3 could be associated with the expression and activity of Na+/H+ exchanger isoform 1 (NHE1) of Lewis lung cancer cells, thus regulating glycolysis as well as migration by actin reorganization. Followed by online public data analysis, Vitamin D3 receptor, the receptor of 1,25(OH)2D3 has been proved to be abundant in lung cancers. We demonstrated that 1,25(OH)2D3 treatment suppressed transcript levels, protein levels, and activity of NHE1 in LLC cells. Furthermore, 1,25(OH)2D3 treatment resets the metabolic balance between glycolysis and OXPHOS, mainly including reducing glycolytic enzymes expression and lactate production. In vivo experiments showed the inhibition effects on tumor growth as well. Therefore, we concluded that 1,25(OH)2D3 could amend the NHE1 function, which leads to metabolic reprogramming and cytoskeleton reconstruction, finally inhibits the cell migration.
Leveraging a comprehensive systems thinking framework to analyze engineer complex problem‐solving approaches
Authors: Dugan Kelley E. , Mosyjowski Erika A. , Daly Shanna R. , Lattuca Lisa R. 
Published: November 2023

AbstractBackgroundTo prepare engineers who can address complex sociotechnical problems, a deep understanding of engineers' complex problem‐solving approaches is needed.Purpose/HypothesisThis study operationalizes comprehensive systems thinking as an analysis framework that attends to aspects of engineering work and relationships among those aspects. Leveraging this framework to analyze engineers' complex problem‐solving approaches enables attention to social and technical dimensions.Design/MethodWe interviewed 46 engineers about their specific complex problem‐solving experiences. To explore a range of perspectives, we purposely sampled participants with varying academic, professional, and personal backgrounds and experiences. Data analysis focused on operationalizing comprehensive systems thinking; we first developed a set of aspects that captured the variety of considerations that participants discussed in their descriptions of solving a complex problem. We then inductively developed a scoring guide to differentiate response quality.ResultsThe scoring approach differentiated the quality of consideration based on a combination of the number of details provided, the degree of specificity, and analytical depth. While most participants discussed the consideration of a wide range of aspects of engineering work, they discussed far fewer possible relationships between these aspects. Contextual aspects of engineering work were consistently the least commonly identified and least likely to be considered in relation to other aspects of a given problem.ConclusionsOur differentiation of various complex problem‐solving approaches can guide the development of educational interventions and tools, ultimately facilitating more comprehensive consideration of aspects—and in particular relationships among aspects—and setting up engineers to be more successful at developing appropriate solutions.
Micromorphological and phytochemical profiling of Delphinium suave Huth. from Hindukush range, Lower Dir Khyber Pakhtunkhwa Pakistan
Authors: Ahmad Imran , Dastagir Ghulam 
Published: November 2023

AbstractThis is a very first attempt to study various parameters of a medicinal plant, Delphinium suave Huth. The plant is erect, geophytic, herbaceous, with tuberous root, trifid in a palmatipartite, strigose cuneate leaf and white spurred zygomorphic flower. The root was isodiametric phellem with single non‐glandular trichomes. The stem revealed single‐layered cuticle, multiseriate epidermis, cortex, pith ray and uniserate bowed non‐glandular trichomes. The leaf was amphistomatic, showed tapering trichomes, prismatic crystals and ranunculaceous stomata with circumference 144.66–182.67 μm. Pollen grains in Light Microscopy (LM), were prolate, spheroidal trizonocolpate, isopolar, radiosymmetric, scabrate, elliptic and monads. Scanning Electron Microscope (SEM) pollen surface was scabrate, monad, size varied from 18.06 to 16.67 μm, colpus to inaperturate, tricolpate, ornamented, echinus, isopolar, isodiametric and circular. SEM roots showed sclerenchymatic tissues, stellate, glandular, non‐glandular trichomes and crystals. The stem showed scalariform, pitted vessels, warty protuberances, unicellular, silicified, non‐glandular trichomes. Leaves powder revealed, simple, unicellular, tapered headed, uniseriate, sessile, capitate, unbranched glandular, non‐glandular, trichomes with crystals. Capitate, stellate, circular, unicellular, branchy trichomes were observed for the first time through SEM. Powder drug study of root, stem leaves through LM revealed different tissues. Preliminary phytochemical revealed alkaloids, anthocyanins, anthraquinones, coumarins, flavones, mucilages, saponins, steroids, terpenoids, volatile oils and proteins. GC/MS showed 36 compounds in roots, 33 in stem while 40 in leaves. Fluorescence analysis of roots, stem and leaves showed variations in color when treated with chemicals. This study will assist pharmacognostic exploration, authentication from adulterants/allied species for consistent quality, resulting in safe use, preservation and efficacy.Research Highlights
This was first attempt on pharmacognostic study on D. suave Huth. which could be used as a foundation for identifying and authenticating the specie from other allied species by these morphological, anatomical, GC/MS profiling, phytochemical analysis and fluorescence analysis.