bluuebunny/crossref_metadata_2025 huggingface dataset:
Do depositors discipline the banking sector? Evidence from an emerging economy
Authors: Afzal Ayesha , Mirza Nawazish , Firdousi Saba
Published: March 2023

Purpose

Market discipline is an important part of financial regulation, under Basel II and III. This paper aims to provide evidence on market discipline in Pakistan. Specifically, the authors have analyzed the impact of CAMEL variables on costs of funds and deposit switching.

Design/methodology/approach

This study has used panel data related to different banking and macroeconomic variables. The sample period is 2004–2017 so it has covered the changing regulations that became binding for banks under Basel II and III. Quarterly data has been collected from the financial disclosure of publicly listed banks. The total number of banks in the sample is 26. Among these, 24 are publicly listed. Foreign banks have not been included because their activities in Pakistan are quite limited.

Findings

It has been found that efficiency, liquidity, asset quality and capital adequacy are negatively related to costs of funds for banks. Capital adequacy, liquidity and profitability are negatively related to deposit switching.

Research limitations/implications

These results indicate the presence of market discipline and have generated valuable implications for bank managers and regulators.

Originality/value

In this study, the case of Pakistan is interesting. The country has experienced financial liberalization that sought to avoid government intervention and encourage a more “market-based” approach. This change in the system was made more pronounced by the privatization of nationalized banks, improvement in the market structure, reduction in barriers to entry and consolidation of smaller banks. As a result, the banking system has emerged as an important source of financing and it provides us motivation to look deeper into depositor discipline in banking sector.
Behavior of partial-length stiffened and full-length stiffened CFDST columns under axial load
Authors: Hassan Aamir , Bhat Javed Ahmad
Published: March 2023

Purpose

Concrete-filled double skin tube (CFDST) columns are considered one of the most effective steel-concrete composite sections owing to the higher load carrying capacity as compared to its counterpart concrete-filled tube (CFT) columns. This paper aims to numerically investigate the performance of axially loaded, circular CFDST short columns, with the innovative strengthening technique of providing stiffeners in outer tubes. Circular steel hollow sections have been adopted for inner as well as outer tubes, while varying the length of rectangular steel stiffeners, fixed inside the outer tubes only, to check the effect of stiffeners in partially and full-length stiffened CFDST columns.

Design/methodology/approach

The behaviour of these CFDST columns is investigated numerically by using a verified finite element analysis (FEA) model from the ABAQUS. The behaviour of 20-unstiffened, 80-partially stiffened and 20-full-length stiffened CFDST columns is studied, while varying the strength of steel (fyo = 250–750 MPa) and concrete (30–90 MPa).

Findings

The FEA results are verified by comparing them with the previous test results. FEA study has exhibited that, there is a 7%–25% and 39%–49% increase in peak-loads in partially stiffened and full-length stiffened CFDST columns, respectively, compared to unstiffened CFDST columns.

Originality/value

Enhanced strength has been observed in partially stiffened and full-length stiffened CFDST columns as compared to unstiffened CFDST columns. Also, a significant effect of strength of concrete has not been observed as compared to the strength of steel.
The evolving copiotrophic/oligotrophic dichotomy: From Winogradsky to physiology and genomics
Authors: Soler‐Bistué Alfonso , Couso Luciana L. , Sánchez Ignacio E.
Published: March 2023

Nearly 100 years ago, Winogradsky published a classic communication in which he described two groups of microbes, zymogenic and autochthonous. When organic matter penetrates the soil, zymogenic microbes quickly multiply and degrade it, then giving way to the slow combustion of autochthonous microbes. Although the text was originally written in French, it is often cited by English‐speaking authors. We undertook a complete translation of the 1924 publication, which we provide as Supporting information. Here, we introduce the translation and describe how the zymogenic/autochthonous dichotomy shaped research questions in the study of microbial diversity and physiology. We also identify in the literature three additional and closely related dichotomies, which we propose to call exclusive copiotrophs/oligotrophs, coexisting copiotrophs/oligotrophs and fast‐growing/slow‐growing microbes. While Winogradsky focussed on a successional view of microbial populations over time, the current discussion is focussed on the differences in the specific growth rate of microbes as a function of the concentration of a given limiting substrate. In the future, it will be relevant to keep in mind both nutrient‐focussed and time‐focussed microbial dichotomies and to design experiments with both isolated laboratory cultures and multi‐species communities in the spirit of Winogradsky's direct method.
Gender inequality in asset ownership and women's food security in sub‐Saharan Africa
Authors: Nga Ndjobo Patrick Marie
Published: March 2023

Unequal asset rights remain an important driver of gender inequality and food insecurity in sub‐Saharan Africa (SSA). Using cross‐sectional data from 31 SSA countries, this study examines the effect of gender inequality in asset ownership on women's food security in the region. The seemingly unrelated (SUR) bivariate probit framework has been adopted in analysing the data. This approach is used for addressing the possible endogeneity bias that occurs when the dependent variable and regressor are both endogenous and binary. The major finding of this study reveals that gender inequality in asset ownership increases women's risk of facing food insecurity. The aforementioned is more pronounced for women who are undereducated, live in rural areas, and suffer various forms of discrimination. It is therefore important that more egalitarian laws on asset ownership and inheritance be adopted in all SSA countries. This will significantly increase women's specific food security and thus contribute to improving inclusiveness in these countries.
Special tea products featuring functional components: Health benefits and processing strategies
Authors: Yang Gaozhong , Meng Qing , Shi Jiang , Zhou Mengxue , Zhu Yin , You Qiushuang , Xu Ping , Wu Wenliang , Lin Zhi , Lv Haipeng
Published: March 2023

The functional components in tea confer various potential health benefits to humans. To date, several special tea products featuring functional components (STPFCs) have been successfully developed, such as O‐methylated catechin‐rich tea, γ‐aminobutyric acid‐rich tea, low‐caffeine tea, and selenium‐rich tea products. STPFCs have some unique and enhanced health benefits when compared with conventional tea products, which can meet the specific needs and preferences of different groups and have huge market potential. The processing strategies to improve the health benefits of tea products by regulating the functional component content have been an active area of research in food science. The fresh leaves of some specific tea varieties rich in functional components are used as raw materials, and special processing technologies are employed to prepare STPFCs. Huge progress has been achieved in the research and development of these STPFCs. However, the current status of these STPFCs has not yet been systematically reviewed. Here, studies on STPFCs have been comprehensively reviewed with a focus on their potential health benefits and processing strategies. Additionally, other chemical components with the potential to be developed into special teas and the application of tea functional components in the food industry have been discussed. Finally, suggestions on the promises and challenges for the future study of these STPFCs have been provided. This paper might shed light on the current status of the research and development of these STPFCs. Future studies on STPFCs should focus on screening specific tea varieties, identifying new functional components, evaluating health‐promoting effects, improving flavor quality, and elucidating the interactions between functional components.
What's in a Name? Defining New Entrants to Farming
Authors: Creaney Rachel , Hasler Hannah , Sutherland Lee‐Ann
Published: March 2023

New entrants to farming are eligible for CAP targeted supports. The intention of these supports is to promote innovativeness and sustainability in the agricultural sector through generational renewal. However, new entrants (successors or those completely new into the industry), still face multiple barriers above other longstanding farmers, including lack of access to necessary capital, land and housing. There is also ambiguity about the success of new entrant supports in achieving their stated objectives. We draw on results from an online survey distributed to anyone involved in farming in Europe, including European new entrants and those working in new entrant support services. Survey respondents were asked how they would define a ‘new entrant farmer’. A clear majority of respondents indicated that new entrants should be new to the industry; that is, not successors to existing farm businesses. A substantial minority of respondents indicated that new entrants should be establishing innovative new businesses, with an overlapping cohort emphasising sustainability. Very few respondents identified age as an important criterion. We argue that the new entrant definition utilised in policy supports could be more targeted towards policy objectives, distinguishing social justice supports (enabling newcomers to enter the sector), from supports for innovation (e.g. venture capital funds) and sustainability (greening the CAP).
How to assess economic progress in the era of discontinuity?
Authors: Hązła Marceli , Mińska‐Struzik Ewa
Published: March 2023

The aim of this article is to contribute to the discussion on designing alternative economic development indices by measuring economic progress in the face of the discontinuity of globalisation. To this end, we use different evaluation criteria for the ‘old’ (1960–1990) and the ‘new’ (1990–2019) globalisation. First, the historical context that has shaped the contemporary globalisation processes is outlined, which makes it possible to identify the 1990s and the subsequent change in the structure of the world industrial production and the world GDP as the most important tipping point. Based on the observation that none of the existing indices sufficiently cover all the issues, a new pilot measure of economic progress is proposed, which takes into account two time periods: the old (1960–1990) and the new (1990–2019) globalisation. The analysis of the data sample of 18 countries (G6, I6 and selected LDCs) using this measure makes it possible to assign their economies to four categories, depending on the results they have achieved; the ‘winners’, the ‘losers’, the ‘late‐bloomers’ and the ‘inmates of industry’. Furthermore, possible directions for the future research on the subject are indicated. The data set supporting this study has been made publicly available to help in its continuation.
Investigating the clinical impact of dose‐banding for weekly paclitaxel in patients with breast cancer: A retrospective and monocentric study
Authors: Puisset Florent , Le Louedec Félicien , Dalenc Florence , Verguet Lorène , De Maio Eleonora , Lacaze Jean Louis , Montastruc Marion , Ung Mony , Vinson Camille , Perriat Sophie , Pacher Sandrine , Chatelut Etienne , Koning Mélanie White
Published: March 2023

Aims

Dose‐banding (DB) consists in approximating the theoretical dose of anticancer drugs calculated according to the body surface area (Dose‐BSA) of patients. This concept is supported by pharmacokinetic but not by clinical data. The aim of this study was to assess the clinical outcome of DB defined as dose‐fitting up to ±10%.

Methods

This was a retrospective study conducted in patients receiving weekly paclitaxel in neoadjuvant (NAT) and metastatic (M+) settings. Three groups of patients were considered according to type of paclitaxel dosing: Dose‐BSA, DB approximated down (DB‐Low) and DB approximated up (DB‐High). Efficacy was evaluated by the rate of pathological complete response for patients in NAT setting and by the median of progression‐free survival plus overall survival for those in M+ setting. Toxicity and efficacy were compared in the 3 groups.

Results

A total of 224 and 209 patients were assessable in the M+ and NAT settings, respectively. A toxic event was observed for 31.7 and 27.3% in M+ and NAT, respectively. The rate of pathological complete response was 41.6% in NAT. The median progression‐free survival was 5.2 (4.1–5.8) months and overall survival was 16.3 (14.6–18.4) months for patients in M+. Efficacy and toxicity were not different in DB‐Low and DB‐High groups compared to Dose‐BSA group.

Conclusion

DB with approximated doses up to ±10% does not seem to influence clinical outcome of patients treated with weekly paclitaxel. This is the first study to include clinical observations, which lends support to DB as a safe and effective dosing method.
Subfield‐specific longitudinal changes of hippocampal volumes in patients with early‐stage bipolar disorder
Authors: Atwood Bruce , Yassin Walid , Chan Shi Yu , Hall Mei‐Hua
Published: March 2023

Background

The hippocampus is a heterogeneous structure composed of biologically and functionally distinct subfields. Hippocampal aberrations are proposed to play a fundamental role in the etiology of psychotic symptoms. Bipolar disorder (BPD) has substantial overlap in symptomatology and genetic liability with schizophrenia (SZ), and reduced hippocampal volumes, particularly at the chronic illness stages, are documented in both disorders. Studies of hippocampal subfields in the early stage of BPD are limited and cross‐sectional findings to date report no reduction in hippocampal volumes. To our knowledge, there have been no longitudinal studies of BPD evaluating hippocampal volumes in the early phase of illness. We investigated the longitudinal changes in hippocampal regions and subfields in BPD mainly and in early stage of psychosis (ESP) patients more broadly and compared them to those in controls (HC).

Methods

Baseline clinical and structural MRI data were acquired from 88 BPD, from a total of 143 ESP patients, and 74 HCs. Of those, 66 participants (23 HC, 43 patients) completed a 12‐month follow‐up visit. The hippocampus regions and subfields were segmented using Freesurfer automated pipeline.

Results

We found general baseline deficits in hippocampal volumes among BPD and ESP cohorts. Both cohorts displayed significant increases in the anterior hippocampal region and dentate gyrus compared with controls. Additionally, antipsychotic medications were positively correlated with the posterior region at baseline.

Conclusion

These findings highlight brain plasticity in BPD and in ESP patients providing evidence that deviations in hippocampal volumes are adaptive responses to atypical signaling rather than progressive degeneration.
How did the disclosure of lobbying targeting Quebec's hospitals become mandatory and with what effect?
Authors: Ouimet Mathieu , Savoie Justin , Montigny Éric
Published: March 2023

In 2015 mandatory disclosure activity for lobbying that targeted health and social service centres in Quebec, a sector which consumes a significant share of the annual spending budget, suddenly became a mandatory disclosure activity for lobbyists operating in the province. This research note traces the trajectory of key events that led to this shift towards greater lobbying transparency in the health care sector. The study also analyzes whether this change was followed by increased lobbying registrations for activities targeting health sector institutions. The article's findings suggest that significant change in lobbying regulation may occur accidentally, against the government's will, rather than as a result of an ethical scandal, cross‐jurisdictional learning, or electoral calculations, as the literature suggests. The article's findings also show that the change was followed by an increase of about 969 registered firm lobbyists (p‐value 0.015) and 254 registered lobbyists from covered NGOs (p‐value 0.00).
Transcriptional and open chromatin analysis of bovine skeletal muscle development by single‐cell sequencing
Authors: Cai Cuicui , Wan Peng , Wang Hui , Cai Xin , Wang Jiabo , Chai Zhixin , Wang Jikun , Wang Haibo , Zhang Ming , Yang Nan , Wu Zhijuan , Zhu Jiangjiang , Yang Xueyao , Li Yulian , Yue Binglin , Dang Ruihua , Zhong Jincheng
Published: March 2023

Skeletal muscle is a complex heterogeneous tissue and characterizing its cellular heterogeneity and transcriptional and epigenetic signatures are important for understanding the details of its ontogeny. In our study, we applied scRNA‐seq and scATAC‐seq to investigate the cell types, molecular features, transcriptional and epigenetic regulation, and patterns of developing bovine skeletal muscle from gestational, lactational and adult stages. Detailed molecular analyses were used to dissect cellular heterogeneity, and we deduced the differentiation trajectory of myogenic cells and uncovered their dynamic gene expression profiles. SCENIC analysis was performed to demonstrate key regulons during cell fate decisions. We explored the future expression states of these heterogeneous cells by RNA velocity analysis and found extensive networks of intercellular communication using the toolkit CellChat. Moreover, the transcriptomic and chromatin accessibility modalities were confirmed to be highly concordant, and integrative analysis of chromatin accessibility and gene expression revealed key transcriptional regulators acting during myogenesis. In bovine skeletal muscle, by scRNA‐seq and scATAC‐seq analysis, different cell types such as adipocytes, endothelial cells, fibroblasts, lymphocytes, monocytes, pericyte cells and eight skeletal myogenic subpopulations were identified at the three developmental stages. The pseudotime trajectory exhibited a distinct sequential ordering for these myogenic subpopulations and eight distinct gene clusters were observed according to their expression pattern. Moreover, specifically expressed TFs (such as MSC, MYF5, MYOD1, FOXP3, ESRRA, BACH1, SIX2 and ATF4) associated with muscle development were predicted, and likely future transcriptional states of individual cells and the developmental dynamics of differentiation among neighbouring cells were predicted. CellChat analysis on the scRNA‐seq data set then classified many ligand–receptor pairs among these cell clusters, which were further categorized into significant signalling pathways, including BMP, IGF, WNT, MSTN, ANGPTL, TGFB, TNF, VEGF and FGF. Finally, scRNA‐seq and scATAC‐seq results were successfully integrated to reveal a series of specifically expressed TFs that are likely to be candidates for the promotion of cell fate transition during bovine skeletal muscle development. Overall, our results outline a single‐cell dynamic chromatin/transcriptional landscape for normal bovine skeletal muscle development; these provide an important resource for understanding the structure and function of mammalian skeletal muscle, which will promote research into its biology.
Synergy between health technology assessments and clinical guidelines for multiple sclerosis
Authors: Hogervorst Milou A. , Vreman Rick A. , Zawada Anna , Zielińska Magdalena , Dawoud Dalia M. , de Jong Brigit A. , Mantel‐Teeuwisse Aukje K. , Goettsch Wim G.
Published: March 2023

Decision‐making for reimbursement and clinical guidelines (CGs) serves different purposes although the decision‐criteria and required evidence largely overlap. This study aimed to assess similarities and discrepancies between health technology assessment (HTA) reports as compared to CGs for multiple sclerosis (MS) medicines. All HTA reports and corresponding CGs for MS from the UK, France, Germany, the Netherlands, Poland, Sweden, and the European Union were assessed to identify synergies in recommendations for MS medicines (approved 1995–2020). A content analysis of HTA reports and CGs was performed to identify similarities and discrepancies in wording of treatment recommendations across documents. We assessed 132 HTA reports and 9 CGs for 16 MS treatments. Final recommendations for reimbursement and inclusion in CGs were mostly similar (90%), albeit with considerable differences in treatment lines and subindications. Since 2010, HTA reports refer to the use of CGs in 42% (55/132) and to consultations with clinicians in 43% (57/132) of cases. Six of nine CGs referred to HTA reports and two referred to HTA consultations, in one case having a formal relation to the HTA organization. CGs referenced pharmacoeconomic studies (4/9) for costs and cost‐effectiveness. To date, not all new HTA recommendations for MS treatments are included in CGs. Some synergy exists between treatment recommendations in HTA reports and CGs, although discrepancies were seen in timelines and in recommended treatment lines and subindications. More stakeholder dialogue and/or consultation of each other's publications may further improve synergy, facilitate transparency, and enhance patient access.
Psychosocial correlates of drinking transitions: A longitudinal study among adolescents in Sweden
Authors: Sjödin Lars , Karlsson Patrik , Raninen Jonas
Published: March 2023

Introduction

Non‐drinkers have been shown in older studies to have poorer mental health and social life compared to their alcohol‐using counterparts. Given the profound decline in adolescent drinking observed in most high‐income countries, this pattern may have changed. This study explores drinking transitions and examines psychosocial factors among adolescents by longitudinal drinking status.

Methods

Data were based on two waves of a prospective longitudinal nationwide study (n = 4018). The first wave (T1) of data was collected in 2017 (age 15/16) and the second wave (T2) was in 2019 (age 17/18). Respondents were asked about their past year drinking status, general health, psychosomatic problems, psychiatric medication, school enjoyment, emotional symptoms, peer relationship problems, prosocial ability, friendships satisfaction and satisfaction with relation to mother/father. Comparisons by mean values were assessed and multinomial logistic regressions were used to examine associations.

Results

Abstainers and later drinkers differed significantly from early drinkers on 9/10 factors respectively at T1. Fewer psychosomatic problems, less psychiatric medication, higher school enjoyment, more emotional symptoms, higher parental relationship satisfaction, more peer problems and lower friendships satisfaction at T1 were associated with abstaining and/or later drinking. All factors were more strongly associated with abstaining. School enjoyment predicted abstaining but not later drinking.

Discussion and Conclusions

Longitudinal drinking status relates to small to moderate systematic psychosocial differences. Adolescents with better mental health, more content relationships with parents and lower friendships satisfaction are more often abstainers. Those generally worse off are more likely early drinkers but they also have better friendships.
Concealing borrowers’ failure history in online P2P lending: A natural experiment
Authors: Bai Jiaru , Gao Qiang
Published: March 2023

Online peer‐to‐peer (P2P) platforms both disclose and conceal borrowers’ information. Minimal research has been conducted on the impact of concealing such information on borrowers’ funding success. We fill this research gap by exploring a natural experiment opportunity at Prosper, an online lending marketplace where the platform enacted a policy to conceal borrowers’ past failure history. We first find that the platform's decision to conceal such information can be rational because when this information was publicly available, borrowers with past failures had lower success rates than borrowers without past failures. We next investigate the effect of hiding this information on lenders' lending decisions. Our empirical results from a series of analyses demonstrate that concealing such information helps some borrowers but also surprisingly leads to an overall lower success rate, which ultimately harms the platform and runs counter to the platform's intention. These effects are strongest for low‐risk borrowers and would attenuate in the long run. We further find that the number of borrowers’ past failures is associated with lower repayment ability.
Metabolomic profiles in serum and urine uncover novel biomarkers in children with nephrotic syndrome
Authors: Hu Lidan , Lin Li , Huang Guoping , Xie Yi , Peng Zhaoyang , Liu Fei , Bai Guannan , Li Wei , Gao Langping , Wang Yan , Li Qiuyu , Fu Haidong , Wang Jingjing , Sun Qingnan , Mao Jianhua
Published: March 2023

Background

Nephrotic syndrome is common in children and adults worldwide, and steroid‐sensitive nephrotic syndrome (SSNS) accounts for 80%. Aberrant metabolism involvement in early SSNS is sparsely studied, and its pathogenesis remains unclear. Therefore, the goal of this study was to investigate the changes in initiated SSNS patients‐related metabolites through serum and urine metabolomics and discover the novel potential metabolites and metabolic pathways.

Methods

Serum samples (27 SSNS and 56 controls) and urine samples (17 SSNS and 24 controls) were collected. Meanwhile, the non‐targeted analyses were performed by ultra‐high‐performance liquid chromatography‐quadrupole time of flight‐mass spectrometry (UHPLC‐QTOF‐MS) to determine the changes in SSNS. We applied the causal inference model, the DoWhy model, to assess the causal effects of several selected metabolites. An ultraperformance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) was used to validate hits (D‐mannitol, dulcitol, D‐sorbitol, XMP, NADPH, NAD, bilirubin, and α‐KG‐like) in 41 SSNS and 43 controls. In addition, the metabolic pathways were explored.

Results

Compared to urine, the metabolism analysis of serum samples was more clearly discriminated at SSNS. 194 differential serum metabolites and five metabolic pathways were obtained in the SSNS group. Eight differential metabolites were identified by establishing the diagnostic model for SSNS, and four variables had a positive causal effect. After validation by targeted MS, except XMP, others have similar trends like the untargeted metabolic analysis.

Conclusion

With untargeted metabolomics analysis and further targeted quantitative analysis, we found seven metabolites may be new biomarkers for risk prediction and early diagnosis for SSNS.
Differential utility of various frailty diagnostic tools in non‐geriatric hospital departments of several countries: A longitudinal study
Authors: Checa‐Lopez Marta , Rodriguez‐Laso Angel , Carnicero Jose Antonio , Solano‐Jaurrieta Juan Jose , Saavedra Obermans Olga , Sinclair Alan , Landi Francesco , Scuteri Angelo , Álvarez‐Bustos Alejandro , Sepúlveda‐Loyola Walter , Rodriguez‐Manas Leocadio
Published: March 2023

Background

There is limited knowledge on the performance of different frailty scales in clinical settings. We sought to evaluate in non‐geriatric hospital departments the feasibility, agreement and predictive ability for adverse events after 1 year follow‐up of several frailty assessment tools.

Methods

Longitudinal study with 667 older adults recruited from five hospitals in three different countries (Spain, Italy and United Kingdom). Participants were older than 75 years attending the emergency room, cardiology and surgery departments. Frailty scales used were Frailty Phenotype (FP), FRAIL scale, Tilburg and Groningen Frailty Indicators, and Clinical Frailty Scale (CFS). Analyses included the prevalence of frailty, degree of agreement between tools, feasibility and prognostic value for hospital readmission, worsening of disability and mortality, by tool and setting.

Results

Emergency Room and cardiology were the settings with the highest frailty prevalence, varying by tool between 40.4% and 67.2%; elective surgery was the one with the lowest prevalence (between 13.2% and 38.2%). The tools showed a fair to moderate agreement. FP showed the lowest feasibility, especially in urgent surgery (35.6%). FRAIL, CFS and FP predicted mortality and readmissions in several settings, but disability worsening only in cardiology.

Conclusions

Frailty is a highly frequent condition in older people attending non‐geriatric hospital departments. We recommend that based upon their current feasibility and predictive ability, the FRAIL scale, CFS and FP should be preferentially used in these settings. The low concordance among the tools and differences in prevalence reported and predictive ability suggest the existence of different subtypes of frailty.
Effects of dosage in new users of lamotrigine inducing epidermal necrolysis: Results of the German Registry of Severe Skin Reactions
Authors: Diederich Sophie , Hemmeter Ulrich , Paulmann Maren , Mockenhaupt Maja
Published: March 2023

Objective

This study was undertaken to determine the impact of dosage in new users of lamotrigine (LTG) and the concomitant intake of valproic acid (VPA) on epidermal necrolysis (EN).

Methods

A total of 102 EN cases with exposure to LTG were identified (1992–2018) in the German Registry of Severe Skin Reactions. All cases are validated by an independent expert committee. Six cases were excluded due to lack of exposure in the relevant time frame. Causality assessment was performed with ALDEN (Algorithm for Assessment of Drug Causality in EN) on definite/probable cases (≥12 years; n = 84). Evaluation of dosing regimen was restricted to cases with complete LTG dosing history (n = 74).

Results

Demography showed a mean age of 42.4 years, female predominance (69%), and low mortality (7.3%). Epilepsy was the indication for use in 87.5%. LTG was the very probable cause in 71.4% and probable cause in 28.6%. On average, one additional antiseizure medication was taken, most frequently VPA (43/84). Combined LTG/VPA treatment showed no statistically significant difference in morbidity or mortality. Mean time latency from initiation of LTG to reaction onset was 24.2 days, varying between 21 days with high initial dose and 29.2 days with low initial dose. Low initial LTG dose (n = 9) revealed higher mortality (22.2%) and higher severity (5/9) than high initial dose (n = 35, mortality = 14.3%, 14/35 higher severity). No patient died when the starting dose was as recommended. The highest mortality (25%) was found in patients with no dose increase (n = 8), which correlated with higher age. Despite the recommended or low initial dose, 52.7% of patients developed EN, in contrast to 39.2% with a slow, recommended, or no dose escalation.

Significance

Neither the initial dose, dose escalation, nor the combination with VPA seems to influence the general occurrence of EN. However, EN patients with the recommended starting dose and the recommended dose escalation had the best outcome in terms of clinical severity and mortality.
The hub genes and their potential regulatory mechanisms in chronic spontaneous urticaria revealed by integrated transcriptional expression analysis
Authors: Liu Runqiu , Lv Dong , Cao Lihua , Liu Yu , Wen Xiaoting , Jiang Yannan , Xu Jiandan , Qin Jie , Qin Pingping
Published: March 2023

Chronic spontaneous urticaria (CSU) is a recurrent disease characterized by wheals and or angioedema, and its pathogenesis is still unclear. The microarray datasets of skin tissue from CSU patients and healthy controls were integrated and analysed in Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified using the NetworkAnalyst tool. Then, the Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Subsequently, a protein–protein interaction (PPI) network of DEGs was constructed by STRING and the related hub genes were identified through the MOCDE tool. The potential miRNAs targeting hub genes were predicted based on the intersection of three online databases, namely TargetScanHuman, TargetBase and miRNet. Differentially expressed lncRNAs (DElncRNAs) was performed using the GEO2R tool. The potential miRNAs targeting DElncRNAs were predicted through miRNet. Finally, the shared miRNAs targeting both hub genes and DElncRNAs were used to construct an mRNA/miRNA/lncRNA regulatory network. A total of 296 DEGs were obtained, which were mainly enriched in inflammatory and immune responses. Further, 14 hub genes were identified by the PPI network of DEGs. Clinical correlation analysis showed that the mRNA expressions of S100A7, S100A8, S100A9, S100A12, IL6 and SOCS3 in CSU were positively correlated with the 7‐day urticaria activity score (UAS7), and their potential diagnostic value was supported by the receiver operating characteristic curve (ROC) analysis. Five up‐regulated lncRNAs in the cytoplasm were obtained by DElncRNAs analysis. The ROC analysis showed that PVT1, SNHG3 and ZBTB20 − AS1 was of potential diagnostic value for CSU. Eight shared miRNAs targeting both hub genes and DElncRNAs were identified and used to construct a competing endogenous RNA (ceRNA) network. It was found that the IL‐6/miR − 149 − 5p/ZBTB20 − AS1 axis might play an important role in the activation of mast cells in CSU. IL‐6 and its related regulatory molecules may be used as potential diagnostic markers and therapeutic targets for CSU.
Autism‐like behavior of murine offspring induced by prenatal exposure to progestin is associated with gastrointestinal dysfunction due to claudin‐1 suppression
Authors: Xiao Li , Feng Jianqing , Zhang Wanhua , Pan Jie , Wang Min , Zhang Cheng , Li Ling , Su Xi , Yao Paul
Published: March 2023

Autism spectrum disorders (ASD) are associated with the contribution of many prenatal risk factors; in particular, the sex hormone progestin and vitamin D receptor (VDR) are associated with gastrointestinal (GI) symptoms in ASD development, although the related mechanism remains unclear. We investigated the possible role and mechanism of progestin 17‐hydroxyprogesterone caproate (17‐OHPC) exposure‐induced GI dysfunction and autism‐like behaviours (ALB) in mouse offspring. An intestine‐specific VDR‐deficient mouse model was established for prenatal treatment, while transplantation of haematopoietic stem cells (HSCT) with related gene manipulation was used for postnatal treatment for 17‐OHPC exposure‐induced GI dysfunction and ALB in mouse offspring. The in vivo mouse experiments found that VDR deficiency mimics prenatal 17‐OHPC exposure‐mediated GI dysfunction, but has no effect on 17‐OHPC‐mediated autism‐like behaviours (ALB) in mouse offspring. Furthermore, prenatal 17‐OHPC exposure induces CLDN1 suppression in intestine epithelial cells, and transplantation of HSCT with CLDN1 expression ameliorates prenatal 17‐OHPC exposure‐mediated GI dysfunction, but has no effect on 17‐OHPC‐mediated ALB in offspring. In conclusion, prenatal 17‐OHPC exposure triggers GI dysfunction in autism‐like mouse offspring via CLDN1 suppression, providing a possible explanation for the involvement of CLDN1 and VDR in prenatal 17‐OHPC exposure‐mediated GI dysfunction with ASD.
High carbon emissions from thermokarst lakes and their determinants in the Tibet Plateau
Authors: Mu Cuicui , Mu Mei , Wu Xiaodong , Jia Lin , Fan Chenyan , Peng Xiaoqing , Ping Chien‐Lu , Wu Qingbai , Xiao Cunde , Liu Jianbao
Published: March 2023

Thermokarst lakes are potentially important sources of methane (CH4) and carbon dioxide (CO2). However, considerable uncertainty exists regarding carbon emissions from thermokarst lakes owing to a limited understanding of their patterns and motivators. In this study, we measured CH4 and CO2 diffusive fluxes in 163 thermokarst lakes in the Qinghai–Tibet Plateau (QTP) over 3 years from May to October. The median carbon emissions from the QTP thermokarst lakes were 1440 mg CO2 m−2 day−1 and 60 mg CH4 m−2 day−1, respectively. The diffusive rates of CO2 and CH4 are related to the catchment land cover type. Sediment microbial abundance and hydrochemistry explain 51.9% and 38.3% of the total variance in CH4 diffusive emissions, respectively, while CO2 emissions show no significant relationship with environmental factors. When upscaling carbon emissions from the QTP thermokarst lakes, the annual average CH4 release per lake area is equal to that of the pan‐Arctic region. Our findings highlight the importance of incorporating in situ observation data with different emission pathways for different land cover types in predicting carbon emissions from thermokarst lakes in the future.
Perspectives on frailty as a total life‐course disease with consideration of the fetal environment
Authors: Mogi Masaki , Liu Shuang , Watanabe Ryusuke , Imai Matome , Yano Akiko , Ikegawa Yasuhito , Kato Hidemasa
Published: March 2023

Frailty attracts research as it represents a significant target for intervention to extend the healthy life span. An unanswered question in this field is the time point during the life‐course at which an individual becomes predisposed to frailty. Here, we propose that frailty has a fetal origin and should be regarded as part of the spectrum of the developmental origins of health and disease. The developmental origins of health and disease theory originated from findings linking the fetal environment to lifestyle‐related disorders such as hypertension and diabetes. Coincidentally, a recent trend in frailty research also centers on vascular dysfunction and metabolic alterations as the causality of lifestyle‐related disorders such as sarcopenia and dementia. Here, we explore the relationship between fetal programming, frailty‐related disorders (sarcopenia and dementia), and other age‐related diseases mainly based on reports on intrauterine growth restriction. We propose a “total” life‐course approach to combat frailty. With this viewpoint, not only physicians and gerontologists but also obstetricians and pediatricians should team up to overcome age‐related diseases in the elderly. Geriatr Gerontol Int 2023; 23: 263–269.
Reconceptualise a dynamic framework of the learning constructs in higher education
Authors: Geng Gretchen , Zhu Yue , Disney Leigh Patrick
Published: March 2023

This paper reconceptualised the interrelated learning constructs in higher education based on the Dynamic Systems Theory (DST). The university students' learning experience before, during and post the Emergency Online Learning (EOL) was investigated to explore the dynamic changes among the learning constructs in higher education. A case study of a Chinese university was conducted, and one hundred and ninety‐three university students participated in the questionnaire. The data collected from this empirical research identify different hierarchical constructs of the conceptualised learning environment and reconceptualise the period of system reformation influenced by the EOL. The key findings include the identifications of the attractors and repellors framed by the DST and the impact on the changes in the learning constructs. The results of this paper contribute to further understanding of the university constructs' changes to better plan and support students' active learning in higher education.
Influence of pre‐gelatinization in conjunction with guar gum addition on texture functionality, bioactive profile, in vitro nutrient digestibility, morphology and secondary structure of protein of quality protein maize pasta
Authors: Joshi Swati , Sharma Savita , Sharma Rajan , Gupta Antima , Kumar Ramesh
Published: March 2023

The current investigation aimed to develop quality protein maize (QPM) specialty pasta (partial: 50% QPM and full replacement of semolina: 100% QPM) and study the influence of pre‐gelatinization in conjunction with guar gum addition (1.5% or 3%) on bio‐techno‐functional properties of pasta. Scanning electron microscopy depicted the encapsulation of swollen starch within a protective sheet developed as a result of gum addition and starch gelatinisation. The Fourier transform infrared spectra denoted a shift from crystalline towards amorphous state in starch as a consequence of partial gelatinisation. The secondary structure of protein signified a drop in the alpha‐helix structure and thereby enhanced the in vitro protein digestibility of the pregelatinised samples. Multivariate principal component analysis was utilised to validate the differences between the parameters. The overall study inferred that the QPM owned an excellent potentiality for the development of nutrient‐dense pasta by employing the functionality of gums and pre‐gelatinisation treatment.
T cell maturation is significantly affected by SARS‐CoV‐2 infection
Authors: Walter Laura Otto , Cardoso Chandra Chiappin , Santos‐Pirath Íris Mattos , Costa Heloisa Zorzi , Gartner Rafaela , Werle Isabel , Mohr Eduarda Talita Bramorski , da Rosa Julia Salvan , Lubschinski Tainá Larissa , Felisberto Mariano , Kretzer Iara Fabricia , Masukawa Ivete Ioshiko , Vanny Patrícia de Almeida , Luiz Magali Chaves , de Moraes Ana Carolina Rabello , Dalmarco Eduardo Monguilhott , Santos‐Silva Maria Cláudia
Published: March 2023

Coronavirus disease 2019 (COVID‐19) is a respiratory tract infection caused by the new severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). An adequate T cell response is essential not only for fighting disease but also for the creation of immune memory. Thus, the present study aims to evaluate the T cells of patients with moderate, severe and critical COVID‐19 not only at the time of illness but also 2 months after diagnosis to observe whether changes in this compartment persist. In this study, 166 COVID‐19 patients were stratified into moderate/severe and critical disease categories. The maturation and activation of T cells were evaluated through flow cytometry. In addition, Treg cells were analysed. Until 15 days after diagnosis, patients presented a reduction in absolute and relative T lymphocyte counts. After 2 months, in moderate/severe patients, the counts returned to a similar level as that of the control group. In convalescent patients who had a critical illness, absolute T lymphocyte values increased considerably. Patients with active disease did not show differentiation of T cells. Nonetheless, after 2 months, patients with critical COVID‐19 showed a significant increase in CD4+ EMRA (CD45RA+ effector memory) T lymphocytes. Furthermore, COVID‐19 patients showed delayed T cell activation and reduced CD8+ suppressor T cells even 2 months after diagnosis. A reduction in CD4+ Treg cells was also observed, and their numbers returned to a similar level as that of healthy controls in convalescent patients. The results demonstrate that COVID‐19 patients have a delayed activation and differentiation of T cells. In addition, these patients have a great reduction of T cells with a suppressor phenotype.
Trophic ecology of co‐occurring fishes in the Sundays River Valley irrigation ponds, assessed using stable isotope and gut content analyses
Authors: Mofu Lubabalo , Dalu Tatenda , Wasserman Ryan J. , Woodford Darragh J. , Weyl Olaf L. F.
Published: March 2023

The analysis of food web structures has increased the understanding of the dynamics of organisms belonging to different trophic levels. In this study, the diet of two native species, Glossogobius callidus and Gilchristella aestuaria, was assessed in the presence of two non‐native species, Oreochromis mossambicus and Gambusia affinis, in irrigation ponds, Eastern Cape Province, South Africa. The proportion of dietary items consumed and assimilated by the four fish species were inferred from gut contents and carbon and nitrogen stable isotope analysis. Stable isotope analysis revealed that both G. affinis and O. mossambicus had a larger isotopic niche size than G. callidus and G. aestuaria. Although G. callidus fed on benthic resources and G. aestuaria fed on phytoplankton, gut content analysis showed that G. callidus, O. mossambicus and G. affinis fed predominantly on benthic resources, whereas G. aestuaria fed mainly on plankton resources. Considerable niche overlap corroborates the view that resource competition is a major factor shaping the composition of the four fish species. This study highlighted the low diversity of the food web within the Sundays River Valley irrigation ponds, where food items are shared by all the small‐bodied fishes.
Recent advances in the treatment of Charcot‐Marie‐Tooth neuropathies
Authors: Bolino Alessandra , D'Antonio Maurizio
Published: March 2023

Charcot‐Marie‐Tooth (CMT) neuropathies are one of the most common neuromuscular disorders. However, despite the identification of more than 100 causative genes, therapeutic options are still missing. The generation of authentic animal models and the increasing insights into the understanding of disease mechanisms, in addition to extraordinary developments in gene and molecular therapies, are quickly changing this scenario, and several strategies are currently being translated, or are getting close to, clinical trials. Here, we provide an overview of the most recent advances for the therapy of CMT at both the preclinical and clinical levels. For clarity, we have grouped the approaches in three different categories: gene therapy based on viral‐mediated delivery, molecular therapies based on alternative delivery systems, and pharmacological therapies.
Kantian equilibria of a class of Nash bargaining games
Authors: Dizarlar Atakan , Karagözoğlu Emin
Published: March 2023

We study Kantian equilibria of an ‐player bargaining game, which is a modified version of the well‐known divide‐the‐dollar game. We first show that the Kantian equilibrium exists under fairly minimal assumptions. Second, if the bankruptcy rule used satisfies equal treatment of equals, and is almost nowhere proportional, then only equal division can prevail in any Kantian equilibrium. On the other hand, we show that an “anything goes” type result emerges only under the proportional rule. Finally, using hybrid bankruptcy rules that we construct in a novel fashion, we can characterize the whole equilibrium set. Our results highlight the interactions between institutions (axiomatic properties of division rules) and agents' equilibrium behavior.
Metabolic flexibility during a trophic transition reveals the phenotypic plasticity of greater duckweed (Spirodela polyrhiza 7498)
Authors: Sun Zuoliang , Zhao Xuyao , Li Gaojie , Yang Jingjing , Chen Yan , Xia Manli , Hwang Inhwan , Hou Hongwei
Published: March 2023

The greater duckweed (Spirodela polyrhiza 7498) exhibits trophic diversity (photoautotrophic, heterotrophic, photoheterotrophic, and mixotrophic growth) depending on the availability of exogenous organic carbon sources and light.

Here, we show that the ability to transition between various trophic growth conditions is an advantageous trait, providing great phenotypic plasticity and metabolic flexibility in S. polyrhiza 7498.

By comparing S. polyrhiza 7498 growth characteristics, metabolic acclimation, and cellular ultrastructure across these trophic modes, we show that mixotrophy decreases photosynthetic performance and relieves the CO2 limitation of photosynthesis by enhancing the CO2 supply through the active respiration pathway. Proteomic and metabolomic analyses corroborated that S. polyrhiza 7498 increases its intracellular CO2 and decreases reactive oxygen species under mixotrophic and heterotrophic conditions, which substantially suppressed the wasteful photorespiration and oxidative‐damage pathways. As a consequence, mixotrophy resulted in a higher biomass yield than the sum of photoautotrophy and heterotrophy.

Our work provides a basis for using trophic transitions in S. polyrhiza 7498 for the enhanced accumulation of value‐added products.