bluuebunny/crossref_metadata_2025 huggingface dataset:
Diurnal expression of Dgat2 induced by time‐restricted feeding maintains cardiac health in the Drosophila model of circadian disruption
Authors: Guo Yiming , Abou Daya Farah , Le Hiep Dinh , Panda Satchidananda , Melkani Girish C.
Published: April 2024

Circadian disruption is associated with an increased risk of cardiometabolic disorders and cardiac diseases. Time‐restricted feeding/eating (TRF/TRE), restricting food intake within a consistent window of the day, has shown improvements in heart function from flies and mice to humans. However, whether and how TRF still conveys cardiac benefits in the context of circadian disruption remains unclear. Here, we demonstrate that TRF sustains cardiac performance, myofibrillar organization, and regulates cardiac lipid accumulation in Drosophila when the circadian rhythm is disrupted by constant light. TRF induces oscillations in the expression of genes associated with triglyceride metabolism. In particular, TRF induces diurnal expression of diacylglycerol O‐acyltransferase 2 (Dgat2), peaking during the feeding period. Heart‐specific manipulation of Dgat2 modulates cardiac function and lipid droplet accumulation. Strikingly, heart‐specific overexpression of human Dgat2 at ZT 0–10 significantly improves cardiac performance in flies exposed to constant light. We have demonstrated that TRF effectively attenuates cardiac decline induced by circadian disruption. Moreover, our data suggests that diurnal expression of Dgat2 induced by TRF is beneficial for heart health under circadian disruption. Overall, our findings have underscored the relevance of TRF in preserving heart health under circadian disruptions and provided potential targets, such as Dgat2, and strategies for therapeutic interventions in mitigating cardiac aging, metabolic disorders, and cardiac diseases in humans.
Substance use patterns, quantities, and associated risk factors in women with polysubstance misuse
Authors: Fogelman Nia , Tate Marshall , Wemm Stephanie , Sullivan Liam , Hart Rachel , Vacey Erin , Fox Helen C. , Sinha Rajita
Published: April 2024

Polysubstance use (PSU), the use of two or more substances proximally, is highly prevalent and has amplified the risk for morbidity and mortality. However, PSU patterns and associated risk factors are not well characterized. This may be especially relevant to women who are known to be vulnerable to stress/trauma, craving, pain, and anxious and depressive symptoms as associated risk factors for PSU. A cross‐sectional observational study was conducted to characterize substance use patterns in women who regularly used cocaine, opioids, marijuana, alcohol, benzodiazepines and/or nicotine and were being assessed for a placebo‐controlled study of guanfacine treatment (n = 94; ages 19–65). Data on stress/traumatic life events, drug cravings for each substance, pain ratings, and anxiety and depressive symptoms were also obtained using standardized well‐validated surveys. High use per day of two or more drugs was observed (72.7% ± 33.3%) and opioid amounts were high relative to other drug amounts (p's < 0.001). Notably, higher stress/trauma events and higher cravings are each associated with cumulative PSU days, amounts and probability of an individual PSU day (p's < 0.02). This remained when PSU versus single substance use was compared. Pain, anxiety and depressive symptoms were not associated with PSU metrics. These findings characterize specific patterns of PSU in women and show that average drug craving and stress/trauma events are associated with PSU. Interventions that focus on stress/trauma and craving management could be of benefit in reducing PSU risk in women.
Genome‐wide association study identified five quantitative trait loci and two candidate genes for digestive traits in Suhuai pigs
Authors: Li Kaijun , Hou Liming , Du Taoran , Pu Guang , Liu Chenxi , Liu Gensheng , Zhou Juan , Huang Ruihua , Zhao Qingbo , Li Pinghua
Published: April 2024

This work aimed to identify markers and candidate genes underlying porcine digestive traits. In total, 331 pigs were genotyped by 80 K Chip data or 50 K Chip data. For apparent neutral detergent fiber digestibility, a total of 19 and 21 candidate single nucleotide polymorphisms (SNP) were respectively identified using a genome‐wide efficient mixed‐model association algorithm and linkage‐disequilibrium adjusted kinship. Among them, three quantitative trait locus (QTL) regions were identified. For apparent acid detergent fiber digestibility, a total of 16 and 17 SNPs were identified by these two methods, respectively. Of these, three QTL regions were also identified. Moreover, two candidate genes (MST1 and LATS1), which are functionally related to intestinal homeostasis and health, were detected near these significant SNPs. Taken together, our results could provide a basis for deeper research on digestive traits in pigs.
Successful treatment of dyshidrotic palmoplantar eczema with tralokinumab
Authors: Parmar Nisha V. , Hammadi Anwar Al
Published: April 2024

Dyshidrotic palmoplantar eczema or pompholyx is considered to be a part of the spectrum of atopic dermatitis with a significant impact on the quality of life and limited treatment options. Tralokinumab is a new fully human monoclonal antibody which neutralizes interleukin 13, a chief cytokine in itch pathogenesis and skin barrier defects. Tralokinumab is FDA‐approved for the treatment of atopic dermatitis in adults and EMA‐approved for the treatment of atopic dermatitis in adults and adolescents. We, hereby, report a 40‐year‐old female with severe dyshidrotic palmoplantar eczema who was successfully treated with tralokinumab. To the best of our knowledge, this is the first report of the efficacious use of tralokinumab in dyshidrotic eczema.
How to deter earnings manipulation in Chinese banks? A study from the combined effects of corporate governance, enterprise resources, and supervisory mechanisms
Authors: Wang Shuangjin , Dang Lili , Downs John , Foley Maggie
Published: April 2024

The study proposes methods for deterring earnings manipulation in Chinese commercial banks, recognizing it as an ongoing problem with the potential to destabilize investors and financial markets. The increasing integration of the global financial system has heightened the importance of addressing this issue, given the systemic risk posed by large individual financial institutions. Utilizing the Fuzzy Set Qualitative Comparative Analysis method (fsQCA) on 139 Chinese commercial banks in 2021, the paper explores factors influencing banks' earnings manipulation behavior. The study reveals several key findings: (1) Factors associated with reducing the likelihood of earnings manipulation in commercial banks are diverse and multifaceted. (2) Multiple paths exist to achieve earnings manipulation, categorized into Resource‐guided, Corporate Governance, Resource and Supervisory Mechanism, Supervisory Mechanism, and Corporate Governance as the main mechanism. Among these, the Supervisory Mechanism exhibits the highest consistency. (3) Hiring “Big Four” accounting firms as auditors emerges as a significant deterrent against earnings manipulation in commercial banks. (4) Banks with powerful major shareholders affiliated with the government or ample resources are effective in deterring earnings manipulation. These two factors are complementary, while a bank's growth prospects and industrial competition serve as substitute factors.
The Australian Constitutional Framers and the Languages of Virtue
Authors: Kennedy Simon P. , Saunders Benjamin B.
Published: April 2024

The historiography of the political concept of virtue has been dominated by examinations of western European and North American sources. This article aims to widen the historical scope for our understanding of the influence of the concept of political virtue by examining how Anglophone conceptions of virtue were employed by the framers of the Australian Constitution during the Federation debates and the impact of those conceptions on the Constitution itself. It examines the strands of thought that provided the backdrop for the colonial adoption of the Victorian‐era British conception of political virtue, subsequently showing how the Australian constitutional framers adopted these languages and concepts in their own writings and speeches. The Australian framers were concerned with the virtue of both the people and their political leaders, applying this concern in their contributions to legal and political discourse in the latter part of the nineteenth century. However, rather than a direct transfer of the more typical languages of republican virtue, the colonial context examined here offers evidence of a shift of emphasis from virtue into the concept of “character”. The framers demonstrated an interest in the question of character as they wrote and deliberated around the constitutional problems of political parties, bicameralism, and responsible government. So, too, they showed an acute concern for the importance of character in their institutional designs for a future federal commonwealth. This article demonstrates that the framers existed within the tradition of thought which held virtue, or character, to be central to the vitality of the polity, and that the framers adapted that language in their deliberations and the institutional design of the Constitution.
Partial planned relocation and livelihoods: Learnings from Narikoso, Fiji
Authors: Yee Merewalesi , McMichael Celia , McNamara Karen E. , Piggott‐McKellar Annah
Published: April 2024

Pacific Island Countries (PICs) are vulnerable to climate change impacts, including sea level rise, extreme weather events and other environmental changes. Planned relocation can be an adaptive response to climatic threats. In Fiji, six communities have already relocated. While there is growing interest in planned relocation, there are few empirical case studies from which to learn. Narikoso village, in the Kadavu Province of Fiji, undertook partial relocation in 2020. Drawing on qualitative research (interviews, group discussions, observation), informed by Vanua methodology in 2022, this study examines the impacts of partial planned relocation on people's lives and livelihoods. Seven sustainable livelihood assets – or forms of ‘capital’ – are explored: natural, social, financial, human, physical and cultural, with the addition of spiritual. Our research found that planned relocation altered forms of capital that underpin sustainable livelihoods, leading to both benefits and problems. We argue that planned relocation must not only reduce exposure to climatic and environmental risk, but promote and preserve the integrity of local ecosystems, value continuity of culture and sustain and develop diverse assets that support sustainable livelihoods. This demands deep engagement with climate change‐affected communities to ensure that planned relocations sustain people's livelihoods, dignity and survival.
Public preferences for pharmacogenetic testing in the NHS: Embedding a discrete choice experiment within service design to better meet user needs
Authors: McDermott John H. , Sharma Videha , Newman William G. , Wilson Paul , Payne Katherine , Wright Stuart
Published: April 2024

Aims

Genetic testing can be used to improve the safety and effectiveness of commonly prescribed medicines—a concept known as pharmacogenetics. This study aimed to quantify members of the UK public's preferences for a pharmacogenetic service to be delivered in primary care in the National Health Service.

Methods

Members of the UK population were surveyed via an online panel company. Respondents completed 1 of 2 survey versions, asking respondents to select their preferred pharmacogenetic testing service in the context of a presentation of low mood or pain. A conditional logit model was estimated, before the best functional form for the dataset was identified. Preference heterogeneity was identified via latent class analysis. Coefficients from the final selected models were used to estimate uptake in the context of different hypothetical pharmacogenetic services.

Results

Responses from 1993 individuals were included in the analysis. There were no differences observed in preference between the 2 clinical scenarios. Conditional logit analysis, using maximum likelihood estimation, indicated that respondents preferred to have noninvasive tests and wanted their data to be shared between different healthcare organizations to guide future prescribing. There was a preference for regional over national data sharing initiatives, and respondents preferred to have access to their data. Predicted uptake varied considerably, ranging from 51% to >99%, depending on design of the service.

Conclusion

This study identifies public preferences for a pharmacogenetic testing service and demonstrates how predicted uptake can be impacted by relatively minor adaptations. This highlights areas for prioritization during development of future pharmacogenetic services.
Physiologically‐based pharmacokinetic modelling guided dose evaluations of nirmatrelvir/ritonavir in renal impairment for the management of COVID‐19
Authors: Ng Tat Ming , Wang Ziteng , Chan Eric Chun Yong
Published: April 2024

We aimed to address factors contributing to the pharmacokinetic changes of nirmatrelvir/ritonavir in renal impaired (RI) patients and recommend dosing adjustment via a physiologically‐based pharmacokinetic (PBPK) modelling approach. A PBPK model of nirmatrelvir/ritonavir was developed via Simcyp® Simulator. Sensitivity analysis of the influence of hepatic CYP3A4 intrinsic clearance and abundance, as well as hepatic non‐CYP3A4 metabolism (other human liver microsomes [HLM] CLint) was performed to evaluate the effects of RI on oral clearance of nirmatrelvir. Other HLM CLint, the most sensitive parameter, was adjusted, and the simulated plasma concentration profiles of nirmatrelvir in severe RI subjects were within the therapeutic index of 292–10 000 ng/mL for dosing regimens of loading doses of 300/100 mg followed by 150/100 mg or 75/100 mg twice daily of nirmatrelvir/ritonavir. Considering that nirmatrelvir is available as a 150 mg tablet, we recommend 300/100 mg followed by 150/100 mg twice daily as the dosing regimen to be investigated in severe RI.
From the lab to the classroom: Improving children's prospective memory in a natural setting
Authors: Cottini Milvia , Palladino Paola , Basso Demis
Published: April 2024

Background

Laboratory‐based studies have shown that children's ability to remember intentions (i.e., prospective memory; PM) can be improved by asking them to imagine performing the PM task beforehand (i.e., episodic future thinking; EFT) or to predict their PM performance. Moreover, combining the two strategies resulted in an additional improvement in children's PM performance. However, the effectiveness of these encoding strategies on real‐life PM tasks is still unknown.

Aims

The aim of the present study was to evaluate the effect of EFT instructions, performance predictions, and of their combination on children's PM in a natural setting, namely in the classroom.

Sample

Twelve classes composed by a total of 121 children (53% females) aged between seven and 9 years participated to the study.

Methods

As a PM task, children were asked by their teachers to deliver a letter to their parents and to bring it back to school the next day. Children were divided into four groups: control, prediction, EFT, and the EFT + prediction group. Parent reports on children's everyday prospective and retrospective memory failures were also collected.

Results

Results showed that encoding strategies were effective in enhancing children's PM performance. However, differences compared to previous laboratory‐based findings emerged since predicting PM performance resulted to be most effective in enhancing real‐life PM performance. Moreover, parent reports were related to children's PM performance.

Conclusions

These novel findings highlight the importance of studying PM interventions in natural settings in order to increase their ecological validity and inform educational practices.
Postcards Post‐Petroleras: Exploring Collaborative Ethnography via Mail from the Venezuelan Diaspora
Authors: Irons Rebecca
Published: April 2024

Postcards, as ‘travelling communication devices’, have been identified as excellent tools for their ability to collapse ‘the field’ in a new, visually experiential way. Though often presented as a (post)colonial medium that has exoticized ‘the other’, they may also be able to give snapshots of diverse biographies otherwise silenced, and can therefore be utilised as a form of collaborative ethnography. This paper analyses postcards sent from Venezuelans living in Bogota during the pandemic. It will suggest that when migrants express lived‐experience via postcards, the coloniality of the medium is challenged and reimagined as collaborative ethnography.
Synergism between remdesivir and ribavirin leads to SARS‐CoV‐2 extinction in cell culture
Authors: García‐Crespo Carlos , de Ávila Ana Isabel , Gallego Isabel , Soria María Eugenia , Durán‐Pastor Antoni , Somovilla Pilar , Martínez‐González Brenda , Muñoz‐Flores Javier , Mínguez Pablo , Salar‐Vidal Llanos , Esteban‐Muñoz Mario , Cañar‐Camacho Elizabeth , Ferrer‐Orta Cristina , Zuñiga Sonia , Sola Isabel , Enjuanes Luis , Esteban Jaime , Fernández‐Roblas Ricardo , Gadea Ignacio , Gómez Jordi , Verdaguer Nuria , Domingo Esteban , Perales Celia
Published: April 2024

Background and Purpose

There is a need for effective anti‐COVID‐19 treatments, mainly for individuals at risk of severe disease such as the elderly and the immunosuppressed. Drug repositioning has proved effective in identifying drugs that can find a new application for the control of coronavirus disease, in particular COVID‐19. The purpose of the present study was to find synergistic antiviral combinations for COVID‐19 based on lethal mutagenesis.

Experimental Approach

The effect of combinations of remdesivir and ribavirin on the infectivity of SARS‐CoV‐2 in cell culture has been tested. Viral populations were monitored by ultra‐deep sequencing, and the decrease of infectivity as a result of the treatment was measured.

Key Results

Remdesivir and ribavirin exerted a synergistic inhibitory activity against SARS‐CoV‐2, quantified both by CompuSyn (Chou‐Talalay method) and Synergy Finder (ZIP‐score model). In serial passage experiments, virus extinction was readily achieved with remdesivir‐ribavirin combinations at concentrations well below their cytotoxic 50 value, but not with the drugs used individually. Deep sequencing of treated viral populations showed that remdesivir, ribavirin, and their combinations evoked significant increases of the number of viral mutations and haplotypes, as well as modification of diversity indices that characterize viral quasi‐species.

Conclusion and Implications

SARS‐CoV‐2 extinction can be achieved by synergistic combination treatments based on lethal mutagenesis. In addition, the results offer prospects of triple drug treatments for effective SARS‐CoV‐2 suppression.
Institutional Investors and ESG Preferences
Authors: Lopez‐de‐Silanes Florencio , McCahery Joseph A. , Pudschedl Paul C.
Published: April 2024

Research Question/Issue

We examine the effect of multiple environmental, social, and governance (ESG) scores on institutional investor ownership of firms and investor portfolio weightings. We are also the first to analyze the three individual components of ESG rankings to estimate the relative preferences of institutional investors.

Research Findings/Insights

Using a unique panel dataset covering US companies and institutional investor portfolios over the 2010–2019 period, we find that while investors are driven to add high‐quality ESG companies to their portfolios, there is a negative relationship with ESG when it comes to taking large ownership stakes. Furthermore, ESG scores are negatively related to the portfolio weightings of institutional investors, which raises concerns of greenwashing. Our analysis of individual ESG scores points to significantly larger effects of G scores in terms of holdings, and G is the only score with no negative impact on portfolio weightings. Finally, in support of systematic stewardship theory, top institutional investors allocate higher proportions of their portfolios to firms with high‐ESG ratings. Our results are robust to the use of a difference‐in‐differences analysis addressing endogeneity concerns.

Theoretical/Academic Implications

The findings in this paper offer important policy implications for institutional investors, managers, and policymakers. Given the ongoing debate on ESG scores, this paper shows the importance of examining greenwashing for investors who have a concern regarding the extent to which the valuation of assets might be influenced by unsupported sustainability claims. In addition, our study adds to the debate regarding ESG investing and stewardship theory.
Physiologically based modeling reveals different risk of respiratory depression after fentanyl overdose between adults and children
Authors: Chakravartula Shilpa , Thrasher Bradlee , Mann John , Chaturbedi Anik , Han Xiaomei , Dahan Albert , Florian Jeffry , Strauss David , Li Zhihua
Published: April 2024

Despite a rapid increase in pediatric mortality rate from prescription and illicit opioids, there is limited research on the dose‐dependent impact of opioids on respiratory depression in children, the leading cause of opioid‐associated death. In this article, we extend a previously developed translational model to cover pediatric populations by incorporating age‐dependent pharmacokinetic, pharmacodynamic, and physiological changes compared to adults. Our model reproduced previous perioperative clinical findings that adults and children have similar risk of respiratory depression at the same plasma fentanyl concentration when specific endpoints (minute ventilation, CO2 tension in the blood) were used. However, our model points to a potential caveat that, in a perioperative setting, routine use of mechanical ventilation and supplemental oxygen maintained the blood and tissue oxygen partial pressures in patients and prevented the use of oxygen‐related endpoints to evaluate the consequences of respiratory depression. In a community setting when such oxygenation procedures are not immediately available, our model suggests that the higher oxygen demand and reduced cerebrovascular reactivity could make children more susceptible to severe hypoxemia and brain hypoxia, even with the same plasma fentanyl concentration as adults. Our work indicates that when developing intervention strategies to protect children from opioid overdose in a community setting, these pediatric‐specific factors may need to be considered.
Prediction of cardiovascular risk factors from retinal fundus photographs: Validation of a deep learning algorithm in a prospective non‐interventional study in Kenya
Authors: White Tom , Selvarajah Viknesh , Wolfhagen‐Sand Fredrik , Svangård Nils , Mohankumar Gayathri , Fenici Peter , Rough Kathryn , Onyango Nelson , Lyons Kendall , Mack Christina , Nduba Videlis , Noorali Saleh Mansoor , Abayo Innocent , Siddiqui Afrah , Majdanska‐Strzalka Malgorzata , Kaszubska Katarzyna , Hegelund‐Myrback Tove , Esterline Russell , Manzur Antonio , Parker Victoria E. R.
Published: April 2024

Aim

Hypertension and diabetes mellitus (DM) are major causes of morbidity and mortality, with growing burdens in low‐income countries where they are underdiagnosed and undertreated. Advances in machine learning may provide opportunities to enhance diagnostics in settings with limited medical infrastructure.

Materials and Methods

A non‐interventional study was conducted to develop and validate a machine learning algorithm to estimate cardiovascular clinical and laboratory parameters. At two sites in Kenya, digital retinal fundus photographs were collected alongside blood pressure (BP), laboratory measures and medical history. The performance of machine learning models, originally trained using data from the UK Biobank, were evaluated for their ability to estimate BP, glycated haemoglobin, estimated glomerular filtration rate and diagnoses from fundus images.

Results

In total, 301 participants were enrolled. Compared with the UK Biobank population used for algorithm development, participants from Kenya were younger and would probably report Black/African ethnicity, with a higher body mass index and prevalence of DM and hypertension. The mean absolute error was comparable or slightly greater for systolic BP, diastolic BP, glycated haemoglobin and estimated glomerular filtration rate. The model trained to identify DM had an area under the receiver operating curve of 0.762 (0.818 in the UK Biobank) and the hypertension model had an area under the receiver operating curve of 0.765 (0.738 in the UK Biobank).

Conclusions

In a Kenyan population, machine learning models estimated cardiovascular parameters with comparable or slightly lower accuracy than in the population where they were trained, suggesting model recalibration may be appropriate. This study represents an incremental step toward leveraging machine learning to make early cardiovascular screening more accessible, particularly in resource‐limited settings.
Combination of retagliptin and henagliflozin as add‐on therapy to metformin in patients with type 2 diabetes inadequately controlled with metformin: A multicentre, randomized, double‐blind, active‐controlled, phase 3 trial
Authors: Wang Yao , Jiang Chengxia , Dong Xiaolin , Chen Mingwei , Gu Qin , Zhang Lihui , Fu Yanqin , Pan Tianrong , Bi Yan , Song Weihong , Xu Jing , Lu WeiPing , Sun Xiaodong , Ye Zi , Zhang Danli , Peng Liang , Lin Xiang , Dai Wei , Wang Quanren , Yang Wenying
Published: April 2024

Aim

This study assessed the efficacy and safety of co‐administering retagliptin and henagliflozin versus individual agents at corresponding doses in patients with type 2 diabetes mellitus who were inadequately controlled with metformin.

Methods

This multicentre, phase 3 trial consisted of a 24‐week, randomized, double‐blind, active‐controlled period. Patients with glycated haemoglobin (HbA1c) levels between 7.5% and 10.5% were randomized to receive once‐daily retagliptin 100 mg (R100; n = 155), henagliflozin 5 mg (H5; n = 156), henagliflozin 10 mg (H10; n = 156), co‐administered R100/H5 (n = 155), or R100/H10 (n = 156). The primary endpoint was the change in HbA1c from baseline to week 24.

Results

Based on the primary estimand, the least squares mean reductions in HbA1c at week 24 were significantly greater in the R100/H5 (−1.51%) and R100/H10 (−1.54%) groups compared with those receiving the corresponding doses of individual agents (−0.98% for R100, −0.86% for H5 and −0.95% for H10, respectively; p < .0001 for all pairwise comparisons). Achievement of HbA1c <7.0% at week 24 was observed in 27.1% of patients in the R100 group, 21.2% in the H5 group, 24.4% in the H10 group, 57.4% in the R100/H5 group and 56.4% in the R100/H10 group. Reductions in fasting plasma glucose and 2‐h postprandial glucose were also more pronounced in the co‐administration groups compared with the individual agents at corresponding doses. Decreases in body weight and systolic blood pressure were greater in the groups containing henagliflozin than in the R100 group. The incidence rates of adverse events were similar across all treatment groups, with no reported episodes of severe hypoglycaemia.

Conclusions

For patients with type 2 diabetes mellitus inadequately controlled by metformin monotherapy, the co‐administration of retagliptin and henagliflozin yielded more effective glycaemic control through 24 weeks compared with the individual agents at their corresponding doses.
Geographic variation in sodium‐glucose cotransporter 2 inhibitor and glucagon‐like peptide‐1 receptor agonist use in people with type 2 diabetes in New South Wales, Australia
Authors: de Oliveira Costa Juliana , Lin Jialing , Milder Tamara Y. , Greenfield Jerry R. , Day Richard O. , Stocker Sophie L. , Neuen Brendon L. , Havard Alys , Pearson Sallie‐Anne , Falster Michael O.
Published: April 2024

Aim

Sodium‐glucose cotransporter 2 inhibitors (SGLT2is) and glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) improve glycaemic control and cardio‐renal outcomes for people with type 2 diabetes (T2D). However, geographic and socio‐economic variation in use is not well understood.

Methods

We identified 367 829 New South Wales residents aged ≥40 years who dispensed metformin in 2020 as a proxy for T2D. We estimated the prevalence of use of other glucose‐lowering medicines among people with T2D and the prevalence of SGLT2i and GLP‐1RA use among people using concomitant T2D therapy (i.e. metformin + another glucose‐lowering medicine). We measured the prevalence by small‐level geography, stratified by age group, and characterized by remoteness and socio‐economic status.

Results

The prevalence of SGLT2i (29.7%) and GLP‐1RA (8.3%) use in people with T2D aged 40‐64 increased with geographic remoteness and in areas of greater socio‐economic disadvantage, similar to other glucose‐lowering medicines. The prevalence of SGLT2i (55.4%) and GLP‐1RA (15.4%) among people using concomitant T2D therapy varied across geographic areas, with lower SGLT2i use in more disadvantaged areas and localized areas of high GLP‐1RA use (2.5 times the median). Compared with people aged 40‐64 years, the prevalence of SGLT2i and GLP‐1RA use was lower in older age groups, but with similar patterns of variation across geographic areas.

Conclusions

The prevalence of SGLT2i and GLP‐1RA use varied by geography, probably reflecting a combination of system‐ and prescriber‐level factors. Socio‐economic variation in GLP‐1RA use was overshadowed by localized patterns of prescribing. Continued monitoring of variation can help shape interventions to optimize use among people who would benefit the most.
Association of single‐point insulin sensitivity estimator index (SPISE) with future cardiovascular outcomes in patients with type 2 diabetes
Authors: Deng Simin , Hu Xinqun , Zhang Xiangyu
Published: April 2024

Aims

To investigate the association of single‐point insulin sensitivity estimator (SPISE) index with future cardiovascular outcomes in patients with type 2 diabetes.

Materials and Methods

SPISE index (= 600 × high‐density lipoprotein cholesterol [mg/dL]0.185/triglycerides [mg/dL]0.2 × body mass index [kg/m2]1.338) was calculated in 10 190 participants. Cox proportional hazard regression models were applied to evaluate the association between SPISE index and future cardiovascular outcomes. Restricted cubic spline analyses and two‐piecewise linear regression models were employed to explore the nonlinear association and to determine the threshold value. Subgroup and interaction analyses were conducted to test the robustness of the results.

Results

After fully adjusting for well‐established metabolic confounders, higher SPISE index was significantly associated with lower risk of future cardiovascular outcomes in patients with type 2 diabetes (major adverse cardiovascular event [MACE]): hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.90–0.98, p = 0.0026; overall mortality: HR 0.90, 95% CI 0.86–0.93, p < 0.0001; cardiovascular disease [CVD] mortality: HR 0.85, 95% CI 0.79–0.92, p < 0.0001; congestive heart failure (CHF): HR 0.72, 95% CI 0.67–0.78, p < 0.0001; major coronary events: HR 0.91, 95% CI 0.87–0.95, p < 0.0001. There was a nonlinear association between SPISE index and future cardiovascular outcomes (the threshold value was 5.68 for MACE, 5.71 for overall mortality, 4.64 for CVD mortality, 4.48 for CHF, and 6.09 for major coronary events, respectively).

Conclusions

Higher SPISE index was independently associated with lower risk of future cardiovascular outcomes in type 2 diabetes patients after full adjustment for well‐established metabolic confounders.
Comparison in microstructure, mechanical properties, and fatigue behavior of 9Cr3W3Co turbine rotor steel and its welded joint
Authors: Mai Jianning , Liu Fulin , Chen Yao , He Chao , Wang Linsen , Zhong Zhengbin , Zhang Wei , Zhang Hong , Wang Chong , Wang Qingyuan , Liu Yongjie
Published: April 2024

The microstructure, mechanical properties, and high/very‐high cycle fatigue behaviors of 9Cr3W3Co turbine rotor steel and its welded joint were investigated. The welded nugget zone (WNZ) exhibited the highest microhardness value, followed by the heat‐affected zone (HAZ), while the base material (BM) showed the lowest hardness value. The WNZ exhibited a higher yield strength compared to the BM with reduced elongation, while maintaining similar ultimate tensile strength. The fatigue strength of the BM at 5 × 107 cycles is roughly 53.7% of the yield strength, whereas that of the WNZ increases to approximately 55.0%. In comparison to the fatigue strength of the BM at 5 × 107 cycles, the WNZ exhibits a notable increase of 10.5%. Smaller grain size and higher dislocation density were observed in the WNZ, which contributed to improved microhardness, yield strength, and fatigue resistance through grain boundary strengthening and dislocation hardening.
Climate‐driven shifts in the diversity of plants in the Neotropical seasonally dry forest: Evaluating the effectiveness of protected areas
Authors: Manrique‐Ascencio Avril , Prieto‐Torres David A. , Villalobos Fabricio , Guevara Roger
Published: April 2024

Given the current environmental crisis, biodiversity protection is one of the most urgent socio‐environmental priorities. However, the effectiveness of protected areas (PAs), the primary strategy for safeguarding ecosystems, is challenged by global climate change (GCC), with evidence showing that species are shifting their distributions into new areas, causing novel species assemblages. Therefore, there is a need to evaluate PAs' present and future effectiveness for biodiversity under the GCC. Here, we analyzed changes in the spatiotemporal patterns of taxonomic and phylogenetic diversity (PD) of plants associated with the Neotropical seasonally dry forest (NSDF) under GCC scenarios. We modeled the climatic niche of over 1000 plant species in five representative families (in terms of abundance, dominance, and endemism) of the NSDF. We predicted their potential distributions in the present and future years (2040, 2060, and 2080) based on an intermediate scenario of shared socio‐economic pathways (SSP 3.70), allowing species to disperse to new sites or constrained to the current distribution. Then, we tested if the current PAs network represents the taxonomic and phylogenetic diversities. Our results suggest that GCC could promote novel species assemblages with local responses (communities' modifications) across the biome. In general, models predicted losses in the taxonomic and phylogenetic diversities of all the five plant families analyzed across the distribution of the NSDF. However, in the northern floristic groups (i.e., Antilles and Mesoamerica) of the NSDF, taxonomic and PD will be stable in GCC projections. In contrast, across the NSDF in South America, some cores will lose diversity while others will gain diversity under GCC scenarios. PAs in some NSDF regions appeared insufficient to protect the NSDF diversity. Thus, there is an urgent need to assess how the PA system could be better reconfigured to warrant the protection of the NSDF.
Effects of nitrogen fertilization rate and seeding density on the forage yield and quality of autumn‐sown triticale in an alpine grazing area of the Qinghai‐Tibetan Plateau, China
Authors: He Junsheng , Liu Hancheng , Ren Yuxin , Liu Haibo , Du Wenhua
Published: April 2024

‘Gannong No. 2’ triticale (×Triticosecale Wittmack) is a cold‐resistant annual forage crop variety, which can be planted as artificial pasture to solve the problem of forage shortage in the Gannan alpine grazing area of the Qinghai‐Tibetan Plateau. However, the optimal nitrogen fertilization rate and seeding density for obtaining high yield and quality forage are still unknown. In this study, the effects of nitrogen fertilization rate and seeding density on the forage yield and quality of autumn‐sown ‘Gannong No. 2’ triticale were studied. We used a split‐plot design, with five nitrogen fertilization rates assigned to the main plots, namely 0 (A1), 120 (A2), 240 (A3), 360 (A4), and 480 kg N ha−1 (A5), and five seeding densities assigned to subplots: 506 × 104 (B1), 675 × 104 (B2), 843 × 104 (B3), 1011 × 104 (B4), and 1180 × 104 seeds ha−1 (B5). Significant differences in lodging rate, tiller number, hay yield, crude protein content, neutral detergent fibre, and relative feed value were observed at different fertilization levels. Significant differences were found in lodging rate, plant height, tiller number, hay yield, contents of neutral detergent fibre and acid detergent fibre, dry matter digestibility, and relative feed value among the seeding density treatments. The interaction of nitrogen fertilization rate and seeding density significantly affected forage yield and quality, with the A3B3 treatment having the highest comprehensive evaluation value. In alpine grazing areas of the Qinghai‐Tibetan Plateau, 240 kg N ha−1 and 843 × 104 seeds ha−1 should therefore be used for autumn‐sown triticale.
Nutritional and inflammation factors associated with current frailty level and effect of co‐morbidities on the progression of frailty
Authors: Urano Tomohiko , Kuroda Tatsuhiko , Shiraki Masataka
Published: April 2024

Aim

Frailty is defined as extreme vulnerability, a syndrome that exposes the individual to a higher risk of disability. While risk factors for frailty have been gradually uncovered, the full identification of biochemical factors and co‐morbidities influencing frailty remains incomplete.

Methods

Cross‐sectional and longitudinal analyses were performed to elucidate the risk factors for the prevalence and progression of frailty. The study included 1035 Japanese female outpatients. At baseline, biochemical markers were measured. Co‐morbidities included diabetes mellitus, dyslipidemia, hypertension, vertebral osteoarthritis, and osteoporosis. Frailty levels were assessed using frailty scores ranging from 0 to 5. Prevalence of frailty was judged by a score of 3 or above, and progression was judged by an increase in the frailty score during the observation period. Multiple regression analysis was used for the cross‐sectional analysis, and the Cox hazard model was used for the longitudinal analysis.

Results

Of the 1035 selected participants, 212 were diagnosed with frailty. Advanced age and log IL‐6 and branched‐chain amino acids (BCAA) levels were significant independent risk factors for frailty. Subjects were followed for 7.7 ± 5.9 years and progression was observed in 130 subjects. Older age, the absence of hyperlipidemia, the presence of osteoporosis, and lower frailty scores were identified as significant risk factors for frailty progression.

Conclusions

Inflammatory and nutritional markers exhibited significant associations with the current frailty status, whereas co‐morbidities such as osteoporosis or hyperlipidemia emerged as independent risk or protective factors of future frailty progression. Geriatr Gerontol Int 2024; 24: 523–528.
Using large‐scale bibliometric data in higher education research: Methodological implications from three studies
Authors: Kwiek Marek , Horta Hugo , Powell Justin J. W.
Published: April 2024

All fields of knowledge are challenged to adopt newer, more sophisticated methodologies to cope with growing complexity. Phenomena under study require further multidisciplinary and mixed methods collaborations to achieve expertise able to improve research strategies and practices. Furthermore, traditional methodological approaches face limits to their analytical reach. Here, we demonstrate opportunities from adopting newer, more sophisticated methodologies in the field of higher education (HE) research by comparing three case studies. We argue that such methods and data innovate the mapping and understanding of global HE. These studies uncover novel field characterizations, enabled via analysis of tens of thousands of HE authors and articles over several decades to assess how journal publication, topics, and levels of analysis (individual, organizational, and system) have evolved. Our results imply that to better understand the future of HE worldwide and to address growing challenges, newer methodological directions and data sources will be key to facilitate more comprehensive examinations of the globalizing field. However, our analysis also highlights the technical and learning challenges in implementing these methodologies; thus, we argue for the need to promote more sophisticated methodological training of current and future generations of HE researchers as well as strengthened collaborations across disciplinary, methodological, and cultural boundaries.
An opportunity for post‐harvest seafood safety: atmospheric pressure air or helium cold plasma to control Salmonella Enteritidis in sea bass
Authors: Üçok Didem , Akan Tamer , Kartal Sehban , Tosun Şehnaz Yasemin , Mol Sühendan , Coşansu Serap , Doğruyol Hande , Ulusoy Şafak , Bostan Kamil
Published: April 2024

Salmonella contamination of fish after harvest is a significant food safety risk. To control this risk, it was aimed to reduce Salmonella Enteritidis in sea bass by helium and air plasma. Considering that preserving the fresh properties of sea bass is important for industrial applicability, determining the sensory effects of plasma treatments was also aimed. Since air plasma would provide a cheaper and easier alternative to helium plasma, their effects were compared. Additionally, the in vitro effects of these treatments on Salmonella Enteritidis were also investigated. Air and helium plasma completely inhibited the initial load of S. Enteritidis (2.79 Log CFU) inoculated on agar surface after 10 min treatment. Then, the inoculated sea bass samples were exposed to air or helium plasma for durations ranging from 1 to 15 min. Air and helium plasma treatments for 10 min provided 0.90 log cfu g−1 and 1.13 Log CFU/g reductions, respectively, but longer treatments did not lead to further significant reductions. Sensory scores were all above 7 (good) when samples were treated with air or helium plasma for 1–10 min, but longer treatments resulted in lower scores. The reduction of S. Enteritidis and changes in sensory characteristics were interpreted together and it was concluded that 10 min of air or helium plasma provided maximum reduction without causing any significant sensory changes. Overall, the current study showed that atmospheric pressure air and helium plasmas can be useful for ensuring post‐harvest safety in the fish trade.
Refugee entrepreneurship in a non‐western country: How do Syrian refugee entrepreneurs respond to diaspora consciousness and negative prejudice?
Authors: Mousa Mohamed
Published: April 2024

The aim of this paper is to identify how the diaspora consciousness of Syrian entrepreneurs in Egypt might affect their business practices. The research sample comprises semi‐structured interviews with Syrian refugee owners of small and medium‐sized businesses in Egypt. Thematic analysis was subsequently used to determine the main ideas in the transcripts from the interviews. The findings showed that diaspora consciousness stimulates Syrian refugees to actively engage in three categories of business‐related practices: contextual (expanding entrepreneurial activities outside their host country, desire to constitute a Western country‐based business venture), functional (reliance on a value chain within the same nationality, tending to adopt shadow economy practices), and procedural practices (preferring to develop family businesses, establishing only small and medium‐sized enterprises). This paper contributes by filling a gap in the literature on refugee entrepreneurship in which empirical studies on the effect of diaspora consciousness on the business practices of refugee entrepreneurs have been limited so far.
Immunotherapy and the ovarian cancer microenvironment: Exploring potential strategies for enhanced treatment efficacy
Authors: Wang Zhi‐Bin , Zhang Xiu , Fang Chao , Liu Xiao‐Ting , Liao Qian‐Jin , Wu Nayiyuan , Wang Jing
Published: April 2024

Despite progress in cancer immunotherapy, ovarian cancer (OC) prognosis continues to be disappointing. Recent studies have shed light on how not just tumour cells, but also the complex tumour microenvironment, contribute to this unfavourable outcome of OC immunotherapy. The complexities of the immune microenvironment categorize OC as a ‘cold tumour’. Nonetheless, understanding the precise mechanisms through which the microenvironment influences the effectiveness of OC immunotherapy remains an ongoing scientific endeavour. This review primarily aims to dissect the inherent characteristics and behaviours of diverse cells within the immune microenvironment, along with an exploration into its reprogramming and metabolic changes. It is expected that these insights will elucidate the operational dynamics of the immune microenvironment in OC and lay a theoretical groundwork for improving the efficacy of immunotherapy in OC management.
Prevalence of multidrug‐resistant bacterial infections in diabetic foot ulcers: A meta‐analysis
Authors: Yang Shaoling , Hu Liye , Zhao Yue , Meng Guangzhe , Xu Sijia , Han Rui
Published: April 2024

Multidrug‐resistant (MDR) bacterial infections have become increasingly common in recent years due to the increased prevalence of diabetic foot ulcers (DFUs). We carried out a meta‐analysis aimed at investigating the prevalence of MDR bacteria isolated from DFUs and analysing the risk factors for MDR bacterial infection in patients with DFUs. The PubMed/Medline, Web of Science, Embase, Cochrane Library, Ovid, Scopus, and ProQuest databases were searched for studies published up to November 2023 on the clinical outcomes of MDR bacteria in DFUs. The main outcome was the prevalence of MDR bacteria in DFUs. A total of 21 studies were included, representing 4885 patients from which 2633 MDR bacterial isolates were obtained. The prevalence of MDR bacteria in DFUs was 50.86% (95% confidence interval (CI): 41.92%–59.78%). The prevalence of MDR gram‐positive bacteria (GPB) in DFUs was 19.81% (95% CI: 14.35%–25.91%), and the prevalence of MDR gram‐negative bacteria (GNB) in DFUs was 32.84% (95% CI: 26.40%–39.62%). MDR Staphylococcus aureus (12.13% (95% CI: 8.79%–15.91%)) and MDR Enterococcus spp. (3.33% (95% CI: 1.92%–5.07%)) were the main MDR‐GPB in DFUs. MDR Escherichia coli, MDR Pseudomonas aeruginosa, MDR Enterobacter spp., MDR Klebsiella pneumoniae, and MDR Proteus mirabilis were the main MDR‐GNB in DFUs. The prevalence rates were 6.93% (95% CI: 5.15%–8.95%), 6.01% (95% CI: 4.03%–8.33%), 3.59% (95% CI: 0.42%–9.30%), 3.50% (95% CI: 2.31%–4.91%), and 3.27% (95% CI: 1.74%–5.21%), respectively. The clinical variables of diabetic foot ulcer patients infected with MDR bacteria and non‐MDR bacteria in the included studies were analysed. The results showed that peripheral vascular disease, peripheral neuropathy, nephropathy, osteomyelitis, Wagner's grade, previous hospitalization and previous use of antibacterial drugs were significantly different between the MDR bacterial group and the non‐MDR bacterial group. We concluded that there is a high prevalence of MDR bacterial infections in DFUs. The prevalence of MDR‐GNB was greater than that of MDR‐GPB in DFUs. MDR S. aureus was the main MDR‐GPB in DFUs, and MDR E. coli was the main MDR‐GNB in DFUs. Our study also indicated that peripheral vascular disease, peripheral neuropathy, nephropathy, osteomyelitis, Wagner's grade, previous hospitalization, and previous use of antibacterial drugs were associated with MDR bacterial infections in patients with DFUs.