bluuebunny/crossref_metadata_2025 huggingface dataset:
Can the choice of artificial tears harm patients? A narrative review with an overview of the Nordic market
Authors: Mikha K. N. , Rasmussen C. E. Ø. , Ahrensberg S. N. G. , Freiberg J. , Wozniak R. A. , Alnoor U. M. K. , Fineide F. , Utheim T. P. , Heegaard S. , Kolko M.
Published: February 2025

Purpose

To provide an overview of artificial tears marketed in the following Nordic countries: Denmark, Finland, Norway, Iceland and Sweden. Furthermore, this review aimed to highlight the different preservatives and other constituents found in artificial tears in the Nordic market, focussing on adverse effects.

Methods

Artificial tears appearing in online pharmacies in Denmark, Norway, Sweden, Finland and Iceland were included, and tables listing their components were created. Based on the preservatives and other constituents found in the artificial tears on the Nordic market, a literature search was conducted to investigate differences and potential adverse effects. This was achieved using PubMed with MeSH and free text search terms. Included articles were (i) studies performed on humans in vivo or in vitro human models, (ii) published between 2000 and 2023 and (iii) focussing on adverse effects, preservatives, toxicity, other constituents and preservative‐free artificial tears.

Results

A total of 88 artificial tears were found on the Nordic market. Approximately 32% (28 out of 88) of the artificial tears contain preservatives. Eleven of these are preserved with benzalkonium chloride (BAK) or cetrimide. After a thorough literature search, evidence has been found for the toxic effects of BAK and cetrimide. There is no evidence of toxic effects of lubricants, osmoprotectants and lipids.

Conclusions

The findings of this review highlight the paradoxical fact that many treatments for ocular surface diseases contain toxic preservatives that may lead to worsening of the condition. In particular, long‐time toxic effects of BAK may contribute to disease progression.
Risk of Hepatocellular Cancer in U.S. Patients With Compensated Cirrhosis Treated With Direct‐Acting Antivirals Versus Interferon
Authors: El‐Serag Hashem B. , Duong Hao , Luster Michelle , Kanwal Fasiha , Hill Deanna D. , Burroughs Margaret , Hernandez Candido , Haber Barbara A. , Larsen Lois M. , Marcinak John F. , Wegrzyn Lani R. , Kramer Jennifer R.
Published: February 2025

Background

Few studies have examined the risk of de novo hepatocellular carcinoma (HCC) among hepatitis C virus (HCV)–infected patients with cirrhosis who received interferon (IFN)‐free direct‐acting antiviral (DAA) therapy relative to patients who received IFN‐containing therapy or remained untreated.

Aims

To estimate the risk of de novo HCC with DAA treatment in cirrhotic HCV patients compared to no anti‐HCV treatment and those treated with IFN‐based therapy.

Methods

We identified patients with chronic HCV infection and compensated cirrhosis in the US Department of Veterans Affairs healthcare system treated with IFN (2005 to 2013) or DAAs (2013 to 2017). We compared the risk of de novo HCC for patients treated with DAAs, IFN‐containing regimens or no treatment after accounting for differences in demographics, alcohol and drug abuse, comorbidities, laboratory values, healthcare utilisation, prior HCV treatment and HCC surveillance.

Results

A total of 53,847 patients contributed to untreated time, 27,147 patients contributed to DAA‐treated time (15,641 contributed to both untreated and DAA‐treated times) and 6809 patients contributed to IFN‐treated time. HCC risk associated with DAA treatment was significantly lower than untreated [adjusted HR: 0.70 (95% CI: 0.65–0.74)]. The risk of HCC was not significantly different for patients treated with DAA compared with those treated with IFN [adjusted HR: 0.98 (95% CI: 0.87–1.10)].

Conclusions

The study shows a reduced risk of de novo HCC among patients with chronic HCV–related compensated cirrhosis who received DAA treatment compared to that of untreated patients. There were no differences in HCC risk between DAA‐treated and IFN‐treated patients.
Linking Up Degrowth in/From the South With Provincialised UPE: Mangrove and Groundwater Conservations in Semarang, Indonesia
Authors: Batubara Bosman , Belland Marie , Kooy Michelle
Published: February 2025

This article brings degrowth into conversation with urbanisation through our analysis of environmental transformations in the coastal Southern city of Semarang, Indonesia. We analyse two collective activisms to build a theoretical dialogue between degrowth and provincialised urban political ecology (UPE). The first activism contests the ongoing development of pro‐growth giant flood infrastructure and is politically rooted in mangrove ecosystem conservation. The second activism conserves groundwater. We identify mangrove and groundwater conservations as spatial practices of degrowth in/from the south. We make connections between the two scholarships and activisms to expand their political and pragmatic possibilities and, therefore, open space for more hopeful alternatives for the city's future.
Evaluating the impact of general practice pharmacist‐led person‐centred medicines reviews on medicines appropriateness and patient‐reported outcome measures
Authors: Kinahan Clare , Kirke Ciara , O'Hagan Leon , Moriarty Frank , Murphy Kevin D. , Sahm Laura J. , O'Mahony Cian , Coyle Emma J. , Byrne Stephen , Dalton Kieran
Published: February 2025

Aim

The aim of this study was to investigate the impact of pharmacist‐led person‐centred medicines reviews in general practices on medicines appropriateness, polypharmacy indicators (high‐risk prescribing markers), and patient‐reported outcome measures (PROMs).

Methods

Four pharmacists conducted person‐centred medicines reviews in ten general practices between January 2021 and December 2022 for patients with hyperpolypharmacy (prescribed ≥10 regular medicines) and/or at high risk of medicines‐related harm. Prescribing recommendations were provided to the general practitioner and followed up with patients and/or healthcare professionals. In this single arm study, pre and post intervention: (1) polypharmacy indicators were documented, and for a sample of patients, the (2) Person‐Centred Medication Appropriateness Index (PC‐MAI) scores and (3) PROMs were gathered.

Results

Of the 1471 included patients, the mean age was 76 years, 88.4% had hyperpolypharmacy, whilst the mean number of medicines was 13.8 pre and 12.3 post review. Of the 1056 polypharmacy indicator occurrences identified, 70.7% were resolved post review. Of the 194 patients with pre‐review and post‐review PC‐MAI scores, 99% had a reduction; the mean reduction was 17.3 (95% confidence interval [CI] 15.8–18.8, P < .0001) per patient and 1.2 (95% CI 1.0–1.3, P < .0001) per medicine. PROMs were collected for 179 patients; 87.7% reported the review helped their medicines understanding, 63.1% their experience of side effects, 36.9% their ability to take medicines correctly, and 30.5% the impact of medicines on their daily activities.

Conclusions

General practice pharmacist‐led person‐centred medicines reviews for patients with hyperpolypharmacy and/or at high risk of medicines‐related harm delivered substantial improvements in medicines appropriateness and patient‐reported outcomes, thus providing evidence to support their wider implementation.
Lung tumor organoids migrate as cell clusters containing cancer stem cells under hypoxic condition
Authors: Li Yanjiao , Zou Jiarong , Fang Yanhua , Zuo Jianing , Wang Ruoyu , Liang Shanshan
Published: February 2025

Background

Tumor hypoxia reshapes the microenvironment, driving progression, invasion, metastasis, and therapy resistance. Patient‐derived tumor organoids, formed under three‐dimensional conditions, preserve cellular heterogeneity and nutrient gradients, making them ideal for studying hypoxia‐induced tumor responses. This study examines hypoxia‐induced changes in lung tumor organoids from two patients, focusing on tumor‐associated markers, stem cell markers, and migration capabilities.

Results

Our findings demonstrate that hypoxia distinctively modulates the expression of lung cancer markers thyroid transcription factor‐1, cytokeratin 7, and ΔNP63 variant. Hypoxia also induces the upregulation of stem cell‐associated markers, resulting in an increased proportion of cancer stem cells. Furthermore, hypoxic lung tumor organoids exhibit unique migratory behavior upon reoxygenation, driven by epithelial‐mesenchymal transition and the elevated expression of matrix metalloproteinases 7 and matrix metalloproteinases 9, indicating their enhanced invasive potential.

Conclusions

These findings highlight the value of lung tumor organoids as models for studying hypoxia's complex role in lung cancer. Hypoxia significantly modulates lung tumor organoids growth, stemness, and migratory behavior, providing critical insights into tumor progression and therapy resistance.
Going green in China: Firms' responses to stricter environmental regulations
Authors: Fan Haichao , Graff Zivin Joshua , Kou Zonglai , Liu Xueyue , Wang Huanhuan
Published: February 2025

This paper finds that major 2006 Chinese environmental reforms creating mandatory emission reduction targets led firms to significantly reduce emissions, especially for firms in more polluting industries. A decomposition of the overall effect shows that firms relied primarily on technology upgrading (75.3%) rather than output cuts (24.7%) in meeting the regulatory changes. The driving forces for this “technique effect” are more water recycling and abatement device adoption. While polluting firms did not increase their green innovation, local equipment manufacturers—likely suppliers—did significantly increase green water patent applications, indicating an expanded environmental service market effect. Tests on firms' economic responses provide more evidence for an “internal” variant of the pollution haven hypothesis because firms' profit, capital, employment, market shares, and entry were all negatively affected by the more stringent regulation.
Real‐Time, AI‐Guided Photodynamic Laparoscopy Enhances Detection in a Rabbit Model of Peritoneal Cancer Metastasis
Authors: Rivera‐Piza Adriana , Lee Sung‐Ho , Lee Hannah HeeJung , Lee Seungho , Shin Su‐Jin , Kim Jaehyuk , Park Jong‐Hyun , Yu Jae Eun , Lee Sang Won , Park Gyuri , Wilson Brian C. , Kim Hyoung‐Il
Published: February 2025

Accurate diagnosis is essential for effective cancer treatment, particularly in peritoneal surface malignancies, where failure to detect metastatic lesions can mislead the treatment plan. This study assessed the diagnostic accuracy of staging laparoscopy using the integration of artificial intelligence (AI)‐guided photodynamic diagnosis (PDD) with the photosensitizer Phonozen, activated at 405 nm in a rabbit model. To create peritoneal carcinomatosis, VX2 cells were inoculated laparoscopically into the peritoneum of female white New Zealand rabbits. Conventional and PDD‐guided laparoscopy utilized a customized light source that emitted broad‐spectrum white light or 405‐nm blue light, respectively. The surgical procedure comprised a tripartite approach: exploration and labeling of suspected nodules under white‐light visualization, identification of additional metastatic tumors under blue‐excitation fluorescent light, and confirmatory open laparotomy to locate overlooked nodules by palpation. Our results showed that the initial experimental data from 371 nodules in 14 rabbits, comparing conventional diagnostic laparoscopy and PDD, showed increased detection sensitivity from 67% ± 1.9% (conventional) to 98% ± 0.7% (PDD) in the small‐size nodule. In the second experimental data set from 265 nodules in 10 rabbits, the addition of a real‐time AI algorithm further increased the sensitivity to 100% ± 0.0%. Combining PDD with AI enhances the detection of peritoneal cancer metastasis in staging laparoscopy.
Detecting Glaucoma in Highly Myopic Eyes From Fundus Photographs Using Deep Convolutional Neural Networks
Authors: Chen Xiaohong , Zhou Chen , Zhu Yingting , Luo Man , Hu Lingjing , Han Wenjing , Zuo Chengguo , Li Zhidong , Xiao Hui , Huang Shaofen , Chen Xuhao , Zhao Xiujuan , Lu Lin , Wang Yizhou , Zhuo Yehong
Published: February 2025

Background

High myopia (HM) is a major risk factor for glaucoma. However, glaucomatous optic neuropathy is often undiagnosed owing to atypical structural alterations with axial elongation. Moreover, an algorithm to detect glaucoma in highly myopic eyes has not yet been reported.

Methods

We recruited 2643 colour fundus photographs to train a ResNet‐50 network for discriminating eyes with highly myopic glaucoma (HMG) from HM or glaucoma alone. We employed a 10‐fold cross‐validation strategy to evaluate the model's performance and applicability across diverse patient groups. Multiple metrics were computed to gauge the model's diagnostic process. The diagnostic ability of the model was then juxtaposed with those made by ophthalmologists to determine concordance. The gradient‐weighted class activation maps were used for visual explanations.

Results

Our model demonstrated an overall accuracy of 97.7% with an area under the curve of 98.6% (sensitivity, 91.2%; specificity, 98.0%) for the differential diagnosis among HM, glaucoma, HMG and normal controls. These metrics notably outperformed the diagnostic performances of two attending ophthalmologists, who achieved accuracies of 64.7% and 69.9%. The activation maps derived from the model suggested that the most discriminative lesions for diagnosing HMG were predominantly in the disc, peripapillary area and inferior region of the disc, which are often displayed with a tessellated fundus. These results were slightly different from the understanding of the attending ophthalmologists.

Conclusions

Our proposed model demonstrates high efficacy and suggests specific features for distinguishing eyes with HMG, enabling potential clinical value in assisting the intricate diagnosis of this vision‐threatening disease.
Neural Activity Alterations and Their Association With Neurotransmitter and Genetic Profiles in Schizophrenia: Evidence From Clinical Patients and Unaffected Relatives
Authors: Guo Zixuan , Xiao Shu , Sun Shilin , Su Ting , Tang Xinyue , Chen Guanmao , Chen Pan , Chen Ruoyi , Chen Chao , Gong Jiaying , Yang Zibin , Huang Li , Jia Yanbin , Wang Ying
Published: February 2025

Background

The pattern of abnormal resting‐state brain function has been documented in schizophrenia (SCZ). However, as of yet, it remains unclear whether this pattern is of genetic predisposition or related to the illness itself.

Methods

A systematical meta‐analysis was performed to identify resting‐state functional differences in probands and their high‐risk first‐degree relatives of schizophrenia (FDRs‐SCZ) using Seed‐based d Mapping software. Subsequently, spatial associations between postmortem gene expression and neurotransmitters distribution data and neural activity alterations were conducted to uncover neural mechanisms underlaying FDRs‐SCZ and SCZ from a multidimensional perspective.

Results

A total of 13 studies comprising 503 FDRs‐SCZ and 605 healthy controls (HCs) and 129 studies comprising 6506 patients with SCZ and 6982 HCs were included. Compared to HCs, FDRs‐SCZ displayed increased spontaneous functional activity in the bilateral anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC); patients with SCZ showed decreased spontaneous functional activity in the bilateral ACC/mPFC, bilateral postcentral gyrus, and right middle temporal gyrus as well as increased spontaneous functional activity in the bilateral striatum. The altered functional activity in FDRs‐SCZ and SCZ shared similar spatial associations with genes enriched in potassium ion transmembrane transport, channel activity, and complex. The FDRs‐SCZ and SCZ‐related brain functional patterns were additionally associated with dopaminergic, serotonergic, and cholinergic neurotransmitter distribution.

Conclusions

SCZ‐related resting‐state functional, neuroimaging transcriptomes, and neurotransmitters abnormalities may exist in high‐risk unaffected FDRs‐SCZ, rather than just in overt SCZ. The study extended the evidence that altered brain function, along with their spatial correlations to genetics and neurotransmitter systems, may associate with genetic vulnerability for SCZ.
Discovery of Novel Pain Regulators Through Integration of Cross‐Species High‐Throughput Data
Authors: Chen Ying , Bajpai Akhilesh K. , Li Nan , Xiang Jiahui , Wang Angelina , Gu Qingqing , Ruan Junpu , Zhang Ran , Chen Gang , Lu Lu
Published: February 2025

Aims

Chronic pain is an impeding condition that affects day‐to‐day life and poses a substantial economic burden, surpassing many other health conditions. This study employs a cross‐species integrated approach to uncover novel pain mediators/regulators.

Methods

We used weighted gene coexpression network analysis to identify pain‐enriched gene module. Functional analysis and protein‐protein interaction (PPI) network analysis of the module genes were conducted. RNA sequencing compared pain model and control mice. PheWAS was performed to link genes to pain‐related GWAS traits. Finally, candidates were prioritized based on node degree, differential expression, GWAS associations, and phenotype correlations.

Results

A gene module significantly over‐enriched with the pain reference set was identified (referred to as “pain module”). Analysis revealed 141 pain module genes interacting with 46 pain reference genes in the PPI network, which included 88 differentially expressed genes. PheWAS analysis linked 53 of these genes to pain‐related GWAS traits. Expression correlation analysis identified Vdac1, Add2, Syt2, and Syt4 as significantly correlated with pain phenotypes across eight brain regions. NCAM1, VAMP2, SYT2, ADD2, and KCND3 were identified as top pain response/regulator genes.

Conclusion

The identified genes and molecular mechanisms may enhance understanding of pain pathways and contribute to better drug target identification.
Impact of CEO's IT Background on Green Technology Innovation: Evidence From China
Authors: Zhang Xue , Zhang Wensong , Wang Jiayuan , Chen Baolian
Published: February 2025

Research Question/Issue

Considering the important role of CEO's background characteristics in formulating firms' innovation strategy decisions, we investigate the relationship between the CEO's information technology (IT) background and corporate green technology innovation.

Research Findings/Insights

We find that the CEO with an IT background results in an addition of 19.6% in corporate green technology innovation outputs. The result is robust to identification tests, including 2SLS, PSM, DID, and system GMM. The channel test shows that the CEO's IT background positively affects green technology innovation by promoting firms' digital transformation. And the financial‐industrial integration strengthens the positive relationship between the CEO's IT background and corporate green technology innovation. Heterogeneity analysis indicates that the relationship is pronounced in state‐owned enterprises, mature enterprises, and non‐high‐tech enterprises.

Theoretical/Academic Implications

The findings of this paper not only enrich the research literature on antecedent variables of green technology innovation but also provide theoretical support for listed companies to improve the background configuration of the executive team.

Practitioner/Policy Implications

Against the backdrop of China's booming digital economy, our results provide important insights for practitioners, suggesting that they should employ more IT professionals to improve their green technology innovation capabilities and gain a sustainable competitive advantage.
Inhibition of Tacrolimus Metabolism by Cannabidiol and Its Metabolites In Vitro
Authors: So Gerald C. , Lu Jessica Bo Li , Cheng Ying‐Hua , Gisch Debora L. , Koyama Sachiko , Melo Ferreira Ricardo , Beamon Travis R. , Desta Zeruesenay , Eadon Michael T.
Published: February 2025

Drug interactions are major causes of interindividual variability in tacrolimus exposure and effect. Tacrolimus, a widely used drug in transplant patients, is metabolized by CYP3A4 and CYP3A5. Cannabidiol (CBD) use after transplant is common. Clinical cases suggest CBD may alter tacrolimus exposure, but the mechanism of this interaction is unknown. We hypothesize that cannabidiol will inhibit tacrolimus metabolism in vitro mainly through CYP3A5 inhibition. In pooled human liver microsomes (HLMs) and recombinant (r) CYP3A4 and CYP3A5 enzymes, tacrolimus (1 μM) metabolism was determined using substrate depletion method in the absence (control) and the presence of 10 μM CBD, 7‐hydroxyCBD, and 7‐carboxyCBD. Ketoconazole (1 μM) served as a positive control for the inhibition of CYP3A. Linear regression analyses were performed to obtain kinetic parameters of the depletion. Tacrolimus depletion half‐life was 2.54, 0.922, and 0.351 min with pooled HLMs, rCYP3A4, and rCYP3A5, respectively. In pooled HLMs, CBD and 7‐hydroxyCBD increased tacrolimus half‐life by 0.8‐ and 2.3‐fold (both p < 0.0001), respectively. In rCYP3A4, CBD, 7‐hydroxyCBD, and ketoconazole prolonged tacrolimus half‐life by 5.8‐, 14‐, and 7.7‐fold, respectively. In rCYP3A5, CBD, 7‐hydroxyCBD, and ketoconazole prolonged half‐life by 29.3‐, 19.7‐, and 0.1‐fold, respectively. In all experiments, 7‐carboxyCBD had minimal effect on tacrolimus depletion. CBD and 7‐hydroxyCBD inhibited tacrolimus metabolism in vitro. CBD showed stronger inhibition in rCYP3A5 than rCYP3A4. The demonstrated CYP3A5 selectivity of cannabidiol may contribute to the in vitro identification of CYP3A5 substrates in new drug development. Our results support the potential of a clinical drug–drug interaction between CBD and tacrolimus.
A mixed‐methods study of staff perspectives on the barriers and facilitators to the implementation of patient‐reported routine outcome measures and feedback in alcohol and other drug treatment
Authors: Pocuca Nina , Campbell Gabrielle , Barnett Anthony , Beck Alison K. , Ellem Rhiannon , Quinn Catherine A. , Kelly Peter J. , Larance Briony , Baker Amanda L. , Connor Jason P. , Marsden John , Chan Gary C. K. , Connelly Luke , Lenzen Sabrina , Farrell Michael , Stirling Robert , Hudson Suzie , Hides Leanne
Published: February 2025

Introduction

Preliminary evidence supports the use of patient‐reported outcome measures (PROM) and feedback for enhancing client outcomes in alcohol and other drug (AOD) treatment. However, successful implementation remains challenging. This mixed‐methods study applied the Consolidated Framework for Implementation Research (CFIR) framework to examine inner setting and staff characteristics that act as barriers and facilitators to the implementation of PROMs in AOD treatment.

Methods

To understand CFIR‐informed barriers and facilitators to implement PROMs in AOD treatment, qualitative interviews were conducted with N = 23 AOD counsellors. A separate quantitative survey was conducted with N = 108 AOD counsellors.

Results

Four qualitative themes emerged: (i) PROMs and feedback are valuable to AOD treatment; (ii) counsellor resistance towards PROMs and feedback is a barrier to successful implementation; (iii) competing interests and logistical issues are barriers to the implementation of PROMs and feedback; and (iv) PROMs are a burden to clients that may serve to disengage them from treatment. Survey results indicated a positive association between leadership support (CFIR inner setting construct) and counsellor knowledge and beliefs regarding PROMs and feedback (CFIR staff characteristics construct; β = 0.35, 95% CI [0.13, 0.60]). Findings demonstrated a positive association between available PROMs resources (CFIR inner setting construct) and both knowledge and beliefs regarding PROMs and feedback (β = 0.31, 95% CI [0.14, 0.48]) and self‐efficacy to implement PROMs and feedback (CFIR staff characteristics construct; β = 0.18, 95% CI [0.04, 0.32]).

Discussion and Conclusions

Findings point to the critical need to adopt a whole‐of‐organisation approach to foster buy‐in for PROMs and feedback to support successful implementation.
Development, dissemination and community response towards the first community notice regarding misrepresented illicit anabolic‐androgenic steroids in circulation in Australia
Authors: Piatkowski Timothy , Volpe Isabelle , Brien Rita , Coomber Ross , Barratt Monica , Kill Emma , Davey Geoff , Francis Cameron , Cresswell Sarah , White Alan , Harding Madeline , Blakey Karen , Reeve Steph , Walters Brooke , Ferris Jason , Puljević Cheneal
Published: February 2025

Introduction

Drug alerts aimed at both people who use drugs and health workers help to prevent acute harms from unpredictable illicit drug markets and by equipping health workers to handle unusual drug events and share vital information with service users. However, there has never been an alert produced for anabolic‐androgenic steroids (AAS), an important class of illicit drugs. We report on the development, implementation and community receptivity of the first‐ever AAS community drug alert.

Methods

Based on findings from samples collected during the first month of an AAS checking trial conducted by drug checking service CheQpoint, we identified contamination in two oxandrolone samples, which prompted issuing of the first‐ever AAS community notice. Drawing on digital ethnographic techniques, we collected and analysed social media comments on the notice to assess AAS community perceptions and the broader impact of this harm reduction initiative.

Results

The Instagram post by CheQpoint reached 1376 users, with 3429 impressions and 87 interactions. Community feedback indicated receptivity to the notice, with several people in the community recognising the prevalence of AAS adulteration. Responses highlighted the need for more thorough testing and indication of sample content, given the perception of a growing number of new people using AAS.

Discussion and Conclusions

This study, the first to describe a community notice for illicit market AAS, reveals a strong demand for harm reduction interventions. We call for the urgent expansion of drug‐checking services to provision for AAS and, thus, provide equitable health support to address systemic gaps for this group.
Mapping Butterfly Species Richness and Abundance in Mountain Grasslands—Spatial Application of a Biodiversity Indicator
Authors: Barkmann Friederike , Tasser Erich , Tappeiner Ulrike , Huemer Peter , Schattanek‐Wiesmair Benjamin , Lechner Kurt , Ortner Alois , Rüdisser Johannes
Published: February 2025

Aim

The integration of high‐quality field data with high‐resolution remote sensing data can give detailed insights into the spatial distribution of biodiversity and provide valuable information for biodiversity conservation at a scale relevant for management action. We developed a framework based on remote sensing data and field surveys for modelling species richness and abundance of butterflies at high spatial resolution to inform about the spatial distribution of butterfly species richness and abundance and analyse their drivers and the scale of effect of landscape factors.

Location

Western Austria.

Methods

We combined structured butterfly surveys at 175 grassland sites in western Austria with remote sensing variables describing topography, grassland characteristics, and the landscape composition and configuration at different radii around a site. For spatial predictions of butterfly species richness and abundance, generalised linear models with elastic net regularisation were used and compared with stepwise variable selection. To analyse the influence of selected variables and their scale of effect, models with landscape variables in different radii around the sites and variables describing topography were applied.

Results

For species richness, the Spearman rank correlation between predicted and measured values was 0.62. For abundance, predictive power was lower with a correlation of 0.52. Models with variables from smaller radii (125 and 250 m) generally showed better predictive performance than those at larger radii (500 and 1000 m). We found an effect of elevation, maximum grassland productivity, northness, and forest ecotone density in most models.

Main Conclusions

Integrating remote sensing data with spatial modelling techniques substantially enhances our ability to understand patterns and identify key drivers of butterfly species richness at high spatial resolution. Our study highlights the positive influence of forest edges, small woody features, and moderate grassland productivity on butterfly species richness and abundance.
Heat shock‐pretreated bone marrow mesenchymal stem cells accelerate wound healing in a diabetic foot ulcer rat model
Authors: Lin Xi , Lin Qi
Published: February 2025

Background

Diabetic foot ulcers (DFUs) are the severe chronic complications of diabetes, amputation is required when ulcers cause severe loss of tissue or evoke a life‐threatening infection. Mesenchymal stem cells (MSCs) have shown a good effect in helping DFU healing, though the efficiency needs to be improved. This study aimed to investigate the effects of heat shock pretreatment on the improvement of the therapeutic effects of MSCs.

Methods

Primary rat bone marrow MSCs (BMSCs) were isolated and stimulated with heat shock pretreatment and then tested on a DFU rat model. Alkaline phosphatase, Alizarin Red S, and Oil Red O were stained to check the osteogenic differentiation ability of heat shock‐pretreated BMSCs. The effect of heat shock pretreatment on the inflammatory response of macrophages was studied with the lipopolysaccharides stimulation model on a mouse macrophage cell line RAW264.7. The impact of heat shock‐pretreated BMSCs on dermal fibroblasts was also checked. Last, heat shock‐pretreated BMSCs were tested on a DFU rat model.

Results

Heat shock‐pretreated BMSCs were characterized by the expression of CD105 and CD44. Heat shock pre‐stimulation did not affect cell viability when cultured up to 96 h. Heat shock pre‐stimulated BMSCs inhibited the inflammatory response by reducing the pro‐inflammatory cytokine production (IL‐1β, IL‐6, and TNF‐α) and enhancing the anti‐inflammatory cytokine production (IL‐10) (at least all p < 0.01), as well as increasing the ratio of M2 polarization macrophages to M1 polarization in vitro (p < 0.001). Heat shock pre‐stimulated BMSCs enhanced the growth and migration of dermal fibroblasts in vitro (p < 0.001). Heat shock‐BMSCs promoted the M2 polarization level of macrophages in wound tissues in a DFU rat model.

Conclusion

Heat shock pretreatment could enhance the therapeutic effect of BMSCs on wound healing in a DFU rat model.
Adding social determinants of health to the equation: Development of a cardiometabolic disease staging model using clinical and social determinants of health to predict type 2 diabetes
Authors: Howell Carrie R. , Tanaka Shiori , Zhang Li , Carson April P. , Yi Nengjun , Shikany James M. , Garvey W. Timothy , Cherrington Andrea L.
Published: February 2025

Aims

Identifying individuals at the highest risk of progression to type 2 diabetes (T2D) using clinical and social determinants of health (SDoH) measures will help prioritize prevention efforts. We aimed to investigate model performance after adding SDoH to a previously validated cardiometabolic disease staging diabetes risk prediction model.

Materials and Methods

We developed a Bayesian predictive model using data [clinical factors: fasting glucose, blood pressure, body mass index, high‐density lipoprotein cholesterol, triglycerides; individual SDoH: income, education, health insurance status, relationship status, self‐reported stress and neighbourhood SDoH: census‐tract level social vulnerability index] from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study to predict T2D with external validation using the Coronary Artery Risk Development in Young Adults (CARDIA) study.

Results

The analysis included 9907 REGARDS participants without T2D at baseline [mean age 63 years (SD 8.5), 54% female, 33% non‐Hispanic Black] who completed a follow‐up visit 10 years later. N = 1268 (12.8%) developed T2D. Adding SDoH to the clinical model modestly improved performance [Area Under the Curve: 0.802 vs. 0.804, p = 0.01]. Calibration plots indicated that the clinical model underpredicted risk in disadvantaged SDoH subgroups, whereas the clinical plus SDoH model improved prediction accuracy in subgroups. Classification tables revealed that the clinical plus SDoH model accurately reclassified individuals categorized as borderline risk in a clinical‐only model.

Conclusion

Including SDoH in T2D risk prediction and stratification at the population level may aid in better classifying T2D risk among vulnerable populations, which has important implications for screening strategies.
Annual prevalence and factors associated with body mass index documentation in German general practices—A retrospective cross‐sectional study
Authors: Orozco‐Ruiz Ximena , Sarabhai Theresia , Kostev Karel
Published: February 2025

Aim

The aim of this study was to assess the prevalence of body mass index (BMI) documentation by general practitioners (GPs) in Germany and identify associated patient characteristics and determinants.

Materials and Methods

A retrospective cross‐sectional analysis was conducted using data from the IQVIA Disease Analyzer database, which provides anonymized medical data from over 3000 office‐based GPs and specialists in Germany. The study included 989 955 patients aged ≥18 years who visited their GP in 2023 and were categorized based on whether they had documented BMI. The prevalence and likelihood of BMI documentation were assessed across age group, sex, health insurance and several health disorders. Associations were analysed using multivariable logistic regression.

Results

BMI documentation was recorded for only 10.8% of the patients. The prevalence increased with age (7.3% for ≤40 years to 13.8% for those >70 years) and with the number of health disorders (7.3% for patients with no disorders to 23.2% for patients with more than four disorders). No notable differences were observed between sexes or insurance. Multivariable logistic regression revealed that older age groups (61–70 years: OR = 1.46, 95% CI: 1.43–1.49) and disorders such as obesity (OR = 2.15, 95% CI: 2.01–2.21) and type 2 diabetes mellitus (OR = 2.12, 95% CI: 2.08–2.17) had the strongest association with BMI documentation.

Conclusions

BMI is not documented routinely by GPs in Germany. However, older age and the presence of several disorders increase the likelihood of recording this information. These findings underscore a need to prioritize obesity assessment and management in primary care settings in Germany.
Increased Afterload in Patients With Acute Reduction in Left Ventricular Ejection Fraction Following Mitral Valve Transcatheter Edge‐to‐Edge Repair
Authors: Hashimoto Kaho , Nagai Tomoo , Kamioka Norihiko , Noda Satoshi , Horinouchi Hitomi , Murakami Tsutomu , Miyamoto Junichi , Yoshioka Koichiro , Ohno Yohei , Ikari Yuji
Published: February 2025

Aim

The mechanisms and clinical importance of acute reduction (ARD) in left ventricular (LV) function following transcatheter edge‐to‐edge repair (TEER) for mitral regurgitation (MR) remains unclear. This study aimed to non‐invasively evaluate the cardio‐mechanical parameters, including end‐systolic elastance (Ees) and arterial elastance (Ea), to explore their association with ARD following mitral TEER.

Methods and Results

We performed a retrospective analysis of serial transthoracic echocardiography (TTE) studies before and after mitral TEER. Cardio‐mechanical parameters were evaluated non‐invasively using a modified single‐beat method. After the exclusion of nine patients requiring intravenous catecholamine infusion, the study cohort comprised 49 consecutive patients (25 men; mean age: 81 ± 9 years) with successful mitral TEER. ARD in LV function was defined as a decrease in LV ejection fraction (LVEF) of ≥5 points following the procedure by TTE, which was reported in 18 patients. The hospitalization period was longer in patients with ARD in LVEF than in those without ARD (5.5 days vs. 4 days, p = 0.031). Following improvement in MR, Ea increased (1.54 ± 0.49 mmHg/mL vs. 1.84 ± 0.55 mmHg/mL, p = 0.004). Linear regression analysis revealed a correlation between Δtotal stroke volume (SV) and ΔEa (r = 0.614, p < 0.0001). Notably, ΔEa was higher in patients with ARD in LVEF than in those without ARD in LVEF (0.60 ± 0.73 mmHg/mL vs. 0.14 ± 0.39 mmHg/mL, p = 0.006).

Conclusion

ARD in LVEF after mitral TEER was reported in a substantial proportion of patients and may have prognostic implications. Evaluating cardio‐mechanical parameters may aid in understanding complex hemodynamics and guiding treatment strategies for patients with MR undergoing TEER.
Artificial Intelligence Applications in Cardiac CT Imaging for Ischemic Disease Assessment
Authors: Siciliano Gianluca G. , Onnis Carlotta , Barr Jaret , Assen Marly van , De Cecco Carlo N.
Published: February 2025

Artificial intelligence (AI) has transformed medical imaging by detecting insights and patterns often imperceptible to the human eye, enhancing diagnostic accuracy and efficiency. In cardiovascular imaging, numerous AI models have been developed for cardiac computed tomography (CCT), a primary tool for assessing coronary artery disease (CAD). CCT provides comprehensive, non‐invasive assessment, including plaque burden, stenosis severity, and functional assessments such as CT‐derived fractional flow reserve (FFRct). Its prognostic value in predicting major adverse cardiovascular events (MACE) has increased the demand for CCT, consequently adding to radiologists’ workloads. This review aims to examine AI's role in CCT for ischemic heart disease, highlighting its potential to streamline workflows and improve the efficiency of cardiac care through machine learning and deep learning applications.
Idiosyncratic spatial scaling of biodiversity–disease relationships
Authors: Gilbert Neil A. , DiRenzo Graziella V. , Zipkin Elise F.
Published: February 2025

High host biodiversity is hypothesized to dilute the risk of vector‐borne diseases if many host species are ‘dead ends' that cannot effectively transmit the disease and low‐diversity areas tend to be dominated by competent host species. However, many studies on biodiversity–disease relationships characterize host biodiversity at single, local spatial scales, which complicates efforts to forecast disease risk if associations between host biodiversity and disease change with spatial scale. Here, our objective is to evaluate the spatial scaling of relationships between host biodiversity and Borrelia (the bacterial taxon which causes Lyme disease) infection prevalence in small mammals. We compared the associations between infection prevalence and small mammal host diversity for local communities (individual plots) and metacommunities (multiple plots aggregated within a landscape) sampled by the National Ecological Observatory Network (NEON), an emerging continental‐scale environmental monitoring program with a hierarchical sampling design. We applied a multispecies, spatially‐stratified capture–recapture model to a trapping dataset to estimate five small mammal biodiversity metrics, which we used to predict infection status for a subset of trapped individuals. We found that relationships between Borrelia infection prevalence and biodiversity did indeed vary when biodiversity was quantified at different spatial scales but that these scaling behaviors were idiosyncratic among the five biodiversity metrics. For example, species richness of local communities showed a negative (dilution) effect on infection prevalence, while species richness of the small mammal metacommunity showed a positive (amplification) effect on infection prevalence. Our modeling approach can inform future analyses as data from similar monitoring programs accumulate and become increasingly available through time. Our results indicate that a focus on single spatial scales when assessing the influence of biodiversity on disease risk provides an incomplete picture of the complexity of disease dynamics in ecosystems.
Intersectoral Conflict, Exchange Rate Uncertainty, and Delays in Macroeconomic Stabilization
Authors: Razmi Arslan
Published: February 2025

An important body of literature explores the political economy reasons underlying delays in macroeconomic stabilization. This paper develops a framework to analyze the conflict between two risk‐averse groups of economic actors, one that has an endowment of internationally tradable goods and another that is endowed with nontradable goods: both endowments require imported inputs to consume. The focus is on the exchange rate policy in a developing country setup, where the government employs seigniorage revenue to finance prestabilization spending, and faces fiscal and balance of payments problems that necessitate stabilization with a step devaluation. Trade misinvoicing, the presence of exchange rate uncertainty and its interaction with import costs, the role of forward‐looking expectations, and the possibility of foreign/IMF aid influence the likelihood, timing, and terms of a consensus on stabilization in interesting ways. Crucially, given instrument uncertainty, delays may occur even if both sets of agents have perfect foresight and nontradable endowment‐holders realize that their relative position deteriorates over time.
Effects of Rainbow Trout (Oncorhynchus mykiss) Introduction on Andean Stream Food Webs
Authors: Cespedes Adriana Marcela Forero , Correa Sandra Bibiana , Villa Navarro Francisco Antonio
Published: February 2025

Introduced species are one of the biggest threats to aquatic ecosystems. Rainbow trout (Oncorhynchus mykiss, Salmonidae) is considered one of the most dangerous introduced predatory fish species, as they often put native species at risk of extinction. This study evaluated the effects of rainbow trout introduction on Andean stream food webs. We tested the hypothesis that the presence of rainbow trout changes Andean stream food webs by changing the diet of other carnivorous species and the energy source supporting native fish species. We sampled streams with and without rainbow trout and with different vegetation cover (i.e., pastures and crops versus forest) and combined data from stomach contents and stable isotopes. We analyed stomach contents from 231 specimens of two native catfish species and 116 rainbow trout specimens. Our results demonstrate that aquatic insects are essential in Andean stream food webs, where collector gatherers and scrapers were the most consumed and assimilated by catfish and rainbow trout species. Leaf litter was predicted to be the primary energy source in streams with forest cover. In contrast, periphyton contributed the most in streams with pastures and crops. We conclude that the presence of trout coupled with use/land cover (i.e., vegetation cover) exerts a substantial effect on Andean stream food webs. Protection of riparian forests of the Andean streams of Colombia is needed to guarantee the stability of aquatic food webs and thus help native species coexist with established non‐native species introduced decades ago.
Suicidality in Primary Care, Youth Mental Health Services: Prevalence, Risk Factors and Implications for Practice
Authors: Albrecht Sabina , Rickwood Debra , Telford Nic , Privitera Georgia , Palfrey Nicola
Published: February 2025

Introduction

Youth suicide is a concern worldwide, and suicidality—the presence of suicidal ideation or intent—is a critical risk for youth mental health services. This study aimed to determine the prevalence of suicidality in primary care, youth mental health services, along with its correlates and the course of treatment offered to clients.

Methods

Routinely collected data from Australia's headspace National Youth Mental Health Foundation, which has over 160 centres across Australia providing mental health care to young people aged 12–25 years, were analysed for new clients who started and completed their first episode of care between 1 July 2022 and 30 June 2023. This included 30 437 young people/episodes of care and 74 393 occasions of service.

Results

Results showed that suicidality was evident in almost one‐quarter of young people, although it was rarely reported as a primary presenting issue. When present, it was usually identified at first visit. Those most at risk were young people in unstable accommodation, who identified as LGBTIQA+ or who were indigenous.

Conclusions

The findings show that suicidality should be anticipated in young people presenting to primary care mental health settings, and youth services need to be able to competently deal with suicide risk rather than using this as exclusion criteria.
Industrial Strikes in Higher Education: Ascertaining Causes and the Levels of Effect From Developing Economy Perspectives
Authors: Addo Edna , Segbenya Moses , Ampofo Samuel Yaw
Published: February 2025

This study examined industrial strikes in higher education: Ascertaining causes and the levels of effect from a developing economy perspective. The study adopted the positivist philosophical position and a quantitative approach to collect data from 523 staff members of 30 Colleges of Education in a developing economy situated in Africa. Data analysis was performed using partial least squares structural equation modelling (PLS‐SEM). The study found that strikes among higher education staff in developing economies were influenced by both economic and non‐economic factors. These factors subsequently affected productivity at Colleges of Education and subsequently affected students, teachers and the country as a whole. Based on the findings of the study, it was recommended that the management of Colleges of Education that also doubles as the representatives of the employer or government should improve the condition of service for employees at the college by enhancing their salary, other allowances and fringe benefits.
Atypical Hairy Cell Leukemia—The Current Status and Future Directions
Authors: Robak Tadeusz , Robak Marta , Majchrzak Agata , Krawczyńska Anna , Braun Marcin
Published: February 2025

Hairy cell leukemia (HCL) is a rare, chronic lymphoid leukemia characterized by circulating lymphocytes with pale, hair‐like cytoplasmic projections, pancytopenia, marked monocytopenia, and splenomegaly. Classic HCL displays distinct morphological, immunophenotypical, and genetic features. Classic HCL cells exhibit central nuclei, abundant cytoplasm with hair‐like projections, and expression of CD20, CD22, CD11c, CD103, CD25, CD123, TBX21, annexin A1 (ANXA1), FMC7, CD200, and weak cyclin D1 (CCND1). While the vast majority of classic HCL cases harbor the BRAF V600E somatic mutation, rare examples have been reported without splenomegaly, with bulky lymphadenopathy, or with an atypical morphology, immunophenotype or genotype. This review analyzes the atypical clinical, morphologic, immunophenotypic, and genetic presentations associated with classic HCL. PubMed, Web of Science, and Google Scholar were searched for articles of hairy cell leukemia, including atypical morphology, atypical immunophenotype, atypical genotype, and rare symptoms. Publications from October 2004 to December 2024 were reviewed, with additional relevant studies obtained by reviewing references from selected articles.