bluuebunny/crossref_metadata_2025 huggingface dataset:
Drainage Pattern Recognition Method Using Graph Convolutional Networks Combined With Three‐Dimensional Elevation Features
Authors: Qiang Bo , Liu Tao , Du Ping , Li Pengpeng , Wang Wenning , Xu Shenglu
Published: January 2025

Drainage pattern recognition plays a crucial role in flood management, hydraulic engineering site selection, and biodiversity maintenance. Although deep learning methods have been widely employed in drainage pattern recognition in recent years, most research has focused on two‐dimensional features, with limited attention given to the impact of three‐dimensional elevation features. This study, therefore, introduces a graph convolutional network (GCN) approach that incorporates three‐dimensional elevation features. This method integrates three‐dimensional elevation features into the feature system of deep learning‐based drainage pattern recognition for the first time, combining two‐dimensional geometric and topological features to comprehensively capture variations in both vertical and planar morphology of drainage patterns. Specifically, this study extracts representative drainage pattern samples (e.g., dendritic, skeleton, parallel, and fan) from OSM and HydroSHEDS river vector data. Six features are designed based on the micro‐to‐macro processes involved in drainage pattern development, and a novel drainage pattern feature description index is proposed. A GCN model architecture based on the first‐order Chebyshev polynomial is then developed to extract both global and local information of drainage patterns under three‐dimensional elevation features. Experimental results demonstrate that the recognition accuracy of this method achieves 90% on the test dataset, with precision, recall, and F1 scores improving by at least 3% compared to methods such as support vector machines (SVM) and GraphSAGE. This suggests that the feature description index incorporating three‐dimensional elevation features more comprehensively reflects the development process of drainage patterns, thereby improving recognition accuracy and offering new methods and perspectives for drainage pattern research.
Unexpected pathway for intercontinental movement into the Nearctic revealed by phylogenetic analyses
Authors: Tomoyasu Kye , Cannizzaro Andrew G. , Berg David J.
Published: January 2025

Much of North America's freshwater biodiversity is derived from Palearctic lineages. Isopods of the Holarctic family Asellidae are among the most widespread and diverse freshwater crustaceans, but Nearctic species are poorly studied. We examined the evolutionary history of the family, utilizing Sanger sequencing of mitochondrial and nuclear DNA, and both maximum likelihood and Bayesian inference. The genera Calasellus and Salmasellus from the western United States are shown to be basally derived, suggesting they have only distant affinity to other Nearctic taxa and represent relictual lineages that likely diverged in the Jurassic. Remaining Nearctic asellids formed a monophyletic group sister to the Lake Baikal endemic genus Baicalasellus, which diverged during the Early Cretaceous. Our results show a close connection between Nearctic and eastern Palearctic asellids, with an Early Cretaceous divergence consistent with limited connections between Asia and North America. We propose that asellids used a Beringian route to colonize the Nearctic from west to east, in contrast to Europe to North America routes hypothesized for other freshwater crustaceans. Many of the genera we analysed were non‐monophyletic; taxonomic revision may shed further light on the route and timing of asellid diversification in the Nearctic and on the processes by which freshwater taxa colonized this realm.
Antibiotics synergize the toxicity of acaricides against the bulb mite, Rhizoglyphus robini
Authors: Samadieh Hosein , Talebi Majid , Izadi Hamzeh , Khajehali Jahangir
Published: January 2025

As the world’s most valuable spice, saffron holds significant economic importance in Iran. Rhizoglyphus robini Claparede (Acari: Astigmata: Acaridae) is one of the most critical and damaging pests affecting corm plants globally, including saffron fields in Iran. The repeated use of acaricides has led to the development of resistance in pest populations. Bacterial communities play a crucial role in the various physiological processes of their insect hosts, including the metabolism involved in detoxification. Bioassays against R. robini were performed with two acaricides, abamectin, and propargite, using a filter paper method. Based on the results, the LC50 values of 2.3 and 25 mg a.i./L were estimated for abamectin and propargite, respectively. The impact of antibiotic pretreatment on acaricide toxicity was assessed using six antibiotics: tetracycline, azithromycin, penicillin, cefalexin, cefixime, and streptomycin. The antibiotics (1.5 mL of 100 mg/L) were added to Petri dishes with a layer of filter paper. Mortality was significantly increased in the tetracycline pretreatment group, whereas the other antibiotics showed negligible effects. A bioassay comparing tetracycline pretreatment with a mixture of the other five antibiotics revealed that the antibiotic mixture also significantly enhanced toxicity. Pretreatment with the antibiotic mixture led to a 5.6-fold increase in abamectin toxicity and a 10.2-fold increase in propargite toxicity. To estimate the density of bacterial community in different treatments, total DNA was extracted, and 16S rRNA gene amplification was performed using a general bacterial primer pair. The semi-quantitative PCR results indicated reduced bacterial density in mites treated with tetracycline or an antibiotic mixture compared with the control. Enzymatic assays showed that the activities of detoxification enzymes, including glutathione S-transferases, carboxyl/cholinesterases, and cytochrome P450 monooxygenases, were significantly reduced in mites pretreated with tetracycline or antibiotic mixture. These findings suggest that bacterial community may influence acaricide metabolism by modulating detoxification enzyme activities in their hosts. This study provides a basis for further research into the mechanisms of symbiont-mediated detoxification in pest management.
Combining two predatory mite species (Phytoseiidae) to control two-spotted spider mites in greenhouse strawberry production
Authors: Wang Endong , Hou Zhengrong , Yan Hong , Dong Jie , Jiang Xiaohuan , Zhang Bo , Xu Xuenong
Published: January 2025

Strawberry is an important economic crop worldwide, whereas two-spotted spider mites (TSSM, Tetranychus urticae) is the major pest in fruit production. To produce the organic and safe fruits in greenhouses, we selected two strawberry varieties that are most widely planted in northern China with popular taste to study the TSSM control efficiency by two predatory mites of Phytoseiulus persimilis and Neoseiulus californicus. We comprehensively evaluated the control methods by analyzing TSSM population dynamics, predatory mite numbers, leaf chlorophyll content, fruit weight, sugar content, and the cost of investing in predatory mites. We found that the mite-resistant variety Miaoxiang can largely maintain TSSM at a relative low-density, and N. californicus can provide sufficient control against TSSM during the whole growth season. When TSSM density was high in Suizhu, the combined use of predatory mites led to a substantial reduction of 85.99% in pest numbers, all at reasonable prices. Our fieldwork has demonstrated the crucial importance of pest monitoring and early warning systems in determining the application of biocontrol agents, taking into account factors such as TSSM population size and rate of expansion. These findings strongly suggest that utilizing suitable biocontrol agents represents a promising approach for effectively managing TSSM infestations in greenhouse strawberry production.
Single- and multiple-dose pharmacokinetics and safety of the SARS-CoV-2 3CL protease inhibitor RAY1216: a phase 1 study in healthy participants
Authors: Hu Yue , Li Haijun , Wang Kun , Wu Dandan , Zhang Hong , Ding Yanhua , Wu Junyan , Ye Suiwen , Peng Yun , Liu Li
Published: January 2025

Coronavirus disease 2019, which leads to pneumonia, is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). RAY1216 is a 3C-like protease inhibitor that targets SARS-CoV-2. The aim of our study was to assess the pharmacokinetics (PK) and safety of RAY1216 in healthy volunteers. This was a randomized, placebo-controlled, double-blind study consisting of four components: a single ascending dose study, a drug-drug interaction study, a multiple ascending dose study, and a food-effect study. All participants were randomly assigned to receive either a single dose or multiple doses of RAY1216 or placebo. A total of 88 healthy adult participants (male-to-female ratio of 1:1) aged 18–50 years were enrolled. A total of 37 participants (42%) experienced at least one adverse event (AE). All AEs were mild or moderate and were resolved without additional treatment. The most commonly reported adverse drug reactions were hypertriglyceridemia, hyperuricemia, and elevated serum creatinine levels. RAY1216 was well-absorbed after administration with exposure increasing in a dose-dependent manner. Food appeared to increase exposure and delay the absorption of RAY1216. Ritonavir significantly inhibited drug metabolism, and increased drug exposure increased the associated safety risks. RAY1216 was found to be well tolerated and safe in healthy participants. On the basis of preclinical results, PK characteristics, and the safety profile of RAY1216, a dosage of 400 mg three times daily was selected, thereby establishing a foundation for future research and for the clinical application of RAY1216.

CLINICAL TRIALS

This study is registered with ClinicalTrials.gov as
NCT05829551
.
Metastable Nanoprecipitates in Alloys: Phenomenology and Atomistic Simulation
Authors: Razumov I. K. , Gornostyrev Yu. N.
Published: January 2025

Metastable disperse states arising from decomposition in alloys are of considerable interest and have an important practice-related significance, providing high strength properties. Recently, the stabilization mechanism of disperse states through the formation of a shell enriched in alloying elements has attracted special attention. The paper presents a concise overview of the theoretical concepts pertaining to the formation and stabilization of disperse states in alloys, along with recent findings from first-principles atomistic simulations of Al–Cu–X, Fe–Cu–X, and Al–Sc–Zr alloys, wherein precipitates with a core–shell structure have been observed. Furthermore, the paper addresses the conditions of kinetic and thermodynamic stabilization of precipitates in relation to coalescence processes during annealing.
Diffuse orbital inflammation: an atypical manifestation of Behcet’s disease
Authors: Miller Evan , Shue Charlyn , Bell Stephen , Elam Rachel
Published: January 2025

Behcet’s disease is a chronic, relapsing systemic vasculitis characterised by multisystem involvement from small, medium and large vessel inflammation. Common manifestations include oral and genital ulcers, rash, uveitis and neurological symptoms, while orbital inflammation is rare. An Asian man in his 40s with Behcet’s disease on immunosuppression presented with 10 days of unilateral periorbital swelling and painful eye movements, unresponsive to oral antibiotics. Imaging revealed diffuse orbital inflammation and optic neuritis. Investigations excluded an infectious cause. Despite broad-spectrum intravenous antibiotics, his condition worsened until typical Behcet’s disease mucocutaneous symptoms emerged, indicating a Behcet’s flare. Treatment with high-dose corticosteroids, followed by cyclophosphamide and azathioprine resolved the diffuse orbital inflammation. Unfortunately, the visual outcome was poor as he remained blind in the affected eye from optic neuritis and corneal ulceration. This case highlights the importance of early diagnosis and treatment of diffuse orbital inflammation in Behcet’s disease to prevent severe ocular complications.
Role of biosimilar introduction on insulin glargine prices: a retrospective analysis in 28 European countries
Authors: Morolla Davide , Beran David , Ewen Margaret , Raviglione Mario , von Schoen-Angerer Tido
Published: January 2025

Objective

Quantify insulin glargine prices following the market introduction of biosimilars. Examine price levels and price changes for originator and biosimilars, by country.

Methods

Retrospective quantitative analysis using insulin glargine pricing data, both of the originator product and its biosimilars. Segmented regression analysis using a dual-model approach: pooled and country-specific.

Setting

28 European countries using data from the European Medicine Price Database for the period 2013–2023.

Main outcome measures

Price variations between countries were analysed to assess trends and correlations before and after biosimilar market entry.

Results

In the 28 countries studied, cost of insulin glargine underwent a median 21.6% decrease overall in the last decade (p<0.001). In 2022, the median price was €9.0 for the originator (first to market) Lantus (IQR €8.1–€10.4), €8.9 for the biosimilar Abasaglar (IQR €7.6–€10.1) and €7.0 for the biosimilar Semglee (median €7.0; IQR €6.8–€7.5). The originator price was higher than biosimilars (p=0.009). Biosimilar market entry was associated with an overall significant price reduction of the originator, both immediately after entry (p<0.001) and in the long-term postentry (p<0.001). No significant correlation was observed between the price of insulin and the countries’ economic indicators.

Conclusion

This is the first study to show the price trend of insulin glargine and its correlation with the introduction of biosimilars, in Europe. A significant price reduction of the originator was observed after biosimilars entered the market. The median cost of biosimilars was lower than the originator, although with substantial differences between individual countries and producers.
What about physician wellness? Impact of a quality improvement intervention
Authors: Mathura Pamela , Pascheto Isabella , Ringrose Jennifer , Ramsay Gillian
Published: January 2025

Background

Emergency department (ED) consultations with general internal medicine (GIM) are required when patients need admission, assistance with safe disposition or evaluation and management of complex or acute medical needs. GIM physicians often balance responsibilities between hospital wards and the ED, which can lead to delayed ED consultations, difficulty balancing workload and potential burn-out. To address this issue, a quality improvement (QI) initiative was trialled, establishing a dedicated GIM ED consultation service to manage these duties independently. This study aimed to evaluate the impact of this intervention on physician wellness.

Methods

A pre–post design was used, with two questionnaires adapted from the validated Mini Z version 2.0 (Zero Burnout Program) Worklife measure for clinicians. These were distributed via Google Forms to collect feedback from participating GIM physicians before and after the intervention. Data were analysed using descriptive statistics and the Mini Z outcome measurement scale.

Results

13 physicians completed the surveys. Applying the Mini Z scale, the GIM ED consultation service had no impact on physician well-being or burn-out. There was a minor increase in satisfaction (1 point) and stress levels (2 points), and the working environment worsened slightly (1 point). Comparing preintervention and postintervention survey responses, job satisfaction improved (36%), while reports of ‘burn-out’ (23%) and ‘beginning to burn out’ (8%) decreased. Postintervention, physicians reported decreased time for documentation (23%), a perception of a more chaotic work environment (23%) and an increase in work encroaching on personal time (15%) when on the ED consultation service. Additionally, there was a 23% reduction in the likelihood of needing to reduce clinical teaching unit service weeks.

Conclusion

When conducting QI initiatives, consider measuring the wellness of physicians and other healthcare providers. Proactively integrating wellness strategies into interventions requires further exploration which may enhance participant experience and initiative sustainability.
Impact of preoperative opioid exposure on cost of care and workplace productivity loss after elective surgery
Authors: Shabet Christina Lynn , Alessio Dominic , Kenney Brooke , Bicket Mark C , Brummett Chad M , Waljee Jennifer F
Published: January 2025

Introduction

A high proportion of surgical patients has previous opioid exposure, which is associated with poorer recovery and increased morbidity. However, much less is known regarding the direct and indirect costs that are associated with healthcare utilization among individuals on preoperative opioid therapy.

Methods

We analyzed The Merative MarketScan Commercial Database linked with the Merative MarketScan Health and Productivity Management Database to include all adult patients admitted and discharged from common elective surgeries between January 1, 2018 and June 30, 2021. Patients were clustered by preoperative opioid exposure and estimates for total direct payments (in USD) generated and workplace absenteeism were assessed for a 6-month period.

Results

10 737 patients were included in our cohort; 17.0% classified as ‘low’ preoperative opioid use (median oral morphine equivalents (IQR)=126 (75–225)), 5.0% as ‘medium’ (370 (225–640)) and 3.0% as ‘high’ (4500 (2120–10 908)). Compared with opioid naive or low preoperative use, individuals with high preoperative use had significantly higher estimated payments for care at 6 months ($4212 for high vs $2706 for naive (p=0.007) and $3059 for low (p=0.045)), while utilizing increased ambulatory care including clinic and outpatient visits after surgery. There was no significant difference in workplace absenteeism between groups.

Conclusion

High preoperative opioid use is associated with increased healthcare utilization and costs following common elective surgery. Future efforts should focus on this patient population to explore interventions that could optimize value-based care by improving outcomes and reducing costs.
Porphyromonas gingivalisassociates with the presence of anti-citrullinated protein antibodies, but not with the onset of arthritis: studies in an at-risk population
Authors: De Vries Charlotte , Cîrciumaru Alexandra , Mathsson-Alm Linda , Westerlind Helga , Dehara Marina , Kisten Yogan , Potempa Barbara , Potempa Jan , Hensvold Aase , Lundberg Karin
Published: January 2025

Objective

The antibody response againstPorphyromonas gingivalis(Pg) is elevated in rheumatoid arthritis (RA), especially in patients with anti-citrullinated protein antibodies (ACPA). Here, we investigated whether antibodies against thePgvirulence factor arginine gingipain (Rgp) are associated with the RA-risk phase and development of arthritis.

Methods

At-risk individuals were included in a prospective study (Risk-RA) based on a positive anti-cyclic citrullinated peptide 2 (CCP2) antibody test, and having musculoskeletal complaints but no signs of arthritis. Study participants were followed for ≥3 years (arthritis-free, n=165) or until arthritis onset (progressors, n=95). Anti-Rgp IgG was measured in Risk-RA (260 baseline and 247 follow-up samples) and healthy controls (n=126); anti-CCP2 IgG was measured in Risk-RA (254 baseline samples). Data were analysed in GraphPad Prism and R using log-transformed antibody levels.

Results

53% of Risk-RA and 26% of controls, p=0.003, were anti-Rgp IgG positive at baseline, with higher levels in Risk-RA compared with controls, p<0.0001. No changes in anti-Rgp IgG levels were observed during follow-up. The anti-Rgp IgG response at baseline did not associate with the development of arthritis; Cox-regression showed an HR of 0.95 (CI 0.80 to 1.13, p=0.6) for anti-Rgp IgG levels, and 0.82 (CI 0.55 to 1.23, p=0.3) for anti-Rgp IgG positivity.

Conclusions

Antibodies against the oral bacteriumPgare elevated during the RA-risk phase, both in individuals progressing to arthritis and in individuals remaining arthritis-free. Hence,Pginfection can be linked to the presence of RA-specific autoimmunity, ACPA, and musculoskeletal symptoms, but not to further development of arthritis in this at-risk population.
Combining hybrid and opaque scintillator techniques in the search for double beta plus decays
Authors: Böhlers Manuel , Böser Sebastian , Eisenhuth Magdalena , Girard-Carillo Cloé , Curiel Kitzia M. Hernandez , Keßler Bastian , Mossel Kyra , Palušová Veronika , Schoppmann Stefan , Weber Alfons , Wurm Michael
Published: January 2025

Double beta plus decay is a rare nuclear disintegration process. Difficulties in its measurement arise from suppressed decay probabilities, experimentally challenging decay signatures and low natural abundances of suitable candidate nuclei. In this article, we propose a new detector concept to overcome these challenges. It is based on the first-time combination of hybrid and opaque scintillation detector technology paired with novel light read-out techniques. This approach is particularly suitable for detecting positrons (beta plus) signatures. We expect to discover two-neutrino double beta plus decay modes within 1 tonne-week exposure and are able to probe neutrinoless double beta plus decays at several orders of magnitude improved significance compared to current experimental limits.
Country-Level Loss Aversion and the Market Response to Earnings News
Authors: Neel Michael
Published: January 2025

Synopsis

The research problem

This study examined whether country-level loss aversion influences how investors respond to earnings news. Specifically, I examined the stock price sensitivity to negative earnings news vis-à-vis positive earnings news.

Motivation

Investor expectations about the amount, timing, and uncertainty of future cash flows largely determine a firm’s stock price. An earnings announcement’s primary role is to update expectations, which in turn leads to an update in firms’ stock prices. Historically, researchers have assumed an efficient and unbiased valuation process. However, the last quarter century has seen advances in areas such as behavioral finance that raise the question of under which conditions these assumptions no longer hold. This study investigated the role of investor loss aversion in the market response to negative and positive earnings news.

The test hypotheses

The first hypothesis is that country-level loss aversion is positively associated with the market response to negative earnings news. Second, country-level loss aversion is negatively associated with the market response to positive earnings news. Third, these associations are moderated by a country’s degree of short-term orientation, restraint vs. indulgence, power distance, and rule of law.

Target population

The target population includes all available publicly traded companies.

Adopted methodology

I used OLS on a pooled sample of archival data.

Analyses

I examined 266,630 annual earnings announcements across 45 countries from 1988 to 2021. I identified country-level loss aversion with two recently developed measures and ascertained investors’ sensitivity to earnings news using earnings response coefficients (ERCs) at both the pooled and country level. ERCs highlight how short-window stock returns covary with earnings news.

Findings

The results indicated that investors are more sensitive to bad earnings news in more loss-averse countries. In contrast, investor sensitivity to good earnings news is generally unassociated with loss aversion. Further analysis indicated that a subsequent return drift to extreme bad news is present among low-loss-aversion countries but not high-loss-aversion countries, suggesting that loss-averse investors more fully incorporate bad earnings news into stock prices. In contrast, the return drift to extreme positive news is detectable regardless of the level of loss aversion. The influence of loss aversion is more pronounced in countries with a short-term orientation and in countries characterized as more restrained.
About this title - Engineering Geology of Groundwater in Design and Construction: Engineering Group Working Party Report
Authors: Duncan I. J. , Lawrence U. L.
Published: January 2025

This publication provides a state-of-the-art review for managing the risks associated with groundwater during design and construction. The book embraces practical applications to address groundwater problems drawn from the world-wide experience of subject matter experts. Groundwater concepts, hazards and risks and mitigation strategies for surface and subsurface engineering applications are given, with comprehensive case studies.
10. Managing Groundwater in the Engineering Design & Construction of Surface Works
Authors: Blower Tim
Published: January 2025

Examples of problems caused by groundwater, and methods of groundwater control are discussed in other chapters of this book. This Chapter deals with how the risks associated with potential groundwater problems may be managed in practice, in certain engineering situations relating to surface works.

For surface works, the problems caused by groundwater can be overcome in a variety of ways. Dealing directly with the groundwater itself (‘groundwater control’) is often an efficient way of addressing the problem and is, in many cases, essential.

However, this is not always the case. For some structures, modifications to the permanent works can avoid the need for a groundwater control solution that involves groundwater pumping, monitoring or maintenance in perpetuity.

Some design guidance documents require designers to assume that groundwater is at ground level unless there is better information. In this case, the optimal solution may include investment in a more comprehensive investigation to obtain the necessary data to challenge this onerous assumption.

In considering the management of groundwater, it is also important to manage surface waters, as these can quickly become sources of groundwater, affecting the groundwater regime.
Similarity Metrics: Chebyshev Coulomb Force and Resultant Force for High Dimensional Data
Authors: Liu Jianying , Zhang Chaowei , Zhang Min , Qin Xiao , Zhang Jifu
Published: January 2025

The similarity metric has garnered widespread attention thanks to its potential applications in the fields of data mining, machine learning, etc. Due to the interference of “distance concentration” caused by “Curse of dimensionality”, however, existing similarity metrics are inadequate in high-dimensional data analysis. In this study, we propose two innovative similarity metrics – Chebyshev Coulomb force and Chebyshev Coulomb resultant force – anchored on Chebyshev p-norms. In the initial phase, we eliminate dependency relationships among attributes by applying a metric matrix – and the theoretical analysis reveals that the Chebyshev p-norms is capable of mitigating the effect of “distance concentration” among high-dimensional data objects. Next, we devise two similarity metrics – Chebyshev Coulomb force and Chebyshev Coulomb resultant force – by adopting the metric matrix and Chebyshev p-norms. Chebyshev Coulomb force and Chebyshev Coulomb resultant force, being effective in characterizing the similarity among data objects, quantify the deviation of data objects from their respective dataset centers. Additionally, the two metrics alleviate the interference of “distance concentration”. Importantly, the discrepancy of data objects in attribute dimensions is captured by Chebyshev Coulomb force vector, rendering the similarity metric interpretable. By utilizing the UCI dataset, the experimental validation demonstrates the superiority of our similarity metrics, confirming their efficacy in mitigating the interference of “distance concentration”. Compared with the existing similarity metric approaches, the AUC index of outlier detection shows an average improvement of 8.18% – and the ARI, NMI and F_score indices of clustering are revamped by averages 6.56%, 6.87% and 6.01%, respectively.
Combining Structured Exercise with Interrupting Sitting Elicits Superior Cardiovascular Benefits Than Either Strategy Alone
Authors: Chang Courtney R. , Sabag Angelo , Francois Monique E.
Published: January 2025

Objective: This study aimed to determine whether interrupting prolonged sitting with brief bouts of light-intensity activity (ISIT), undertaking structured high-intensity interval training (HIIT), or the combination of both interventions would elicit greater cardiometabolic benefits.

Methods: Seventeen healthy adults (22-50 years) were recruited to undertake three 2-week interventions in a random order: i) HIIT (6 HIIT sessions + <5000 steps following the session and on the next day), ii) ISIT (2.5 min light-intensity walking every hour for 12 h/day on weekdays), and iii) HIIT+ISIT. Participants underwent a 6-day lead-in phase prior to each condition (day 1-3: normal activity, day 4-6 sedentary: <5000 steps/day). Pre and post assessments included glycemic control (primary outcome 2-h postprandial glucose), endothelial function via flow-mediated dilation (FMD), cardiorespiratory fitness and body composition. Changes in primary and secondary outcomes were assessed via repeated measures ANOVA.

Results: Eleven participants completed all conditions (8 Female, 33±5 years, 23±4 kg/m2, habitual activity 7,156±2,272 steps/day). FMD significantly improved following HIIT+ISIT when compared to ISIT (+1.04±1.20%, p=0.02), but there were no differences when ISIT was directly compared to HIIT. Cardiorespiratory fitness improved significantly following HIIT+ISIT when compared to ISIT (+1.88±2.03 mL/kg/min, p=0.01) but there were no differences when ISIT alone was compared to HIIT. There were no significant differences between groups for outcomes related to glucose control or body composition.

Conclusion: HIIT+ISIT elicits greater improvements in cardiovascular outcomes when compared to ISIT but not HIIT. The benefits of structured exercise, such as HIIT, may go beyond those achieved by limiting sedentary behavior alone.
A 3D Self-Assembly Platform Integrating Decellularized Matrix Recapitulates In Vivo Tumor Phenotypes and Heterogeneity
Authors: Buckenmeyer Michael J. , Brooks Elizabeth A. , Taylor Madison S. , Orenuga Ireolu K. , Yang Liping , Holewinski Ronald J. , Meyer Thomas J. , Galloux Melissa , Garmendia-Cedillos Marcial , Pohida Thomas J. , Andresson Thorkell , St. Croix Brad , Wolf Matthew T.
Published: January 2025

Three-dimensional (3D) in vitro cell culture models are invaluable tools for investigating the tumor microenvironment (TME). However, analyzing the impact of critical stromal elements, such as extracellular matrix (ECM), remains a challenge. Here, we developed a hydrogel-free self-assembly platform to establish ECM-rich 3D “MatriSpheres” to deconvolute cancer cell-ECM interactions. Mouse and human colorectal cancer (CRC) MatriSpheres actively incorporated microgram quantities of decellularized small intestine submucosa ECM, which proteomically-mimicked CRC tumor ECM compared to traditional formulations like Matrigel. Solubilized ECM, at sub-gelation concentrations, was organized by CRC cells into intercellular stroma-like regions within 5 days, displaying morphological similarity to CRC clinical pathology. MatriSpheres featured ECM-dependent transcriptional and cytokine profiles associated with malignancy, lipid metabolism, and immunoregulation. Model benchmarking with scRNA sequencing demonstrated that MatriSpheres enhanced correlation with in vivo tumor cells over traditional ECM-poor spheroids. This facile approach enables tumor-specific tissue morphogenesis, promoting cell-ECM communication to improve fidelity for disease modeling applications.
Figure 5 from Targeting Pancreatic Cancer Cell Stemness by Blocking Fibronectin-Binding Integrins on Cancer-Associated Fibroblasts
Authors: Wu Chengsheng , Von Schalscha Tami , Sansanwal Diva , Qian Chen , Jiang Qinlin , Shepard Ryan M. , Wettersten Hiromi I. , McCormack Stephen J. , Weis Sara M. , Cheresh David A.
Published: January 2025

Disrupting FN-binding integrins prevents the ability of CAFs to enhance tumor initiation. A, CAFs enhance tumor initiation via FN and FN-binding integrins (subcutaneous xenograft model). PANC1 human PDAC cells were injected subcutaneously (with or without CAF-1299) into the flank areas of nu/nu mice. Mice were monitored twice weekly to detect the earliest emergence of palpable tumors. The graph shows tumor take rate vs. time for 10–12 mice per group, using a volume of 100 mm3 (computed as length × width2) as the threshold for tumor take. At the endpoint of the experiment (day 56), tumors were harvested and prepared for histologic analysis. B, BsAb treatment reduces tumor stroma and increases necrosis. Tumor sections were stained using hematoxylin and eosin. Areas of stroma (S) and necrosis (N) are noted. C, BsAb treatment reduces tumor stiffness. Cryosections of tumors were analyzed using atomic force microscopy to evaluate tissue stiffness. Dots depict the mean value for each 20 × 20 μm region of interest (ROI). Fifteen ROIs were evaluated per tumor, for two tumors per group.
Figure 2 from Targeting Pancreatic Cancer Cell Stemness by Blocking Fibronectin-Binding Integrins on Cancer-Associated Fibroblasts
Authors: Wu Chengsheng , Von Schalscha Tami , Sansanwal Diva , Qian Chen , Jiang Qinlin , Shepard Ryan M. , Wettersten Hiromi I. , McCormack Stephen J. , Weis Sara M. , Cheresh David A.
Published: January 2025

FN-binding integrins mediate ECM production. Knockdown of FN or FN-binding integrins in CAFs prevents the formation of FN and COL fibers. CAF-1299 cells were treated with siRNA for a scramble control vs. FN, ITGA5, or ITGB3. After 72 hours, IF staining shows FN and COL content. The top set of images were not permeabilized. Images are representative of at least three independent experiments. Blots confirm knockdown. si-CTRL, CAFs with siRNA for a Universal Negative Control; si-FN, CAFs with siRNA-mediated knockdown of FN1; si-α5, CAFs with ITGA5 knockdown; si-β3, CAFs with ITGB3 knockdown.
An ACTH-Producing Neuroendocrine Tumor: Clinical Course of Multidisciplinary Therapy Including Peptide Receptor Radionuclide Therapy – A Case Report
Authors: Koizumi Tomonobu , Sato Ai , Kitajima Kohei , Yamazaki Masanori , Kanazawa Sana , Notake Tsuyoshi , Sato Yoshinori , Kobayashi Shota , Iwaya Mai , Umeda Takako , Komatsu Mitsuhisa
Published: January 2025

Introduction: Clinical experiences of peptide receptor radionuclide therapy (PRRT) in patients with adrenocorticotropic hormone (ACTH) producing neuroendocrine tumor (NET) were extremely rare. Case Presentation: A 60-year-old woman with hypertension, lower-extremity edema, hypoalbuminemia, hypokalemia, and multiple hepatic tumors was hospitalized for further examination and treatment. Endocrine testing detected excessive levels of ACTH and cortisol in her blood. Pathohistological examination revealed the hepatic lesions to be ACTH-positive grade 2 NETs (G2). A diagnosis of ectopic ACTH-producing NET was made. The patient was initially treated with the 11-hydroxylase inhibitor, metyrapone, to control hypercortisolemia and the long-acting somatostatin analog, lanreotide. Simultaneously, everolimus was continued for about 1 year. Subsequently, hepatic tumors were surgically resected, leading to successful and rapid normalization of ACTH secretion and resolution of hypercortisolemia. However, the disease relapsed and presented with multiple hepatic masses and increased ACTH 18 months after surgery. As sunitinib and subsequent streptozocin chemotherapy failed to control the disease, PRRT with 177Lu-DOTATATE was performed. ACTH levels increased after initiation of PRRT, and clinical manifestations, such as pigmentation, hypertension, and hyperglycemia, were remarkable. The patient was treated with antihypertensive and antidiabetic agents, and required an increased dose of metyrapone and addition of the cortisol biosynthesis inhibitor, osilodrostat. After four cycles of PRRT, the hepatic tumors showed a remarkable reduction in size with normalization of ACTH level and withdrawal of cortisol synthesis inhibitors. Conclusion: Although PRRT was effective, we should consider the occurrence of hormonal crisis during the therapy. Due to the rarity and complexity of hormone-producing tumors, cooperation between medical oncologists and endocrinologists is important for patient management.
A real-world pharmacovigilance analysis for Demethylation drug: findings from the FDA adverse event reporting database
Authors: Chen Shupeng , Liu Jie , Gao Yao , Tang Nana , Zeng Yingjian
Published: January 2025

Introduction:
The real-world safety profiles of the demethylating agents Azacitidine and Decitabine remain inadequately characterized despite their widespread clinical use. Both drugs are extensively employed for the treatment of hematologic malignancies such as myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). This study aims to evaluate their adverse event (AE) profiles by leveraging data from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database.
Methods: All adverse drug event (ADE) data related to Azacitidine and Decitabine were collected from the FAERS database from its inception through the second quarter of 2024 (Q2). After standardizing the data, four disproportionality methods were applied to evaluate the association between Azacitidine, Decitabine, and ADEs. The Weibull shape parameter (WSP) was used to analyze the time-to-onset curves.
Results: Among the 15,538 ADEs where Azacitidine was the primary suspect drug, a total of 439 preferred terms (PTs) and two system organ classes (SOCs) showed significant disproportionality across all four algorithms. These SOCs included INFECTIONS AND INFESTATIONS (n=7328, ROR 3.78) and BLOOD AND LYMPHATIC SYSTEM DISORDERS (n=5613, ROR 8.92). Compared with the Azacitidine label, 52 previously unreported ADEs were identified at the PT level. Among the 3,064 ADEs where Decitabine was the primary suspect drug, a total of 200 PTs and two SOCs exhibited significant disproportionality across all four algorithms. These SOCs included BLOOD AND LYMPHATIC SYSTEM DISORDERS (n=1284, ROR 6.53) and SURGICAL AND MEDICAL PROCEDURES (n=571, ROR 3.41). Compared with the Decitabine label, 29 previously unreported ADEs were identified at the PT level. Furthermore, the Bayesian Confidence Propagation Neural Network (BCPNN) algorithm revealed that the highest IC025 values for both Azacitidine and Decitabine were concentrated in SOCs related to benign, malignant, and unspecified tumors.
Conclusion: In summary, using the FAERS database, we compared the real-world safety profiles of two demethylating agents, Azacitidine and Decitabine. The results indicate that adverse drug reactions (ADRs) related to these two agents are concentrated in the hematologic, respiratory, circulatory, and digestive systems, as well as in neoplasms of unspecified nature, warranting close clinical attention.
Impact of Personnel Scarcity on Urolithiasis Treatment: A Comparative Study of the Pre- and Post-Pandemic Eras
Authors: Yurdakul Ozan , Seitz Christian , Tuncel Altug , Veser Julian , Hassler Melanie , Shariat Shahrokh , Remzi Mesut
Published: January 2025

Introduction: This research investigates the influence of the medical personnel shortage on the treatment of urolithiasis by comparing the complication rates in patients with urinary stones who undergo ureterorenoscopy with laser lithotripsy before and after the emergence of this unprecedented situation.
Methods: One hundred sixty patients undergoing ureterorenoscopy with laser lithotripsy for urolithiasis were retrospectively evaluated, segmented into pre- and post-pandemic cohorts. Complications that occurred preoperatively (during the waiting period for operation), intraoperatively, and postoperatively were documented to compare the complication rates between the two cohorts.
Results: The investigation demonstrated a significant elevation of complications during the preoperative waiting period in the post-pandemic cohort (p < .001), concurrent with a substantial increase in the median waiting time from 20 days to 94 days (p < .001). No significant differences were present in intra- and postoperative complications between the two cohorts.
Conclusion: In the new era of personnel shortage, increased complication rates during the preoperative waiting time were observed, concomitant with a significant increase in the waiting times for surgery. This novel challenge of increased preoperative morbidity also led to additional resource consumption. It is imperative to adapt the therapeutic landscape of urolithiasis to the new circumstances.
Phyllodes tumor of the breast – histomorphological transformation to high-grade tumor during pregnancy and challenging oncoplastic surgery
Authors: Preuss Caroline Ines , Schrenk Peter , Affortunati Marco , Brandstetter Nina , Schuster Stefanie , Schwarz Heike Kathleen , Schneeweiss Bruno , Gitter Thomas , Oppelt Peter , Shamiyeh Andreas , Langer Rupert , Moinfar Farid , Grosse Claudia , Steinmair Maria
Published: January 2025

Introduction:
Phyllodes tumors of the breast are a very rare tumor entity. There are two different classifications according to AFIP (low-grade and high-grade phyllodes tumors of the breast) and WHO (three subtypes: benign, borderline and malignant phyllodes tumors). Phyllodes tumors have an increased risk of recurrence.
Primary clinical treatment of phyllodes tumors is surgery, although the width of the required resection margins often presents a challenge for surgical management.
Case Presentation:
This case report deals with a 24-year-old woman with second recurrence of borderline phyllodes tumor.
The challenge of this case lays firstly in surgical removal of the large tumor by breast-conserving therapy with tumor-free margins and favorable aesthetic outcome. Achieving this goal by tumor-adapted reduction mammoplasty, skin excision and slide-swing skin flap was challenging. The second exciting aspect of this case is the histomorphology of the tumor and the transformation in vivo from fibroadenoma with stromal atypia in 2021 to the first recurrence with a low-grade phyllodes tumor in 2022 and the further transformation to a high-grade tumor with stromal overgrowth in the second recurrence of phyllodes tumor in 2023 during pregnancy and childbed.
Conclusion:
This case of a phyllodes tumor shows how quickly tumor characteristics can change in fast-growing tumors due to transformation from low-grade to high-grade tumor. The influence of pregnancy on this process remains unclear at present. Surgical removal of phyllodes tumors should be performed during pregnancy.
The hypothalamus and pituitary gland regulate reproduction and are involved in the development of polycystic ovary syndrome
Authors: Long Bin-Yang , Liao Xipeng , Liang Xin
Published: January 2025

Background
Polycystic ovary syndrome is a complex condition with unclear mechanisms, posing a challenge for prevention and treatment of PCOS. The role of the hypothalamus and pituitary gland in regulating female reproduction is critical. Abnormalities in the hypothalamus and pituitary can impair reproductive function. It is important to study hypothalamic and pituitary changes in patients with polycystic ovary syndrome.
Summary
This article reviews articles on the hypothalamus and polycystic ovary syndrome with the goal of summarizing what abnormalities of the hypothalamic-pituitary-ovarian axis are present in patients with polycystic ovary syndrome and to clarify the pathogenesis of polycystic ovary syndrome. We find that the mechanisms by which the hypothalamus and pituitary regulate reproduction in girls are complex and are associated with altered sex hormone levels, obesity and insulin resistance. Different animal models of polycystic ovary syndrome are characterized by different alterations in the hypothalamus and pituitary, and respond differently to different treatments, which correspond to the complex pathogenesis of patients with polycystic ovary syndrome.
Key Messages
ARC is associated with luteinizing hormone (LH) surges
SCN, ARC and RP3V are associated with LH surges
Animal models of PCOS have different characteristics
Sobre as espécies neotropicais de Neosphaerocera Kim, 1972 (Diptera, Sphaeroceridae)
Authors: Mourgués-Schurter Lea R.
Published: January 2025

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Redescription of Cis olivieri Mellié, 1849 (Coleoptera: Ciidae), with a new synonym and the first records from Brazil
Authors: Souza-Gonçalves Igor , Lopes-Andrade Cristiano , Sandoval-Gómez Vivian Eliana , Grossi Paschoal Coelho
Published: January 2025

Cis olivieri Mellié, 1849 is redescribed based on specimens from the type series and additional material from the Northeast and Southeast Regions of Brazil. Cis lemoulti Pic, 1923 is proposed as a junior synonym of Cis olivieri, and lectotypes are designated for both names. This study represents the first report of Cis olivieri in Brazil. Images of male and female terminalia, along with a distribution map, are provided.
O dilema paraguaio: entre a reexportação e o Mercosul
Authors: Peruffo Luiza , Santos Kevin Wanderlan Fernandes dos
Published: January 2025

O Paraguai possui um desenvolvimento econômico único em relação aos seus parceiros do Mercosul. Enquanto a maioria dos membros do bloco adotaram o modelo de substituição de importação para fomentar a indústria, o Paraguai optou pelo que é chamado de “regime de reexportação”, ou triangulação comercial, que se firmou como um dos pilares de sua economia na segunda metade do século XX. Essa política faz uso da discrepância alfandegária entre os países para efetivamente tornar o Paraguai um “reexportador” de produtos vindos de fora do continente. Ao se beneficiar das assimetrias regionais, o modelo vai de encontro com os ideais de cooperação esperados por um mercado comum, como o Mercosul busca tornar-se. Também torna o Paraguai um caso atípico entre pequenas economias: apesar de ser o integrante do Mercosul mais dependente do comércio com seus vizinhos, é historicamente o mais receoso em promover e adotar as medidas de integração propostas pelo resto do bloco. Esse trabalho se propõe a explorar a origem e escopo do regime de reexportação, sua perspectiva atual, e se o dilema historicamente enfrentado pelo Paraguai se mantém válido com a crescente diversificação econômica do país.
Desenvolvimento sustentável e constitucionalismo decolonial: a valorização do trabalho da natureza como fundamento da ordem econômica
Authors: Jobim Marcelo Barros
Published: January 2025

O presente artigo visa identificar um novo fundamento, ainda que implícito, no artigo 170 da Constituição brasileira de 1988, referente aos fundamentos constitucionais da Ordem Econômica. Argumenta-se que se a valorização do trabalho humano, ao lado do fundamento na livre iniciativa, tem seu princípio correspondente no ideal de busca do pleno emprego (inciso VIII), deve o ideal de defesa do meio ambiente, enquanto princípio previsto no inciso VI, também ter o seu fundamento correspondente previsto no caput. A partir do pensamento decolonial, como método de análise voltado para a própria sistemática jurídica, sustenta-se que tal reconhecimento faria o Brasil acompanhar a evolução de outros Países da América Latina no sentido de um constitucionalismo que contemple a Natureza como sujeito de direito, a exemplo de países como Equador e Bolívia. Assim, sob a perspectiva do Constitucionalismo decolonial, aprimora-se o conceito de desenvolvimento sustentável para incluir a ideia de valorização do trabalho da Natureza.