bluuebunny/crossref_metadata_2025 huggingface dataset:
Circulating growth differentiation factor‐15 levels are associated with early echocardiographic signs of diastolic function impairment in the STANISLAS cohort: A 20‐year follow‐up study
Authors: Monzo Luca , Xhaard Constance , Ferreira João Pedro , Baudry Guillaume , Lamiral Zohra , Duarte Kevin , Bozec Erwan , Boivin Jean‐Marc , Huttin Olivier , Rossignol Patrick , Zannad Faiez , Girerd Nicolas
Published: January 2025

Aims

Early identification of healthy subjects prone to develop cardiac dysfunction may be instrumental to prevention strategies. Our study aimed to evaluate whether circulating levels of growth differentiation factor‐15 (GDF‐15) could predict adverse changes in echocardiographic indexes of cardiac structure and function in an initially healthy populational familial cohort with a long follow‐up (STANISLAS cohort).

Methods and results

We evaluated 1679 participants (49 ± 14 years, 48% males) included in the fourth visit (V4) of the STANISLAS cohort with available GDF‐15 measurements (Olink proteomic analysis) and echocardiographic parameters. Among them, 1562 had also GDF‐15 measurements at the first visit (V1) (18.2 ± 1.4 years before V4). We evaluated both prospective (GDF‐15 at V1) and cross‐sectional (GDF‐15 at V4) associations between GDF‐15 levels and echocardiographic variables. In adjusted analyses, higher baseline GDF‐15 levels were associated with lower left ventricular (LV) end‐diastolic volume and higher E/e' ratio nearly two decades later (both p ≤ 0.01). The cross‐sectional analysis at V4 also found significant associations between GDF‐15 and LV end‐diastolic volume and higher E/e' ratio, further identifying significant associations with impaired LV strain.

Conclusion

In the STANISLAS cohort, initial circulating GDF‐15 levels were associated with echocardiographic signs of reduced LV size and increased filling pressure almost two decades later. This association was also confirmed by evaluating GDF‐15 at the follow‐up visit (V4). These findings suggest a potential role for GDF‐15 as an easy screening and prognostic tool of diastolic dysfunction in the general population.
Review, part 3: Lifting the Veil on Enrollment Management
Authors: Dennis Marguerite J.
Published: January 2025

In the previous two articles, I critiqued the negative impact of specific enrollment management practices during the past 40 years and outlined several recommendations made in the book Lifting the Veil to improve how students are recruited and how they finance their education.
Aerodynamic Phenomena of Controlling Passive Flow of a Time‐Independent Ground Vehicle Under the Scope of Optimally Slanted Rear Wing‐Spoiler Combination
Authors: Abid Abyaz
Published: January 2025

Notwithstanding the abundance of different expository efforts by the engineers and scientists of the aerodynamic—transonic domain for the ever‐beseeched question of whether a supercar needs a rear spoiler or a rear wing, the query requires further exploration to come to any satisfactory conclusion. This state‐of‐the‐art bottleneck area is considered as the prime motivation of the paper as it seeks to investigate the aerodynamic phenomena of a notchback type supercar configuration with two different series of modifications—one with a rear spoiler attachment and the other one with a rear wing attached. A simplified Nissan Skyline GT34R CAD model is taken as the base ground vehicle for the computational study while the slant angles of both the rear wing and rear spoiler are changed within the range of 10° to 45°. RANS based k‐omega SST turbulence model is used to find the optimal slant angles for the corresponding rear wing and spoiler in terms of drag and lift coefficients, drag and lift force and rolling moment. The modified models with optimally slanted rear wing and rear spoiler along with the base configuration are inspected under different visualization techniques for understanding the aerodynamic phenomena. Contour and vector plots reveal that rear wing attached model has the maximum pressure drop along and over its body showing a sharp increase of 13.7% when compared with the rear spoiler attached model. Aftereffects show that both the turbulent intensity and Y+ wall shear stress is found to be most economical for the rear spoiler attached model, approximately 1.52% and 0.98% less than the base notchback model. Considering, overall aerodynamic performance of all the three proposed notchback type supercar configurations—the one with a rear spoiler attachment is found to be the most equipped one to integrate into future research.
Unlocking the Power of Gene Banks: Diversity in Base Growth Temperature Provides Opportunities for Climate‐Smart Agriculture
Authors: Gambart Clara , Van Wesemael Jelle , Swennen Rony , Tardieu François , Carpentier Sebastien
Published: January 2025

Implementation of context‐specific solutions, including cultivation of varieties adapted to current and future climatic conditions, have been found to be effective in establishing resilient, climate‐smart agricultural systems. Gene banks play a pivotal role in this. However, a large fraction of the collections remains neither genotyped nor phenotyped. Hypothesizing that significant genotypic diversity in Musa temperature responses exists, this study aimed to assess the diversity in the world's largest banana gene bank in terms of base temperature (Tbase) and to evaluate its impact on plant performance in the East African highlands during a projected climate scenario. One hundred and sixteen gene bank accessions were evaluated in the BananaTainer, a tailor‐made high throughput phenotyping installation. Plant growth was quantified in response to temperature and genotype‐specific Tbase were modelled. Growth responses of two genotypes were validated under greenhouse conditions, and gas exchange capacity measurements were made. The model confirmed genotype‐specific Tbase, with 30% of the accessions showing a Tbase below the reference of 14°C. The Mutika/Lujugira subgroup, endemic to the East African highlands, appeared to display a low Tbase, although within subgroup diversity was revealed. Greenhouse validation further showed low temperature sensitivity/tolerance to be related to the photosynthetic capacity. This study, therefore, significantly advances the debate of within species diversity in temperature growth responses, while at the same time unlocking the power of gene banks. Moreover, with this case study on banana, we provide a high throughput method to reveal the existing genotypic diversity in temperature responses, paving the way for future research to establish climate‐smart varieties.
Design and Development of a Web‐Based Registry for Outpatient Rehabilitation: A Delphi Multi‐Disciplinary, Expert Consensus Study
Authors: Mousavi Baigi Seyyedeh Fatemeh , Sarbaz Masoumeh , Sobhani‐Rad Davood , Nazary‐Moghadam Salman , Heravian Shandiz Javad , Ghaddaripouri Kosar , Norouzi Aval Reyhane , Kimiafar Khalil
Published: January 2025

Background and Aims

The goal of this research was to create a minimum data set (MDS) and design a web‐based registry for outpatient rehabilitation, focusing on four disciplines: speech therapy, audiology, optometry, and physical therapy. The registry was intended to enhance assessment, guide optimal care, and provide value‐based and evidence‐based rehabilitation management for patients.

Methods

This cross‐sectional study utilized the Delphi technique at Mashhad University of Medical Sciences in northeastern Iran from 2022 to 2023. First, the PubMed, Scopus, Embase, and Web of Science databases were searched in an untimed systematic review. Additional information was gathered from websites and forms related to rehabilitation systems. Coding guidelines were derived from the International Classification of Functioning, Disability, and Health. A questionnaire containing data elements of outpatient rehabilitation was developed based on the systematic reviews. The data items were validated in two stages using the Delphi approach. Subsequently, an MDS and a web‐based registry were designed for outpatient rehabilitation.

Results

The study included 25 eligible articles, 6 websites, and 24 forms to establish the rehabilitation MDS. A total of 470 information elements were extracted from the systematic review and rehabilitation registries. Through two rounds of the Delphi technique, 423 data elements were refined. The MDS was categorized into basic information and specialized information. Basic information comprised 12 subcategories of demographic details, socioeconomic information, referral information, service provider information, follow‐up information, death information, history, past medical history, environmental factors, treatment measures, rehabilitation measures, and assessment of body systems; specialized information included four subcategories of optometry information, audiology information, physiotherapy information, and speech therapy information. Following the finalization of the MDS, a web‐based registry for outpatient rehabilitation was created.

Conclusion

This work offers a combined MDS that reflects the priorities and viewpoints of multidisciplinary experts for an outpatient rehabilitation registry that aids in clinical decision‐making.
Aggressive characteristics of tumor deposits in colorectal cancer highlight the need for staging refinement in patients with 0–3 metastatic lymph nodes
Authors: Hu Xi'e , Xie Shuang , Yang Zhenyu , Zhao Xin , Gong Li , Yang Ping , Yang Lin , Wang Shoujia , Bao Guoqiang , He Xianli
Published: January 2025

Accurate staging is essential for the optimal management of patients with colorectal cancer (CRC). The role of tumor deposits (TDs) in CRC staging has been contentious due to a lack of comprehensive understanding of their clinical and biological traits. In this retrospective study, we analyzed large data from 5718 CRC patients diagnosed between 2011 and 2022, ensuring rigorous data collection and long‐term follow‐up. Patients with positive TDs displayed aggressive clinical features. The risk factors for TDs varied among patients with different backgrounds of lymph node (LN) involvement, and the numbers of TDs and metastatic LNs showed a significantly positive correlation. TDs significantly impacted CRC prognosis, resulting in unfavorable outcomes irrespective of LN status. To delve into the biological characteristics of TDs, we performed transcriptome sequencing, immunohistochemistry, and Kaplan–Meier analyses on tissue samples from the additional CRC cohort and The Cancer Genome Atlas datasets. TDs exhibited aggressive biological phenotypes that were distinct from primary tumors and metastatic LNs, characterized by elevated signatures of epithelial‐mesenchymal transition, angiogenesis, and immune suppression. Cox proportional hazards analysis was then applied to reassess the appropriate role of TDs within the TNM staging system, revealing that the prognostic weightiness of TDs in CRC corresponded to N2a rather than N1 in patients with 0–3 LN metastases. Overall, our comprehensive analysis showed that TDs, with their aggressive clinical and biological characteristics, could optimize the staging of CRC, highlighting the need to refine their role within the TNM staging system.
3D‐printed patient‐specific instrumentation and the freehand technique in high‐tibial osteotomy: A prospective cohort‐comparative study in an outpatient setting
Authors: Grillo Giovanni , Coelho Alexandre , Pelfort Xavier , Fillat‐Gomà Ferran , Figuerola Arnau Verdaguer , Gil‐Gonzalez Sergi , Peñalver Juan Manuel , Yela‐Verdú Christian
Published: January 2025

Purpose

Tibial valgus osteotomy has shown to be a successful and cost‐effective procedure. The advent of image processing and three‐dimensional (3D) printing is an interesting tool for achieving more accurate and reproducible results. The aim of our study was to compare the accuracy of the conventional technique and the use of customized guides in the correction of tibial deformities in tibial varus patients, the surgical and clinical benefits, and the impact of treatment in the outpatient setting.

Methods

A prospective cohort of 30 patients who underwent tibial valgus osteotomy were selected and randomized into two groups (3D‐printed guidewires and conventional techniques). All patients underwent a complete radiological study to plan the surgical procedure. During the surgical procedure, the surgical time and X‐ray exposure were analysed. The following results were evaluated: surgical time and X‐ray exposure, the correlation between the planned correction and the correction obtained at 3 post‐operative months, pre‐ and post‐operative knee injury and osteoarthritis outcome score (KOOS) value at 3 and 12 months, and differences between the two groups in terms of the correction obtained.

Results

Radiation exposure in the ‘3D‐guide’ group was significantly different (8 [±4.51], p < 0.05), whereas surgical time was not significantly different between the control and guide 3D groups (60.69 [±8.89] and 53.43 [±11.69], respectively). At the 3‐month follow‐up, the post‐operative hip–knee–ankle and post‐operative mechanical–proximal–tibial angle were not significantly different (p > 0.05). At 3‐ and 12‐month post‐surgery, the Knee Injury and Osteoarthritis Outcome Score (KOOS) did not significantly differ between the conventional technique and the 3D‐guide technique (p > 0.05). The KOOS at 3 months were 87.86 (±5.64) for the control group and 88.46 (±3.53) for the 3D‐guide group, while at 12 months they were 91.5 (±5.72) for the control group and 88.57 (±8.81) for the 3D‐guide group.

Conclusion

Customized 3D‐printed guides do not permit better correction or functional results than the conventional technique; rather, they reduce surgical time and intraoperative radiation exposure.

Level of Evidence

II.
A Qualitative Study of Attitudes Toward HPV Vaccine Recommendation in Otolaryngology Clinics
Authors: Janio Emily A. , Walker Cori , Steere Eliza , Seaman Aaron T. , Askelson Natoshia , Pagedar Nitin A.
Published: January 2025

Objective

The incidence of human papillomavirus (HPV)‐related oropharyngeal cancers has increased such that they are now the most prevalent HPV‐related cancer. In 2020, the Food and Drug Administration (FDA) expanded the indication for Gardasil‐9 to include the prevention of oropharyngeal and other head and neck cancers caused by selected HPV types, but uptake remains low. Otolaryngology office interactions may provide opportunities to increase uptake, given the relevance of HPV to clinical practice. This study explored the feasibility of recommending HPV vaccination in otolaryngology clinics.

Methods

Participants were recruited between February to June of 2022 from the alumni of the residency and fellowship training programs at the University of Iowa Hospitals and Clinics. Participant interviews comprised open‐ended questions pertaining to otolaryngologists' attitudes toward HPV vaccination recommendation. Interview recordings were transcribed, coded, and analyzed for themes.

Results

Participants were willing to respond if patients asked about the HPV vaccine, although a common attitude toward vaccine discussions was that they were a pediatrician's responsibility. One barrier to recommending HPV vaccination was providers' concern that discussing the vaccine when not directly relevant to the patient's chief complaint could result in patient frustration. Nevertheless, participants endorsed the feasibility of discussing the vaccine during follow‐up visits after the patient's needs had been addressed or via the distribution of educational materials to patients.

Conclusion

Otolaryngologists do not currently identify recommending HPV vaccine uptake as their clinical responsibility. While such recommendations may not be feasible in every patient encounter, there could be a role for this in the appropriate clinical scenario. These findings can be used to inform interventions aimed at recommending the vaccine in otolaryngology clinics.
Unleashing the Power of Covalent Drugs for Protein Degradation
Authors: Fu Meng‐Jie , Jin Hang , Wang Shao‐Peng , Shen Liang , Liu Hong‐Min , Liu Ying , Zheng Yi‐Chao , Dai Xing‐Jie
Published: January 2025

Targeted protein degradation (TPD) has emerged as a significant therapeutic approach for a variety of diseases, including cancer. Advances in TPD techniques, such as molecular glue (MG) and lysosome‐dependent strategies, have shown substantial progress since the inception of the first PROTAC in 2001. The PROTAC methodology represents the forefront of TPD technology, with ongoing evaluation in more than 20 clinical trials for the treatment of diverse medical conditions. Two prominent PROTACs, ARV‐471 and ARV‐110, are currently undergoing phase III and II clinical trials, respectively. Traditional PROTACs are encountering obstacles such as limited binding affinity and a restricted range of E3 ligase ligands for facilitating the protein of interest (POI) degradation. Covalent medicines offer the potential to enhance PROTAC efficacy by enabling the targeting of previously considered “undruggable” shallow binding sites. Strategic alterations allow PROTAC to establish covalent connections with particular target proteins, including Kirsten rat sarcoma viral oncogene homolog (KRAS), Bruton's tyrosine kinase (BTK), epidermal growth factor receptor (EGFR), as well as E3 ligases such as DDB1 and CUL4 associated factor 16 (DCAF16) and Kelch‐like ECH‐associated protein 1 (Keap1). The concept of covalent degradation has also been utilized in various new forms of degraders, including covalent molecule glue (MG), in‐cell click‐formed proteolysis targeting chimera (CLIPTAC), HaloPROTAC, lysosome‐targeting chimera (LYTAC) and GlueTAC. This review focuses on recent advancements in covalent degraders beyond covalent PROTACs and examines obstacles and future directions pertinent to this field.
Stability Analysis of Stochastic Benjamin–Bona–Mahony Equation With Poisson Jumps
Authors: Dhayal Rajesh
Published: January 2025

This paper develops a new class of stochastic Benjamin‐Bona‐Mahony equations with Poisson jumps, which is a third‐order nonlinear partial differential equation describing wave propagation. First, we established the existence of mild solutions for the considered problem under the non‐Lipschitz conditions. Moreover, we investigate the asymptotic behavior of mild solutions for the proposed system. The outcomes are formulated and proved using the successive approximation approach and Bihari inequality. Finally, an illustrative example is given to demonstrate the obtained results.
CESTsimu: An open‐source GUI for spectral and spatial CEST simulation
Authors: Zhang Huabin , Qiu Bensheng , Xu Jiadi , Chan Kannie WY , Huang Jianpan
Published: January 2025

Purpose

The aim of this study was to create a user‐friendly CEST simulation tool with a GUI for both spectral (1D Z‐spectra) and spatial (2D phantom) CEST experiments, making the CEST simulation easier to perform.

Methods

CESTsimu was developed using MATLAB App Designer. It consists of three modules: Saturation Settings, Exchange Settings, and Phantom Settings. CESTsimu can not only import/export files in the defined format but can also import files generated by other existing simulation platforms (e.g. pulseq‐CEST).

Results

The 1D Z‐spectrum simulation results demonstrated the effectiveness of CESTsimu in simulating Z‐spectra under various saturation ( and ) and exchange settings (concentration and exchange rate). The 2D simulation results showed that CESTsimu can generate an arbitrary number of phantoms with different shapes under different noise conditions. Notably, CESTsimu could also simulate and inhomogeneity in 2D patterns that mimicked practical conditions. Moreover, the accuracy of CESTsimu was validated by simulating 8 cases in the BMsim challenge.

Conclusion

We developed a user‐friendly CESTsimu GUI for intuitively simulating CEST experiments under diverse saturation and exchange settings in 1D and 2D conditions. CESTsimu has the potential to facilitate the broad utilization of CEST MRI among a wide range of users.
Connecting resonance theory with social‐ecological thinking: Conceptualizing self‐world relationships in the context of sustainability transformations
Authors: Brossette Florian , Bieling Claudia
Published: January 2025

Relationships and interactions between humans and their environment play an important role in sustainability transformations. However, their conceptualization remains a big challenge in current social‐ecological research. We propose resonance theory by the German sociologist Hartmut Rosa as a fruitful framework to advance social‐ecological thinking. Resonance theory investigates the quality of the relationships between self and world and scrutinizes their relevance for transformations.

To illustrate the potentials of resonance theory, we use a vignette approach to cases of landscape stewardship initiatives in the Black Forest Biosphere Reserve in Germany.

In distinguishing between self and world and highlighting the role of relationships, resonance theory brings ontological and epistemological clarity, while overcoming a strict dichotomy between social and ecological. We find that resonance theory provides a much needed framework to describe how system‐wide transformations emerge from interactions and out of relationships at the individual level.

We argue that resonance theory contributes to social‐ecological systems thinking by adding the notion of uncontrollability in transformations and shifting the debate on agency towards relationships.

Synthesis and applications: This paper demonstrates the meaningfulness of relational paradigms for real‐world transformations in theory and practice.

Read the free Plain Language Summary for this article on the Journal blog.
C‐Reactive Protein Changes in Adult and Pediatric People With Cystic Fibrosis During Treatment of Pulmonary Exacerbations
Authors: Zuckerman Jonathan B. , Hinton Alexandra C. , Lahiri Thomas , Teneback Charlotte C. , Jia Shijing , Mermis Joel , Polineni Deepika , Dasenbrook Elliott , Sadeghi Hossein , DiMango Emily , Dezube Rebecca , West Natalie E. , Zemanick Edith T. , Samya Z. Nasr , Gifford Alex H.
Published: January 2025

Objective

Although studies have examined changes in C‐reactive protein (CRP) during pulmonary exacerbations (PEX) in people with cystic fibrosis (PwCF), few have evaluated CRP profiles across age groups. Here, we characterize age‐related CRP responses to PEX treatment.

Methods

We measured CRP concentrations at the beginning and end of intravenous (IV) antibiotic therapy for PEX in 100 pediatric and 147 adult PwCF at 10 US CF Centers. We examined relationships between CRP and age, lung function, severity of PEX symptoms, and time to next PEX.

Results

CRP measured at initiation of IV antibiotic treatment for PEX was higher in adults than children, median 8 mg/L (IQR 4, 32) versus 5 mg/L (IQR 2, 10), respectively (p < 0.001). There was a significant correlation between the initial CRP and drop in lung from baseline to the beginning of IV antibiotics in adults and children. Adjusted CRP dropped in response to PEX treatment more commonly in adults than in children (70% vs. 48%, respectively). The range of treatment responses was greater in adults, in those with higher symptom scores, and in those with more advanced lung disease. In adults elevated CRP at the end of treatment was also associated with incomplete recovery of lung function. CRP at the start of IV antibiotics was inversely related to time until the next PEX.

Conclusion

In children and adults with CF, CRP is increased at the initiation of IV antibiotic therapy for PEX and declines with treatment. The response is more pronounced in highly symptomatic adults with advanced lung disease.
Featured Cover
Authors: Clarke Stewart J.
Published: January 2025

The cover image is based on the article Full floodplain connectivity: Realising opportunities for ‘Stage 0’ river restoration by Stewart Clarke et al., https://doi.org/10.1002/rra.4283.

image
Preclinical evaluation of 68Ga‐labeled peptides for targeting CD44 imaging
Authors: Pan Xiaoyu , Liu Yi , Liu Xuwei , Zhang Fengsheng , Bai Liyan , Xi Yue , Ji Mengjing , Xu Xiaoping , Liu Fei , Li Jindian , Song Shaoli
Published: January 2025

CD44 is a cell surface transmembrane glycoprotein that has recently been considered a cancer marker. Therefore, monitoring the expression of CD44 in tumors in vivo has great potential for guiding clinical treatment. In this study, a CD44‐targeted peptide labeled with 68Ga was constructed. Its ability to target tumors with high CD44 expression and its clinical applications were evaluated. Micro positron emission tomography/computed tomography (microPET/CT) was used to explore the imaging properties of the probes. The imaging effects of [68Ga]Ga‐DOTA‐A6 were compared with [18F]FDG via a head‐to‐head experiment. Results showed that [68Ga]Ga‐DOTA‐A6 remained stable both in vivo and in vitro for at least 120 min. Both in vivo and in vitro experiments confirmed that CD44 positive model exhibits specific uptake of [68Ga]Ga‐DOTA‐A6. microPET/CT revealed that [68Ga]Ga‐DOTA‐A6 had a high tumor‐to‐muscle ratio. Pharmacokinetic and biological distribution experiments confirmed that [68Ga]Ga‐DOTA‐A6 was characterized by rapid clarity and minimal harm to major organs. Immunohistochemistry confirmed the positive expression of CD44 in PC9, MDA‐MB‐468, and B16F10 tumors. Blood analysis and H&E staining of different organs from treated mice demonstrated biosafety of [68Ga]Ga‐DOTA‐A6. Results prove that this probe has excellent imaging properties and can be rapidly metabolized. [68Ga]Ga‐DOTA‐A6 may be useful for guiding clinical therapeutic strategies.
Allosteric probe‐driven catalytic CRISPR‐Cas12a and dual‐colored persistent luminescence nanoparticles tandem biosensing for ultrasensitive MRSA detection
Authors: Liu Shuai , Ding Zishan , Liu Zhiyong , Zhou Yang , Lu Xing , Shen Man , Dai Xianling , Xu Hanqing , Wang Jun , Bao Jing , Chen Ming
Published: January 2025

Methicillin‐resistant Staphylococcus aureus (MRSA) is a prevalent and highly virulent bacterium encountered in clinical settings. Due to its uneven drug resistance profile and the multitude of factors influencing detection rates, precise and sensitive identification of MRSA is essential. Herein, we developed a detection system (called “APC‐Cas‐PLNPs”) that can ultrasensitive detection for MRSA, using a nucleic acid‐based allosteric probe, CRISPR‐Cas12a, and dual‐colored persistent luminescent nanoparticles tandem detection. Simply, an allosteric probe was used to specifically recognize MRSA and cyclic signal amplification and then initiated catalytic CRISPR‐Cas12a collateral cleavage. Meanwhile, red‐emitting ZnGa2O4:Cr (ZGC) bonded with BHQ3‐modified single‐stranded DNA to create a detection probe known as ZGC@BHQ3, and green‐emitting Zn2GeO4:Mn (ZGM) was served as the reference probe and electrostatically bound to both probes, forming the ratiometric luminescence sensor ZGC@BHQ3‐ZGM for CRISPR‐Cas12a detection. With this strategy, the nonnucleic acid targets were dexterously converted into fluorescent signals. This tandem detection system eliminates interference from background fluorescence and external factors and provides a novel signal amplification and conversion strategy, which enables accurate and sensitive quantification of MRSA (1–105 CFU/mL) without requiring isolation and DNA extraction. Moreover, APC‐Cas‐PLNPs are capable of detecting low levels of MRSA in food samples such as milk and orange juice, as well as in mouse serum, demonstrating greater sensitivity compared with real‐time PCR. This method holds significant potential application value in food detection and early diagnosis of pathogenic bacteria, highlighting its broad applicability.
Plant‐derived extracellular vesicles: Current status and challenges for developing a new paradigm in therapeutics development
Authors: Jo Ha Young , Kang Su Jin , Kim Gunhee , Gwak Seongjin , Baek Gichan , Rhee Won Jong
Published: January 2025

Extracellular vesicles (EVs) are nano‐sized vesicles surrounded by a lipid bilayer containing bioactive materials, including proteins, nucleic acids, lipids, and metabolites. They function as messengers secreted by cells, playing a crucial role in cell‐to‐cell communication. Plant‐derived extracellular vesicles (P‐EVs), secreted by plant cells, are being investigated as therapeutic agents and drug delivery carriers due to their high biocompatibility, productivity, and effective cellular delivery, exerting therapeutic effects through physiological pathways. However, methods for EV production directly from plants and P‐EV identification components have not yet been established. A comprehensive understanding of the therapeutic potential and biodistribution of P‐EVs is essential for their application as systemic therapeutics and drug delivery carriers. This review covers recent methods for separating P‐EVs from plants and explores potential identification components for their identification. It also summarizes the intrinsic therapeutic effects and applications of engineered P‐EVs. Finally, it provides tailored strategies by examining biodistribution according to the route of administration and analyzing the potential for effective delivery and therapeutic application. Given the diversity and distinctiveness of plants, the development of therapeutic agents using P‐EVs shows great promise and are anticipated to create a new paradigm in therapeutics.
Intergenerational Ethics and Climate Change
Authors: Hourdequin Marion
Published: January 2025

Global climate change is a multigenerational challenge that raises significant questions of intergenerational ethics. What do we owe to future generations? How should we think about intergenerational relations in the context of climate change? Many common moral theories—particularly those that assume a shared community of contemporaries who have the capacity to make agreements among themselves—encounter challenges in relation to intergenerational ethics. These challenges include the nonexistence and nonidentity problems, as well as issues involving power asymmetries, motivation, and accountability. This review suggests that the prominence of generational individualism—in which generations are conceptualized as distinct and potentially in conflict—can be an impediment to the robust consideration of future generations in climate ethics and policy. Conceptions of intergenerational ethics that emphasize transgenerational community and mutual flourishing over time may help to temper generational individualism, alleviating “intergenerational buck passing” on climate change and supporting climate action that takes past, present, and future generations more fully into account.
An optimized irrigation water quality index for evaluating surface water sustainability status of an agricultural watershed
Authors: Damiba Wendyam Arsene Flavien , Gathenya John Mwangi , Raude James Messo , Home Patrick Gathogo
Published: January 2025

Maintaining good water quality is essential for drinking and agriculture. High water quality is crucial for irrigation to boost agricultural productivity and ensure sustainable water resource management. This study used in‐depth physical and chemical analysis of water samples to evaluate the Kakia‐Esamburmbur watershed's irrigation water sustainability. The Irrigation Water Quality Index (IWQI), developed using 19 indicators and Principal Component Analysis (PCA), addressed concerns about soil salinity, sodicity, and plant water toxicity. The analysis revealed SO4.Cl‐Na is the predominant pollutant. Qualitative water parameter analysis showed 70% of samples were adequate for EC, 90% for SAR and RSBC, and 100% for PI and SSP. However, Na (%), RSC, KI, and MH were lower. PCA identified eight key indicators, with IWQI values ranging from 14.48 to 433.76, with 50% of sites rated ‘excellent.’ The correlation matrix indicated significant hydrogeochemical impacts from geogenic and anthropogenic pressures. These findings inform policies to promote sustainable agricultural productivity.

Practitioner Points

Primary ions ranked as Na+ > K+ > Ca2+ > Mg2+ and HCO3− > SO42− > Cl‐ > CO32−

PCA identified Na+, EC, TDS, HCO3−, SAR, RSC, RSBC, and KI as key indicators.

Combining the unique quality rating scale (Qi) and weighting formula makes the IWQI innovative and original.

50% of water samples were rated “excellent” for irrigation.

Significant geogenic and anthropogenic impacts stress the need for informed policies on sustainable water management.
Correlation on metabolic complete response on positron emission tomography and pathological complete response in patients with breast cancer after neoadjuvant chemotherapy
Authors: Ma Lorraine Wai Yan , Cheung Polly Suk Yee , Ho Chi Lai , Wong Yuet Hung , Luk Wing Pan , Fung Ling Hiu
Published: January 2025

Purpose

The use of neoadjuvant chemotherapy in treating breast cancer has expanded in recent years. There was increased interest in using positron emission tomography (PET) for the evaluation of treatment response. We aimed to study the accuracy of metabolic complete response (mCR) on PET scan in predicting pathological complete response (pCR) after neoadjuvant treatment.

Methods and Results

Between January 1, 2014 and June 30, 2019, 356 consecutive patients who completed neoadjuvant treatment underwent PET scan before surgery. 207 patients (58.1%) achieved mCR and 128 patients (36.0%) achieved pathologic CR. Among mCR patients, 101 (48.8%) had pCR. Among pCR patients, 27 (21%) did not achieve mCR on PET. The overall sensitivity of predicting pCR with mCR was 78.9% and specificity of 53.5%. The overall accuracy was 0.691 by area under the receiver operating characteristic curve (AUC). Analysis using mCR to predict breast/axilla pCR had a sensitivity of 76.2%/67.9%, specificity of 54%/62.1%, and AUC of 0.682/0.675, respectively. Sensitivity and specificity were highest among HR−/HER2+ (87.1% and 57.1%), followed by HR+/HER2− (85% and 59.6%) and triple negative (82.1% and 54.1%) and the lowest were HR+/HER2+ (triple positive) (69.4% and 40.3%). There was little difference in sensitivity and specificity among the high and low Ki67 proliferation index (78.3% vs. 75% and 52.1% vs. 62.5%).

Conclusion

PET was useful in evaluation of tumor response to neoadjuvant chemotherapy especially in the HR−HER2+ subtype. However, its accuracy was not high enough to replace surgery.
Drivers of hunter compliance and satisfaction with mandatory harvest reporting
Authors: Van Buskirk Amanda N. , Bynum Boley B. , Killmaster Charlie H. , Johannsen Kristina L. , D'Angelo Gino J.
Published: January 2025

Hunter harvest data are important components of game species management and conservation, and natural resource agencies often use self‐reporting mechanisms to collect harvest data. Despite the advantages of self‐reporting systems, hunter noncompliance with mandatory reporting remains a challenge for managers. Our objective was to utilize the theory of planned behavior (TPB) and concepts of organizational trust to understand factors influencing hunter compliance and satisfaction with mandatory harvest reporting. We distributed questionnaires through email channels and postcards mailed to resident deer hunters in Georgia, USA. Structural equation model results from the 1712 survey responses suggest that TPB constructs (attitudes, perceived behavioral control, social norms), organizational trust, and satisfaction with hunting experience positively influenced satisfaction with mandatory reporting. In contrast, the number of years an individual has been hunting negatively influenced satisfaction. Further, we tested a binary logistic regression model to predict potential drivers of compliant behavior with harvest reporting requirements. Our model found that attitudes, social norms, and satisfaction with reporting positively impacted reporting compliance. However, results also indicate that older, more experienced hunters were less likely to report harvests. Our findings suggest that targeting efforts towards increasing trust, positive attitudes, and satisfaction with regulations and regulatory systems among older, more experienced hunters may positively influence compliant behavior. Our study emphasizes the importance of engaging hunters in regulatory decision‐making processes and improving agency–hunter relationships to achieve greater regulatory compliance and satisfaction.
Efficacy of prophylactic laxatives against opioid-induced constipation: retrospective propensity score matching analysis
Authors: Okuda Yuka , Kuriyama Toshiyuki , Tsukiyama Yoshi , Shimokawa Toshio , Wan Ke , Kawamata Tomoyuki
Published: January 2025

Purpose

Opioid-induced constipation (OIC) is problematic for patients with cancer receiving opioid therapy. Some guidelines recommend initiating regular laxatives at the same time as opioid analgesics. However, the effectiveness of prophylactic laxatives on OIC has not been widely demonstrated. We therefore examined the incidence of OIC among patients with and without prophylactic laxatives within one week after initiating strong opioid analgesics and the factors associated with the incidence of OIC.

Methods

Eligible patients were adults with cancer for whom strong opioid analgesics were initiated after admission and who remained hospitalized for over a week. Propensity score matching analysis was used to compare outcomes after adjusting for patient background.

Results

In total, 928 patients were enrolled, from which 536 were selected after propensity score matching analysis. The incidence of OIC in patients with prophylactic laxatives was not significantly different from that without prophylactic laxatives (48.1% vs 48.9%, odds ratio (OR) = 0.97, 95% confidence interval (CI): 0.69–1.36). In multivariable logistic analysis, age ≥ 65 years (OR = 1.53, 95% CI: 1.07–2.19) and Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥ 3 (OR = 1.69, 95% CI: 1.04–2.77) were associated with a higher incidence of OIC.

Conclusion

Prophylactic laxatives did not affect the incidence of OIC in our study. Our results suggest that prophylactic laxatives are not necessarily required when initiating opioid therapy. In addition, we found that age ≥ 65 years and ECOG PS ≥ 3 were associated in our study with a higher incidence of OIC.
Large language model based mutations in genetic improvement
Authors: Brownlee Alexander E. I. , Callan James , Even-Mendoza Karine , Geiger Alina , Hanna Carol , Petke Justyna , Sarro Federica , Sobania Dominik
Published: January 2025

Ever since the first large language models (LLMs) have become available, both academics and practitioners have used them to aid software engineering tasks. However, little research as yet has been done in combining search-based software engineering (SBSE) and LLMs. In this paper, we evaluate the use of LLMs as mutation operators for genetic improvement (GI), an SBSE approach, to improve the GI search process. In a preliminary work, we explored the feasibility of combining the Gin Java GI toolkit with OpenAI LLMs in order to generate an edit for the tool. Here we extend this investigation involving three LLMs and three types of prompt, and five real-world software projects. We sample the edits at random, as well as using local search. We also conducted a qualitative analysis to understand why LLM-generated code edits break as part of our evaluation. Our results show that, compared with conventional statement GI edits, LLMs produce fewer unique edits, but these compile and pass tests more often, with the model finding test-passing edits 77% of the time. The and LLMs are roughly equal in finding the best run-time improvements. Simpler prompts are more successful than those providing more context and examples. The qualitative analysis reveals a wide variety of areas where LLMs typically fail to produce valid edits commonly including inconsistent formatting, generating non-Java syntax, or refusing to provide a solution.
Revisited and Revalorised: Technological and Refitting Studies at the Middle Stone Age Open-Air Knapping Site Jojosi 1 (KwaZulu-Natal, South Africa)
Authors: Möller Gunther Heinz Dietrich , Mazel Aron David , Sommer Christian , Botha Gregory Allan , Conard Nicholas John , Riedesel Svenja , Will Manuel
Published: January 2025

The Middle Stone Age (MSA) of southern Africa is mainly known from rock shelters and caves. How early modern humans interacted with their landscapes remains comparatively understudied. The site of Jojosi 1, situated north of Nquthu in north central KwaZulu-Natal, is set within erosional badlands known locally as ‘dongas’. This locality offers a rare opportunity to study MSA technology and settlement dynamics in an open-air context. G. Botha initially discovered Jojosi 1 in 1991. He brought it to A. Mazel’s attention who excavated the site in the same year, but did not publish the lithic assemblage. Here, we report on the site’s rediscovery coupled with the first lithic analysis and luminescence dating. This work provides insights into the site formation processes of Jojosi 1 and lithic reduction strategies, raw material provisioning, and landscape use. Our techno-typological analysis draws upon Mazel’s collection of 7529 artefacts, combining attribute analysis and refitting studies. The results show the exclusive use of hornfels and its reduction via platform cores and Levallois methods to produce flakes and blades. Retouched tools are scarce and comprise mostly notched or denticulate pieces but lack backed tools, unifacial, and bifacial points. The museum collection features abundant small debitage and a strong component of cortical, initial stage, and core preparation flakes. The 48 refitted artefacts and ample small debitage in a spatially constricted band suggest high assemblage integrity with minimal post-depositional disturbance. Infrared stimulated luminescence dating of coarse grain feldspars brackets the archaeological occurrence to ~ 139–106 ka. Comparisons with contemporary lithic assemblages link the assemblage to the early MSA in southern Africa. We interpret Jojosi 1 as a knapping event aimed at blank production and exploitation of local high-quality hornfels. With little evidence for other behaviours, the site likely reflects a short-term knapping workshop on a source of abundant hornfels slabs. Our ongoing excavations in the Jojosi Dongas will be able to test this hypothesis and will work to characterise the technological adaptations and settlement dynamics of the MSA hunter-gatherers in this area.
Protective effects of sevoflurane conditioning against myocardial ischemia-reperfusion injury: a review of evidence from animal and clinical studies
Authors: Lin Jiefu , Li Xia , Yang Yuhui , Ge Zhi-dong , Liu Danyong , Yang Changming , Zhang Liangqing , Xia Zhongyuan , Xia Zhengyuan
Published: January 2025

Pharmacological interventions with the inhaled anesthetic sevoflurane, widely used in cardiac surgery, have been reported to mimic the cardioprotection produced by ischemic conditioning against myocardial ischemia–reperfusion injury. Beneficial effects of sevoflurane conditioning vary with dose, time window and duration and have been reported in a variety of studies involving both laboratory experiments and clinical trials. However, sevoflurane conditioning effects are impaired or lost in subjects with diabetes in both laboratory and clinical settings with mechanisms incompletely understood. This article summarizes the major findings investigating sevoflurane-induced myocardial protection. Our aim is to provide a better understanding of the interrelated but poorly described sevoflurane conditioning signaling pathways. Moreover, this may facilitate the development of more effective therapeutic or preventive strategies for myocardial ischemia-reperfusion injury.
Comparative study of Mg/Al-LDH and Mg/Fe-LDH on adsorption and loss control of 2,4-dichlorophenoxyacetic acid
Authors: Zhang Zeyuan , Tang Liangjie , Luo Jing , Tan Jinfang , Jiang Xiaoqian
Published: January 2025

Low efficiency and high surface runoff of 2,4-dichlorophenoxyacetic acid (2,4-D) from agricultural field threaten crop yield severely. Layered double hydroxides (LDH) have shown promising adsorption properties for 2,4-D. However, the comparison of two environmentally friendly LDHs (i.e. Mg/Al-LDH vs Mg/Fe-LDH) on adsorption of 2,4-D and corresponding intrinsic mechanisms are still unclear, and the studies on the leaching control of 2,4-D by LDHs in soil environment are particularly limited. In this study, Mg/Al-LDH and Mg/Fe-LDH were selected to conduct their adsorption kinetics experiment for 2,4-D combined with the characterization technology. The results showed that the adsorption capacity of Mg/Al-LDH and Mg/Fe-LDH for 2,4-D was up to 242 mg kg−1 and 64 mg kg−1, respectively, which were negatively correlated with pH. Adsorption mechanisms of both Mg/Al-LDH and Mg/Fe-LDH for 2,4-D are dominated by chemical adsorption, including electrostatic attraction and inner sphere complexation, but no interlayer adsorption mechanism. Mg/Al-LDH contains smaller metal ion radius, which provides greater surface charge density, resulting in greater electrostatic attraction and inner sphere complexation to 2,4-D compared to Mg/Fe-LDH. The greater adsorption capacity of Mg/Al-LDH for 2,4-D was driven by the higher adsorption energy (E
ads) and lower electron density, as corroborated by density functional theory (DFT) calculation. The soil column experiment further verified that Mg/Al-LDH could control the loss of 2,4-D more effectively, and the leaching amount could be significantly reduced by 61.7%, while the effect of Mg/Fe-LDH was only 24.2%. This study provides theoretical guidance for screening more potential LDH types to solve the leaching loss of 2,4-D from soil and improve its effectiveness in agricultural production.

Graphical Abstract
Owl Cave Revisited: Examining the Evidence for a Folsom-Bison Association
Authors: Henrikson L. Suzann , Clements Joshua G. , Loftus Shannon L. , Duke Daron
Published: January 2025

The discovery of green-fractured mammoth bone in Owl Cave in the 1970s inspired the original investigators to focus primarily on the possible association between these remains and Folsom points recovered from the same stratum. With the Museum of Idaho's recent acquisition of the complete Owl Cave collection, we have gained a better understanding of the periglacial processes that appear to have displaced and mixed mammoth remains with a younger Folsom component. New efforts to date bison bone also recovered from the lowest levels of the cave have produced radiocarbon dates that fall within the accepted age range of Folsom technology. These results have prompted efforts to investigate the potential for an association between the lithic assemblage and bison, a scenario that is much more plausible given our current understanding of the Folsom archaeological record.