bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictive, preventive and personalized project of vascular cognitive impairment in China (P3): Study design and interim baseline patient characteristics of a Nationwide multicenter prospective registry
Authors: Wang Linlin , Jiang Jiwei , Wang Yanli , Liu Gaifen , Li Wenyi , Ren Qiwei , Jiang Shirui , Zhao Min , Zhang Huiying , Jiang Tianlin , Yang Shiyi , Cui Mei , Dong Qiang , Xu Jun
Published: December 2024

Objectives

To outline the design of the P3 study and serve as a summary of the interim baseline patient characteristics.

Methods

P3 study is a multicenter, prospective cohort study targeting 1000 acute ischemic stroke (AIS) and cerebral small vessel disease (CSVD) patients with a 2‐year follow‐up from 80 participating hospitals across China. Comprehensive multimodal imaging, neuropsychological tests, and biological samples were collected prospectively on admission and follow‐up visits. Patients were interviewed face to face for 2 years and followed up.

Results

Until 30 December 2023, 642 patients were enrolled from 67 centers. In the AIS cohort, 219 patients (72.5%) were diagnosed with acute post‐stroke cognitive impairment (PSCI). Compared to those without PSCI, the acute PSCI group exhibited significantly lower levels of education and a history of stroke (all P < 0.05). In the CSVD cohort, 53 patients (41.4%) were diagnosed with cognitive impairment. Compared to those with normal cognitive function, the impaired cognitive function group had a significantly higher prevalence of hypertension and diabetes history (all P < 0.05). All 642 patients completed 20 tests, as well as clinical information and blood sample collection. Nearly 95% of the patients underwent structural MRI and ASL, and 60% of patients completed fMRI and DKI or DTI.

Conclusions

P3 study aims to establish a comprehensive spatiotemporal profile of VCI. Through multidimensional analysis of clinical information, radiomics, proteomics, metabolomics, microbiomics, and genetics, provide a more comprehensive understanding of VCI trajectories and individual variability, enhancing early detection and prognosis management.
The memory of past water abundance shapes trees 7 years later
Authors: Chin Alana R. O. , Gessler Arthur , Laín Omar , Østerlund Isabella , Schaub Marcus , Théroux‐Rancourt Guillaume , Voggeneder Klara , Lambers Janneke Hille Ris
Published: December 2024

Premise

Tree structure and function are constrained by and acclimate to climatic conditions. Drought limits plant growth and carbon acquisition and can result in “legacy” effects that last beyond the period of water stress. Leaf and twig‐level legacy effects of past water abundance, such as that experienced by trees that established under wetter conditions are unknown.

Methods

In an 18‐year forest irrigation experiment, we explored the lasting structural impact of past water richness on leaves and twigs of Pinus sylvestris using synchrotron‐based X‐ray microscopy. We compared 47 anatomical traits among never‐irrigated control trees, trees irrigated for 18 years, and formerly irrigated trees, 7 years after their return to control‐level water availability in this naturally dry forest.

Results

We found that legacy effects induced by a period of experimental irrigation continue to shape the structure of new leaves and twigs long after a sharp decrease in water availability. Legacy effects shaping twigs were present but dissipating, while leaf traits displayed long‐lasting effects on structural strategy, with extreme values for traits associated with high water stress and low productivity.

Conclusions

Mature trees acclimating to an increasingly dry world may be at a disadvantage compared to young trees that have known only chronic drought. However, these young trees may be capable of thriving in sites of drought‐related forest decline especially if planted while larger individuals are still present to support tree establishment. Without a legacy of past water abundance, trees in future forests may be better equipped to cope with our rapidly changing climate.
Placental and Fetal Microbiota in Rhesus Macaque: A Case Study Using Metagenomic Sequencing
Authors: Du Qiao , Liu Xu , Zhang Rusong , Hu Gang , Liu Qinghua , Wang Rui , Ma Wen , Hu Ying , Fan Zhenxin , Li Jing
Published: December 2024

Recent evidence challenging the notion of a sterile intrauterine environment has sparked research into the origins and effects of fetal microbiota on immunity development during gestation. Rhesus macaques (RMs) serve as valuable nonhuman primate models due to their similarities to humans in development, placental structure, and immune response. In this study, metagenomic analysis was applied to the placenta, umbilical cord, spleen, gastrointestinal tissues of an unborn RM fetus, and the maternal intestine, revealing the diversity and functionality of microbes in these tissues. Additionally, gut metagenomic data of adult Rhesus macaques from our previous study, along with data from a human fetus obtained from public databases, were included for comparison. We observed substantial microbial sharing between the mother and fetus, with the microbial composition of the placenta and umbilical cord more closely resembling that of the fetal organs than the maternal intestine. Notably, compared with other adult RMs, there was a clear convergence between maternal and fetal microbiota, alongside distinct differences between the microbiota of adults and the fetus, which underscores the unique microbial profiles in fetal environments. Furthermore, the fetal microbiota displayed a less developed carbohydrate metabolism capacity than adult RMs. It also shared antibiotic resistance genes with both maternal and adult RM microbiomes, indicating potential vertical transmission. Comparative analysis of the metagenomes between the RM fetus and a human fetus revealed significant differences in microbial composition and genes, yet also showed similarities in certain abundant microbiota. Collectively, our results contribute to a more comprehensive understanding of the intrauterine microbial environment in macaques.
The Influence of Provisioning on the Intergroup Relationships of Rhesus Macaque in Hainan, China
Authors: Wu Cheng‐Feng , Xu Zhi‐Hong , Fan Yu‐Xuan , Chen Tao , Xie Pu‐Zhen
Published: December 2024

Intergroup competition for limited resources is a significant selection pressure that drives the evolution of animal society. The rhesus macaque (Macaca Mulatta) is the most widely distributed nonhuman primate in the world and can adapt well to environments disturbed by humans. In some areas, human provisioning provides ample food resources for rhesus macaques, leading to an increase in their population size, inevitably affecting competition patterns within and between groups. In this study, we focused on seven provisioned groups of rhesus macaque in an eco‐tourism park in Hainan, China, to verify how provisioning impacted their intergroup relationships. The results showed that: (1) Peaceful coexistence was the most common form of Intergroup contacts; (2) Provisioning led to an increase in intergroup contact and conflicts, but monkeys tended to avoid direct contact with other groups at main‐provisioned sites with high conflict risk. (3) Larger groups did not interfere with each other's space use in the park, but smaller groups were more easily tolerated by other groups. (4) There were no strict linear dominance relationships among monkey groups. Overall, intensive provisioning satisfied the energy requirement of all monkeys in our study site, leading to a reduction in the relative benefit of intergroup conflict. Consequently, monkeys have adopted an intergroup contact strategy that avoids direct conflicts and prevents conflict escalation. We should pay more attention to the behavior patterns of provisioned animal populations, which will help us better understand how resources such as food have influenced the evolution of social strategies of animal groups, as well as how to manage such human disturbed animal populations in the future.
Unveiling the Photoluminescence Mechanism of Carbonized Polymer Dots: Evolution and Synergistic Photoluminescence of Multiple Molecular Fluorophores
Authors: Han Xiao , Xia Chunlei , Wu Han , Xie Yadian , Li Rui , Sui Bowen , Yu Yue , Wang Bo , Yang Bai
Published: December 2024

Carbonized polymer dots (CPDs) are a class of exceptional fluorescent materials with diverse applications. However, their photoluminescence (PL) mechanism remained enigmatic and controversial, hindering further development and application. While molecular fluorophores explain primary fluorescence in some CPDs, the overall PL of CPDs still cannot be fully explained, such as their excitation‐dependent behaviors, let alone the modulation of PL. Besides, the extracted molecular fluorophores are dissociative, raising questions including the purity of CPDs and whether the PL of CPDs nanoparticles come from these molecular fluorophores. Here, the emission around 510 nm of citric acid‐ethylenediamine CPDs (CA‐EDA CPDs) was proved to be contributed by a molecular fluorophore, which evolved from another molecular fluorophore following the quantum confinement effect. Further research revealed the whole PL mechanism of CA‐EDA CPDs to be the evolution and synergistic PL of multiple molecular fluorophores linked on CPDs nanoparticle. The evolution of molecular fluorophores had also been observed in another two systems, indicating the universality of this mechanism, and a new approach for regulating the optical properties of CPDs was put forward inspired by this mechanism. This study not only refined the PL mechanism but also paved the way for future advancements of CPDs.
Photoredox/Cobalt‐Catalyzed Chemo‐, Regio‐, Diastereo‐ and Enantioselective Reductive Coupling of 1,1‐Disubstituted Allenes and Cyclobutenes
Authors: Wu Qianghui , Zhang Zhihan , Chong Qinglei , Meng Fanke
Published: December 2024

A dual photoredox/cobalt‐catalyzed protocol for chemo‐, regio‐, diastereo‐ and enantioselective reductive coupling of 1,1‐disubstituted allenes and cyclobutenes through chemo‐, regio‐, diastereo‐ and enantioselective oxidative cyclization followed by stereoselective protonation promoted by a chiral phosphine–cobalt complex is presented. Such process represents an unprecedented reaction pathway for cobalt catalysis that enables selective transformation of the less sterically congested alkenes of 1,1‐disubstituted allenes with cyclobutenes, incorporating a broad scope of tetrasubstituted alkenes into the cyclobutane scaffolds in up to 86 % yield, >98 : 2 chemo‐ and regioselectivity, >98 : 2 dr and >99.5:0.5 er. Functionalization delivered a variety of enantioenriched cyclobutanes that are otherwise difficult to access. Preliminary mechanistic studies revealed that the reactions proceeded through oxidative cyclization followed by protonation and protonation might be the rate‐determining step.
The glymphatic system: A new insight into the understanding of neurological diseases
Authors: Liao Junbo , An Zhihan , Cheng Quan , Liu Yaxue , Chen Yibing , Su Zhangjie , Usman Ahsan Muhammad , Tang Zhi , Xiao Gelei
Published: December 2024

The glymphatic system (GS) is a newly discovered transport system in the central nervous system (CNS) that plays a crucial role in maintaining homeostasis by facilitating the clearance of metabolic waste and fluid transport. This groundbreaking discovery has significantly advanced our understanding of CNS physiology. Historically, the brain was thought to lack a lymphatic system, leaving its mechanisms for waste clearance largely enigmatic. This review elaborates on the anatomical structures of the GS, including the perivascular space, aquaporin 4 (AQP4) channels, and the meningeal lymphatic system, as well as their functional dynamics, to elucidate the GS's waste clearance mechanism. It also explores the key factors influencing GS activity, such as sleep, arterial pulsation, aging, and pharmacological interventions. Moreover, it examines the implications of GS dysfunction in various neurological diseases, including stroke, Alzheimer's disease, and Parkinson's disease. Furthermore, it discusses the latest diagnostic and therapeutic strategies targeting this vital system. Understanding the role of the GS in CNS homeostasis not only provides new insights into the pathophysiology of neurological diseases but also opens novel avenues for therapeutic interventions to enhance brain health and mitigate neurodegenerative processes.
Machine Learning Enabled Prediction of Biologically Relevant Gene Expression Using CT‐Based Radiomic Features in Non‐Small Cell Lung Cancer
Authors: Sukhadia Shrey S. , Sadée Christoph , Gevaert Olivier , Nagaraj Shivashankar H.
Published: December 2024

Background

Non‐small‐cell lung cancer (NSCLC) remains a global health challenge, driving morbidity and mortality. The emerging field of radiogenomics utilizes statistical methods to correlate radiographic tumor features with genomic characteristics from biopsy samples. Radiomic techniques automate the precise extraction of imaging features from tumor regions in radiographic scans, which are subjected to machine learning (ML) to predict genomic attributes.

Methods

In a retrospective study of two NSCLC patient cohorts separated by 5 years, we performed a radiogenomic analysis of previously disseminated data from 2018 (n = 116) and newly acquired data from 2023 (n = 44) using RNA sequencing and lung CT images. Combining the data from two cohorts post binarization (of gene expression) or batch normalization (of radiomic features) in each cohort proved to be a better approach as compared to training the model on one cohort and validating on the other.

Results

Our ML‐based radiogenomic modeling identified specific imaging features—wavelet, three‐dimensional local binary patterns, and logarithmic sigma of gray‐level variance—as predictive indicators for high (1) vs. low (0) gene expression of pivotal NSCLC‐related genes: SLC35C1, BCL2L1, and MAPK1. These genes have recognized implications in a variety of biological pathways and mechanisms of drug resistance pertinent to NSCLC.

Conclusion

The successful integration of heterogeneous radiogenomic datasets underscores the potential of imaging biomarkers in uncovering NSCLC biological processes through gene expression profiles.
Keep your eye on…
Authors: Knopf Alison
Published: December 2024

Placebo response in TD

TMS for depression in teens

Deprescribing antidepressants
Final commentary for this editor: Musing about mental health in children and families
Authors: Walters Anne S.
Published: December 2024

After 8 years of sharing monthly thoughts about child and adolescent mental health, this will be my last commentary. I retired last winter, so I'll turn this over to an editor still active in the scholarly and clinical world. It's the daily practice that creates opinions and ideas to research and write about. I'm looking forward to seeing what the following newsletters bring.
Make sure transition‐age youth have access to needed mental health care
Authors: Knopf Alison
Published: December 2024

“Transition‐age youth” sounds like fancy talk for coming‐of‐age years. In fact, it's a time when youth are particularly vulnerable to stress, and also when serious mental health problems can derail their move into adulthood. The years of being home and protected by parents, perhaps, are over. College, jobs, and concerns about the “real world” can take over. Furthermore, the inner world — depression, anxiety, suicide, substance use, bullying, romance, even possible first‐episode psychosis which takes place during these years, can emerge. Medically, the pediatrician is probably leaving the child's medical team, and new providers — adult providers — will be taking over. These providers don't know the child the way the pediatrician does.
Comparative Analysis of Central and Noncentral Degenerative Mitral Regurgitation Treated With Transcatheter Mitral Valve Edge‐To‐Edge Repair
Authors: Wei Peijian , Feng Shuyi , Zhang Fengwen , Li Hang , Zhuang Donglin , Jiang Hong , Zhao Guangzhi , Dong Jing , Wang Cheng , Ouyang Wenbin , Wang Shouzheng , Fang Fang , Pan Xiangbin
Published: December 2024

Background

Mitral valve transcatheter edge‐to‐edge repair (M‐TEER) was initially indicated for central degenerative mitral regurgitation (DMR) lesions, but advancements in technology have enabled successful treatment in an increasing number of noncentral DMR patients.

Aims

This study aims to compare procedural outcomes and prognosis between noncentral DMR patients, outside clinical trial anatomical criteria, and central DMR patients undergoing M‐TEER.

Methods

Drug‐refractory moderate‐to‐severe DMR patients treated with M‐TEER at Fuwai Hospital from January 2021 to February 2024 were retrospectively analyzed. Patients were categorized into central (N = 77) and noncentral (N = 59) lesion groups. Baseline characteristics, procedural outcomes, and prognoses were collected and compared.

Results

There were no significant differences in baseline characteristics and preoperative echocardiographic parameters between the groups except for left ventricular ejection fraction. Both groups exhibited similar procedural success rates (central: 93.51% vs. noncentral: 91.53%, p = 0.92) with comparable procedural complication rates. The ideal M‐TEER success rate at discharge for noncentral DMR patients was similar to that for central DMR patients (83.05% vs. 71.43%, p = 0.11). Kaplan–Meier analysis indicated similar 3‐year recurrence‐free survival rates (noncentral: 94.9% vs. central: 90.3%, p = 0.46). Cox regression analysis identified higher discharge mitral valve gradient and a leaflet‐to‐annulus index ≤ 1.2 as independent risk factors for recurrence or death.

Conclusion

Noncentral DMR patients undergoing M‐TEER achieve similar procedural success rates without increased risk of complications compared to central DMR patients. The seemingly higher success rate in noncentral DMR patients may be due to the smaller impact on valve area, warranting further investigation.
Ruptured Sinus of Valsalva Aneurysm: Transcatheter Closure Through Retrograde Approach
Authors: Bagur Manjunath , Alva Prem , N Shivakumar
Published: December 2024

The ruptured sinus of Valsalva aneurysm (RSOV), a rare but well‐recognized clinical entity, is invariably a form of left‐to‐right shunt due to rupture into right‐sided chambers. It causes profound hemodynamic effects, especially when the rupture is acute. Like most other left‐to‐right shunts, it was only a matter of time before this rare defect also became amenable to transcatheter closure (TCC). Since the first report of TCC of RSOV by Cullen et al. in 1994 using the Rashkind umbrella, in recent times, there has been a spate of case reports, brief communications, and interesting case presentations at interventional meetings using the much more user‐friendly and effective devices. We report a case of a 59‐year‐old female diagnosed with RSOV (noncoronary cusp to right atrium) treated with device closure by using a vascular plug through a retrograde approach without resorting to the usual antegrade technique involving the formation of an arteriovenous loop.
Impact of Below‐the‐Knee Runoff in Patients With Lower Extremity Artery Disease Who Underwent Endovascular Therapy Using Drug‐Coated Balloons in Femoropopliteal Lesions
Authors: Yamada Takehiro , Tokuda Takahiro , Yoshioka Naoki , Koyama Akio , Nishikawa Ryusuke , Shimamura Kiyotaka , Tsuruoka Takuya , Mitsuoka Hiroki , Sato Yusuke , Aoyama Takuma
Published: December 2024

Background

The impact of below‐the‐knee (BK) runoff after drug‐coated balloon (DCB) treatment in femoropopliteal (FP) lesions has not been well investigated.

Methods

This retrospective multicenter observational study enrolled 291 consecutive patients with lower extremity artery disease who underwent endovascular therapy with DCBs for FP lesions between January 2018 and December 2021. Patients were classified into four groups based on the BK runoff. Outcome measures included primary patency, freedom from clinically driven target lesion revascularization (CD‐TLR) and amputation, and overall survival rates at 24 months. The predictors of restenosis at 24 months were also investigated.

Results

In total, 43, 98, 117, and 33 patients were classified into three, two, one, and no BK runoff groups, respectively. In three, two, one, and no BK runoff groups, the primary patency rates were 72.1%, 67.3%, 61.4%, and 44.1% (p = 0.028); freedom from CD‐TLR rates were 87.1%, 78.8%, 71.7%, and 47.1% (p < 0.001); freedom from amputation rates were 95.2%, 97.9%, 92.8%, and 91.5% (p = 0.499); and overall survival rates were 89.4%, 83.2%, 76.6%, and 61.2% (p = 0.007), respectively, at 24 months. Multivariate analysis showed that chronic limb‐threatening ischemia, no BK runoff, Lutonix use, and residual stenosis > 30% were independent predictors of primary patency loss at 24 months. The risk score, calculated as the number of predictors, reflected the risk of restenosis.

Conclusion

No BK runoff was associated with worse midterm primary patency, freedom from CD‐TLR, and overall survival rates than at least one BK runoff.
Physiological Performance of Drug‐Coated Balloons in Small Coronary Arteries PICCOLETO II μFR
Authors: Fezzi Simone , Trevisanello Aurora , Buccheri Dario , Borgi Marco , Orrego Pedro Silva , Zoccai Giuseppe Biondi , Cortese Bernardo
Published: December 2024

Background

Drug‐coated balloons (DCB) are emerging as an alternative to permanent implants for managing de novo coronary artery disease, particularly in small vessels (SVD). This sub‐analysis of the PICCOLETO II study aimed to compare the performance of DCB and DES in terms of Murray's law‐based quantitative flow ratio (μFR) changes between baseline, post‐percutaneous coronary intervention (PCI), and follow‐up.

Methods

Patients with a clinical indication for PCI were assigned to receive either Xience DES or Elutax SV/Emperor DCB. Coronary angiograms were blindly analyzed by an independent Core Laboratory (Consorzio Futuro in Ricerca, University of Ferrara, Italy).

Results

Among 232 patients, 59 were included in this analysis. Pre‐PCI μFR was comparable between groups (0.65 ± 0.29 vs. 0.58 ± 0.25; p = 0.20). Post‐PCI, the DCB group had a lower acute functional gain compared to DES (+0.21 vs. +0.31; p = 0.064), with lower μFR values (0.86 ± 0.36 vs. 0.89 ± 0.3; p = 0.074). At 6‐month follow‐up, μFR values were similar between groups (0.84 ± 0.29 vs. 0.84 ± 0.31, p = 0.93), with a comparable late functional loss (−0.02 vs. −0.05; p = 0.93). Angiographic late lumen loss was significantly lower in the DCB group (−0.03 vs. +0.29 mm; p = 0.027).

Conclusions

DCB‐based PCI showed a trend toward less favorable immediate post‐PCI functional result but a comparable performance at follow‐up, suggesting its potential in treating de novo SVD.
Head‐to‐Head Comparison of Learning Curves Between QFR and FFRangio Software Users
Authors: Salihu Adil , Zulauff Jade , Gadiri Mehdi Ali , Metzinger Anais , Muller Joanne , Skalidis Ioannis , Meier David , Noirclerc Nathalie , Mauler‐Wittwer Sarah , Zimmerli Aurelia , Muller Olivier , Fournier Stephane
Published: December 2024

Background

Quantitative flow ratio (QFR) and FFRangio are angiography‐based technologies used to perform functional assessment of coronary lesions from angiographic images, validated across multiple clinical studies. There is limited information on the learning curves associated with each technology.

Aims

This study aims to compare the learning curves of QFR and FFRangio in evaluating coronary stenoses, focusing on changes in analysis speed and accuracy compared to invasive measurements.

Methods

A team of five blinded investigators, including two nurses, one medical student, and one physician in training, underwent identical standardized training on both technologies. The time taken for each analysis and the computed FFR values were documented and compared against the invasive gold standard.

Results

A total of 270 lesions (54 coronary lesions in 44 patients) were retrospectively analyzed. The median invasive FFR value was 0.88 [IQR 0.5, 0.9]. The median time for analysis with QFR and FFRangio was 245 [IQR 62, 319] and 252 [IQR 82, 315] s, respectively (p = 0.171). Both QFR and FFRangio demonstrated a significant reduction in the time required for analysis as experience increased (p < 0.01). Regarding accuracy, the median difference with invasive FFR for QFR and FFRangio was 0.06 [IQR: 0, 0.12] and 0.06 [IQR: 0, 0.12], respectively (p = 0.620). Both technologies reached a performance plateau early on, exhibiting comparable results throughout the study.

Conclusion

Initial training in QFR and FFRangio enables quick attainment of maximal performance, but further practice primarily enhances analysis speed while maintaining accuracy, for both software.
De Novo Design of Lipopeptide‐Based β‐Sheet‐Like Self‐Assemblies: A Strategy to Develop Fusion Inhibitors as Broad‐Spectrum Antivirals
Authors: Sardar Avijit , Bhowmick Sucharita , Kamble Mithila , Dewangan Nikesh , Hazra Bibhas , Mallick Amirul I. , Tarafdar Pradip K.
Published: December 2024

The recent surge in emerging viral infections warrants the design of broad‐spectrum antivirals. We aim to develop a lead molecule that targets a common biochemical feature of many enveloped viruses, membrane fusion. To achieve the broad‐spectrum ability, instead of targeting the fusion machinery, we plan to modulate the physicochemical properties of the host and viral membranes to block fusion. The approach is based on the Coronin‐1 protein of Mycobacterium, which presumably inhibits the phagosome‐lysosome fusion, and a unique Trp–Asp (WD) sequence is placed at the distorted β‐meander motif. We designed a WD‐based branched lipopeptide (Myr‐D(WD)2) that supported the intermolecular interactions to create a β‐sheet‐like supramolecular assembly at the membrane surface. TEM and confocal fluorescence experiments also suggest that the lipopeptide self‐assembled at the bilayer interface and modulated the interfacial order and the water penetration. We demonstrated that the supramolecular organization of Myr‐D(WD)2 could block artificial membrane fusion completely and restrict pH‐dependent influenza virus (H1N1, H9N2), and pH‐independent mouse hepatitis virus, human coronavirus (HCoV‐OC43) infections. The present study provided an evidence‐based broad‐spectrum antiviral potential of a designed self‐assembled lipopeptide.
Electrochemiluminescence Immunoassay of cTnI with Ruthenium‐Based Metal Covalent Organic Framework and Dual DNAzymes Cascade Amplification Strategy
Authors: Tang Sheng‐Han , Qin Ling , Yang Wei‐Guo , Yuan Ruo , Yang Jun , Li Yan , Hu Shan‐Shan
Published: December 2024

Currently, metal‐organic frameworks (MOFs) with tunability and covalent organic frameworks (COFs) with high stability are promising nanomaterials for electrochemiluminescence (ECL), while Ru‐based metal covalent organic frameworks (Ru‐MCOFs) have rarely been reported. Herein, an ECL immunosensor based on a strong ECL‐emitting Ru‐MCOF was proposed for the sensitive detection of the cardiac troponin‐I (cTnI). Imine‐linked Ru‐MCOF was prepared as an ECL emitter via solvothermal method using tris (4,4′ ‐diamino‐2,2′ ‐bipyridine) ruthenium (II) (Ru(dbpy)32+) as a precursor. Compared with monomers, the imine‐linked Ru‐MCOF achieved structural extension through covalent bonds, which not only effectively facilitated the electrochemical activation of the luminophores, but also shortened the transmission distance between electrons and co‐reactants, generating significant ECL emission. In addition, the porous Ru‐MCOF provided a microreactor with nanoconfinement effect, which could accelerate the diffusion of co‐reactants into the framework and promote the excitation of internal and external ECL emitters, significantly enhancing the ECL intensity. Considering the excellent ECL performance of Ru‐MCOF, combined with dual DNAzymes‐driven catalytic hairpin amplification, the ECL immunosensor achieved sensitive detection of cTnI with a detection limit as low as 0.42 fg/mL. The proposed highly stable Ru‐MCOF raises a new approach for exploring MCOF‐based luminophores, highlighting the potential of MCOFs in advanced ECL emitters.
A preclinical study of allogeneic CD19 chimeric antigen receptor double‐negative T cells as an off‐the‐shelf immunotherapy drug against B‐cell malignancies
Authors: Wang Dan , Wang Liuyang , Liu Shuai , Tong Jianjun , Zhu Honglin , Xu Man , Li Xiancai , Xiang Zhiqiang , Sun Qinghua , Wang Hengcai , Wang Yuli , Wang Shuyang , Yang Liming
Published: December 2024

Objectives

To evaluate the manufacturability, efficacy and safety of allogeneic CD19 chimeric antigen receptor double‐negative T cells (CD19‐CAR‐DNTs) as an off‐the‐shelf therapeutic cell product.

Methods

A membrane proteome array was used to assess the off‐target binding of CD19‐CAR. DNTs derived from healthy donors were transduced with lentiviral vectors encoding the CD19‐CAR. The manufacture of the CD19‐CAR‐DNTs was under GMP conditions, and their surface molecule expression patterns were characterised using flow cytometry. We investigated the off‐the‐shelf potential of CD19‐CAR‐DNTs by evaluating the cryopreserved CD19‐CAR‐DNTs in terms of cell viability as well as their cytotoxicity against various CD19+ target cell lines and primary patient blasts in vitro. We evaluated the persistence and safety of the cryopreserved CD19‐CAR‐DNTs in xenograft models in vivo.

Results

GMP‐grade CD19‐CAR‐DNTs were manufactured and cryopreserved for use in advance. The cryopreserved CD19‐CAR‐DNTs maintain their viability and antitumor activity against various CD19+ target cell lines and primary patient blasts. These cells significantly prolonged the survival in Raji‐Luc‐xenografted NOG mice. Multiple infusions of the cells can further augment their efficacy. Remarkably, following a single infusion in mice, CD19‐CAR‐DNTs rapidly got distributed among well‐perfused organs initially, and progressively spread to most tissues, peaking at Day 43. In toxicity studies, CD19‐CAR‐DNTs significantly reduced tumor burden and ameliorated tissue damage in tumor‐bearing NOG mice. Critically, no immunotoxicity or graft versus host disease was observed in non‐tumor‐bearing NOG mice.

Conclusions

The allogeneic CD19‐CAR‐DNTs fulfil the requirements of an off‐the‐shelf therapeutic cell product, offering a promising new approach to the treatment of haematological malignancies.
Phthalazine Derivatives as VEGFR‐2 Inhibitors: Docking, ADMET, Synthesis, Design, Anticancer Evaluations, and Apoptosis Inducers
Authors: Bayoumi Hatem Hussein , Ibrahim Mohamed‐Kamal , Dahab Mohammed A. , Khedr Fathalla , El‐Adl Khaled
Published: December 2024

New phthalazine‐derived inhibitors for VEGFR‐2 were synthesized for anticancer evaluations. Also, docking studies were performed to explore the suggested binding orientations of the novel derivatives inside the binding site of VEGFR‐2. The achieved biological data were extremely interrelated to that of docking study. In specific, derivative 3f was the greatest effective compound against HepG2 and MCF‐7 cancer cell lines with IC50 = 0.17 ± 0.01 and 0.08 ± 0.01 µM individually. The six highly active derivatives 3b, 3e, 3f, 3g, 6a, and 6b were estimated for their VEGFR‐2 inhibitory effects. Derivative 3f was the greatest effective compound which inhibited VEGFR‐2 at IC50 = 0.0557 ± 0.002 µM. The activities of 3f were assessed against MCF‐7 cancer cells for apoptosis induction, cell cycle distribution, and growth inhibition. Compound 3f induced early apoptosis (21.44%) by more than 36 folds over the control (0.59%). The obtained results showed that compound 3f induced necrotic effect (6.03%) by more than threefolds over the control (1.75%). On the other hand, compound 3f improved the level of the pro‐apoptotic protein; Bax by approximately fivefolds. Moreover, compound 3f noticeably decreased the levels of the anti‐apoptotic proteins Bcl‐2 by nearly fourfolds in comparison to the control. In addition, derivative 3f remarkably enhanced the Bax/Bcl2 ratio by nearly 18 folds, as compared to the control. Finally, our derivatives 3f, 3g, and 6b revealed good in silico considered ADMET profile in comparing to sorafenib.
From banks to burrows: Habitat preferences and nesting behaviours of platypuses in the Snowy River
Authors: Crane Joseph , Bino Gilad , Jordan Neil R. , Hawke Tahneal , O'Brien Justine K.
Published: December 2024

Platypuses are a unique freshwater mammal native to eastern Australia. They are semi‐aquatic, predominantly nocturnal, and nest in burrows dug into the banks of waterbodies. Quantifying nesting burrow characteristics is challenging due to the species' cryptic nature. We radio‐tagged 11 female platypuses during their breeding season (September to November) on the Snowy River, located their resting and nesting burrows by radiotracking, and assessed plasma triglyceride concentration as a biomarker of egg production. We quantified and tested for differences in height and distance from water of resting and nesting burrows, as well as for differences in both canopy and ground cover in the vicinity of resting and nesting burrows in comparison with background control sites in the area. Female platypuses displayed a strong selection for trees and shrubs, placing both their resting and nesting burrows within 5 m of these features. Compared with resting females, nesting females selected to dig nesting burrows higher above the river (nesting 1.98 m ± 0.27 SE vs. resting 1.15 m ± 0.10 SE) that were also further away from water (9.10 m ± 1.08 SE vs. 4.77 m ± 0.53 SE). Camera trap footage captured mice (Mus musculus) and black rats (Rattus rattus) entering two confirmed nesting tunnels on numerous occasions. During the first 3 weeks following the onset of nesting behaviour in two platypuses, rats entered the nesting tunnel a total of eight times and 31 times. Whether this is a previously unconsidered predator by invasive species remains to be evaluated. Synthesis: Riparian vegetation is a critical component of platypus habitat, providing stability for burrows, protection from predators, retaining high bank necessary to avoid inundation of burrows, and providing organic matter for nesting material and for abundant macroinvertebrate communities. Given ongoing declines and habitat degradation across their range, riparian habitat must be conserved and restored to promote breeding and population persistence.
Prevalence and Transmission Cycle of Avian Pathogens in the Isolated Oceanic Islands of Japan
Authors: Inumaru Mizue , Kimura Rui , Suzuki Naoko , Suzuki Hajime , Horikoshi Kazuo , Nishiumi Isao , Kawakami Kazuto , Tsuda Yoshio , Murata Koichi , Sato Yukita
Published: December 2024

Avian haemosporidian parasites and avian pox virus (APV) are well‐known pathogens for their impact on avian populations, especially in oceanic islands where introduced pathogens show strong virulence for endemic and naïve birds. The Bonin Islands are a group of oceanic islands 1000 km south of Tokyo. Like the Hawaiian Islands, there are many endemic and endangered species as well as introduced species, which have greatly affected the native avian fauna. However, pathogens in wild birds of this archipelago had not been investigated. In this study, we investigated the prevalence of avian haemosporidian parasites and APV among birds and mosquitoes in this unique ecosystem of the Bonin Islands. From 2014 to 2020, 524 birds of 39 species either rescued, deceased, or caught by mist‐netting were sampled. APV‐like lesions were sampled from nine birds. 262 mosquitoes were collected by sweeping nets or CDC traps. All samples were tested via PCR for haemosporidian infection, and lesions were tested for APV.209 birds (39.9%) of 11 species were positive for haemosporidian parasite DNA, and all three parasite genera were detected. Prevalence was particularly high for Plasmodium elongatum (pGRW06) and Prelictum relictum (pGRW04). The former was detected from both resident birds and mosquitoes, suggesting local transmission. An introduced species, the warbling white‐eye (Zosterops japonicus), had a particularly high prevalence of pGRW06 (68.3%) and may be a reservoir of this lineage. Both APV and Plasmodium spp. were detected from all APV‐tested birds, suggesting that these two pathogens may be transmitted simultaneously via mosquitoes. The presence of avian haemosporidian parasites and APV was confirmed in the Bonin Islands for the first time. However, the virulence and origin of these pathogens remain unknown, and many bird species are still understudied. Further investigations are required to contribute to the conservation of this unique avifauna.
Unveiling the Threat to Vulture Diversity: A Comprehensive Ethno‐Ornithological Study Uncovers Regional Trade Effects in Côte d'Ivoire
Authors: Asso Asso Armel , Salewski Volker , Koné N'golo Abdoulaye
Published: December 2024

In recent decades, African vulture populations have experienced a distressing decline, with certain species plummeting by over 90%. This decline can largely be attributed to various human‐induced pressures. In West Africa, the trade of vultures for magico‐traditional medicine stands out as a significant threat. However, there remains a dearth of knowledge regarding the extent and economic ramifications of poaching and its associated trade on the biodiversity of these raptors in Côte d'Ivoire. This study sets out to gauge the scope of vulture trade and trafficking in Côte d'Ivoire, as well as its national and subregional repercussions, while also scrutinizing the potential constraints such activity imposes on the biodiversity of these raptors. Ethno‐ornithological investigations were conducted across 24 cities in Côte d'Ivoire, delving into the markets where various animals are showcased. The aim was to analyze the challenges stemming from the demand for vultures for magico‐traditional medicinal purposes and to examine the economic values entwined with poaching and trading these vultures. The findings illuminate the existence of a network dedicated to poaching and trading vultures in Côte d'Ivoire, driven by robust demand and regularly supplied by local and regional sources from neighboring countries. Predominantly, the Hooded Vulture (Necrosyrtes monachus) emerges as the most frequently encountered species on the market. In response to this imminent threat, it is advocated that national and regional awareness campaigns be undertaken to bolster enforcement of pertinent wildlife protection laws, particularly concerning vultures. Furthermore, fostering enhanced cooperation among West African governments is advised to avert the extinction of these species.
Effect of the change of foundation stiffness on the dynamic characteristics of base‐isolated structure
Authors: Zhuang Haiyang , Chen Pan , Liu Ying , Yu Xu
Published: December 2024

The safety of an isolated structure built on the soft soil ground under the action of earthquakes is of major concern because the current seismic design of isolated structures has not considered the motions of the foundations caused by the effects of the soil‐isolated structure dynamic interaction (SISI). On this basis, a shaking‐table test method for base‐isolated structures on change of soil foundation stiffness was proposed and implemented. The foundation stiffness was controlled by the duration compression ratio and intensity of the input ground motion based on the influence of the increase in the excess pore water pressure ratio on the stiffness of the saturated sandy foundation. Meanwhile, the influence laws of foundation stiffness on the dynamic characteristics of base‐isolated structures were summarized and analyzed. The results showed that the first‐order natural frequency of base‐isolated structures on change of foundation stiffness decreased with an increase in the relative stiffness ratio of the structure–soil foundation (Rs), while its damping ratio increased significantly. The seismic isolation efficiency of the seismic isolation layer and the amplification effect on the rotational angular acceleration of the pile cap were significantly weakened. Meanwhile, under the same conditions, for the soil foundation with relatively small stiffness, the amplitudes of the bending moment and horizontal lateral displacement in the middle and upper parts of the pile remarkably increase because of the effects of the ISI. The research results of this test provide a certain scientific basis and reference for the seismic design of base‐isolated structures considering the SISI effects.
Experimental study on mechanical behavior of bolted steel‐neosinocalamus affinis‐based bamboo scrimber and steel connections
Authors: Fan Haodong , Ma Lintao , Li Hui , Zhang Ming , Yu Zhixiang , Zhao Shixing , Zhou Qiaoling , Chen Shuwei
Published: December 2024

Bamboo materials are known for their excellent toughness and seismic performance, which makes them a promising option for advancing their application in the field of structural engineering to enhance the seismic resilience of engineering structures. This study focused on mechanical behavior of bolted steel‐neosinocalamus affinis‐based bamboo scrimber and steel connections, and conducted shear test research and analysis on 54 specimens divided into 18 groups, aiming to promote the application of bamboo scrimber in the field of structural engineering. The study indicates that connections with thin steel plates (t = 0.5d, t = 1d) predominantly exhibit a single‐hinge yield mode, while those with thick steel plates (t = 2d) are inclined towards a double‐hinged yield mode. The yield and ultimate load‐carrying capacities of a connection are enhanced with the increase in bolt diameter. However, the influence of the steel plate's strength grade on these capacities is minimal. The yield load‐carrying capacity of connections with thick steel plates has a significant increase compared with the connection with thin steel plates. The thickness of the steel plate does not significantly affect the connection ultimate load‐carrying capacity. The initial stiffness of a connection is positively correlated with the bolt diameter, yet it remains unaffected by variations in the steel plate's thickness. The stiffness of a connection is categorized into two distinct types based on the steel plate strength grade. Connections using steel plates with a strength grade above Q235 exhibit similar stiffness levels, which are consistently higher than those using Q235‐grade steel plates. The angle between the load direction and the grain direction has an effect on the connection ductility. The ductility coefficient across various connections predominantly centers around 2.5. The research also validates that the Foschi theoretical model, traditionally applied to wood structures with bolted, nailed, and similar dowel‐type connections, accurately delineates the nonlinear load–displacement behavior of bolted steel–bamboo scrimber and steel connections for the entire duration of the process. When comparing the same configurations, connections utilizing neosinocalamus affinis‐based bamboo scrimber demonstrate a higher load‐carrying capacity than those using phyllostachys pubescens‐based bamboo scrimber, with a maximum enhancement in load‐carrying capacity of 18%. The design carrying capacity meets the test load requirements for the given end distances of 7d. This research can provide theoretical support for the engineering application of neosinocalamus affinis‐based bamboo scrimber.
Seismic fragility and life‐cycle loss analyses of high‐speed railway bridges supported by segmentally assembled round‐end hollow piers
Authors: Li Hao , Hu Zhiyuan , Zhong Tieyi , Qin Hongyu , Ji Xinlin , Zhou Lianxu
Published: December 2024

The shortcomings of segmentally assembled round‐end hollow‐section piers (SRHPs), such as weak segment joints and poor energy‐dissipation capacity, have limited their application in high‐intensity earthquake regions. Therefore, this article particularly focuses on the seismic performance of SRHPs. Three high‐speed railway bridges are designed, which are equipped with three different types of round‐end hollow‐section piers (RHPs): cast‐in situ RHP (CRHP), segmentally assembled RHP with energy‐dissipation bar (E‐SRHP), and segmentally assembled RHP with low‐yield point steel connection buckles (L‐SRHP). Subsequently, three nonlinear finite element models of the corresponding bridges were established and validated by quasi‐static test results. Furthermore, compared to CRHP, the seismic performance of E‐SRHP and L‐SRHP was evaluated from the perspectives of seismic fragility and life‐cycle seismic loss. Research results revealed that the seismic fragility performance of the bridge with L‐SRHP is the best among all three bridges, followed by the bridge with E‐SRHP. Notably, the life‐cycle cost considering seismic loss for E‐SRHP is 83% of that for CRHP, whereas L‐SRHP is only 65% of that for CRHP. In general, the high‐speed railway bridge supported by L‐SRHP possesses the best seismic performance and economic benefits among the three bridges, which shows promising application prospects in high‐intensity earthquake‐prone regions.
Case Studies of Dimensionality in Chemical Data
Authors: Blokhuis Alex , Pollice Robert
Published: December 2024

The ambition to relate intrinsic features of chemical data to the underlying chemical reaction networks (CRNs) is not new, but has experienced only modest success. This may partly be attributed to a lack of theoretical groundwork connecting idealized theory to actual experimental data with added complexity. In particular: i) many CRNs have species that cannot be directly observed experimentally; ii) the apparent number of underlying reactions is a function of the resolution of the data; iii) chemical phenomena can change the number of discernable independent processes of the data. In this work, we illustrate the application of the recently introduced concept of data dimension, which quantifies the linearly independent dimensions the system composition in a CRN can change. We perform case studies inspecting the dimensionality of chemical data characterizing CRNs, and outline how it can be used for mechanistic interpretation. In some instances, these extended considerations allow us to directly recover the CRN proposed in the literature without any fitting. This demonstrates that, with incomplete information, important clues about CRN structure can still be recovered. Additionally, our approach detects critical subtleties, preventing important candidate reactions from being discarded in mechanistic studies.
Physical activity patterns in adolescents: A longitudinal study
Authors: da Penha Freire Silva Juliana Maria , da Costa Silva Eduarda Cristina , Mendonça Gerfeson , Mota Jorge , Hallal Pedro C. , Cazuza de Farias Júnior José
Published: December 2024

The present study aimed at describing and comparing the physical activity (PA) patterns of adolescents from a middle‐income country over a 4‐year period. This is a longitudinal observational study (four waves of data collection, 2014–2017) with 668 adolescents aged 10–13 years in 2014 (mean age of 11.8 ± 0.8 years), of both sexes (53.3% girls), from public schools in João Pessoa, Paraíba state, Brazil. PA was measured using a questionnaire and pattern operationally defined based on the following indicators: type, frequency, duration, and PA recommendations. The most practiced physical activities during the study period were active commuting, games, dancing, cycling, soccer, and futsal. There was a linear trend to a decline in the number of adolescents engaging in nearly all the physical activities, in the duration of activities and the proportion that met the PA recommendations (52.8% in 2014 to 32.2% in 2017). The adolescents engaged in different physical activities, but these declined over the years.