bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of frailty in patients with heart failure: A new Heart Failure Frailty Score developed by Delphi consensus
Authors: Vitale Cristiana , Berthelot Emmanuelle , Coats Andrew J.S. , Loreena Hill , Albert Nancy M. , Tkaczyszyn Michal , Adamopoulos Stamatis , Anderson Lisa , Anker Markus S. , Anker Stefan D. , Bell Derek , Ben‐Gal Tuvia , Bistola Vasiliki , Bozkurt Biykem , Brooks Poppy , Camafort Miguel , Carrero Juan Jesus , Chioncel Ovidiu , Choi Dong‐Ju , Chung Wook‐Jin , Doehner Wolfram , Fernández‐Bergés Daniel , Ferrari Roberto , Fiuzat Mona , Gomez‐Mesa Juan Esteban , Gustafsson Finn , Jankowska Ewa , Kang Seok‐Min , Kinugawa Koichiro , Khunti Kamlesh , Hobbs F.D. Richard , Lee Christopher , Lopatin Yuri , Maddocks Matthew , Maltese Giuseppe , Marques‐Sule Elena , Matsue Yuya , Miró Òscar , Moura Brenda , Piepoli Massimo , Ponikowski Piotr , Pulignano Giovanni , Rakisheva Amina , Ray Robin , Sciacqua Angela , Seferovic Petar , Sentandreu‐Mañó Trinidad , Sze Shirley , Sinclair Alan , Strömberg Anna , Theou Olga , Tsutsui Hiroyuki , Uchmanowicz Izabella , Vidan Maria Teresa , Volterrani Maurizio , von Haehling Stephan , Yoo Byungsu , Zhang Jian , Zhang Yuhui , Metra Marco , Rosano Giuseppe Massimo Claudio
Published: February 2025

Aims

The Heart Failure Frailty Score (HFFS) is a novel, multidimensional tool to assess frailty in patients with heart failure (HF). It has been developed to overcome limitations of existing frailty assessment tools while being practical for clinical use. The HFFS reflects the concept of frailty as a multidimensional, dynamic and potentially reversible state, which increases vulnerability to stressors and risk of poor outcomes in patients with HF.

Methods and results

The HFFS was developed through a Delphi consensus process involving 54 international experts. This approach involved iterative rounds of questionnaires and interviews, where a panel of experts provided their opinions on specific questions prepared by the Steering Committee. The experts were invited to vote and share their views anonymously, using a 5‐point Likert scale over iterative rounds. An 80% threshold was set for agreement or disagreement for each statement. Twenty‐two variables from four domains (clinical, functional, psycho‐cognitive and social) have been selected for inclusion in the HFFS after the third round of the Delphi process. A shorter version (S‐HFFS), including 10 variables, has also been developed for daily clinical use.

Conclusions

The HFFS is a new multidimensional tool for the identification of frailty in patients with HF. It should also enables healthcare providers to identify potential ‘red flags’ for frailty in order to develop personalized care plans. The next step will be to validate the new score in patients with HF.
NHC‐Free Ketone Synthesis via Radical Coupling Mechanisms
Authors: Wang Lifeng , Cai Yuxing , Huang Yong
Published: February 2025

Ketone synthesis via radical coupling mechanisms has recently gained significant attention. Traditionally, these methods have relied on N‐heterocyclic carbenes (NHCs) to generate the key ketyl radical intermediate, either through single‐electron reduction of acyl azolium or single‐electron oxidation involving the Breslow intermediate. In this report, we introduce a novel photoredox protocol that directly generates ketyl radicals from stable acyl imidazoles without the need for NHCs. This approach not only simplifies the process, but also demonstrates broad tolerance for various alkyl radical substrates. Additionally, it can be extended to facilitate relay‐radical coupling reactions.
Exogenous ATP Functions in Alleviating the Decrease in Quality of Grape (Vitis vinifera L.) Fruits After Harvest
Authors: Deng Yaxin , Zhao Mengjie , Jia Lingyun , Liang Junyu , Wang Fei , Yao Meiling , Mitina Irina , Zhang Ji , Feng Hanqing , Arpentin Gheorghe
Published: February 2025

Our current study investigated the effects of exogenous ATP (adenosine triphosphate) on the post‐harvest quality of grape (Vitis vinifera L.) fruits. The results demonstrated that treatment with exogenous ATP effectively alleviated the decreases in fruit firmness, total soluble solids (TSS), vitamin C content and soluble protein of the harvested grape fruits. Furthermore, exogenous ATP also significantly enhanced the content of the titratable acidity (TA) of grape fruits after harvest. This was reflected by the observations that ATP treatment increased the hardness, TSS content, vitamin C content and soluble protein content of the harvested grape fruits by 14.39%, 6.29%, 31.05% and 15.18% on average during 8 days of storage, respectively, compared to the controls. In addition, the harvested grape fruits treated with exogenous ATP had higher activities of SOD (superoxide dismutase) and CAT (catalase) and higher contents of total phenolics and flavonoids compared to the controls. This was reflected by the observations that ATP treatment increased the SOD activity, CAT activity, flavonoid content and total phenol content by 39.79%, 19.43%, 17.74% and 15.06% on average during 8 days of storage, respectively, compared to the controls. These observations highlighted that exogenous ATP can function in alleviating the decrease in quality of grape fruits after harvest and increasing the antioxidative ability of harvested grape fruits during the storage period. Consequently, treatment with exogenous ATP could offer an efficacious approach for preserving the quality of grape fruits during the storage period.
Evaluation of serum and peritoneal fluid mannose‐binding lectin associated serine protease‐3, adipsin, properdin, and complement factor‐H levels in endometriosis patients
Authors: Eşkin Tanrıverdi Merve Didem , Kaya Sezginer Ecem , Erol Koç Esin Merve , Moraloğlu Tekin Özlem
Published: February 2025

Objective

Endometriosis is a chronic disease which has been reported to be associated with distorted immune mechanisms. The alternative pathway is a complement system which plays a role in immune defense. The present study aimed to evaluate whether the level of alternative complement molecules differ in women with endometriosis compared to heathy individuals.

Methods

A total of 58 women participated in this prospective research. Women with a diagnosis of endometriosis confirmed by laparoscopy (n = 32) were compared to healthy women (n = 26) in terms of serum adipsin, properdin, mannose‐binding lectin‐associated serine protease‐3 and complement factor‐H (CFH) levels. The peritoneal fluid samples which were taken during the endometriosis surgery were also analyzed in terms of the complement levels. The clinical and demographic data including the serum CA‐125 level and pelvic pain were also analyzed. SPSS version 23.0 was used in statistical analysis.

Results

The serum levels of adipsin and CFH were found to be significantly increased in women with endometriosis (P = 0.027 and P = 0.040, respectively). Serum adipsin level was found to significantly correlate with serum CA‐125 level (r = 0.320, P = 0.015), serum CFH level (r = 0.705, P < 0.001), and degree of the pelvic pain complaint (r = 0.326, P = 0.013). A strong, positive correlation was also observed between peritoneal fluid levels of adipsin, and CFH (r = 0.593; P < 0.001).

Conclusion

To the best of our knowledge, the present study is the first to evaluate the alternative complement system in women with endometriosis. The current findings may be noteworthy to elucidate the possible role of the key molecules of the alternative pathway in endometriosis pathogenesis.
Possible new mechanisms of primary drug resistance in NSCLC with EGFR mutation treated with Osimertinib
Authors: Shao Lujing , Li Tong , Jia Xinyan , Zhang Xinyu , Li Qi , Dong Chunyan
Published: February 2025

In this study, a patient with lung adenocarcinoma harboring an EGFR mutation exhibited primary resistance to the targeted EGFR inhibitor Osimertinib after 2 months of treatment. As the disease advanced, further genetic analysis revealed the emergence of additional mutations in ARID1A, NTRK1, and ZRSR2, alongside the existing EGFR mutation. Subsequent treatment with Pemetrexed resulted in a significant reduction in liver metastases. Protein mass spectrometry sequencing and immunohistochemical analysis collectively indicated that the PI3K/mTOR pathway mediates the mechanism through which these gene mutations confer primary drug resistance. Evidence demonstrates that the co‐occurrence of EGFR and ARID1A mutations diminishes the efficacy of EGFR tyrosine kinase inhibitors (EGFR TKIs). Consequently, it is hypothesized that mutations in NTRK1 and ZRSR2, which are implicated in the PI3K/mTOR pathway, contribute to the primary resistance observed with Osimertinib treatment. In this case, the illness was effectively managed through prompt adjustments to the treatment regimen and the rapid administration of chemotherapy drugs. This finding also constitutes the first evidence that mutations in NTRK1 and ZRSR2 are pivotal in the development of primary resistance to Osimertinib. Consequently, it is imperative to conduct genetic testing at the earliest opportunity and modify the treatment plan accordingly.
Approximating Fixed‐Horizon Forecasts Using Fixed‐Event Forecasts
Authors: Knüppel Malte , Vladu Andreea L.
Published: February 2025

Many forecast surveys ask their participants for fixed‐event forecasts. As fixed‐event forecasts have seasonal properties, users often employ an ad hoc approach to approximate fixed‐horizon forecasts based on these fixed‐event forecasts. We derive an optimal approximation for fixed‐horizon forecasts by minimizing the mean‐squared approximation error. Like the ad hoc approach, our approximation employs a weighted average of the fixed‐event forecasts. The optimal weights tend to differ substantially from those of the ad hoc approach. In empirical applications, the gains from using optimal instead of ad hoc weights turn out to be sizeable. The approximation approach proposed can also be useful in other applications.
Physicochemical Characterization of Hyaluronic Acid‐Methylcellulose Semi‐Gels for Mitochondria Transplantation
Authors: Ahmed A. Jamie , Gallegos Zoe A. , Dinar Md Abu Monsur , Sullivan Patrick G. , DeRouchey Jason E. , Patel Samir P. , Rabchevsky Alexander G. , Dziubla Thomas D.
Published: February 2025

Traumatic spinal cord injury (SCI) presents a significant medical challenge due to its intricate nature and treatment complexities. SCI can cause physical impairments by affecting neural and motor functions as well as initiating a series of pathophysiological events exacerbating the initial trauma. Leakage from ruptured neurons and vessels disrupt ionic balance and induces excitotoxicity, leading to progressive cellular degeneration. Introducing mitochondria to the SCI lesion has shown potential in attenuating secondary injury. Mitochondria transplantation improves cellular bioenergetics and reduces concentration of reactive oxygen species achieving homeostasis and neuroprotection. Nonetheless, keeping mitochondria viable outside cell environment for a time longer than a few minutes proves to be challenging. Additionally, localized delivery to the injury site has also been limited by other factors including flow rate of cerebrospinal fluid that washes away mobilized organelle from the compromised tissue site. Previously we showed that using hyaluronic acid‐methylcellulose semi‐gels (HAMC) as a biocompatible, erodible thermogelling delivery vehicle helped to overcome some of these challenges. HAMC allows for controlled release at and around the injury site, utilizing the reverse thermogelling property of MC. Sustained release of mitochondria at slower rate can increase their uptake in spinal tissue. To better optimize the semi‐gel delivery of mitochondria requires a more complete understanding of the physicochemical properties of the HAMC semi‐gels. We have used ultraviolet–visible spectroscopy to measure optical density of HAMC semi‐gels for different HA to MC ratios and examine the temperature dependent gelation properties above their low critical solution temperature (LCST). The viscosity and degree of crystallinity of the resulting HAMC semi‐gels were also assessed. Semi‐gel erosion and mitochondrial release over time were studied using a fluorescence microplate reader. Lastly, seahorse assay was used to study released mitochondria respiration and viability after incubation in HAMC semi‐gel.
Hypoxic Secretome and Exosomes Derived From Human Glioblastoma Cells (U87MG) Promote Protumorigenic Phenotype of Microglia in Vitro
Authors: Pancholi Sangati , Shah Ritvi , Bose Utsav , Yadav Ankit , Murukan Karthik , Pillai Prakash
Published: February 2025

Glioblastoma multiforme (GBM), a highly heterogeneous CNS tumor known for its highest incidence rates and poor prognosis has shown limited success in the therapies due to hypoxia—driving immune‐suppression in the tumor microenvironment (TME). Emerging evidence highlights the involvement of tumor cell‐derived exosomes in tumor‐associated microglia polarization via transfer of exosomal onco‐proteins and miRNAs. Although the regulatory role of long noncoding RNAs (lncRNAs) in immune signaling are known, its mechanism in microglial polarization via exosomes in GBM still remains poorly understood. In our study, we found that in comparison to the normoxic GBM‐derived exosomes lncRNA H19 was significantly upregulated in hypoxic GBM‐derived exosomes. Hypoxic GBM‐derived exosomes and secretome (conditioned media) caused the reduction in the % phagocytosis of microglia as compared with the control group. Moreover, GBM secretome caused increase in the M2‐specific genes (IL10, STAT‐3, CD163, CD206) in microglia indicating its polarization to the protumorigenic (M2) phenotype. LncRNA H19 knocked down GBM‐secretome treatment in microglia further reduced the STAT‐3 expression indicating H19 mediated signaling. Overall, our results suggest the involvement of hypoxic exosomes and lncRNA H19 in microglial polarization and H19 as a potential target.
Characteristics of the parent‐child relationship at 18‐months of age predict the onset and type of mental disorders in childhood and adolescence: A longitudinal nested birth cohort study
Authors: Nilsson Kristine Kahr , Grønnebæk Lasse , Østergård Ole Karkov , Landorph Susanne , Houmann Tine , Olsen Else Marie , Skovgaard Anne Mette
Published: February 2025

Background

The quality of the parent‐child relationship in the first years of childhood has been associated with various long‐term mental health outcomes. However, it is unclear whether specific characteristics of the early parent‐child relationship predict the onset of mental disorders. The aim of this study was therefore to examine child, parent, and dyadic characteristics of the early parent‐child relationship as predictors of mental disorders in childhood and adolescence.

Method

As a part of the Copenhagen Child Cohort 2000, a child cohort of 295 children participated in the study at 18‐months of age and were subsequently followed until late adolescence. Child, parent, and dyadic dimensions of the early parent‐child relationship were assessed using the observational Parent‐Child Early Relational Assessment. The outcomes were mental disorders subsequently diagnosed in childhood and adolescence.

Results

Cox‐regression analyses suggested that parent characteristics involving negative affect and behavior, intrusiveness and insensitivity during early parent child interactions were associated with increased risk of the child being diagnosed with a mental disorder at later ages. However, variation was noted across specific diagnoses. Parental negative affect and behavior was specifically associated with increased risk of attention deficit hyperactivity disorder, while infant dysregulation and irritability was specifically associated with increased risk of autism spectrum disorders. These results remained significant after adjusting for parental mental disorders and early mental health problems of the child.

Conclusion

Disorder‐specific associations were observed between dysfunctions in the early parent‐child relationship and subsequent mental disorders. Improving such early relational dysfunctions may support the goals of early interventions that aim to mitigate the risk of mental disorders from a very early age.
UHPLC‐QTOF‐MS‐Based Metabolic Profiling, Estimation of Antioxidants and Anticancer Potential Assessment of Dicliptera bupleuroides Nees by Caspase Activation, and ROS and MMP Evaluation by Using Fluorescence Microscopy
Authors: Sarfraz Mehak , Alam Fiaz , Uddin Zia
Published: February 2025

Dicliptera bupleuroides has been used traditionally for treating various ailments in many countries. Its detailed phytochemical profiling and pharmacological evaluation in treating cancer based on reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) analysis along with caspase activation studies has not been done previously. This study was conducted for detailed phytochemical profiling of D. bupleuroides by using ultra‐high performance liquid chromatography‐quadrupole time‐of‐flight mass spectrometry (UHPLC‐QTOF‐MS) and to evaluate its antioxidant and anticancer potential against hepatocellular carcinoma (HepG2) cells. The extract was subjected to UHPLC‐QTOF‐MS analysis for metabolite profiling, and GNPS Molnet enhancer determined its major phytochemical classes. Phytochemical tests and multimode antioxidant assays were also executed. The extract was pharmacologically evaluated for its anticancer potential against HepG2 cells using CCK‐8 assay. Intracellular ROS generation and loss in MMP were studied by fluorescence microscopy. Network pharmacology and molecular docking of selected compounds were executed. The extract contains total phenolic content as 58.37 ± 0.32 μg GAE/mg extract, and remarkable antioxidant potential was revealed in total antioxidant contents (TAC) and total reducing power (TRP) assays, i.e., 70.4 ± 0.4, 83.2 ± 1.9 μg ascorbic acid equilant (AAE) Borges/mg extract. The UHPLC‐QTOF‐MS analysis showed that the extract contains flavonoid glycosides, phenolic acids, flavans, O‐methylated flavonoids, linoleic acids, terpene glycosides, triterpenoid saponins, and certain other phytoconstituents. Maximum inhibition of 77.13% ± 1.60% against HepG2 cells was observed at 24 h. Loss in MMP by JC‐1 (5,5′,6,6′‐tetrachloro‐1,1′,3,3′‐tetraethylbenzimi‐ dazolylcarbocyanine iodide) staining and increased ROS generation, and caspase‐3, caspase‐8 activation by extract significantly illustrated the cancer cell death by apoptosis. D. bupleuroides could be a potential source of safe and therapeutically active compounds that can be purified to develop safer, selective, and efficacious anticancer agents with fewer side effects.
The Anti‐Inflammatory Effects of Liraglutide in Equine Inflammatory Joint Models
Authors: Scheike Ann‐Sofie , Plomp Saskia , Fugazzola Maria Carlotta , Meurot Coralie , Berenbaum Francis , van Weeren Paul René , Tryfonidou Marianna Andriana , von Hegedus Johannes Hendrick
Published: February 2025

This study investigates the anti‐inflammatory properties of liraglutide, a glucagon‐like peptide 1 receptor agonists, in equine in vitro models and in an in vivo acute synovitis model in Shetland ponies. The anti‐inflammatory effect of liraglutide was assessed by measuring concentrations of inflammatory biomarker C‐C Motif Chemokine Ligand 2 (CCL2) in culture media of equine whole blood, peripheral blood mononuclear cells (PBMCs), chondrocytes, and synoviocytes, with or without lipopolysaccharide (LPS) or interleukin‐1β. In the in vivo experiment, acute synovitis was bilaterally induced with 0.25 ng LPS in the intercarpal joints of seven healthy Shetland ponies. The ponies were subsequently treated with either 6 mg liraglutide or a placebo as a paired control in each joint. The impact of liraglutide on biomarkers associated with inflammation (including white blood cell count, total protein, CCL2, and bradykinin) and cartilage metabolism (such as glycosaminoglycans, general matrix metalloproteinase activity, carboxypropeptide type II collagen, and collagen‐cleavage neoepitope of type II collagen) was assessed across serial synovial fluid samples. Liraglutide was found to have an anti‐inflammatory effect by reducing CCL2 concentrations in culture media of whole blood, PBMCs, chondrocytes, and synoviocytes. In contrast, no significant differences in synovial fluid inflammatory nor cartilage metabolism biomarker levels were found between joints treated with LPS and 6 mg liraglutide, versus LPS and placebo. In conclusion, liraglutide demonstrates the potential to attenuate inflammatory processes in joint cells. Additional research is necessary to validate its efficacy within the complex milieu of an inflamed joint.
Placental Microvascular Architecture Imaging in Normal and Congenital Heart Disease Pregnancies
Authors: Chen Peiwen , Zhao Sheng , Sun Liqun , Huang Hui , Cheng Chen , Wang Weiyun , Sun Luming , Chen Jianping , Liu Fang , Pan Shengbao , Wang Dan , Li Qinghua , Tian Zhiyun , Chen Xinlin , Rychik Jack
Published: February 2025

Objectives

To evaluate the placental vascular architecture using MV Flow™ imaging for analyzing vascular distribution per region of biological tissue in isolated congenital heart diseases (CHD), CHD associated with extracardiac malformations (EXM) and normal pregnancies, and to explore the relationship of fetal Doppler flow parameters and growth to placental perfusion in these conditions.

Methods

Placental microvascular structure was assessed using MV‐Flow™ in a total of 227 normal fetuses and 139 with CHD; fetuses with gestational age ranging from 11 to 41 weeks were included. Placental vascular indices (VIMV %) was acquired at three different segments of each placenta (upper, middle, and lower regions). Doppler pulsatility indices of fetal umbilical artery (UA), middle cerebral artery (MCA), ductus venosus (DV), uterine artery (UtA), and cerebroplacental ratio were measured in both normal and CHD groups. The CHD group was divided into two subgroup based on whether it is associated with EXM.

Results

Compared to the control group, the CHD with EXM group exhibited a significantly lower VIMV % for the upper, middle, and lower regions of the placenta (P = .005; P = .018; P = .039, respectively). In the total CHD group, VIMV % decreased in the middle segment of placenta in the 2nd trimester compared to the control group. But the VIMV % of upper and middle segments decreased in the 3rd trimester. Both subgroups, EXM and isolated CHD, showed similar distribution of gestational weeks. Doppler vascular indices were significantly different compared to normal in the total CHD group for UA‐pulse index (PI), DV‐PI, right UtA‐PI, and left UtA‐PI, with similar differences from normal for the CHD with EXM group. DV‐PI was the only significantly different Doppler vascular parameter for the isolated CHD group compared to normal.

Conclusions

For the first time, MV‐Flow™ imaging demonstrated reduced placental vascularity in fetuses with CHD and ECM and in fetuses with isolated CHD in the 3rd trimester of pregnancy. Application of MV‐Flow™ as part of serial fetal echocardiographic surveillance in cases of CHD may allow for better understanding of the development of placental abnormalities.
Photocarcinogenesis of the skin: Current status and future trends
Authors: Yang Ting‐Ting , Lan Cheng‐Che E.
Published: February 2025

Solar radiation is essential for life on Earth but is also a major contributor to skin carcinogenesis. Solar radiation, particularly ultraviolet (UV) B (280–320 nm) and UVA (320–400 nm), induces photocarcinogenesis via various pathways. UV light can directly cause DNA damage, resulting in genetic mutations if not repaired correctly. UV light can also induce photocarcinogenesis by generating reactive oxygen species, inducing immunosuppression and inflammation. Recently, visible light (400–760 nm) has been shown to contribute to photocarcinogenesis by activating oxidative pathways. In addition to the irradiation dose (fluence, J/m2), UVB irradiance (W/m2) is also considered a factor influencing photocarcinogenesis. In this review, we summarize the mechanisms of photocarcinogenesis and provide strategies to prevent skin cancer.
Global Perspectives on Lead Contamination and Health Risks in Surface Water, Rice Grains, and Soils
Authors: Kumar Amit , Kumar Vinod , Thakur Monika , Singh Kirpal , Jasrotia Rakesh , Kumar Rupesh , Radziemska Maja
Published: February 2025

Lead (Pb), a pervasive and highly toxic metal, and poses significant environmental and health risks due to its extensive biogeochemical cycling, driven by anthropogenic activities. This review evaluates the health hazards allied with Pb contamination in surface water bodies, soils, and rice grains, based on a comprehensive analysis (2015–2024) of 118, 133, and 102 literature studies, respectively. The year‐wise assessment of Pb concentration in surface water bodies and soils frequently exceeded their permissible limits in 2015, 2017, 2018, 2019, 2020, and 2022. However, the mean Pb concentration in rice grains consistently surpassed the Codex Alimentarius limit (2.5 μg/g) across the analyzed years. Geographically, Bangladesh, India, Pakistan, and China surpassed their limits for surface water bodies, rice grains and soils, emphasizing regional vulnerabilities. Health risk analysis indicated hazard quotient values exceeding one for children and adults in surface water bodies and rice grains, exhibiting significant non‐carcinogenic risks. In soils, dermal exposure identified as the predominant pathways contributing to health hazard followed by ingestion, while inhalation presented the lower risk. These findings emphasize the imperative necessitate for implementing strict regulatory frameworks and preventive measures to mitigate Pb contamination in the environment and minimize its potential health impacts. This study advances understanding of Pb exposure pathways and risks, offering valuable insights for targeted mitigation strategies and public health interventions.
Midwater anoxia disrupts the trophic structure of zooplankton and fish in an oxygen deficient zone
Authors: Gutiérrez‐Bravo Juan Gerardo , Altabet Mark A. , Sánchez‐Velasco Laura , Jiménez‐Rosenberg Sylvia Patricia Adelheid
Published: February 2025

Anoxic waters in the ocean's oxygen deficient zones (ODZs) limit the vertical migrations of zooplankton and mesopelagic fish impacting their ecology and influence on biogeochemical processes. Using an oxypleth‐tracking, nighttime‐only sampling protocol, this research reconstructed the trophic interactions of fish larvae and adults, and zooplankton, across the Eastern Tropical North Pacific ODZ. Bulk zooplankton δ15N increased latitudinally by ~ 3.3‰ from Costa Rica to Baja California due to anoxia‐derived denitrification and consequent enrichment of nitrogen sources for producers. Zooplankton δ15N also increased with depth, with an abrupt 3.4‰ increase below the anoxic core (~ 900 m depth), indicating a distinct trophic structure in the resident zooplankton community. Above the anoxic core, δ15N was similar for fish larvae (10.1‰) and zooplankton (10.5‰), reflecting a shared food source. An exception was the hypoxia‐tolerant myctophid Diogenichthys laternatus (δ15N = 7.5‰) that possibly feeds on chemoautotrophy‐derived material at the oxic‐anoxic interface. The δ15N of fish adults residing below the anoxic core, like the meso‐bathypelagic Notolychnus valdiviae (17.11‰) and Cyclothone spp. (15.89‰), was, on average, 4.8‰ higher than larval stages sampled at shallower depths, and 1.2‰ higher than zooplankton below the anoxic core. This stark increase in fish and zooplankton δ15N directly below the anoxic core suggests that anoxic waters act as a barrier for the downward trophic transfer by vertical migrants into the deep sea. Considering the current trends of ocean deoxygenation, this anoxia‐derived disruption of the migrant pump could limit the carbon sequestration potential of ODZs.
Friction stir welding of high iron‐containing cast aluminum‐silicon‐magnesium alloys.
Authors: Phongphisutthinan C. , Rattanathaworn W. , Waree K. , Suga T. , Liu H. , Morisada Y. , Fujii H.
Published: February 2025

High iron‐containing cast aluminum‐silicon‐magnesium alloys have been developed for utilization recycled aluminum alloys. Iron‐containing intermetallic compounds (IMCs) are commonly considered as harmful to mechanical properties in the cast aluminum alloys containing Fe impurities. Friction stir welding (FSW) is applied to weld butt joint between cast aluminum‐silicon‐magnesium‐iron alloys plates with 1 wt.‐%, 2 wt.‐% and 4 wt.‐% Fe contents. Iron‐containing intermetallic compounds become finely fragmented and distributed in the aluminum matrix by friction stir welding. Friction stir welding clearly improves mechanical properties of the joints over the base materials. Fragmented intermetallic compounds in high iron‐containing aluminum‐silicon‐magnesium alloys can enhance tensile strength over the commercial A356 aluminum alloy.
Motor Symptom Variability in Parkinson's Disease: Implications for Personalized Trial Outcomes?
Authors: Janssen Daalen Jules , van der Heiden Maudy , Meinders Marjan , Post Bart
Published: February 2025

Background

The Movement Disorders Society Unified Parkinson Disease Rating Scale (MDS‐UPDRS), Part III, is the gold standard for assessing motor symptoms in Parkinson's disease (PD). However, motor symptoms fluctuate significantly from day to day, potentially limiting the sensitivity of this scale for trials with short duration and crossover designs. This study investigated whether day‐to‐day variability in motor symptoms exceeds the minimal clinically important difference (MCID) in the MDS‐UPDRS, Part III.

Methods

Twenty PD participants (Hoehn & Yahr stages 1.5–3) underwent 10 weekly off‐medication assessments by one assessor on the same morning. Several determinants of day‐to‐day variability were explored.

Results

Symptom variability often exceeded the MCID for worsening and improvement. Current mental stress and fatigue did not correlate with worse scores, nor did physical activity and sleep quality in the previous week.

Conclusions

These findings suggest that day‐to‐day symptom variability impacts MDS‐UPDRS scores in smaller and shorter‐duration trials of symptomatic interventions. Continuous monitoring using wearable sensors may offer more accurate and reliable measures for evaluating PD motor symptoms in clinical studies. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Gene Expression Signatures of Immaturity, Decreased pH, and Neural Hyperexcitation in the Hippocampus of Alzheimer's Disease Model Mice
Authors: Naganishi Sayaka , Hagihara Hideo , Miyakawa Tsuyoshi
Published: February 2025

Aims

Alzheimer's disease (AD) is a leading cause of dementia, with increasing prevalence. Mutations in genes like MAPT, PSEN1, and PSEN2 are risk factors, leading to the development of several AD model mice. Recent hypotheses suggest AD brain pathology involves abnormal neurodevelopment, decreased pH, and neural hyperexcitation. However, it remains unclear to what extent these pathologies are reflected in the gene expression changes of AD models. This study aims to compare gene expression patterns in the brains of multiple AD model mice with those related to these three factors, evaluating the extent of overlap.

Methods

We conducted a comprehensive search of public databases, collecting 20 gene expression datasets from the hippocampus of AD model mice. These datasets were compared with gene sets related to hippocampal maturation, brain pH, and neural hyperexcitation to statistically assess overlap. Pathway enrichment analysis explored the biological relevance of these gene expression changes.

Results

The extent of overlap with maturity‐, pH‐, and hyperexcitation‐associated genes varied across AD models, showing significant correlations between lower maturity, lower pH, and increased neural hyperexcitation. In MAPT mutant and APP+PSEN1 homozygous transgenic mice, these signatures became more pronounced with age. Pathway meta‐analysis revealed that genes associated with maturity, pH, and hyperexcitation in AD models are involved in synaptic and channel functions, as well as inflammatory responses, consistent with previous studies.

Conclusion

These findings suggest that pathophysiological changes related to maturity, pH, and neural hyperexcitation play varying roles across individual AD model mice. Our recent study found a negative correlation between disease progression and actual pH levels in human AD patients. Considering the results presented in this study, maturity and neural hyperexcitation, which are correlated with pH, may also be linked to disease progression. Thus, gene expression changes in these factors could be useful markers for assessing the pathology in AD models.
A Trust‐Region Method for p‐Harmonic Shape Optimization
Authors: Wyschka Henrik , Wollner Winnifried
Published: February 2025

The appropriate scaling of deformation fields has a significant impact on the performance of shape optimization algorithms. We introduce a pointwise gradient constraint to an efficient algorithm for ‐Laplace problems, while the complexity of the algorithm remains polynomial. Using this algorithm, we compute descent directions for shape optimization using ‐harmonic approach that fulfill a trust‐region type constraint. Numerical experiments show the advantages of deformations computed with this approach when compared to deformations that are scaled after computation. This considers, in particular, the approximation of the limit setting and the preservation of mesh quality during an optimization with a fixed step size.
Improving Time to Bleeding Disorder Treatment in the Emergency Department
Authors: Littner Lisa , Thomas Evan , Mooney Laura , Doyle Julie , Hendrickson Julie , Tarango Cristina
Published: February 2025

Introduction

Knowledge of the guidelines for treating people with bleeding disorders (PwBD) is vital for emergency department (ED) staff, as PwBD rely on the ED for treatment of acute bleeding episodes or injuries. Unfamiliarity with these guidelines can delay treatment. We aimed to improve the timely treatment of PwBD seeking emergency care by reducing the mean time‐to‐factor administration in the ED by 20%, from the baseline of 110 to 88 minutes.

Methods

Our quality improvement (QI) initiative (2019–2024) used Plan‐Do‐Study‐Analyze cycles. Weekly electronic health record (EHR) reports tracked PwBD's time of arrival, admission, clotting factor concentrate ordering, and administration. Interventions targeted delays identified in the process.

Results

Baseline data showed a 110‐mean time‐time‐to‐factor. Our aim of reducing the time‐to‐factor by 20% from the baseline of 110 minutes was reached in May 2020. This improvement was exceeded and sustained throughout the project. At the conclusion, we achieved a 62% reduction in time‐to‐factor and a mean time‐to‐factor of 42 minutes.

Conclusion

By using an EHR tool, we were able to identify when during the ED visit process delays occurred, which helped us better target our interventions. Our educational‐based interventions were adapted to reach our intended audiences while working around barriers related to the COVID‐19 pandemic, such as high patient volumes and staff shortages. Our results show a decrease in time to factor in the ED and an increase in the PwBD receiving factor within 60 minutes of arrival time. This has been a sustainable improvement.
Re‐Irradiation for the Progressive Pediatric Diffuse Intrinsic Pontine Glioma: A Report on 109 Children From a Single Center
Authors: Zaghloul Mohamed Saad , Bishr Mai K. , Refaat Amal , Hemaly Ahmed El , Ayadi Moatssem Al , Ahmed Soha , Maher Eslam , Todary Engy S.
Published: February 2025

Background

Diffuse intrinsic pontine glioma (DIPG) is a challenging pediatric tumor that frequently progresses within the first year following local radiotherapy. However, several small studies have suggested that re‐irradiation may improve quality of life and extend overall survival.

Patients and Methods

This retrospective study included 109 children who experienced disease progression ≥3 months after their initial radiotherapy, and subsequently received re‐irradiation at a single institution. These patients were compared with a cohort of 60 children, meeting the same criteria, who were treated before adopting the re‐irradiation policy and received only the best supportive care (BSC). Most of the re‐irradiated children (94%) received first radiation dose as hypofractionation (39 Gy/13 fractions).

Results

The re‐irradiation group demonstrated significantly higher overall survival (OS) rates after the first progression, with a 6‐month OS of 42% (95% CI: 34%–53%) compared to 16% (95% CI: 8.9%–32%) in the BSC group (p < 0.001). Re‐irradiation reduced the hazard of death by more than half (HR = 0.45, p < 0.001). Clinical response (p < 0.001) and radiological response (p = 0.016) were significant predictors of improved survival. While the time from initial radiotherapy to progression (p = 0.059) and higher re‐irradiation doses (p = 0.074) were associated with improved OS, these factors did not reach statistical significance but may represent potential prognostic indicators.

Conclusion

Re‐irradiation improved the OS in children with progression of DIPG and alleviated their signs and symptoms.
Investigating mechanical properties of composites reinforced with jute/cotton natural fibers in hybridized epoxy/vinylester and epoxy/polyester resins
Authors: Ahmad Hammad , Abid Muhammad Hamza , Gazo‐Hanna Eddie , Shah Atta Ur Rehman , Ghumman Imran Sajid Shahid , Arif Saad , Naseem Muhammad Shoaib , Zohaib Hafiz Muhammad
Published: February 2025

This study explores the hybrid effect of environmental friendly jute and cotton fabrics as reinforcement in a multiresin based composite system. Two hybrid resins (containing epoxy/vinylester and epoxy/polyester) were reinforced with hybrid jute and cotton fabrics, which makes it a multihybrid composite material. Effect of hybridization and varying the content of fibers (10, 20, and 15 wt%) was analyzed by employing tensile, bending, and charpy impact tests of the composites. The fractured surfaces after tensile testing were examined using scanning electron microscopy (SEM) whereas the bonding structure of multiresin and the interaction of reinforcement with the resins were scrutinized through Fourier transformation infrared spectroscopy (FTIR). The results showed that higher content of cotton fiber has a superior impact on mechanical properties as compared with jute fiber, this is because of the higher cellulose content found in the cotton fiber. Moreover, in terms of resins, epoxy/vinylester hybrid resin proved to be dominant in enhancing mechanical properties compared with epoxy/polyester resin. For reference, the tensile strength of cotton/jute/epoxy/vinylester hybrid composite (61.12 MPa) was observed to be 11.71% higher than that of cotton/jute/epoxy/polyester (54.71 MPa). A similar behavior was observed in flexural and impact tests. The SEM analysis provided evidence that the composites mainly failed due to matrix failure rather than interfacial failure, which is a reason of enhancement in mechanical strength. Such newly developed materials are auspicious for high‐performance engineering applications in addition to environmental friendliness.

Highlights

Two hybrid resins were reinforced with hybrid jute/cotton natural fibers.

IPN structure was formed in epoxy/polyester and epoxy/vinyl ester resins.

The multi hybridization enhanced the mechanical properties of the composites.

Cotton fiber exhibited more influence on the properties of the composites.

Epoxy/vinylester has better fibril removal resistant than epoxy/polyester.
Lowering Onset Temperature and Improving Oxidation of Aluminum Alloys Containing Gallium and Indium
Authors: Harper Caleb N. , Pech Nicholas , Bradley Catherine , Grimsich Tyler , Collard Diane , Ӧrnek Metin , Wu Chi‐Chin , Son Steven F.
Published: February 2025

The formation of an inhibiting oxide layer on the surface of aluminum not only offers significant thermal stability at ambient temperatures but also presents a significant barrier toward intentional ignition in energetic formulations. Therefore, we demonstrate that the oxide‐disrupting properties of gallium and indium in aluminum–gallium/indium alloys significantly reduce the onset temperature for oxidation and enhance the overall reactivity of the aluminum while maintaining reasonable thermal stability. This increased oxidation is likely due to weakened oxide layer adherence through significantly reduced surface energies. Neat, spherical micron‐aluminum powders oxidize between 7 and 14 wt.% of their total mass by 1200°C in a thermogravimetric analyzer operated in 20% oxygen‐containing argon. In contrast, similarly sized aluminum–gallium/indium alloy powders fabricated using mechanical processing (containing 3–16 wt.% Ga–In) oxidize 49%–86% of their total mass under the same conditions. While the increased reactivity of the mechanically processed aluminum–gallium/indium alloys can be partially explained by an increase in surface area due to mechanical processing, neat aluminum particles with similar surface areas are not as reactive, oxidizing only 22.4 wt.% of the active aluminum by 1200°C.
Robust Semi‐Global Output Regulation of Uncertain Two‐Time‐Scale Systems With Input Saturation
Authors: Lei Yan , Wang Yan‐Wu , Morărescu Irinel‐Constantin , Astolfi Daniele
Published: February 2025

This paper investigates the robust semi‐global output regulation of uncertain linear systems with input saturation. In this setup, one cannot apply off‐the‐shelf techniques to reject structural uncertainties due to numerical issues caused by the two time scales but also due to technical issues generated by the input saturation. To solve this problem, we combine internal model principle with low gain technique and singular perturbation theory. Explicitly, the regulator design is based on the computation of the solutions of a Sylvester equation, which can be ill‐conditioned in the two‐time scales setting. To overcome this, we propose an easily solvable equation, and the existence and uniqueness of its solution are guaranteed under some standard assumptions. Accordingly, an internal model‐based controller is designed such that the semi‐global robust output regulation problem can be solved. In order to cope with the input saturation, we impose that the ultimate upper bound of the infinity norm of the exosystem state is limited and satisfies certain constraints. Finally, three examples are provided to illustrate the effectiveness of the results.
Lower Limb Exoskeletons, Application‐Centric Classifications: A Review
Authors: Karthik Venkatakrishnan , Das Subhashree , Nayak Smaranika , Pandey Anish
Published: February 2025

Exoskeletons are a relatively new field of technology used as assistive devices. Since the first development of the exoskeleton in the late 19th century, this field has seen significant advancements, as it has potential in numerous applications. Although this field is rapidly growing, it remains unable to be fully implemented in various applications. It is due to the limitations in the existing technology used to develop the exoskeleton, the lack of standardization, and the rapid growth in the exoskeleton field. To address the existing challenge, this review paper attempts to develop a classification model of lower limb exoskeletons (LLEs), which researchers and engineers can use to understand the relation between various application scenarios and different design aspects while developing an LLE. The classification model has been divided into two levels: application and design aspects of an exoskeleton. In this paper, 53 LLEs have been analyzed and classified into a flexible model, allowing future exoskeletons also to be added. It has also been discussed why each exoskeleton is classified into various categories.
Biomimetic Hydrogels – Tools for Regenerative Medicine, Oncology, and Understanding Medical Gas Plasma Therapy
Authors: Martinet Alice , Miebach Lea , Weltmann Klaus‐Dieter , Emmert Steffen , Bekeschus Sander
Published: February 2025

Biomimetic hydrogels enable biochemical, cell biology, and tissue‐like studies in the third dimension. Smart hydrogels are also frequently used in tissue engineering and as drug carriers for intra‐ or extracutaneous regenerative medicine. They have also been studied in bio‐sensor development, 3D cell culture, and organoid growth optimization. Yet, many hydrogel types, adjuvant components, and cross‐linking methods have emerged over decades, diversifying and complexifying such studies. Here, an evaluative overview is provided, mapping potential applications to the corresponding hydrogel tuning. Strikingly, hydrogels are ideal for studying locoregional therapy modalities, such as cold medical gas plasma technology. These partially ionized gases produce various reactive oxygen species (ROS) types along with other physico‐chemical components such as ions and electric fields, and the spatio‐temporal effects of these components delivered to diseased tissues remain largely elusive to date. Hence, this work outlines the promising applications of hydrogels in biomedical research in general and cold plasma science in particular and underlines the great potential of these smart scaffolds for current and future research and therapy.
Substrate‐Tight Graphene Transmembrane‐nanofluidic Devices
Authors: Kang Xiaofang , Chen Buhang , van Geest Erik P. , Fu Wangyang , Gao Jianwei , Sun Luzhao , Liu Zhongfan , Schneider Grégory F.
Published: February 2025

Nanopores in 2D membranes like graphene have great potential for applications such as single‐molecule sensing, ion sieving, and harvesting osmotic power. A critical challenge, however, has been to ensure the stability of these nanofluidic transmembrane devices, as the ultrathin graphene membranes tend to delaminate and peel away from their substrates when exposed to aqueous solutions. In this study, it is shown that using a pyrene‐based coating prevents delamination and allows graphene to remain freestanding over a SiN aperture for several days in an electrolyte. The pyrene molecules interact strongly with the graphene through π–π bonding, adhering the graphene to the substrate. Additionally, the pyrene‐based adhesion layer remarkably increases the success rates of the graphene transmembrane devices from 4% to 76.2%. The results underscore the importance of using adhesion layers to enhance the stability of graphene in nanofluidic devices and prolong their operational lifespan. It enables the development of more robust graphene‐based nanofluidic devices for a wide range of applications necessitating free‐standing graphene.
Bioinspired Intelligent Electronic Skin for Medicine and Healthcare
Authors: Liu Zhirong , Hu Junhao , Shen Guozhen
Published: February 2025

Intelligent electronic skin aims to mimic, enhance, and even surpass the functions of biological skin, enabling artificial systems to sense environmental stimuli and interact more naturally with humans. In healthcare, intelligent electronic skin is revolutionizing diagnostics and personalized medicine by detecting early signs of diseases and programming exogenous stimuli for timely intervention and on‐demand treatment. This review discusses latest progress in bioinspired intelligent electronic skin and its application in medicine and healthcare. First, strategies for the development of intelligent electronic skin to simulate or even surpass human skin are discussed, focusing on its basic characteristics, as well as sensing and regulating functions. Then, the applications of electronic skin in health monitoring and wearable therapies are discussed, illustrating its potential to provide early warning and on‐demand treatment. Finally, the significance of electronic skin in bridging the gap between electronic and biological systems is emphasized and the challenges and future perspectives of intelligent electronic skin are summarized.