bluuebunny/crossref_metadata_2025 huggingface dataset:
Peptide‐Based Functional Amyloid Hydrogel Enhances Wound Healing in Normal and Diabetic Rat Models
Authors: Shaw Ranjit , Patel Komal , Chimthanawala Niyamat M. A. , Sathaye Sadhana , Maji Samir K
Published: February 2025

The inability to heal on time is a key component of chronic wounds, which can result in economic, psychological, and physiological burdens. Hydrogels based on amyloid can imitate the extracellular matrix and function as scaffolds for healing wounds. In this direction, a wound dressing inspired by peptide‐based amyloid hydrogel is fabricated here. The results demonstrate that the amyloid hydrogel improves the three essential components of skin tissue regeneration: cell migration, proliferation, and collagen remodeling, both in vitro and in vivo. Furthermore, the amyloid hydrogel accelerates wound healing and promotes wound closure within 9 and 15 d in normal and diabetic rats, respectively. Microscopic evaluation of the wound region demonstrates the ultimate stages of regeneration and skin reformation toward normal skin compared to the untreated wound. Hematoxylin and eosin‐stained hydrogel‐treated wound sites reveal faster dermal bridging, angiogenesis, and epidermal repair in both acute and chronic conditions. The hydrogel creates an environment that encourages the growth of dermal fibroblasts and the release of cytokines, decreasing inflammation with concomitant enhancement of collagen production at the site of injury. Thus, these findings suggest that amyloid‐based hydrogel can be a promising candidate for application in acute and chronic wound healing.
Nitrogen‐Doped Ultrananocrystalline Diamond – Optoelectronic Biointerface for Wireless Neuronal Stimulation
Authors: Yao Yue , Ahnood Arman , Chambers Andre , Tong Wei , Prawer Steven
Published: February 2025

This study presents a semiconducting optoelectronic system for light‐controlled non‐genetic neuronal stimulation using visible light. The system architecture is entirely wireless, comprising a thin film of nitrogen‐doped ultrananocrystalline diamond directly grown on a semiconducting silicon substrate. When immersed in a physiological medium and subjected to pulsed illumination in the visible (595 nm) or near‐infrared wavelength (808 nm) range, charge accumulation at the device‐medium interface induces a transient ionic displacement current capable of electrically stimulating neurons with high temporal resolution. With a measured photoresponsivity of 7.5 mA W−1, the efficacy of this biointerface is demonstrated through optoelectronic stimulation of degenerate rat retinas using 595 nm irradiation, pulse durations of 50–500 ms, and irradiance levels of 1.1–4.3 mW mm−2, all below the safe ocular threshold. This work presents the pioneering utilization of a diamond‐based optoelectronic platform, capable of generating sufficiently large photocurrents for neuronal stimulation in the retina.
Dynamic and Reversible Tuning of Hydrogel Viscoelasticity by Transient Polymer Interactions for Controlling Cell Adhesion
Authors: Scott Shane , Villiou Maria , Colombo Federico , la Cruz‐García Angeles De , Tydecks Leon , Toelke Lotta , Siemsen Katharina , Selhuber‐Unkel Christine
Published: February 2025

Cells are highly responsive to changes in their mechanical environment, influencing processes such as stem cell differentiation and tumor progression. To meet the growing demand for materials used for high throughput mechanotransduction studies, simple means of dynamically adjusting the environmental viscoelasticity of cell cultures are needed. Here, a novel method is presented to dynamically and reversibly control the viscoelasticity of naturally derived polymer hydrogels through interactions with poly (ethylene glycol) (PEG). Interactions between PEG and hydrogel polymers, possibly involving hydrogen bonding, stiffen the hydrogel matrices. By dynamically changing the PEG concentration of the solution in which polymer hydrogels are incubated, their viscoelastic properties are adjusted, which in turn affects cell adhesion and cytoskeletal organization. Importantly, this effects is reversible, providing a cost‐effective and simple strategy for dynamically adjusting the viscoelasticity of polymer hydrogels. This method holds promise for applications in mechanobiology, biomedicine, and the life sciences.
Alkaline Adjuvant Regulates Proteolytic Activity of Macrophages for Antigen Cross‐Presentation and Potentiates Radioimmunotherapy
Authors: Li Bei , Tan Yan , Lei Josh Haipeng , Deng Min , Yu Xinwang , Wang Xinyi , Lei Lek Man , He Lin , Deng Chu‐Xia , Dai Yunlu
Published: February 2025

Failures of radiotherapy (RT) in adaptive antitumor immunomodulation often associate with recruited tissue‐repairing macrophages. Although training these macrophages to phagocytose post‐RT cancer cells reverses their protumoral performance, engulfed tumor antigens are severely underrated. In fact, regulating the processing and presentation of tumor antigens, a key determinant of tumor immunogenicity, can fundamentally affect adaptive immune responses. Here it is reported that a simple Alum‐like adjuvant (MgAl‐based hydrotalcite, bLDH) improves radioimmunotherapy via inducing antigen cross‐presentation by macrophages, independent of phenotypes. It is identified that cytidine monophosphate guanosine oligodeoxynucleotide engenders macrophages to phagocytose irradiated cancer cells. However, as semiprofessional antigen‐presenting cells, macrophages possess powerful proteolytic function that is detrimental to antigen presentation. The administration of alkaline bLDH intriguingly relieves the activity of phagolysosomal proteases with acidic pH optima by preventing phagosomal acidification resulting from the vacuolar‐type ATPase proton pump. The adjuvant‐modulated phagolysosomes thus limit antigen degradation and enhance tumor antigen cross‐presentation over tenfold. To examine from an in vivo breast tumor model, trained macrophages successfully cross‐prime antigen‐specific CD8+ T cells and curb RT‐associated metastasis. The findings propose to pay close attention to the effect of adjuvants on precision immunotherapy and highlight the positive contribution of cross‐presenting macrophages in radioimmunotherapy.
Spheroid‐on‐a‐Chip Platforms for Tumor Microenvironment and Drug Development
Authors: Uzabakiriho Pierre Claver , Jiajun Fan , Nguchu Benedictor Alexander , Iqbal Sajid , Manishimwe Clarisse , Shaw Peter
Published: February 2025

Despite significant advancements in oncology research and therapeutic interventions, cancer continues to be the leading cause of mortality worldwide. The key challenge in addressing this pressing issue lies in the lack of precision diagnosis and a limited understanding of the nature and how the tumor microenvironment responds to therapeutic interventions. Research focusing on understanding the impact of tumor microenvironment (TME) heterogeneity on the response to cancer drugs is crucial to ensure efficient therapy. Conventional models exhibit significant constraints, including the inability to accurately imitate tumors’ complex 3D architecture and dynamic microenvironment. Recent developments in Spheroid‐On‐a‐Chip (SoC) technology provide a significant alternative, offering a tumor microenvironment closer to that of human tissue. This review explores the recent developments in SoC modeling, highlighting key spheroid formation mechanisms and techniques. The applications of the SoC platform to mimic the essential features of the tumor microenvironment and their potential role in anticancer drug development are summarized. The advantages and challenges of the technologies behind SoC devices compared to traditional in vitro models are further discussed. Lastly, future directions for transforming cancer research and improving drug development are suggested.
The Impact of Channel Geometry and Flow Regime on Endothelial Orientation and Morphology in Vessel‐on‐Chip
Authors: Jouybar Mohammad , van der Kallen Sophie , Sahebali Sheen , Bouten Carlijn , den Toonder Jaap M.J.
Published: February 2025

This study investigates the impact of channel geometry and applied flow on the orientation and morphology of endothelial cells (ECs) within vessel‐on‐chip (VoC) models. Traditional organ‐on‐chip models often utilize rectangular cross‐section channels, resulting in flat walls, sharp corners, and non‐uniform wall shear stress profiles, which do not accurately mimic physiological conditions. Tubular channels with circular cross‐sections provide a more in vivo‐like geometry and result in a physiological uniform wall shear stress. Here, tubular channels fabricated using sugar 3D‐printing are compared with rectangular channels made via stereolithography 3Dprinting. The results show that ECs from both blood and lymph vessels exhibit more uniform coverage and circumferential alignment in tubular channels than in rectangular channels. Unidirectional or bidirectional flow conditions align ECs parallel to the flow, overruling the circumferential alignment induced by curvature in tubular channels. Pulsatile flow enhances circumferential orientation in tubular channels, while alignment along the flow is maintained in rectangular channels. Additionally, EC orientation induced by flow impacts monocyte rolling velocities, crucial for understanding immune cell motility. This study underlines the importance of the combined effect of channel geometry and flow conditions in VoC models, and advocates for the continued development of advanced organ‐on‐chip systems that better replicate human physiology.
Development of Pectin/Gelatin/Glutathione/Calcium Chloride Crosslinked Hybrid Composite Antioxidant Edible Coatings for the Preservation of Local Butter
Authors: Al‐Ibresam Orass T. , Al‐Ali Rawdah M. , Al‐Temimi Anfal A. , Dinh Le N. M. , Yao Yin , Al‐Hilifi Sawsan A. , Agarwal Vipul
Published: February 2025

Given the vulnerability of butter to rancidity there continues to be a drive to develop active edible coatings to preserve the characteristics and prolong shelf‐life of butter. In this work, inspiration is taken from biomedical and pharmaceutical research and crosslinked pectin‐based edible composite coatings are developed for the preservation of butter. Pectin is blended with gelatin and glutathione to induce antioxidant characteristics and crosslinked with calcium chloride to overcome the problem of moisture sensitivity of neat pectin‐based coatings. The blended active edible coatings exhibit significant preservation characteristics in coated butter in terms of peroxide, acid, and fatty acid values during the 60 days storage period with 15 days examination intervals in a calcium chloride dose dependent response. Furthermore, the developed coatings exhibit significantly improved antioxidant properties as assessed from β‐carotene and 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) activity in coated samples compared to control prolonging the shelf‐life of coated butter. For the first time, it is demonstrated that pectin can be crosslinked to prepare edible coatings and extent of crosslinking can directly influence coating performance in food preservation. The obtained results are believed to be significant to the field and have the potential to disrupt the status quo in edible coating research and inspire commercial development of such coatings.
Full Recovery of Polyimide Wastes Into High‐Value Products Through Break and Reconstruction of Imide Ring
Authors: Chen Haodi , Liu Xuehui , Zhang Shouqin , Xu Shimei , Fu Teng , Wang Yu‐Zhong
Published: February 2025

Polyimide (PI) is a promising engineering plastic but difficult to recycle due to its aromatic heterocyclic structures, especially for thermosetting PI. Herein, an ingenious cascade pathway for high‐value and full recovery of thermosetting PI under mild conditions is presented. Specifically, the imide ring is first broken through aminolysis to degrade PI and is reconstructed under following hydrolysis to achieve excellent thermal stability in subsequent products. When recycling thermoplastic PI, the yield of 91% and 82% appears in diamines and polyhydroxylated compounds, respectively. As focusing on the recovery of thermosetting PI, aside from the efficient recovery of diamines, the crosslinked component is converted into hyperbranched flame retardant carbonizers for preparing copolyester, and it correspondingly achieves good flame retardant effect with an addition of merely 4 wt.%. The success of this work capitalizes on the unique structure and properties of the raw material, stimulating innovative pathways in the field of thermoset waste recovery and new material design.
A Shared Control Method of Multiobjective Motion Fusion for Surgical Robot
Authors: Xiao Xilin , Li Xiaojian , Mo Hangjie , Shi Yudong , Fang Jing , Li Ling , Ouyang Bo , Yang Shanlin
Published: February 2025

Shared control combines human intelligence with autonomous algorithms, demonstrating potential for enhancing the intricate and dynamic operational capabilities of robots. In robotic surgery, shared control can integrate autonomous functions into master–slave control, which enables surgeons to receive certain control assistance while maintaining control of the operation. Such a shared control system must handle multiple types of dynamically changing motion tasks, for instance, trajectory tracking, obstacle avoidance, spatial constraint, and safety guarantee. This article proposes an innovative shared control method based on multiobjective motion fusion (MoMF) by integrating multiple objective controllers into master–slave control mode. In addition, a state feedback mechanism with prediction and evaluation model is developed to balance the control inputs of different control objectives. Further, an objective priority partition function is designed to overcome the conflicts between control objectives. In the proposed method, objective controllers can be added or removed as needed. The theoretical stability of the proposed MoMF method is proved. As an example, a fusion controller that considers four control objectives of a surgical cutting operation is designed to demonstrate the practicability of this method. Finally, the feasibility and effectiveness of the proposed MoMF method are validated by simulations and prosthesis experiments.
Toward Improving Initial Therapy of Acute Graft Versus Host Disease
Authors: Mehta Ansh Krishnachandra , Koreth John
Published: February 2025

Acute graft versus host disease (aGVHD) is a major complication of hematopoietic stem cell transplantation; it results from donor‐derived immune response against host tissues and typically involves the liver, skin and the GI tract. The incidence of acute GVHD is declining due to the advances in HLA typing, reduced intensity conditioning and GVHD prophylaxis. However, corticosteroids remain the mainstay frontline treatment of aGVHD for many decades and as the number of allogeneic transplants continues to increase, there remains a large unmet need to improve frontline treatment for aGVHD. In this review, we outline risk factors, epidemiology and pathogenesis of aGVHD. We discuss the evolving risk stratification, beginning from the initial Gluckesberg system to more recent biomarker‐based strategies. We summarize the completed trials that underpin current frontline management and outline future directions.
Halogenated Donor‐Acceptor Cyclopropanes as Donor‐Acceptor Cyclopropene Surrogates
Authors: Werz Daniel B. , Oliver Gwyndaf A. , Kolb Simon , George Malini
Published: February 2025

Herein we report (3+2) cycloaddition reactions of halogenated donor‐acceptor cyclopropanes (HDACs) as surrogates for donor‐acceptor cyclopropenes. Upon reaction with a variety of 2π‐components, cycloaddition followed by elimination generates the unsaturated five‐membered ring products. A series of HDACs were shown to be effective in reactions with thioketones. Five further cycloaddition reactions were used to showcase the broad applicability of these donor‐acceptor cyclopropene surrogates. Kinetic studies allowed the proposal of a plausible mechanism for this reaction.
The Synergistic Effect of Ammonium Polyphosphate and a N/P/Si‐Containing Intumescent Flame Retardant on the Flame‐Retardant Properties of Polylactic Acid
Authors: Xu Feijing , Yin Nian , Gao Shanjun , Shen Chunhui
Published: February 2025

Ammonium polyphosphate (APP) and intumescent flame‐retardant di‐(3‐amin‐opropyltriethoxysilane) spirocyclic pentaerythritol diphosphate (PDAP) were prepared as an intumescent flame retardant with synergistic effect, and polylactic acid (PLA) was modified by melt blending. The flame retardancy of PLA/PDAP/APP was evaluated by limiting oxygen index (LOI), vertical combustion test (UL‐94), and cone calorimetry test (CCT), and the thermal stability of PLA/PDAP/APP was studied by thermogravimetric analysis and thermogravimetry‐Fourier transform infrared spectroscopy (FTIR). The possible flame‐retardant mechanisms of PLA/PDAP/APP were analyzed based on the results of laser Raman spectroscopy and FTIR. When PDAP:APP = 2:1 and the addition amount of PDAP/APP is 20 wt%, the LOI value of PLA/IFR‐modified material is as high as 43%, and the UL‐94 test reaches V‐0 level, and in the CCT, the PHRR and THR of PLA/PDAP/APP (2:1)‐modified material are reduced by 80.7% and 76.8%, respectively, compared with pure PLA, and the carbon residue is as high as 62.01%. The results show that the compound APP/PDAP has an excellent flame‐retardant effect on PLA, which provides a good research case for PLA flame‐retardant‐modified plastic materials.
Choosing Words to Limit Stigma: The Use of Person‐First Language in Birth Defects Research
Authors: Bascom Jacqueline T. , Agopian A. J.
Published: February 2025

Background

Birth defects are associated with psychosocial stress and stigma, in addition to increased mortality and lifelong disabilities. The language and phrasing used to describe individuals with birth defects in scientific writing can affect attitudes that contribute to stigma. Using a “person‐first” writing structure (e.g., “infants with Down syndrome”) instead of “identity‐first” language (e.g., “Down syndrome infants”) is intended to promote respect and inclusivity. Our work aims to enhance awareness and advocacy of person‐first language among researchers and professionals in birth defects research, with the goal of reducing stigma and adopting language that prioritizes dignity for individuals and their families.

Methods

We analyzed 52 population‐based birth defects articles published by the National Birth Defects Prevention Network (NBDPN) between 2002 and 2024, which we expect to exemplify writing practices among U.S. birth defects epidemiologists. We evaluated the use of person‐first and identity‐first language in population‐based birth defects research and advocated for increased consideration of person‐first language in the field.

Results

Among 52 NBDPN articles reviewed, seven (13%) articles used person‐first language only, N = 6 (12%) used identity‐first language only, 38 (73%) used both, and one (2%) used neither.

Conclusion

We encourage researchers to consider using person‐first language when describing individuals with birth defects in epidemiologic studies and in training birth defects epidemiologists, while acknowledging that some communities may also prefer an identity‐first framework (e.g., the “Deaf community”).
A Survey on the Criteria Used to Judge (Fake) News in Italian Population
Authors: Battista Fabiana , Lanciano Tiziana , Curci Antonietta
Published: February 2025

Introduction

Fake news detection falls within the field of deception detection and, consequently, can be problematic due to no consensus on which cues increase the detection accuracy and because people's ability to detect is poor.

Methods

The present study aimed to investigate the criteria used by general population to establish if a given news item is true or fake by surveying a sample of the Italian population. We recruited 329 participants who had to reply to some questions on which criteria they used to conclude a given news item was true. The same questions were also asked to investigate the ones used for fake news judgments.

Results and Conclusion

Our results showed that, overall, people use similar criteria (e.g., reliability of the source and presence of scientific references) to conclude that news is true versus fake, although their use rates differ for true and fake news.
Effects of Low Intensity Focused Ultrasound Stimulation Combined With Functional Electrical Stimulation on Corticospinal Excitability and Upper Extremity Fine Motor Function
Authors: Desai Naaz , Grippe Talyta , Arora Tarun , Bhattacharya Amitabh , Gunraj Carolyn , Chen Robert
Published: February 2025

Introduction

Functional electrical stimulation (FES) is used to retrain motor function in neurological disorders but typically requires multiple sessions and shows limited benefits in chronic cases. Low‐intensity transcranial focused ultrasound stimulation (TUS) is a noninvasive brain stimulation (NIBS) method offering greater focality and deeper penetration than current NIBS techniques. TUS delivered in a theta burst pattern (tbTUS) for 80 s produces neuroplastic changes with long‐term potentiation‐like effects lasting up to 60 min in healthy adults. Since tbTUS increases cortical excitability, combining it with FES may enhance neuroplasticity. We hypothesized that combining tbTUS with FES would result in increased corticospinal excitability compared to FES alone and lead to greater improvement in fine motor skills as assessed by Nine‐Hole Peg Test (NHPT) scores.

Methods

Fifteen healthy participants underwent two study visits consisting of real or sham tbTUS of the left motor cortex immediately followed by 30 min of FES of the first dorsal interosseous (FDI) and the opponens pollicis (OP) muscles for fine motor function training of the right hand. Motor‐evoked potentials (MEPs) were recorded from the right FDI, OP, and abductor digiti minimi (ADM) muscles at baseline (BL), immediately after real or sham tbTUS (T0), immediately after 30 min of FES training (T45), and at 15 (T65) and 30 min (T80) post‐FES. NHPT was delivered at BL and at T80.

Results

Data from 14 participants were analyzed. It showed a significant decrease in MEP amplitudes of FDI and OP at T45 following only real tbTUS+FES with a return to BL at T80. No significant changes were seen in the NHPT scores in either condition.

Conclusion

Real tbTUS+FES combined with voluntary movement results in immediate corticospinal inhibition with a return to BL at ∼20 min post‐stimulation suggestive of homeostatic metaplasticity. These findings highlight the potential of tbTUS+FES as a neuromodulatory intervention, warranting further exploration in neurological conditions for therapeutic applications.
Effect of Mind Mapping Combined With Behavior Rating Scale on Medical Compliance Behavior of Atrial Fibrillation Patients Underwent Radiofrequency Ablation
Authors: Xu Huan , Qiu Yuncheng , Wang Yanshan , Song Kunqing , Guo Xuemin , Wang Li , Zhang Yonglou
Published: February 2025

Background:

Atrial fibrillation (AF) patients undergoing radiofrequency ablation require diligent postoperative care for optimal outcomes. This study investigated the impact of combining mind mapping with behavior rating scales on medical compliance behavior in this population.

Methods:

A total of 108 AF patients post‐radiofrequency ablation were randomly assigned to a control group (n = 54) or an intervention group (n = 54). Both groups received standard education, while the intervention group additionally received education using mind mapping and behavior rating scales. Compliance was assessed using a medical compliance behavior scale at baseline, discharge, and 1‐ to 3‐month follow‐ups.

Results:

The intervention group demonstrated significantly higher medication compliance rates at discharge (86.9% vs. 65.9%, p = 0.027), 1 month (73.9% vs. 46.8%, p = 0.011), and 3 months (60.9% vs. 36.2%, p = 0.023) compared to the control group. They also scored higher in medical compliance behavior across all dimensions and had improved quality of life scores at 3 months post‐discharge.

Conclusions:

Integrating mind mapping with behavior rating scales into post‐radiofrequency ablation care significantly enhances medication compliance, medical compliance behavior, and quality of life among AF patients.
Positive effect of carbon monolith porosity sealing with MgO in the CO2 hydrogenation to CH4 using NiO‐CeO2 active phase
Authors: Martínez-López Iván , Davó-Quiñonero Arantxa , Guillén-Bas Esteban , Martín-García Iris , Bailón-García Esther , Lozano-Castelló Dolores , Bueno-López Agustín
Published: February 2025

Carbon monolith supports have been manufactured using 3D printed channels template and resorcinol‐formaldehyde carbonizable resin. These carbon monoliths were loaded with NiO‐CeO2 nanoparticles (Np) as the active phase and tested for CO2 hydrogenation to CH4, focusing on the effect of sealing the carbon porosity with MgO. The MgO coating improves CO2 conversion to CH4 by preventing the NiO‐CeO2 nanoparticles from settling within the microporous structure of the carbon support, where gas diffusion limitations hinder access to the active phase. This was confirmed by SEM images, which evidence the introduction of NiO‐CeO2 (Np) into the carbon matrix of the bare carbon monolith support and the accumulation of the active phase at the surface of the monolith channels once the porosity is sealed. Other characterization techniques, like N2 adsorption and Hg porosimetry, confirm that the porosity is blocked by MgO. On the other hand, it has been demonstrated that there is not a relevant chemical effect of MgO on the NiO‐CeO2 (Np) catalytic performance for the carbon monoliths‐supported catalysts, because the contact between the MgO and NiO‐CeO2 phases is poor due to the dispersing effect of carbon.
What can we learn from 100,000 freshwater forecasts? A synthesis from the NEON Ecological Forecasting Challenge
Authors: Olsson Freya , Carey Cayelan C. , Boettiger Carl , Harrison Gregory , Ladwig Robert , Lapeyrolerie Marcus F. , Lewis Abigail S. L. , Lofton Mary E. , Montealegre‐Mora Felipe , Rabaey Joseph S. , Robbins Caleb J. , Yang Xiao , Thomas R. Quinn
Published: February 2025

Near‐term, iterative ecological forecasts can be used to help understand and proactively manage ecosystems. To date, more forecasts have been developed for aquatic ecosystems than other ecosystems worldwide, likely motivated by the pressing need to conserve these essential and threatened ecosystems and increasing the availability of high‐frequency data. Forecasters have implemented many different modeling approaches to forecast freshwater variables, which have demonstrated promise at individual sites. However, a comprehensive analysis of the performance of varying forecast models across multiple sites is needed to understand broader controls on forecast performance. Forecasting challenges (i.e., community‐scale efforts to generate forecasts while also developing shared software, training materials, and best practices) present a useful platform for bridging this gap to evaluate how a range of modeling methods perform across axes of space, time, and ecological systems. Here, we analyzed forecasts from the aquatics theme of the National Ecological Observatory Network (NEON) Forecasting Challenge hosted by the Ecological Forecasting Initiative. Over 100,000 probabilistic forecasts of water temperature and dissolved oxygen concentration for 1–30 days ahead across seven NEON‐monitored lakes were submitted in 2023. We assessed how forecast performance varied among models with different structures, covariates, and sources of uncertainty relative to baseline null models. A similar proportion of forecast models were skillful across both variables (34%–40%), although more individual models outperformed the baseline models in forecasting water temperature (10 models out of 29) than dissolved oxygen (6 models out of 15). These top performing models came from a range of classes and structures. For water temperature, we found that forecast skill degraded with increases in forecast horizons, process‐based models, and models that included air temperature as a covariate generally exhibited the highest forecast performance, and that the most skillful forecasts often accounted for more sources of uncertainty than the lower performing models. The most skillful forecasts were for sites where observations were most divergent from historical conditions (resulting in poor baseline model performance). Overall, the NEON Forecasting Challenge provides an exciting opportunity for a model intercomparison to learn about the relative strengths of a diverse suite of models and advance our understanding of freshwater ecosystem predictability.
Inbreeding Depression Manifested in Progeny From Fragmented Populations of the Wind‐Pollinated Dioecious Conifer Afrocarpus gracilior (Pilg.) C. N. Page
Authors: Abate Nigussu Begashaw , Degu Hewan Demissie , Kalousová Marie , Abebe Tesfaye
Published: February 2025

Human activities such as agriculture, urbanization, and logging have caused widespread destruction of forests, leading to forest fragmentation. Fragmentation has been shown to reduce genetic diversity and increase inbreeding in forest populations, potentially leading to inbreeding depression manifested through decreased reproductive success and progeny vigor. The severity of these impacts, however, varies among species and is largely influenced by their mating systems. This study examines the effects of forest fragmentation on Afrocarpus gracilior, a dioecious, wind‐pollinated conifer, by assessing genetic diversity, reproductive success, and early progeny fitness. Our analysis revealed alarmingly low genetic diversity and high genetic drift, especially in small and isolated populations. Consistent with these findings, reduced progeny fitness was observed, with small populations showing 53% lower germination rates, 33% reduced acclimatization, 30% slower diameter growth, 41% reduced height growth, and an 80% increase in leaf scorch. Correlation analysis further confirmed a strong relationship between the genetic diversity and progeny fitness traits. These findings suggest that inbreeding depression severely affects the fitness of progeny from small and isolated populations of A. gracilior, posing a serious threat to their long‐term survival. The implications for conservation and restoration efforts are immense, underscoring the need to prioritize genetically diverse populations for conservation and strategically procure seeds to support the survival of this species.
Whole Genome Sequencing Reveals Clade‐Specific Genetic Variation in Blacklegged Ticks
Authors: Cassens Jacob , Oliva Chávez Adela S. , Tufts Danielle M. , Zhong Jianmin , Faulk Christopher , Oliver Jonathan D.
Published: February 2025

Ticks and tick‐borne pathogens represent the greatest vector‐borne disease threat in the United States. Blacklegged ticks are responsible for most human cases, yet the disease burden is unevenly distributed across the northern and southern United States. Understanding the genetic characteristics influencing phenotypic differences in tick vectors is critical to elucidating disparities in tick‐borne pathogen transmission dynamics. Applying evolutionary analyses to molecular variation in natural tick populations across ecological gradients will help identify signatures of local adaptation, which will improve control and mitigation strategies. In this study, we performed whole genome nanopore sequencing of individual (n = 1) blacklegged ticks across their geographical range (Minnesota, Pennsylvania, and Texas) to evaluate genetic divergence among populations. Our integrated analyses identified genetic variants associated with numerous biological processes and molecular functions that segregated across populations. Notably, northern populations displayed genetic variants in genes linked to xenobiotic detoxification, transmembrane transport, and sulfation that may underpin key phenotypes influencing tick dispersal, host associations, and vectorial capacity. Nanopore sequencing further allowed the recovery of complete mitochondrial and commensal endosymbiont genomes. Our study provides further evidence of genetic divergence in epidemiologically relevant gene families among blacklegged tick clades. This report emphasizes the need to elucidate the genetic basis driving divergence among conspecific blacklegged tick clades in the United States.
Training‐induced change of diastolic function in heart failure with preserved ejection fraction
Authors: Gevaert Andreas B. , Winzer Ephraim B. , Mueller Stephan , De Schutter Stephanie , Beckers Paul J. , Hommel Jennifer , Linke Axel , Wisløff Ulrik , Adams Volker , Pieske Burkert , Halle Martin , Van Craenenbroeck Emeline M. , Van De Heyning Caroline M.
Published: February 2025

Aims

Exercise training improves aerobic capacity (V̇O2peak) in patients with heart failure and preserved ejection fraction (HFpEF), but underlying mechanisms remain unclear. We aimed to evaluate whether exercise training could improve systolic and diastolic function during exercise.

Methods

This was a substudy of the multicentre Optimizing Exercise Training in HFpEF (OptimEx‐Clin) trial, in which 180 patients with HFpEF were randomized 1:1:1 to guideline control, moderate continuous training or high‐intensity interval training. All patients included at two out of five participating sites underwent exercise echocardiography at baseline and 3 months. Patients of both training groups were pooled and compared with guideline control.

Results

A total of 61 patients (mean age 73 ± 7 years, 72% female) were included. At baseline, E/e′ increased from 17.0 ± 5.7 to 19.5 ± 6.1 and systolic pulmonary artery pressure from 31 ± 8 to 51 ± 11 mmHg (both P < 0.001). Right ventricular function did not change significantly (maximal tricuspid annular plane systolic excursion 24.7 ± 4.0 mm, P = 0.051 vs. baseline).

At 3 months, patients randomized to exercise training improved V̇O2peak (control +0.2, training +2.7 mL/kg/min, P = 0.006) and demonstrated small but significant improvements in exercise E/e′ (control 21.7 ± 7.5 to 22.8 ± 9.2, training 18.3 ± 5.0 to 17.2 ± 4.1, P = 0.044). No significant changes were observed in ejection fraction, mitral or tricuspid annular plane systolic excursion, S′, A′ or systolic pulmonary artery pressure (P > 0.05). Changes in E/e′ were not associated with the change in V̇O2peak.

Conclusions

In patients with HFpEF, exercise echocardiography revealed increases in filling pressures as well as a failure to augment right ventricular function during exercise. After 3 months of exercise training, HFpEF patients demonstrated a small improvement in diastolic function (exercise E/e′), but this did not explain the improved aerobic capacity.
Comorbidity trajectories before and after the diagnosis of heart failure: A UK Biobank cohort study
Authors: MacGowan Hugo , Brown Oliver I. , Drozd Michael , Walker Andrew M.N. , Giannoudi Marilena , Straw Sam , Paton Maria F. , Gierula John , McGinlay Melanie , Griffin Kathryn J. , Witte Klaus K. , Kearney Mark T. , Cubbon Richard M.
Published: February 2025

Aims

Heart failure (HF) is frequently associated with multiple comorbidities. We aimed to define their trajectory of accrual to identify opportunities for disease prevention.

Methods and results

We identified all participants in the UK Biobank cohort study diagnosed with HF prior to enrolment or during follow‐up, who had disease occurrence data available from both primary and secondary care records (n = 9824). We established the time between diagnosis of HF and 16 common comorbidities to determine the rate and sequence of comorbidity accrual in relation to HF. Stratified analyses considered associations with sex and age at diagnosis of HF. In chronological sequence, HF was the median fourth diagnosis for men and women. As the age at HF diagnosis increased, HF came later in the sequence of diseases (median second in under 50 years to fifth in those aged 80–90 years). In all age strata, comorbidities accumulated for over a decade before HF and this accelerated in the years immediately before HF. The median time between comorbidity and HF diagnoses ranged from depression preceding HF by 10.7 years to dementia proceeding HF by 0.7 years; all comorbidities presented earlier in women. Atrial fibrillation/flutter was the commonest disease to immediately precede HF, followed by hypertension, cancer, myocardial infarction and osteoarthritis.

Conclusion

Heart failure is most often diagnosed in people with established multiple long‐term conditions. There is a protracted window of opportunity during which interventions to prevent HF could be applied, often in disease contexts where this is not routine care, such as cancer and osteoarthritis.
Mathematical Modeling of Cancerous Tumor Evolution Incorporating Drug Resistance
Authors: Ochieng Francis Oketch
Published: February 2025

Cancer is a deadly disease characterized by the uncontrolled growth and spread of abnormal cells. Tumors, the masses formed by these abnormal cells, can vary significantly in size, composition, and behavior. Understanding tumor dynamics is crucial for the development of effective treatments. A novel computational model is presented to analyze the evolution of tumor tissue over time, incorporating drug resistance and the convective mass flux of tumor cell movement for a more realistic representation of tumor dynamics. The governing equations are numerically solved using the finite difference method with forward‐time central‐space discretization. The predictive capabilities of the model were evaluated by investigating the impact of drug therapy on cell death and the sensitivity of the model's outcome to initial nutrient and drug concentrations. Key findings revealed that higher initial nutrient concentrations promote tumor growth, highlighting the importance of monitoring and managing nutrient levels in patients. The tumor consumes nutrients at a faster rate than they can diffuse inward, leading to nutrient gradients and potential necrosis in the core. High drug concentrations do not always correlate with increased cell death due to factors such as drug toxicity or resistance development. The relationship between drug concentration and cell death is nonlinear, suggesting that there might be an optimal drug concentration range to maximize efficacy. These insights offer valuable guidance for optimizing drug delivery and designing effective tumor control strategies. This study contributes to a deeper understanding of tumor growth and the development of more effective cancer treatments to improve patient outcomes. In addition, the proposed model serves as a valuable tool for researchers and clinicians to explore different treatment regimens and predict patient responses to therapy.
HMGB1 blood levels and neurological outcomes after traumatic brain injury: Insights from an exploratory study
Authors: Ngadimon Irma Wati , Mohan Devi , Shaikh Mohd Farooq , Khoo Ching Soong , Tan Hui Jan , Lee Yu Mey , Chamhuri Nor Syazwani , Fadzil Farizal , Zolkafli Nursyazwana , Arulsamy Alina , Thanabalan Jegan , Aledo‐Serrano Angel , Cheong Wing Loong
Published: February 2025

Objective

Posttraumatic epilepsy (PTE) and cognitive impairment are severe complications following traumatic brain injury (TBI). Neuroinflammation likely contributes, but the role of specific inflammatory mediators requires clarification. High‐mobility group box 1 (HMGB1) is an inflammatory cytokine released after brain injury that may be involved. This prospective longitudinal study investigated whether serum HMGB1 levels are associated with PTE development and cognitive decline over 12 months post‐TBI.

Methods

Serum samples were collected from 41 TBI patients, including mild and moderate to severe, at baseline, 6, and 12 months following TBI. HMGB1 was quantified by ELISA alongside interleukin‐1β (IL‐1β) and tumor necrosis factor (TNF). Cognitive assessments using validated neuropsychological assessments were performed at 6 and 12 months. The occurrence of PTE was also tracked.

Results

HMGB1 remained elevated at 12 months post‐TBI only in the subgroup (n = 6) that developed PTE (p = 0.026). PTE was associated with moderate to severe TBI cases. Higher HMGB1 levels at 12 months correlated with a greater decline in Addenbrooke's Cognitive Examination scores (p < 0.05). Reductions in HMGB1 (p < 0.05), IL‐1β (p < 0.05) and TNF (p < 0.001) levels from 6 to 12 months correlated with improvements in cognitive scores. Multivariate regression analysis confirmed that HMGB1 level changes were independently associated with cognitive trajectory post‐TBI (p = 0.003).

Significance

The study highlights the importance of understanding the interactions between HMGB1 and inflammatory markers in posttraumatic neuroinflammatory responses. Targeting HMGB1 and associated markers may offer a promising strategy for managing chronic neuroinflammation and mitigating cognitive deficits in TBI patients, emphasizing the potential for targeted therapeutic interventions in this context.

Plain Language Summary

This study examines how a protein called HMGB1 may contribute to epilepsy and cognitive deficits after traumatic brain injury (TBI). Patients with higher HMGB1 levels were more likely to develop epilepsy and experience significant cognitive decline within a year. Reducing HMGB1 and related inflammation was associated with better cognitive function and overall brain health. These findings suggest that HMGB1 could be a valuable marker and a potential target for treatments to prevent epilepsy and improve brain recovery after TBI.
User Experience and Therapeutic Alliance of Treatment Completers of Clinician‐Supported Versus Self‐Help Online Intervention for Eating Disorders: A Mixed Methods Approach
Authors: Barakat Sarah , Rom Sean , Kim Marcellinus , Aouad Phillip , Maguire Sarah
Published: February 2025

Background

Poor rates of retention associated with digital interventions necessitate understanding of factors influencing engagement. This study presents a secondary analysis of a three‐arm, randomised controlled trial of an online self‐help treatment for bulimia nervosa (clinician‐supported, self‐help and waitlist control).

Aims

The study aimed to understand the effect of added clinician‐support, or lack of support, upon user experience and therapeutic alliance.

Method

At post‐treatment, 61 participants completed a battery of self‐report questionnaires assessing user experience and therapeutic alliance. Data were analysed using mixed methods (regression and thematic analyses).

Results

Quantitative analyses indicated clinician‐supported participants reported higher levels of treatment satisfaction and therapeutic alliance, however differences were not significant after controlling for covariates. Intervention effectiveness ratings were positively associated with post‐treatment reductions in binge episodes and eating disorder psychopathology. Qualitative data were organised into four themes: (1) human support, (2) content, structure and digital set up, (3) process of therapeutic change and (4) positive feedback.

Conclusions

Overall, the intervention was found to have positive ratings of user experience and therapeutic alliance in both supported and unsupported versions. The qualitative analyses revealed a strong preference for human support. The findings shed light on the complex interactions between digital and human elements of blended treatment delivery.

Trial Registration

The trial was pre‐registered with the Australia New Zealand Clinical Trials Registry (ACTRN12619000123145p)
Gastrodia flavilabellaSS Ying (Orchidaceae: Gastrodieae), a New Addition to the Flora of India With Unique Characteristics and Red List Assessment
Authors: Sarkar Kingsuk , Khanal Madhusudhan , Sarkar Shuvadip , Rai Santosh Kumar , Ashraf Syed Abdul Hakeem , Sariga K. S. , Bora Devanjal , Sen Animesh
Published: February 2025

Gastrodia flavilabella SS Ying (Orchidaceae: Epidendroideae: Gastrodieae) a holomycotrophic terrestrial orchid has been reported for the first time in India from Sikkim Himalaya. A detailed taxonomical description along with color photo plates have been provided to aid in easy identification along with details regarding the phenology and habitat. Conservation assessment of G. flavilabella has been done following IUCN guidelines.
Impact of Coronavirus Disease 2019 on Fertility: An Integrative Review
Authors: Ikeda Wakaha , Yamazaki Yuka , Inaba Yutaka
Published: February 2025

This integrative review aimed to explore the impact of the spread of coronavirus disease 2019 (COVID‐19) on fertility to establish foundational knowledge and guide future epidemiological studies. The PubMed and Central Journal of Medicine databases were searched, yielding 80 relevant articles published between 2019 and 2021. Of these, 14 were published in Japanese and 66 in English. None of the Japanese studies met the inclusion criteria. Fourteen English‐language studies, all of which were retrieved from PubMed, were included in the final analysis. No relevant literature was found in the Central Journal of Medicine. The keywords used were COVID‐19, fertility, and demographics. COVID‐19 led to an increase in unplanned pregnancies and abortions in developing countries. Fever associated with the infection was suggested to have reduced sperm concentration and motility, and the spread of the infection caused young couples to delay childbearing, potentially decreasing fertility. Conversely, relatively older couples showed fewer changes in their childbearing plans, indicating that COVID‐19 had both positive and negative effects on fertility. Physical, psychological, and economic factors as well as sex, age, and cultural background exerted complex effects on fertility. Herein, the impact of social crises on fertility rates has been discussed in the context of the recent COVID‐19 pandemic. Analysing the effects of this pandemic on fertility rates is crucial for understanding future demographic trends and national strengths. This study provides valuable data for future research in this field.
Internal Heat Source and Doubly Concentrated Newtonian Fluid Layer Dynamics Under Modulated Induced Magnetic Field
Authors: Singh Pervinder , Chadha Naresh M. , Gupta Vinod K.
Published: February 2025

Regarding the various issues and incidents pertaining to Rayleigh–Bénard convective system in industrial and technical domains, a great deal of important information and research has emerged. However, there are still certain physical phenomena that are not explored but have a significant impact on the Rayleigh–Bénard convective system. One example of such a phenomenon is the simultaneous action of two concentrated solutes mixed with Newtonian fluid from opposite ends, with an external time‐modulated magnetic field influenced by the internal heat source. The mathematical representation of the considered problem is based on the fundamental laws of fluid dynamics. This article attempts to shed some light on the impact of the internal Rayleigh number and the Chandrasekhar number on the convective system. To understand the impact of two concentrations with internal heat source and magnetic field modulation on the transport process, a weakly nonlinear theory and Fredholm's solvability condition are applied. A nonautonomous differential equation, known as the Ginzburg–Landau (GL) equation, is derived in terms of the amplitude of convection. An in‐built function of the software MATHEMATICA is used to determine the solution of GL equation and to plot the graphs of dimensionless parameters vs transport phenomena. The Chandrasekhar number (), delayed the transport process while and contribute to increase the heat and mass transport.