bluuebunny/crossref_metadata_2025 huggingface dataset:
The Development of Yellow Mealworm (Tenebrio molitor) as a Cheap and Simple Model to Evaluate Acute Toxicity, Locomotor Activity Changes, and Metabolite Profile Alterations Induced by Nanoplastics of Different Sizes
Authors: Sun Miao , Zhao Xiaomei , Luo Sihuan , Jiang Miao , Liu Qing , Cao Yi
Published: February 2025

Due to the wide uses of plastic products, nanoplastics are ubiquitous contaminants in the environment. Hence, extensive studies used various models to evaluate the toxicity of nanoplastics. In the present study, we developed yellow mealworm (Tenebrio molitor) as an alternative model to investigate the acute toxicity of nanoplastics. Our results showed that microinjection with 500 mg/kg nanoplastics significantly increased death rate of yellow mealworms after 24 or 48 h, with 100 nm particles being more effective compared with 20 nm ones. Meanwhile, dose‐dependent increase of death rate was observed in yellow mealworms after injection with 2–200 mg/kg 100 nm nanoplastics. Exposure to 2 mg/kg 100 nm but not 20 nm nanoplastics also led to hyperactivity of yellow mealworms. Both types of nanoplastics altered metabolite profiles, that 20 nm nanoplastics significantly up‐regulated and down‐regulated 9 and 12 metabolites, whereas 100 nm nanoplastics significantly up‐regulated and down‐regulated 16 and 25 metabolites, respectively. Enrichment analysis revealed that 100 nm but not 20 nm nanoplastics significantly affected alpha‐linolenic acid metabolism (ko00592) and purine metabolism (ko00230). For the metabolites belonging to these pathways, 100 nm nanoplastics significantly up‐regulated stearidonic acid but down‐regulated guanine. Combined, these results revealed size‐dependent effects of nanoplastics on acute toxicity, hyperactivity and metabolite profile changes in yellow mealworms. These results also indicated the potential uses of yellow mealworms as a cheap and simple model to evaluate the toxicity of nanoplastics.
Unlocking Naringin's Potential: A Systematic Review and Meta‐Analysis of Its Nephroprotective Effects in Pre‐Clinical Models
Authors: Das Akanksh , Bhardwaj Vibhu , Viswanatha Gollapalle Lakshminarayanashastry , Shylaja Hanumanthappa , Gajendra Hemavathi , Anjana Male Ch K V L S N
Published: February 2025

This systematic review and meta‐analysis aimed to evaluate and summarize the therapeutic effects of naringin on various kidney diseases, based on preclinical research. A comprehensive literature search was performed using electronic databases such as PubMed/Medline and Google Scholar, concentrating on the impact of naringin in different experimental animal models of kidney disease. After applying the inclusion and exclusion criteria, 27 studies were chosen for analysis. The meta‐analysis revealed that naringin treatment significantly improved body weight gain and markers of kidney function, as evidenced by decreased serum urea, creatinine, and blood urea nitrogen (BUN) levels. Additionally, naringin treatment normalized antioxidant parameters, restored enzymes like superoxide dismutase and catalase, and alleviated oxidative stress markers, comprising myeloperoxidase and reactive oxygen species. Besides, naringin also alleviated inflammation as indicated by reduced levels of markers such as NF‐κB, IL‐6, KIM‐1, COX‐2, and TNF‐α. Furthermore, it regulated apoptosis by decreasing the Bax, caspase‐3, and p53 levels while increasing Bcl‐2. In summary, the meta‐analysis demonstrated that naringin significantly mitigates nephrotoxicity induced by oxidative stress, chemotherapy, drugs, and chemicals. This nephroprotective effect is mediated through a combination of several mechanisms, including antioxidant, anti‐inflammatory, and anti‐apoptotic pathways. These cellular and molecular improvements were associated with enhanced kidney structure, function, and overall physiology following naringin treatment. Overall, this systematic review and meta‐analysis provide strong scientific evidence supporting the therapeutic potential of naringin in managing kidney diseases.
How simple models explain complex protein folding behaviors
Authors: Tsai Min‐Yeh
Published: February 2025

Understanding complex protein folding behaviors requires simplified models that capture the essential features of the folding process. Protein folding involves a delicate interplay between short‐range (secondary) and long‐range (tertiary) interactions, which together dictate the thermodynamic and kinetic properties of the system. In this study, we employ a mean‐field framework to investigate these interactions using three progressively refined models. The regular model considers only short‐range, nearest‐neighbor interactions and reveals a cooperative folding transition driven by localized secondary interactions, consistent with standard two‐state folding behavior. The Bryngelson–Wolynes (BW) model incorporates stochastic nonlocal interactions, demonstrating long‐range cooperativity and introducing energy landscape ruggedness that shifts the folding transition. The modified Bryngelson–Wolynes (M‐BW) model integrates both short‐range and long‐range effects, leading to the emergence of a hysteresis loop characteristic of first‐order‐like phase transitions, even in finite systems. These results suggest that the interplay between secondary and tertiary interactions is sufficient to induce phase transition‐like properties in proteins. By providing a unified framework, this study highlights how simplified models can elucidate the complex dynamics of protein folding, misfolding, and aggregation, offering critical insights into the underlying mechanisms of these fundamental biological processes.
Mathematical Albumin Function for Neonates Undergoing Therapeutic Hypothermia in Comparison with Control Neonates
Authors: Vander Elst Zoë , Stultjens Thibault , Annaert Pieter , Clarke Paul , Iglesias‐Platas Isabek , Agathos Elisabeth , Kaykı Gozdem , Laenen Annouschka , Yalçın Nadir , Smits Anne , Allegaert Karel
Published: February 2025

Hypoxic‐ischemic encephalopathy (HIE) resulting from perinatal asphyxia presents a substantial risk of mortality and long‐term sequelae in neonates. Therapeutic hypothermia (TH) improves both short‐ and long‐term outcomes in near‐term/term neonates with moderate to severe HIE. While neonates with perinatal asphyxia and TH often require polypharmacy, the impact of both covariates on pharmacokinetics and pharmacodynamics is only partially described and quantified. In this pooled, multicenter retrospective study, longitudinal trends of human serum albumin (HSA, the major drug binding protein) and total protein (TP) concentrations in near‐term/term neonates were described using linear mixed models and compared between cohorts (TH vs control neonates, and moderate vs severe HIE TH cases). A mathematical function for HSA concentrations in neonates with HIE undergoing TH was derived (AlbuCool function). The pooled dataset to estimate these functions contained 330 TH neonates and 425 controls with 1725 and 1415 HSA observations, respectively. The median (interquartile range) HSA concentration was 27.0 (23.0–31.0) g/L for the TH cohort, and 32.1 (28.4–35.7) g/L for the control cohort. Estimated mean HSA concentrations were significantly lower (P < .001) in TH compared to control cases, as well as in severe compared to moderate HIE cases (P < .001) over the first 7 postnatal days. The HSA function for neonates with HIE undergoing TH was: HSA (g/L) = 32.28 − 2.94 * PNA + 0.33 * PNA2 (PNA is postnatal age). The integration of this function in pharmacokinetic models holds the promise to improve the predictive performance of these models, and consequently, the pharmacotherapy of HSA‐bound drugs in this vulnerable population.
Intraplaque Hemorrhage: A Comparative Study of Vulnerable Plaque With Magnetic Resonance Imaging and Doppler Ultrasonography
Authors: Sezgin Mine , Yusifli Sevil , Barburoğlu Mehmet , Ekizoğlu Esme , Yeşilot Nilüfer
Published: February 2025

Purpose

We compared various plaque features including intraplaque hemorrhage (IPH) by carotid Doppler ultrasonography (USG) and MRA in individuals with symptomatic and asymptomatic carotid artery disease (CAD).

Methods

Symptomatic and asymptomatic CAD cases were included in the study. Surface features and constituents of the atherosclerotic plaque were examined, and internal carotid artery (ICA) systolic flow velocity was measured. Intra‐plaque hemorrhage was assessed with a 3D TFE sequence.

Results

Each carotid artery was inspected separately, and evaluations were made on 52 vessels for Doppler and 3D TFE analysis. In Doppler USG, heterogeneous plaques were found in 65% of symptomatic ICAs and 39% of asymptomatic ICAs (p = 0.08). There was a moderate correlation between the presence of IPH and heterogeneous plaque (Cramer V = 0.36, p = 0.01), moderate correlation with the presence of irregular plaque surface (Cramer V = 0.45, p = 0.003), mild correlation with the presence of flow acceleration (Cramer's V = 0.26 p = 0.064); strong association of 50% or more stenosis according to NASCET criteria (Cramer's V = 0.53 p = 0.00) were found.

Conclusions

Heterogeneous plaque and surface irregularity that show moderate association with IPH can be used as a helpful tool in the screening, follow‐up, and management of patients at high risk of ischemic stroke and determining risk groups for cerebrovascular diseases.
The Immunogenicity of Coxsackievirus A6 (D3a Sub‐Genotype) Virus‐Like Particle and mRNA Vaccines
Authors: Lu Huanhuan , Xiao Jinbo , Song Jingdong , Song Yang , Li Hai , Ren Hu , Li Jichen , Cong Ruyi , Li Hangwen , Fang Yi , Yan Dongmei , Zhu Shuangli , Sun Qiang , Liu Ying , Zhang Yong
Published: February 2025

In recent years, coxsackievirus A6 (CVA6) has surpassed enterovirus A71 to become the main pathogen causing severe Hand, Foot, and Mouth disease (HFMD) in China with a substantial disease burden. However, there is currently no commercial CVA6 vaccine. The D3a genotype of CVA6 is the predominant genotype in China. In this study, virus‐like particles (VLPs) and mRNA vaccines based on the CVA6 sub‐genotype D3a were successfully developed. The immunogenicity and protective effects of the VLP of CVA6 combined with Al(OH)3 and CpG adjuvant indicated that VLP‐induced neutralizing antibodies against three CVA6 sub‐genotype (D2, D3a, and D3b) strains in Institute of Cancer Research (ICR) mice, and the combination of the two adjuvants enhanced cellular immunity. Passive immunization with serum from mice immunized with VLPs protected suckling mice against CVA6 lethal challenge in both antiserum transfer and maternal immunization experiments. The immunogenicity and protective effects of the mRNA vaccine of CVA6 indicate that it induces robust T‐cell immunity. T‐cell immunity was found to cross‐protect against coxsackievirus A10 infection in mice. This is the first trial of a CVA6 mRNA vaccine worldwide and the first comparison of the immunogenicity and protective effects of VLP and mRNA vaccines based on D3a CVA6. The study provides a theoretical basis for the development of enteroviruses vaccines and the formulation of immunization strategies.
Identification of a Novel Alkaloid Zj6‐11 as a Potent Inhibitor of Influenza Virus Infection via Repression of Virus‐Induced Mitochondria‐Dependent Apoptosis
Authors: Liang Hanbai , Zhang Ying , Sun Wenhao , Xiao Xiaomei , Zhao Xiwen , Tan Bin , Zhang Jian , Song Xun , He Zhengdan , Ye Liang
Published: February 2025

Influenza A virus (IAV) remains a major global public health threat, especially with the emergence of antiviral resistance, highlighting the urgent need for novel therapeutics. Alkaloids are known for their antiviral properties, and chemical synthesis has become a key strategy in developing new alkaloid compounds. In this study, we synthesized a series of novel alkaloids using the Ugi reaction and assessed their antiviral potential and mechanisms. Through screening and validation, Zj6‐11 was identified as a promising compound that effectively inhibits IAV infection in vitro. Molecular docking and binding affinity assays showed that Zj6‐11 binds with high affinity to IAV nucleoprotein (NP) and inhibits its interaction with nucleic acids. Further, in vitro nuclear translocation assays confirmed that Zj6‐11 suppresses NP nuclear import. Mechanistically, Zj6‐11 significantly inhibits IAV‐induced apoptosis and mitigates mitochondrial membrane potential dysfunction. Zj6‐11 also inhibits cytochrome c release, reduces the expression of cleaved Caspase‐9 and Caspase‐3, and suppresses IAV‐induced apoptosis‐inducing factor (Aif) expression, suppressing IAV‐induced mitochondrial apoptosis. More importantly, Zj6‐11 plays a crucial role in protecting mice from IAV infection and reducing IAV pathogenicity. Our study provides mechanistic insights into Zj6‐11's control of IAV infection in vitro and in vivo, offering new perspectives for antiviral therapy development.
Transcorneal Electrical Stimulation Modulates Visual Pathway Function in Mice
Authors: Castoldi Valerio , Rossi Elena , Marenna Silvia , Comi Giancarlo , Leocani Letizia
Published: February 2025

Due to its ability to modulate neuronal activity, electrical stimulation of the eye may be a promising therapy for preserving or restoring vision. To investigate how electrical currents can influence visual function, Transcorneal Electrical Stimulation (TES) was tested on both female and male C57BL/6 mice to evaluate its neuromodulatory effect from the retina to the cerebral cortex through visual evoked potential (VEP) and electroretinogram (ERG) recording. VEP or ERG was acquired before (baseline), immediately (t0), after 5 min (t5), and 10 min (t10) of sham (i.e., no stimulation) or TES applied on the eye of anesthetized C57BL/6 mice. Notably, TES affected neuronal activity in the visual pathway since a significant increase in VEP and ERG amplitude was detected and persisted 10 min after TES. The amplitude increase induced by TES could underlie an enhancement of neuronal excitability that may ameliorate retinal‐genicular‐cortical function in diseases involving the visual system.
Frequency, cost, and time to re‐treatment after active periodontal therapy
Authors: Alhazmi Shahad , Abu‐Reyal Sawsan , Chiang Yi‐Chen , Saleh Muhammad H. A. , Wang Hom‐Lay
Published: February 2025

Background

Supportive periodontal therapy (SPT) reduces the probability of infection reoccurrence further disease progression. Despite that, several patient/tooth related variables have been linked to tooth loss during SPT. This longitudinal study examines the correlation between periodontal staging, grading, initial therapy, and frequency, cost, and time‐to‐re‐treatment following active periodontal therapy (APT).

Methods

Patients who received scaling and root planing (SRP) or surgery (SUR) were included. Demographics, annual SPT visits, and medical history were collected. Radiographic bone loss (RBL), probing depths (PD), and clinical attachment loss were collected at six sites/tooth. A simple binary logistic regression model assessed the probability of re‐treatment. Multiple models were constructed while adjusting for confounding factors: sex, age, number of SPT visits, and baseline data.

Results

Three hundred patients underwent SRP, and 142 underwent SUR as their APT. 191 patients (63.7%) required a second intervention over 24 ± 8.2‐year follow‐up. The second intervention type was correlated with the first (p = 0.035). The likelihood of a second intervention was higher in SUR patients (p < 0.001). Significant differences in time to first intervention based on stage (p = 0.019) and compliance (p < 0.001). Similar patterns were observed for time‐to‐recurrence based on stage (p = 0.03) and compliance (p = 0.017) but not grade (p = 0.144). Mean teeth “free of intervention time” was 16.3 years before the first additional therapy. However, SSD was found between stages (p = 0.028) and grades (p = 0.043) for SUR interventions, but not for SRP.

Conclusion

In this long‐term study, higher stage patients and those who had surgical treatments received more frequent retreatments. The first intervention affected the likelihood and type of the second intervention. 12.4% of patients were responsible for 64% of the entire retreatment spending.

Plain language summary

Patients with more severe periodontitis who initially underwent surgery needed more frequent therapy. Patients who had surgery as their intervention during active periodontal therapy were more prone to have surgery as their additional therapy during follow‐up.
Carbon Flux of Biological Soil Crusts Associated With Xeric Shrublands During Drying and Wetting Cycles
Authors: Flores‐Rentería Dulce , Guillen‐Cruz Gabriela , Ayala‐Niño Fernando , Campuzano Emmanuel F.
Published: February 2025

Background

Biological soil crusts (BSCs) play a pivotal role in arid ecosystems, influencing carbon (C) dynamics in response to changing conditions, especially water availability. Understanding their adaptability is crucial for ecosystem management.

Aims

This study aims to elucidate the C dynamics of BSCs in regulated drying‐wetting cycles, exploring immediate responses across different temporal scales (hourly and daily) and their relationship with environmental factors (air temperature, relative humidity, and radiation).

Methods

BSCs were collected at nine sites in the Chihuahuan Desert with preserved xeric shrublands. Samples were subjected to controlled drying‐wetting cycles, and C fluxes were measured at different daily and hourly periods. Environmental conditions (air temperature, relative humidity, and photosynthetically active radiation) were also monitored.

Results

Following wetting, significant BSC respiration was observed, with a quick decrease throughout the day, related to air temperature. In contrast, C uptake was less affected by wetting and showed a delayed response. C uptake was more sensitive to relative humidity.

Conclusions

We identified the potential role of BSCs in C dynamics (respiration and uptake) in xeric shrublands and the main controls. Our study reveals BSC adaptability to drying‐wetting cycles, emphasizing significant respiration and different metabolic activation.
Term infant formula macronutrient composition: An update for clinicians
Authors: Larson‐Nath Catherine , Bashir Anam , Herdes Rachel E. , Kiernan Bridget , Lai Joanne , Martin Nicole , Misner Nicole , Pandey Akash , Puri Kanika , Zong Wenjing , Duro Debora
Published: February 2025

Protein, carbohydrates, and fats comprise the macronutrient components of infant formulas. While all infant formulas in the United States meet specific nutrition standards, the macronutrient composition of formulas is diverse. Each macronutrient in the formula may play a role in treating or managing the disease. In addition, many formulas are marketed as resembling the composition of human milk or improving symptoms such as colic and irritability. For these and other reasons, families are often interested in different formula properties. When choosing a formula for their infant families, they may reach out to clinicians for advice. Therefore, clinicians need to understand the macronutrient composition of the formulas their patients are using. This manuscript discusses the macronutrient composition of term infant formulas and indications of the use of different macronutrient components.
Incidence of biliary atresia in the United States before and during the COVID‐19 pandemic
Authors: Qwaider Yasmeen Z. , Amarin Justin Z. , Spieker Andrew J. , Hayek Haya , Chappell James D. , Halasa Natasha B. , Lovvorn Harold N.
Published: February 2025

Objectives

The etiology of biliary atresia (BA) is unclear and potentially involves viral triggers. We aimed to compare the incidence of BA in the United States before and during the coronavirus disease 2019 (COVID‐19) pandemic, focusing on potential associations with viral circulation disruptions caused by nonpharmaceutical interventions (NPIs).

Methods

We queried the Pediatric Health Information System® (PHIS) for all patients discharged with BA between January 1, 2010, and January 31, 2024. Using CDC WONDER, we calculated monthly and overall incidence rates of BA per 1,000,000 live births. We fit a Poisson regression model to assess the association between the widespread implementation of stay‐at‐home orders (using April 1, 2020, as the cutoff date) and the incidence of BA, accounting for national natality fluctuations.

Results

We identified 3456 newborns with BA from 42 hospitals; 2997 (86.7%) were born before and 459 (13.3%) were born during the pandemic. The mean monthly number of newborns with BA was 24.0 (95% confidence interval, 23.0–25.0) for an overall incidence rate of 74.4 (71.5–77.4) per 1,000,000 live births. We did not identify a statistically significant year‐to‐year contrast in the incidence of BA before (incidence rate ratio [IRR] = 0.995 [0.983–1.008]; p = 0.49) or after the cutoff date (IRR = 0.999 [0.895–1.116]; p = 0.99). In addition, we did not identify sufficient evidence that trends differed between the two periods (IRR = 1.00 [0.893–1.128]; p = 0.95).

Conclusions

The NPIs implemented during the COVID‐19 pandemic were not significantly associated with changes in the incidence or temporal pattern of BA.
Have we hit the JAK‐pot? Success of selective JAK 1 inhibitor following failure of pan‐JAK inhibitor in refractory pediatric ulcerative colitis
Authors: Black Jessica A. , Pasternak Brad
Published: February 2025

The treatment options available for pediatric ulcerative colitis (UC) are challenging due to few with Federal Drug Administration approval. Newer medications approved for adults include additional biologics with differing mechanisms of action and small molecule drugs, such as Janus kinase (JAK) inhibitors. Our case outlines a patient with refractory UC who failed mesalamine, adalimumab, tofacitinib, and vedolizumab. She was evaluated for colectomy, but upadacitinib was trialed. She achieved rapid clinical remission and avoided surgery. This case demonstrates the failure of a pan‐JAK inhibitor (tofacitinib) and response to a more selective JAK 1 inhibitor (upadacitinib).
Identification of nutritional characteristics of Haliotis discus hannai in different China sea areas and health risks of heavy metal accumulation
Authors: Li Quanquan , Chang Yajie , Lu Jie , Wu Jinxia , Feng Liubin , Shen Guiping , Feng Jianghua
Published: February 2025

Background

The nutritional compositions of abalones (Haliotis discus hannai) vary with geographical origins and environmental factors. Traceability is an important part of food safety, and the heavy metals in the aquatic environment pose a threat to living organisms. Therefore, we present a comparative analysis of the nutrient and heavy metal content in abalones from three different sea areas in China: the Bohai Sea, East China Sea, and South China Sea. This study uniquely addresses the correlation between nutrient composition and heavy metal accumulation. By employing weighted gene co‐expression network analysis, we reveal the biological implications of heavy metal exposure, specifically focusing on chromium, copper (Cu), manganese, zinc, arsenic (As), cadmium, and lead.

Results

Betaine, glycine, and glycogen appeared in three comparisons. The abalone in the East China Sea had the highest content of betaine, and the abalone in the South China Sea had the highest contents of glycine and glycogen. Among the measured metals, the heavy metals accumulated in the viscera were significantly higher than that in the muscle, except Cu, and As showed a high target hazard quotient and carcinogenic risk.

Conclusion

Betaine, glycine, and glycogen might be important indicators for origin traceability of abalone. Abalones from the South China Sea provide higher nutritional value. Cu had different accumulation patterns and As showed high health risks, and heavy metals brought oxidative stress to abalone. Our findings not only contribute to the understanding of abalone safety and quality but also provide a novel approach to assessing impact of heavy metals on marine food sources. © 2025 Society of Chemical Industry.
Ultrasonographic Optic Nerve Sheath Diameter Technical Pitfalls and Imaging Artifacts
Authors: Hirzallah Mohammad I. , Sarwal Aarti , Dentinger Aaron M. , Robba Chiara , Valaikienė Jurgita , Lochner Piergiorgio , Schlachetzki Felix , Mills David M. , Ertl Michael , Hakimi Ryan , Bhise Shreya , Pansell Jakob
Published: February 2025

Ultrasonographic optic nerve sheath diameter (ONSD) is a non‐invasive intracranial pressure (ICP) surrogate. This article discusses the effect of ultrasound settings and imaging artifacts on ONSD assessment. Ultrasound settings that may affect ONSD assessment include gain, dynamic range, frequency, harmonic imaging, and focal zones. Artifacts can be related to imaged structures (acoustic shadowing, enhancement, comet tail, and speckle artifacts) or to beam properties (partial volume and refraction artifacts). In addition, optic nerve sheath (ONS) properties such as echogenicity changes based on ICP or ONS kinking are discussed.
Ultrasound Evaluation of the Changes of Ophthalmic Artery Doppler and Optic Nerve Sheath in Pregnant Women With FGR
Authors: Chen Yunqi , Lv Xiaoli , Yang Lijuan , Wang Mingmin , Hu Dan , Ren Min
Published: February 2025

Objectives

This study aimed to compare changes in ultrasonic Doppler parameters, particularly the peak ratio (PR) of the ophthalmic artery (OA) and optic nerve sheath diameter (ONSD), in pregnancies complicated by fetal growth restriction (FGR). Furthermore, it sought to evaluate differences in these parameters across various subgroups and analyze the cut‐off value of PR for predicting delivery within 1 week in pregnancies complicated by FGR.

Methods

A total of 62 pregnant women in the mid‐to‐late stages of gestation were enrolled, comprising 31 participants in the FGR group and 31 in the control group. The general conditions, pregnancy outcomes, Doppler parameters of the OA, and ONSD were compared between the two groups. Comparative analysis was performed to investigate differences in OA Doppler parameters and ONSD across FGR subgroups. The predictive value of PR for delivery within 1 week was assessed using the area under the receiver operating characteristic curve.

Results

The PR of the OA was significantly elevated in the FGR group compared to the control group, demonstrating a statistically significant difference. The threshold PR value for predicting delivery within 1 week was 0.565, with a sensitivity of 0.88 and a specificity of 0.58.

Conclusions

The PR value of the OA in pregnant women with FGR is significantly increased and may serve as a reliable predictor for pregnancies complicated by FGR.
AKIRA: Deep learning tool for image standardization, implant detection and arthritis grading to establish a radiographic registry in patients with anterior cruciate ligament injuries
Authors: Lu Yining , Yang Linjun , Mulford Kellen , Grove Austin , Kaji Ellie , Pareek Ayoosh , Levy Bruce , Wyles Cody C. , Camp Christopher L. , Krych Aaron J.
Published: February 2025

Purpose

Developing large‐scale, standardized radiographic registries for anterior cruciate ligament (ACL) injuries with artificial intelligence (AI) tools can enhance personalized orthopaedics. We propose deploying Artificial Intelligence for Knee Imaging Registration and Analysis (AKIRA), a trio of deep learning (DL) algorithms, to automatically classify and annotate radiographs. We hypothesize that algorithms can efficiently organize radiographs based on laterality, projection, identify implants and classify osteoarthritis (OA) grade.

Methods

A collection of 20,836 knee radiographs from all time points of treatment (mean orthopaedic follow‐up 70.7 months; interquartile range [IQR]: 6.8–172 months) were aggregated from 1628 ACL‐injured patients (median age 26 years [IQR: 19–42], 57% male). Three DL algorithms (EfficientNet, YOLO [You Only Look Once] and Residual Network) were employed. Radiograph laterality and projection (anterior‐posterior [AP], lateral, sunrise, posterior‐anterior, hip–knee–ankle and Camp‐Coventry intercondylar [notch]) were labelled by a DL model. Manually provided labels of metal fixation implants were used to develop a DL object detection algorithm. The degree of OA, both as measured by specific Kellgren–Lawrence (KL) grades, as well as based on a binarized label of OA (defined as KL Grade ≥2), on standing AP radiographs were classified using a DL algorithm. Individual model performances were evaluated on a subset of images prior to the deployment of AKIRA to registry construction using all ACL radiographs.

Results

The classification algorithms showed excellent performance in classifying radiographic laterality (F1 score: 0.962–0.975) and projection (F1 score: 0.941–1.0). The object detection algorithm achieved high precision–recall (area under the precision‐recall curve: 0.695–0.992) for identifying various metal fixations. The KL classifier reached concordances of 0.39–0.40, improving to 0.81–0.82 for binary OA labels. Sequential deployment of AKIRA following internal validation processed and labelled all 20,836 images with the appropriate views, implants, and the presence of OA within 88 min.

Conclusion

AKIRA effectively automated the classification and object detection in a large radiograph cohort of ACL injuries, creating an AI‐enabled radiographic registry with comprehensive details on laterality, projection, implants and OA.

Study Design

Cross‐sectional study.

Level of Evidence

Level IV.
Pilot Study of Speech and Ventilation Quality of Life After Cleft Palate Repair in Chinese Patients
Authors: Sui Hao , Liu Weilong , Wu Min , Yin Heng , Du Meijun , Chen Jiali , Zhang Shiming , Huang Hanyao , Shi Bing , Lu Yong
Published: February 2025

Objective (s)

This pilot study aimed to assess the quality of life (QoL) in Chinese patients with velopharyngeal competence (VPC) after primary cleft palate surgery or after secondary posterior pharyngeal flap (PPF) surgery.

Methods

A two‐center cross‐sectional study was conducted in two stomatological hospitals in China between December 2021 and December 2022. A total of 68 patients and healthy volunteers were enrolled in this study, categorized into the control group, the group of patients with VPC after primary cleft palate repair, and the group of patients with VPC after secondary PPF. The Velopharyngeal Insufficiency (VPI) Effects on Life Outcomes (VELO) instrument and the Quebec Sleep Questionnaire (QSQ) were used for the assessment of speech‐related QoL and ventilation‐impairment‐related QoL.

Results

Healthy subjects had better VELO total scores (speech‐related QoL) than patients with VPC. Patients who reached VPC by secondary PPF surgery had better VELO scores in the domain of perception by others, compared with patients who reached VPC after the primary cleft palate surgery. Ventilation‐impairment‐related QoL assessment showed that patients who underwent secondary PPF surgery had worse QSQ total scores and domain scores than those who only had primary surgery. Surgical age only had a negative correlation with VELO scores of swallowing problems in patients who underwent PPF surgery.

Conclusions

Despite achieving VPC after both primary and secondary surgery, patients could still exhibit worse speech‐related QoL than healthy individuals. Among patients with VPC, patients who underwent secondary PPF could have worse ventilation‐impairment‐related QoL than those who only had primary cleft palate surgery.

Level of Evidence

3 Laryngoscope, 2025
Microbial Necromass Nitrogen Accumulation and Its Response to Soil Multifunctionality Following Plantation Restoration in a Subtropical Karst Region
Authors: Lei Junjie , Peng Yuanying , Dang Peng , Gao Xiaoqian , Chen Xiaoyong , Yan Wende
Published: February 2025

Microbial necromass nitrogen (MNN) is increasingly recognized as a major source of soil N, playing a crucial role in N sequestration and sustaining N balance. However, quantitative data on the contribution of MNN to total N and its relationship with soil multifunctionality (SMF) in karst plantation ecosystems remain lacking. In this study, MNN (measured via amino sugar analysis) and SMF (calculated using the mean value method) were determined across five plantations and unafforested land (control) in the Wuling Mountains of subtropical China. The soil MNN content ranged from 1.02 to 1.67 g kg−1, contributing 53.8% to 75.4% of the total N, with Cinnamomum camphora pure forest exhibiting the highest values among all stand types and control. The afforestation of Cinnamomum camphora enhanced soil nutrient provision, microbial activity, and biomass, increasing SMF by 54% compared to the control. The soil functional parameters were generally higher in the organic horizon than in the topsoil and subsoil, and the contribution of MNN to total N was greater in the subsoil. Enzyme stoichiometry ratios indicated that microbial P limitation was prevalent in both plantation and control soils, with MNN content positively correlated with C/P and N/P ratios (p < 0.001). Increases in MNN were closely associated with SMF, encompassing nutrient provision, microbial activity, and biomass, with available N (AN) being a key predictor of MNN accumulation. The partial least squares path model revealed that nutrient provision contributed positively to MNN accumulation, and AN had a direct effect path coefficient of 0.72 on it (p < 0.01). This work underscored the critical role of MNN in contributing to N sequestration and its potential to support ecosystem functioning in the karst region.
Recovery from drought‐induced dieback may lead to modified salt marsh vegetation composition
Authors: Yang Zhicheng , D'Alpaos Andrea , Marani Marco , Blount Tegan , Alber Merryl , Murray Brad , Silvestri Sonia
Published: February 2025

Salt marshes are vital but vulnerable ecosystems. However, our understanding of disturbance‐induced dieback and recovery processes in multi‐specific marshes remains limited. This study utilized remote sensing data (2001–2021) to analyze a dieback event and subsequent recovery in the multi‐specific San Felice marsh within the Venice lagoon, Italy. A significant dieback of Spartina maritima (Spartina) was identified in 2003, likely triggered by a drought event and heat stress. This resulted in a conversion of 4.6 ha of marsh predominantly colonized by Spartina (fractional cover of Spartina > 50%) in 2001 to bare soil in 2003. These bare areas were then gradually encroached by vegetation, indicating the occurrence of the recovery. Despite gradually gaining ground, Spartina only dominated 6.4 ha marshes in 2021, significantly lower than its pre‐dieback area (21.3 ha). However, other species also encroached on the dieback area, such that the aboveground biomass returned to pre‐dieback levels, indicating that the shift in marsh species composition that occurred as a consequence of the event compensated for this ecosystem service. Vegetation recovery, spanning from 1 yr to more than 18 yr, was found to be slowest in areas of lowest elevation. This study provides evidence that dieback and recovery can modify the species composition of multi‐specific marshes over decades. These insights contribute to a better understanding of marsh resilience to drought and elevated temperature, both of which are likely to increase in the future.
Near‐Unity Internal Quantum Efficiency and High Thermal Stability of Sr3MgGe5O14: Cr3+ Phosphor for Plant Growth
Authors: Lin Qiuming , Wu Xiaozhong , Peng Jiaqing , You Weixiong , Ye Xinyu , Huang Decai
Published: February 2025

Near‐infrared phosphor‐converted light‐emitting diodes (NIR pc‐LEDs) are regarded one of the most promising light sources for food analysis, plant growth, bioimaging, night vision, and so on. Cr3+‐activated NIR phosphors have garnered increasing attention due to their exceptional photoluminescence properties for NIR pc‐LED. However, most of them suffer from poor thermal stability or low efficiency which limits their large‐scale application. Herein, a novel Sr3MgGe5O14: Cr3+ (SMGO: Cr3+) NIR phosphor is presented, which exhibits a broadband NIR emission ranging the range of 650–1000 nm with a peak at 735 nm. SMGO: 0.005Cr3+ phosphor demonstrates an almost near‐unity internal quantum efficiency (99.4%) and excellent thermal quenching performance (I423 K/I298 K = 86%). First‐principles theory calculation indicates that Cr3+ ions preferentially occupy the [Ge2/MgO4] and [Ge3O4] sites at high doping concentration within the SMGO host, illustrating the concentration quenching mechanism. Furthermore, a NIR pc‐LED is manufactured by utilizing SMGO: 0.005Cr3+ with a 445 nm blue LED chip, and the NIR output power is 140.5 mW with a photoelectric conversion efficiency of 15.5% at 300 mA. Potential applications of plant growth and the detection of several mental ions are also demonstrated, which demostrates its promising application in plant growth.
Self‐Healing Waterborne Polyurethane Elastomers Based on Multiple Reversible Bonds with Good Mechanical Performance for Composite Conductors
Authors: Wu Jiajia , Ren Mengqing , Chen Ming , Liu Xuanyu , Jin Tao , Wu Lili
Published: February 2025

As a functional material, polyurethane elastomers have a wide range of applications in fields such as flexible wearable devices and healthcare but are prone to damage during use. As a result, they are often incorporated with self‐healing properties to prolong their service life. The preparation of polyurethane elastomers with excellent mechanical and self‐healing properties has become crucial to addressing this issue. In this study, a new self‐healing system with excellent mechanical properties is developed by reacting butanedione oxime (DMG) and gallic acid (GA) with isocyanate (─NCO) to introduce oxime‐carbamate bonds and phenol‐carbamate bonds into waterborne polyurethane. The triple dynamic reversible synergistic network formed through multiple reversible covalent bonds and hydrogen bonds enhances the mechanical and self‐healing properties of the waterborne polyurethane elastomers. The results demonstrate that the synthesized polyurethane elastomer films exhibit excellent mechanical properties (strength of 41.02 MPa, elongation at break of 955.9%, toughness of 112.17 MJ m−3) and self‐healing properties (healing efficiency of 91.21%). In addition, the composite conductor (DG‐WPU‐CNTs) prepared by incorporating this polyurethane elastomer with carbon nanotubes (CNTs) exhibits excellent sensitivity, stability, and self‐healing properties, providing a basis for its application in flexible wearable devices.
The Stab Resistance of Bombyx Mori Silk Cocoons
Authors: Rehman Ateeq Ur , Koutsos Vasileios , Alam Parvez
Published: February 2025

This study considers the mechanical response of Bombyx mori silk cocoons to knife stabbing, a simple but controlled way of simulating predaceous penetration. Here, we stab test both entire cocoons (EC) and cocoon wall segments (CWS) statically and dynamically, and note that the process can be broken down in three stages. The first stage involves material deflection, the second is knife penetration, and the third is knife perforation. It is found that ca. 95 % of the kinetic energy is lost during the penetration stage. There are noticeable differences in strain between the equatorial ( = 13 %) and meridional ( = 1.5 %) directions before and after the stabbing of EC specimens (p <0.001). The apparent area of the cocoon is noted to be on average 7 % lower after stabbing than it is prior to being stabbed (p <0.01). It is found that while compression of the cocoon from stabbing results in equatorial expansion (with a Poisson's ratio, ν = 0.25), in the meridional direction the cocoon contracts (ν = ‐0.05) thus displaying auxetic behavior. Force‐deflection curves are different in CWS specimens as compared to EC specimens, and this is attributable to natural curvatures in CWS specimens remaining even after a being flattened for mounting and testing. Differences between EC and CWS specimens are also noticeable in the sizes of the stab footprints, with EC samples exhibiting 33 % smaller footprints than CWS samples (p < 0.001). It is concluded that testing whole cocoon structures provides a more accurate understanding of their properties as compared to cut and flattened structures. This is because flattening cocoon wall specimens induces delamination and multiple failure zones, reducing the natural stab resistance of the material.
Impact of Raster Angle on 3D Printing of Poly(Lactic Acid)/Thermoplastic Polyurethane Blends: Effects on Mechanical and Shape Memory Properties
Authors: Olalla Águeda Sonseca , Cerezo Joaquín Lluch , Abarca Vicente Ruedas , Soriano Lucas Rovira , Mazzinari Guido , Torres Enrique Giménez
Published: February 2025

In this study, a 60:40 blend of poly(lactic acid) and thermoplastic polyurethane (PLA/TPU) is fabricated using fused material extrusion. The morphological, thermal, mechanical and thermoresponsive cyclic shape memory effect (SME) characteristics of 3D‐printed specimens at various raster angles are investigated. This work introduces the innovative utilization of TPU's fibrillar alignment within a PLA matrix to achieve enhanced mechanical anisotropy and consistent shape memory performance. Morphological analysis reveals excellent printability, with the immiscible TPU phase forming submicron‐diameter fibrils (≈0.78 ± µm) within the PLA matrix, leading to significant improvements in toughness and elongation at break when aligned with the printing direction and the load. Tensile test demonstrates anisotropy, with 0° raster specimens achieving a UTS of 16.1 ± 0.2 MPa and elongation at 305.5 ± 71.9%, compared to 4.5 ± 0.6 MPa and 10.8 ± 1.5% at 90°. Notably, despite the mechanical anisotropy, shape fixity ratios exceeded 95% and recovery ratios between 91 and 95% were achieved across all raster angles, demonstrating robustness in thermomechanical properties. These findings offer valuable insights into the relationship between morphology, mechanical characteristics, and shape memory behavior of PLA/TPU blends fabricated using fused material extrusion, positioning the material as a strong candidate for biomedical applications requiring precise shape recovery performance.
Reevaluation of the Impact of the Novel Likely Pathogenic Variant c.1286_1288delAGA in the ATP8A2 Gene: A 7‐Year Follow‐Up With Clinical, Genetic, and ACMG Insights in an Iranian Family
Authors: Kalayinia Samira , Hesami Hamed , Badv Reza Shervin , Rabbani Maryam , Rezaei Zahra , Hosseinkhani Zohreh , Nikbakht Sedighe , Sharifi Ameneh , Akbari Bahman , Mirab Samiee Siamak , Mahdieh Nejat
Published: February 2025

Background

Cerebellar ataxia, mental retardation, and dysequilibrium (CAMRQ) syndrome is a rare neurodevelopmental disorder characterized by non‐progressive cerebellar ataxia, intellectual disability, and cerebellar atrophy. Despite its rarity, CAMRQ syndrome poses significant challenges due to its heterogeneous genetic etiology and complex clinical presentation. This study details the evolving clinical phenotype over 7 years in a male with CAMRQ4 syndrome caused by an in‐frame deletion variant in ATP8A2 gene.

Methods

A detailed clinical evaluation was performed, accompanied by tests and imaging studies. Clinical and genetic investigations, including segregation analysis, were carried out to confirm the pathogenicity of the identified variant. The evolving clinical phenotype of the patient, including developmental delay, cerebellar ataxia, and hand‐foot crawling, was thoroughly investigated.

Results

A 10‐year‐old male patient with CAMRQ syndrome exhibited typical clinical manifestations including impaired motor coordination, cognitive impairment, and balance disturbances. Genetic analysis revealed a homozygous in‐frame deletion variant (c.1286_1288delAGA) in the ATP8A2 gene, implicating ATP8A2 in the pathogenesis of CAMRQ syndrome. This variant was predicted to be likely pathogenic and deleterious, in accordance with its segregation in affected family members. Our findings expand the mutational spectrum of ATP8A2‐associated CAMRQ syndrome and underscore the importance of comprehensive genetic testing in diagnosing rare neurological disorders.

Conclusion

The identification of an in‐frame deletion variant in the ATP8A2 gene enhances our understanding of CAMRQ syndrome and highlights the phenotypic variability of the disorder. Our study contributes to the elucidation of CAMRQ syndrome by identifying a novel genetic variant and elucidating its clinical and genetic implications. Further research is warranted to advance our understanding of CAMRQ syndrome and to improve patient care and management strategies.
A Novel Polysaccharide From Tremella fuciformis Alleviated High‐Fat Diet‐Induced Obesity by Promoting AMPK/PINK1/PRKN‐Mediated Mitophagy in Mice
Authors: Lu Jing , Zhang Yanhui , Song Haizhao , Wang Fang , Wang Luanfeng , Xiong Ling , Shen Xinchun
Published: February 2025

Scope: Polysaccharides from Tremella fuciformis have gained significant interest due to their diverse biological activities. This study focuses on characterizing a purified polysaccharide, TPSP2, extracted from T. fuciformis and evaluating its antiobesity effect and underlying mechanisms in vivo. Methods and results: Structural analysis revealed that TPSP2, with a molecular weight of 1.51 × 103 kDa, is composed of mannose, rhamnose, glucuronic acid, galactose, xylose, arabinose, and fucose in specific molar ratios. The primary linkages identified include t‐Fuc(p), 1,2‐Xyl(p), t‐GlcA(p), 1,3‐Man(p), and 1,2,3‐Man(p), with their corresponding ratios being 12.987%, 11.404%, 16.050%, 16.527%, and 26.624%, respectively. In vivo experiments demonstrated that TPSP2 significantly alleviated high‐fat diet‐induced weight gain, hyperlipidemia, hepatic steatosis, hyperglycemia, and insulin resistance in mice. Mechanistically, TPSP2 was found to enhance AMPK/PINK1‐PRKN‐dependent mitophagy by upregulating the p‐AMPK/AMPK ratio, LC3‐II/I ratio, and expression of PINK1, PRKN, prohibitin 2 (PHB2), and LAMP2, while downregulating p62 and TOM20 expression. Conclusion: This study suggested that TPSP2 could be a promising candidate for addressing obesity‐related metabolic disorders by targeting mitochondrial quality control mechanisms.
Metabolomics Reveal the Anti‐Hyperuricemia Effects and Mechanisms of Sunflower Head Extract in Hyperuricemia Mice Model
Authors: Li Gang , Zhang Ying , Cheng Yu , Chao Hong , Yang Xiaolei , Dong Yan‐Mei , Li Xingsan , Xue Haifeng , Wang Mingxia , Qi Lei , Liu Jicheng
Published: February 2025

Hyperuricemia (HUA) is a globally prevalent metabolic disease characterized by excessive production or insufficient excretion of uric acid in the serum. Although several drugs are available for the treatment of HUA, they have been associated with undesirable side effects. Therefore, this study aims to evaluate the therapeutic effects of sunflower head extract (KHE) on HUA in a mouse model and explore its potential mechanisms. All mice were randomly divided into three groups: Normal control (NC, 0.5% CMC‐Na), HUA model (MD, yeast extract paste 20 g/kg), and KHE treatment group (KHE, 1 g/kg). Biochemical indicators, the oxidative stress state, and metabolomics were analyzed. KHE reduced the levels of 5‐aminoimidazole ribonucleotide, xanthine, hypoxanthine, and uric acid in the serum of mice with HUA but increased the levels of adenine and taurine. KHE decreased the activities of superoxide dismutase (SOD) enzymes, the hepatic hydrogen peroxide (H2O2) and malondialdehyde (MDA) levels, and the serum levels of betaine aldehyde and beta‐D‐glucosamine. KHE improved oxidative stress levels and mitigated potential damage to the kidneys and joints caused by urate deposition. These findings provide comprehensive evidence supporting the anti‐HUA effects and underlying mechanisms of KHE in HUA mice.