bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uterine peristalsis of adenomyosis patients on cine magnetic resonance imaging
Authors: Kido Aki , Ohta Ikuko , Himoto Yuki , Fujii Shinya , Noguchi Kyo , Nakamoto Yuji , Ogawa Toshihide 
Published: February 2025

AbstractObjectiveAdenomyosis, a common gynecologic disease, can cause infertility. Uterine peristalsis (UP) is a wave‐like contraction. Abnormal UP has been linked to infertility. The aim of this study using magnetic resonance imaging (MRI) was to compare UP between uterine walls with adenomyosis and normal walls to ascertain the possible effects of adenomyosis on UP.MethodsUsing cine MRI, UP of 139 adenomyosis patients were evaluated. The uterine walls were divided into those with and without lesions. One radiologist evaluated the presence of UP depending on the menstrual cycle phase. In cases where peristalsis was present, the peristaltic frequency and direction were evaluated. For uterine walls with adenomyosis, characteristic movement of peristalsis was evaluated, including low signal conduction, change of endometrial configuration, and irregular signal change. Peristalsis was evaluated further between focal and diffuse adenomyosis.ResultsUP was observed significantly more in adenomyosis lesions (113/182) than in normal myometrium (47/96), especially in the luteal phase, but the frequency was not significantly different (6.9 vs. 7.3). Comparison between diffuse adenomyosis and focal adenomyosis revealed that the presence of peristalsis was not significantly different in any cycle phase. Peristaltic direction was observed as cervix‐to‐fundus in the proliferative and luteal phase. Almost half of the cases showed low signal conduction (48%–59%), change of endometrial configuration (31%–53%), and irregular signal change (41%–56%) in adenomyosis lesions.ConclusionUP in adenomyosis showed a tendency of hyperperistalsis in the luteal phase. It accompanies characteristic peristaltic movement in adenomyosis in about half of patients.
Patterns of Change in Healthcare Use and Cost Before and During Psychotherapy
Authors: Yonatan‐Leus Refael , Abargil Maayan , Shulman Shmuel , Cooper‐Kazaz Rena 
Published: February 2025

ABSTRACTPrevious research has found an increase in healthcare costs before psychotherapy, followed by a decrease thereafter—a pattern also observed in our sample. However, research on the patterns of change is still lacking. Healthcare quarterly cost patterns of change were examined in a field study of 1508 patients before and during outpatient psychotherapy. Several models assess the patterns of change of the entire sample and in subgroups of those undergoing prolonged psychiatric treatment versus the rest. An exponential pattern (increasing rate of change) had the best fit during the waiting period for the prolonged psychiatric treatment group. A linear pattern was selected for the rest. A logarithmic pattern (decreasing rate of change) best fits the prolonged pharmacotherapy group during therapy. A linear pattern was selected for the rest. The economic implication of the findings is that the prolonged psychiatric treatment group is expected to have the highest return on investment when the waiting period for treatment is shortened. This unique pattern of change may also be a marker of increasing distress in this group while waiting for treatment and the rapid effect that the start of psychotherapy has on this. Therefore this group should be the focus of attention.
Role of microbiota in pain: From bench to bedside
Authors: Ren Huiguang , Cao Bo , Xu Qixuan , Zhao Ruiyang , Li Hanghang , Wei Bo 
Published: February 2025

AbstractInteractions between the microbiota and host have been proven to be critical regulators of homeostasis, and pain perception is no exception. Emerging evidence has identified the mechanisms by which microbiota dysbiosis contributes to hyperalgesia and revealed the potential value of microbiota‐associated therapies in pain management. Herein, the authors introduce the basic knowledge of pain and microbiota for readers who are not simultaneously majoring in these two fields. The clarified mechanisms underlying the regulation of pain by the microbiota are outlined in terms of three ways. This review summarizes the current advancements in pain management and microbiology research for clinicians who wish to focus on this area. Probiotics, fecal microbiota transplantation, and other methods of microbiota modulation for pain management have entered clinical translation. The authors further propose the present limitations and prospects for high‐quality development of preclinical and clinical investigations. Importantly, despite the large amount of attention given to gut bacteria, this review also puts forward great expectations on the role of nongut and nonbacterial microbiota in pain sensation. Efforts to decipher the mechanisms of microbiota functions will help to promote achievements in pain management from bench to bedside.
Continuous glucose monitor outcomes in Latino populations across multiple federally qualified health centers
Authors: Hernandez‐Calderon Ana , Gonzalvo Jasmine , Triboletti Jessica S. , Walroth Todd A. , Lewis Samuel P. , Pence Lauren 
Published: February 2025

AbstractBackgroundUtilization of continuous glucose monitoring (CGM) leads to a greater reduction in hemoglobin A1C (A1C) in individuals with diabetes compared with fingerstick blood glucose monitoring (BGM) alone. CGM also reduces diabetes‐related hospitalizations. Evidence shows CGM is underutilized in racial or ethnic minority groups.ObjectivesThere is a need to increase CGM access and evaluate the impact in underrepresented populations to prevent health disparities. Eskenazi Health added CGM devices as a covered product on the Eskenazi Health Financial Assistance Program (EH FAP) formulary. CGMs were approved for patients with diabetes taking insulin or a sulfonylurea. The purpose of this study was to assess the clinical impact of improving CGM access following EH FAP coverage with a focus on Latino populations across multiple Federally Qualified Health Centers (FQHCs).MethodsA retrospective, cohort study of nine FQHCs was conducted for all adults with EH FAP who were dispensed CGMs at Eskenazi Health outpatient pharmacies between June 1, 2022 and December 31, 2023. The primary outcome was A1C pre‐ and post‐CGM use. Secondary outcomes included CGM adherence as characterized by proportion of days covered (PDC). All outcomes were also assessed in predetermined subgroups comparing Pharm.D. versus Primary Care and Endocrinology providers and Latino versus non‐Latino individuals.ResultsA total of 184 individuals were included. Median (interquartile range) A1C at baseline was 9.6% (8.1, 11.8). At 3 months, median A1C decreased to 8.4% (n = 96; change of −0.9%; p < 0.001); at 1 month, median A1C decreased to 7.9% (n = 19; change of −1.1%; p = 0.028); and at 6 months, median A1C decreased to 8.4% (n = 55; change of −0.7; p = 0.007). PDC resulted as a median of 100% (77, 100). No difference in A1C outcomes were observed between Pharm.D. versus other prescribers.ConclusionA1C significantly improved post‐CGM use at 1, 3, and 6 months in a population that has historically experienced disparities in diabetes care.
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

ABSTRACTDue 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

ABSTRACTThis 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

AbstractUnderstanding 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

AbstractHypoxic‐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

ABSTRACTPurposeWe 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).MethodsSymptomatic 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.ResultsEach 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.ConclusionsHeterogeneous 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

ABSTRACTIn 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

ABSTRACTInfluenza 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

ABSTRACTDue 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

AbstractBackgroundSupportive 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).MethodsPatients 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.ResultsThree 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.ConclusionIn 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 summaryPatients 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.