bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rat models of frozen shoulder: Classification and evaluation
Authors: Gu Hezirui , Xie Wenqing , Li Hengzhen , Liu Shuguang , Li Yusheng 
Published: December 2024

AbstractFrozen shoulder (FS), also known as adhesive capsulitis, is a condition that causes contraction and stiffness of the shoulder joint capsule. The main symptoms are persistent shoulder pain and a limited range of motion in all directions. These symptoms and poor prognosis affect people's physical health and quality of life. Currently, the specific mechanisms of FS remain unclear, and there is variability in treatment methods and their efficacy. Additionally, the early symptoms of FS are difficult to distinguish from those of other shoulder diseases, complicating early diagnosis and treatment. Therefore, it is necessary to develop and utilize animal models to understand the pathogenesis of FS and to explore treatment strategies, providing insights into the prevention and treatment of human FS. This paper reviews the rat models available for FS research, including external immobilization models, surgical internal immobilization models, injection modeling models, and endocrine modeling models. It introduces the basic procedures for these models and compares and analyzes the advantages, disadvantages, and applicability of each modeling method. Finally, our paper summarizes the common methods for evaluating FS rat models.
Influence on the lipase concentration and substrate on the lipid profile and sensory characteristics of enzyme‐modified cheese
Authors: Vieitez Ignacio , Miraballes Marcelo , Irigaray Bruno , Ellis Ana Claudia , Callejas Nicolás , Hodos Natalia , Cano Andrea , Romero Melissa , da Rosa Gonzalo , Gámbaro Adriana 
Published: December 2024

AbstractEnzymatically modified cheeses (EMC) aim to achieve, in a shorter time frame, a composition and sensory characteristics akin to those of aged cheese. This study analyzed the lipid profile, composition, free fatty acid (FFA) content, and sensory attributes of EMC pastes with the objective of emulating the flavor profile of a red smear‐ripened cheese (SR). Two different smear ripened cheeses were utilized as references: SR1, aged for 2–3 months, and SR2 aged for 10 months. Twelve formulations of EMC were prepared using a fatty medium moisture cheese corresponding to Mercosur's Danbo type cheese (MD) as sole base, with the addition of the two types of SR cheeses and enzymes including exopeptidase, endopeptidase, and lipase, with varying concentrations of the latter. The EMC formulations exhibited a different physicochemical composition compared to the SR cheeses, with higher moisture, ash content, lower fat, and protein content. The highest total FFA contents were found in formulations with SR2, followed by formulations with SR1. As the concentration of lipase increased in the formulations, a greater degree of lipolysis was observed. Sensory profile was not influenced by the concentration of lipase, but rather depended on the type of cheese used as the base. All EMC samples prepared with SR1 besides those prepared with SR2 as the base cheese and the highest concentration of lipase, exhibited sensory profiles more closely resembling that of lightly aged SR1. The enzymatic modification of cheeses proved to be a useful tool for generating sensory profiles similar to slightly aged SR cheese.
Glutathione S‐Transferase Contributes to the Resistance of Megalurothrips usitatus Against Lambda‐Cyhalothrin by Strengthening Its Antioxidant Defense Mechanisms
Authors: Dong Wenbo , Wang Chaozheng , Li Xia , Huang Tianbao , Li Fen , Wu Shaoying 
Published: December 2024

ABSTRACTThe damage caused by Megalurothrips usitatus, a common pest, has significantly affected the Chinese vegetable industry. The inappropriate application of chemical pesticides has caused M. usitatus to become highly resistant to conventional insecticides. Glutathione S‐transferase (GST), known for its multifunctional properties, contributes to detoxification and antioxidation. It enhances insects' adaptability to pesticides by facilitating the elimination of lipid peroxidation products resulting from pyrethroid insecticides. This research employed RT‐qPCR to identify GST genes that exhibited significant expression in response to lambda‐cyhalothrin stress. It also quantified changes in antioxidant and apoptosis markers within the M. usitatus under lambda‐cyhalothrin exposure. The functional significance of GST was validated by assessing alterations in the antioxidant defense system and resistance to lambda‐cyhalothrin following the inhibition of GST activity. The study's outcomes indicated that MuGSTs1 was markedly upregulated in response to lambda‐cyhalothrin stress (p < 0.0001). The GST activity was effectively suppressed by the specific inhibitor, diethyl maleate, achieving an inhibition rate of 64.05%. Following the inhibition of GST, the overall antioxidant capacity was reduced by 3.1‐fold compared with the control, and the M. usitatus exhibited a 7.91‐fold increase in sensitivity to lambda‐cyhalothrin. These findings confirm the pivotal role of GST in the oxidative stress response of the M. usitatus and their contribution to the development of resistance to lambda‐cyhalothrin through enhanced antioxidant defenses. This research offers valuable perspectives on the adaptive reactions of insects to chemical stressors, facilitating the management of resistance and the formulation of effective pest control strategies.
NiFe‐NO3 Layered Double Hydroxide as a Novel Anode for Sodium Ion Batteries
Authors: Fortunato Marco , Sarapulova Angelina , Schwarz Björn , Cardinale Anna Maria , Dsoke Sonia 
Published: December 2024

Abstract2D materials are emerging materials for energy storage and among these layered double hydroxides (LDHs) seem particularly promising due to their structure, easily adjustable composition, and cheapness. This study marks the first reported application of an LDH, specifically NiFe‐NO3 LDH, as conversion anode material in a sodium half‐cell, to the best of our knowledge. Despite an initial loss in capacity, the material demonstrates notable stability, retains a high specific capacity even after 50 discharge/charge cycles (~500 mAh/g). The intricate reaction mechanism was explored using various ex‐situ techniques such as DC magnetometry and FTIR, as well as in‐operando X‐ray Absorption Spectroscopy (XAS). The proposed Na‐storage mechanism in NiFe‐NO3 LDH involves an initial irreversible “activation” during the first sodiation, characterized by a phase change reaction that leads to the formation of NiOx and Fe3O4, followed by a reversible mechanism involving both intercalation and conversion in subsequent cycles.
Design Principles of an Engineered Metastatic Niche for Monitoring of Cancer Progression
Authors: Escalona Guillermo , Ocadiz‐Ruiz Ramon , Ma Jeffrey A. , Schrack Ian A. , Ross Brian C. , Morrison Alexis K. , Jeruss Jacqueline S. , Shea Lonnie D. 
Published: December 2024

ABSTRACTAcross many types of cancer, metastatic disease is associated with a substantial decrease in 5‐year survival rates relative to only a localized primary tumor. Many patients self‐report metastatic disease due to disruption of normal organ or tissue function, and earlier detection could enable treatment with a lower burden of disease. We have previously reported a subcutaneous biomaterial implant for early detection by serving as an engineered metastatic niche, which has been reported to recruit tumor cells before colonization of solid organs. In this report, we investigated the design principles of the scaffold and defined the conditions for use in disease detection. Using the metastatic 4T1 triple‐negative breast cancer model, we identified that a porous structure was essential to capture tumor and immune cells. Scaffolds of multiple diameters were investigated for their ability to serve as a metastatic niche, with a porous scaffold with a diameter as small as 2 mm identifying disease accurately. Additionally, scaffolds that had been in vivo for 1–5 weeks were able to identify disease accurately. Finally, the sensitivity of the scaffold relative to liquid biopsies was analyzed, with scaffolds accurately detecting disease at earlier time points than liquid biopsy. Collectively, these studies inform the design principles and use conditions for porous scaffolds to detect metastatic disease.
Comparison of Back Tuina and Oral Astragalus Methods to Enhance Immunosuppression in Rabbits and Prediction of Astragalus Targets for Immune Function Improvement
Authors: Dai Mengyao , Fan Enshuo , Pan Ting , Li Xuefeng , Li Mengqi , Lu Qi , Wang Weizheng , Guo Xiaole , Shang Kun , Zhang Xin 
Published: December 2024

ABSTRACTBack tuina massage and oral administration of astragalus are two methods used in traditional Chinese medicine (TCM) to improve immune function. The aim of this study is to analyze the effects of tuina and orally administered astragalus on immunosuppressed rabbits using proteomics technology. Additionally, we investigate the potential mechanism of action of astragalus components on immunosuppression using an integration of network pharmacology and molecular docking technology. The findings suggested that cyclophosphamide‐induced immunosuppression is primarily mediated through signaling pathways that include complement and coagulation cascades and chemical carcinogenesis. Immunosuppression is modulated by tuina and the oral administration of astragalus through various proteins and signaling pathways. A network pharmacology analysis indicated that quercetin, trichothecene isoflavones, and kaempferol in astragalus exhibited immunomodulatory effects. Molecular docking validation demonstrated that 15 major targets showed strong binding affinities to their respective interacting active ingredients. This trial provides references for future studies on the immune‐boosting properties of tuina and oral astragalus.
Effects of CYP3A4 Variants on Methadone Metabolism In Vitro
Authors: Wang Chen‐chen , Zhang Ming‐lei , Xu Yan‐dan , Hu Guo‐xin , Cai Jian‐ping , Lan Tian , Bai Yong‐feng 
Published: December 2024

ABSTRACTIn hepatic drug metabolism, cytochrome P450 (CYP450) enzymes, particularly CYP3A4, catalyze the majority of drug biotransformations, accounting for over 50% of the CYP450 family's metabolic capacity. This study aimed to assess the catalytic efficiency of 22 CYP3A4 allelic variants on the in vitro oxidative metabolism of methadone. We utilized a baculovirus‐insect cell expression system to produce recombinant CYP3A4 variants and subsequently assessed their catalytic activity in the N‐demethylation of methadone. Of the 23 tested CYP3A4 allelic variants, CYP3A4*1 represents the wild type. Compared with CYP3A4*1, 12 variants displayed significantly lower intrinsic clearance of methadone, while 3 variants showed increased intrinsic clearance of methadone. Additionally, six variants demonstrated no significant difference in intrinsic clearance of methadone compared to CYP3A4*1, and one variant showed no detectable expression. Our evaluation of the enzymatic activity of CYP3A4 gene polymorphisms on methadone can aid in the personalized clinical use of methadone and facilitate the investigation into the relationship between genetic variations and clinical phenotypes.
Investigating the Mediating Role of Mental Disorders in the Relationship Between Early Sexual Intercourse and Intentional Self‐Harm: A Two‐Step and Multivariable Mendelian Randomization Study
Authors: Dong Dameng , Saeed Saboor , Chen Rucheng , Chen An , Zheng Weijun 
Published: December 2024

AbstractBackgroundEpidemiological studies have established an association between early sexual intercourse and intentional self‐harm. However, the causal mechanisms, particularly the role of mental health disorders, remain elusive.MethodsIn this Mendelian randomization (MR) study, we leveraged genome‐wide association study data from multiple sources. Age at first sexual intercourse (AFSI) statistics were derived from the UK Biobank, encompassing up to 406,457 participants of European ancestry. Intentional self‐harm (ISH) genome‐wide association study (GWAS) data were obtained from the FinnGen Biobank, comprising 218,792 European‐descent individuals. We investigated the causal relationship between AFSI and ISH and quantified the mediating effects of major depressive disorder (MDD; n = 173,005), schizophrenia (SCZ; n = 127,906), and attention deficit hyperactivity disorder (ADHD; n = 55,374). Both two‐step and multivariable MR approaches were employed to estimate the mediation effects of these psychiatric disorders.ResultsThe F‐statistics of all retained SNPs are over 10, indicating our study has no weak instrument bias. The odds ratio (OR) indicated that early sexual intercourse substantially increases the risk of ISH (IVW: OR = 0.60, 95% CI = 0.54–0.66, p < 0.05). Specifically, MDD was found to mediate 31% of this effect and SCZ 12%, collectively accounting for 46% of the total effect.ConclusionsEarly sexual intercourse is associated with an increased risk of intentional self‐harm, potentially mediated by psychiatric disorders. These findings emphasize the need for mental health screening and early intervention in adolescents with early sexual debuts.
Evaluation of the Clinical Safety of the Low‐Cost Warburg Therapy for the Treatment of Patients With Advanced Cancers
Authors: Lu Peihua , Tsang Tom , Badowski Michael S. , Pennington Michael E. , Meade‐Tollin Linda C. 
Published: December 2024

ABSTRACTBackgroundRising cancer care costs are becoming cost prohibitive for lower income people worldwide. We developed the Warburg protocol as a low‐cost option for the treatment of cancer that was inspired. It was developed to exploit an Achilles heel which is a hallmark of cancer cells; the metabolic requirement for higher levels of glucose than normal cells.ObjectiveThe purpose of this report is to assess the clinical safety and affordability of the Warburg therapy as an option for patients with advanced cancers.MethodsBetween 2021 and 2023, 251 patients with advanced cancers received a total of 8542 treatments with the Warburg therapy. To restrict the supply of blood glucose to cancerous tumors, regular human insulin was administered (IV) sufficient to reduce blood glucose concentrations to hypoglycemic levels for 40–60 min. Subroutine doses of fluorouracil and cyclophosphamide were administered intravenously during this hypoglycemic period. Food or intravenous glucose was given as needed to return blood glucose to euglycemic levels after treatment. Patient symptoms, status, vitals, blood glucose, and hypoglycemic symptoms were monitored throughout treatment. Various blood parameters were measured before and after patients' course of treatment.ResultsThere were no irreversible adverse reactions in advanced tumor patients of different ages and different cancer types after treatment. There was no significant fluctuation in blood glucose levels in diabetic and non‐diabetic patients after treatment, and the weight, vital index and blood biochemical index of patients before and after multiple treatments exhibited little variation.ConclusionWarburg therapy for the treatment of advanced tumors is clinically feasible, and safe for multiple treatments. It is inexpensive and widely applicable to different patient groups.
Consumer Adoption of Internet of Things
Authors: Ladeira Wagner Junior , Lim Weng Marc , de Oliveira Santini Fernando , Rasul Tareq , Frantz Bernardo , de Oliveira Rosa Jean Carlos , Azhar Mohd 
Published: December 2024

ABSTRACTThe Internet of Things (IoT), a pivotal technology in enhancing user connectivity, faces a paradox: its widespread potential yet limited consumer adoption. This study addresses this dichotomy by synthesizing a large‐scale meta‐analytic structural equation modeling (MASEM) and hierarchical linear meta‐analysis (HiLMA) of 2736 effect sizes from 52,629 respondents across 138 studies. We propose an integrated and heterogeneous model, underpinned by appraisal theory and the technology acceptance model (TAM), to explain the dynamics of IoT adoption among consumers across heterogeneous settings. Our findings reveal that consumers' primary appraisals of IoT, influenced significantly by hedonic motivation and social influence, are instrumental in forming perceptions of IoT's ease of use and usefulness. These perceptions subsequently guide consumers in navigating the complexities of IoT, such as privacy, risk, and trust issues. These layered appraisals inform consumers' attitudes and intentions toward IoT adoption, wherein its efficacy is heightened in contexts involving critical services versus non‐critical ones, in Eastern versus Western regions, within healthcare rather than fashion sectors, and among more experienced and younger demographics, particularly students over the general public. The study also underscores the distinct impact of branded IoT devices over unbranded ones, delineating a heterogeneous understanding of IoT adoption. Therefore, the interpretation of heterogeneities in the combination of effect sizes from extant studies is a seminal attempt to address the IoT paradox by demonstrating which factors explain the variations in the relationship between attitude and intention toward IoT from the consumer's perspective.
Synthesis of Thiazolidinedione‐ and Triazole‐Linked Organoselenocyanates and Evaluation of Anticancer Activities Against Breast Cancer with Mechanistic Investigations
Authors: Pal Nikita , Banerjee Kaustav , Sarkar Shilpi , Mandal Tapas K. , Bhabak Krishna P. 
Published: December 2024

AbstractOrganoselenocyanates are important classes of organoselenium compounds having potential pharmaceutical applications in cancer biology. In the present study, two different series of organoselenocyanates (15 a–15 c and 16 a–16 c) incorporating crucial heterocyclic pharmacophores such as 2,4‐thiazolidine‐1,3‐dione and 1,2,3‐triazole were rationally designed. The organoselenocyanates were synthesized using multi‐step organic synthesis and investigated for their anticancer activities against triple‐negative breast cancer cells. Based on the preliminary anti‐proliferative activities and the selectivity index towards cancer cells over the normal cells, 2,4‐thiazolidine‐1,3‐dione‐based selenocyanate 15 a was identified as the lead analogue for detailed investigations. In addition to the anti‐migratory activity, compound 15 a induced G1‐phase arrest of the cell cycle and led to early apoptosis. Further studies on the redox balance of MDA‐MB‐231 cells indicated the antioxidant nature of 15 a with the quenching of ROS level and upregulation of TrxR1 expression. Detailed mechanistic investigations with the expression levels of key‐cancer marker proteins revealed that the selenocyanate 15 a induced the activation of ERK pathway by upregulating p‐ERK expression with the subsequent downregulation of p‐Akt and c‐Myc levels leading to the inhibition of cellular proliferation. Therefore, the primary outcomes of the study would be valuable in the development of chemotherapeutic agents towards the treatment of triple‐negative breast cancer.
pH Controlled Transient Cyclization of Peptides for Increased Stability towards Oral Delivery
Authors: Paprocki Maciej P. , Sørensen Kasper K. , Jensen Knud J. 
Published: December 2024

AbstractPeptides are highly efficient for treatment of many diseases, especially in oncology and diabetes. Oral delivery of peptides is desirable, but is challenged by low bioavailability and new chemical methods to enable oral delivery are needed. Here, we developed pH responsive linearization as a strategy for transient protection of peptides to extend their half‐life in model systems. Peptides were cyclized to increase their stability at the low pH in the stomach, while they linearize at neutral pH to form the active peptide. We developed ester based responsive linkers with a protonable amine for O‐to‐N acyl shift, which allowed linearization strategies based on pyroglutamoyl (pGlu) or diketopiperazine (DKP) formation. After coupling of the linker, peptides were cyclized by CuAAC. We studied the stability against simulated gastric fluid (SGF) at different pH and the ability of cyclic peptides to linearize. This led to PYY3–36 analogues with pH responsive linearization for increased stability.
Reusable Iron‐Copper Catalyzed Cross‐Coupling of Primary Amides with Aryl and Alkyl Halides: Access to N‐Arylamides as Potential Antibacterial and Anticancer Agents
Authors: Roy Keya , Saha Anay , Saha Bijay , Banerjee Subhrajyoti , Mukhopadhyay Chitrangada Das , Sahu Sumanta Kumar , Adak Laksmikanta 
Published: December 2024

AbstractWe present, for the first time, an efficient ligand‐free iron‐copper catalyzed cross‐coupling reaction involving a variety of aryl, heteroaryl halides (including chlorides, bromides, and iodides), and alkyl bromides with diverse aryl and aliphatic primary amides, conducted under solvent‐minimized conditions. This economically competitive protocol successfully yielded the corresponding cross‐coupling products, N‐arylamides and N‐alkylamides, in good to excellent yields with broad substrate scope (65 examples) and tolerance to several sensitive functionalities (including heterocycles). No conventional work‐up is required for this protocol, and the developed method is applicable for gram‐scale synthesis. Notably, the catalyst is inexpensive, environmentally friendly, and can be reused at least four times with minimal loss of catalytic activity. A series of experiments, including X‐ray photoelectron spectroscopy (XPS), UV spectroscopy, cyclic voltammetry (CV), electron paramagnetic resonance (EPR), and X‐ray diffraction (XRD) were conducted to identify the oxidation state of active catalytic species and radical clock experiment was performed using a radical probe to investigate the reaction mechanism. Furthermore, we evaluated the antibacterial and anticancer properties of selected synthesized products (3 ii, 3 xii, and 3 xxxx) in‐vitro. The results indicated that the prepared compounds exhibited promising antibacterial and anticancer activities (MTT and Molecular Docking).
At‐Home Self‐Collection of Pharmacokinetic Data: Design and Results From a Phase 1 Open‐Label Feasibility Trial
Authors: Raoufinia Arash , Shoaf Susan E. , Rothman Brian , Ye Chelsea , Chung Chris 
Published: December 2024

AbstractPharmacokinetic (PK) studies pose unique technical challenges. We present the design of a Phase 1, open‐label, fixed‐sequence, PK trial that aimed to compare the timing accuracy of participant‐ versus staff‐collected data, and we provide safety and tolerability outcomes for centanafadine treatment. Healthy adults aged 18‐55 years received a single 100‐mg centanafadine sustained‐release tablet at Visits 1, 2, and 4. PK samples (venous sampling and blood microsampling) and safety assessments (12‐lead electrocardiograms [ECGs] and vital signs) were collected by clinical site staff only at Visit 1. At Visit 2, site staff collected venous blood, and participants obtained blood microsamples, a 6‐lead ECG, and vital signs under staff supervision. At Visit 4, participants obtained blood microsamples, a 6‐lead ECG, and vital signs remotely. The absolute differences between actual and scheduled collection times for PK samples, ECGs, and vital signs are reported descriptively. Of the 20 participants, at least 75% obtained blood microsamples within 10 minutes of the planned nominal time. Absolute differences between actual and scheduled collection times of ECGs and vital signs were small. No adverse events were related to treatment. Overall, results support the feasibility of at‐home collection of PK samples, ECGs, and vital signs.