bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of systemic immune-inflammation index with the risk of incident pre-frailty or frailty: the Chinese Longitudinal Healthy Longevity Survey
Authors: Li Xiaoli , Gao Weiyang , Xu Hong , Xu Juan 
Published: January 2024

Abstract

Background: Inflammation is a significant factor in the pathogenesis of frailty. While previous research has indicated that the systemic immune-inflammation index (SII) serves as a reliable marker for inflammation, the relationship between SII and newly developed frailty remains understudied. This study aims to explore the relationship between SII and incident pre-frailty and frailty among community-dwelling older adults. Methods: Data were drawn from participants in the 2008 wave of the Chinese Longitudinal Healthy Longevity Survey (CLHLS). A 38-item frailty index (FI) was employed to assess frailty status and to classify participants into one of three categories: “robust” (FI ≤ 0.1), “pre-frail” (0.1 < FI ≤ 0.21), or “frail” (FI > 0.21). The SII was determined using the formula: SII = (white blood cell – lymphocyte) × (platelet count) / lymphocyte. A Cox regression model was utilized to evaluate the relationship between SII and the onset of pre-frailty and frailty. Results: The analysis included 676 participants classified as robust, with a median age of 80.0 years (interquartile range, 67.0, 91.0). Over a 3-year follow-up period, 159 participants progressed to a state of pre-frailty or frailty. The incidence of pre-frailty or frailty was 17.8%, 25.3%, and 27.6% across SII tertile groups, respectively (p < 0.05). Among participants initially categorized as robust in 2008, those in the highest SII tertile had a greater risk of developing pre-frailty or frailty compared to those in the lowest tertile (HR = 2.03; 95% CI: 1.12–3.70). Sensitivity analysis using the Fine-Gray model, accounting for death as a competing risk, also indicated an elevated risk for those in the highest SII tertile (HR = 1.53; 95% CI: 1.18–1.98). Conclusion: Among community-dwelling older adults, higher SII levels were associated with an increased risk of incident pre-frailty or frailty.
Extracellular Proximity Labeling Reveals an Expanded Interactome for the Matrisome Protein TIMP2
Authors: Peeney David , Gurung Sadeechya , Rich Josh , Coates-Park Sasha , Liu Yueqin , Toor Jack , Jones Jane , Richie Christoper , Jenkins Lisa , Stetler-Stevenson William 
Published: January 2024

Abstract

Classical methods of investigating protein-protein interactions (PPIs) are generally performed in non-living systems, yet in recent years new technologies utilizing proximity labeling (PL) have given researchers the tools to explore proximal PPIs in living systems. PL has distinct advantages over traditional protein interactome studies, such as the ability to identify weak and transient interactions in vitro and in vivo. Most PL studies are performed on targets within the cell or on the cell membrane. We have adapted the original PL method to investigate PPIs within the extracellular compartment, using both BioID2 and TurboID, that we term extracellular PL (ePL). To demonstrate the utility of this modified technique, we investigate the interactome of the widely expressed matrisome protein tissue inhibitor of metalloproteinases 2 (TIMP2). Tissue inhibitors of metalloproteinases (TIMPs) are a family of multi-functional proteins that were initially defined by their ability to inhibit the enzymatic activity of metalloproteinases (MPs), the major mediators of extracellular matrix (ECM) breakdown and turnover. TIMP2 exhibits a broad expression profile and is often abundant in both normal and diseased tissues. Understanding the functional transformation of matrisome regulators, like TIMP2, during the evolution of tissue microenvironments associated with disease progression is essential for the development of ECM-targeted therapeutics. Using carboxyl- and amino-terminal fusion proteins of TIMP2 with BioID2 and TurboID, we describe the TIMP2 proximal interactome. We also illustrate how the TIMP2 interactome changes in the presence of different stimuli, in different cell types, in unique culture conditions (2D vs 3D), and with different reaction kinetics (BioID2 vs. TurboID); demonstrating the power of this technique versus classical PPI methods. We propose that the screening of matrisome targets in disease models using ePL will reveal new therapeutic targets for further comprehensive studies.
Fluoranthene degradation in a persulfate system activated by sulfidated nano zero-valent iron (S-nZVI): performance and mechanisms
Authors: Zhang Ruzhuang , Zhu Yi , Dong Jiaqi , Yao Zhennan , Zeng Guilu , Sheng Xianxian , Xu Ziqian , Lyu Shuguang 
Published: January 2024

Abstract

Fluoranthene (FLT) has received mounting focus due to its hazardous properties and frequent occurrence in groundwater. In this study, sulfidated nano zero-valent iron (S-nZVI) was selected as an efficient catalyst for activating persulfate (PS) to degrade FLT. The effects of reagent doses, various water conditions (pH, anions, and humic acid), and the presence of surfactants on FLT degradation were investigated. Radical probe experiments, electron paramagnetic resonance (EPR) spectrum detection, and scavenging tests were performed to identify the major reactive oxygen species (ROS) in the system. The results showed that in the PS/S-nZVI system, 96.2% of FLT was removed within 120 min at the optimal dose of PS = 0.07 mM and S-nZVI = 0.0072 g L−1. S(-II) in the S-nZVI surface layer promoted Fe(II) regeneration. Furthermore, HO• and SO4−• were identified as the main contributors to FLT degradation. The intermediates of FLT degradation were detected by gas chromatograph-mass spectrometry (GC-MS) and a possible FLT degradation pathway was proposed. Finally, the effective degradation of two other common polycyclic aromatic hydrocarbons (PAHs) (naphthalene and phenanthrene) demonstrated the broad-spectrum reactivity of the PS/S-nZVI process. In conclusion, these findings strongly demonstrate that the PS/S-nZVI process is a promising alternative for the remediation of PAH-contaminated groundwater.
Network Pharmacology and Experimental Validation Explore the
Pharmacological Mechanisms of Herb Pair for Treating Rheumatoid
Arthritis
Authors: Xu Xi-Xi , Shao Hua , Wang Qiao-Xue , Wang Zi-Yuan 
Published: January 2024

Objective:
This study aimed to elucidate the multitarget mechanism of the Mori Ramulus
- Taxilli Herba (MT) herb pair in treating rheumatoid arthritis (RA).

Methods:
The targets of the herb pair and RA were predicted from databases and screened
through cross-analysis. The core targets were obtained using protein-protein interaction (PPI)
network analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG)
pathway enrichment analysis were performed. Finally, animal experiments were conducted to
validate the anti-RA effect and mechanism of this herb pair.

Results:
This approach successfully identified 9 active compounds of MT that interacted with 6
core targets (AKT1, TNF, IL6, TP53, VEGFA, and IL1β). Pathway and functional enrichment
analyses revealed that MT had significant effects on the TNF and IL-17 signaling pathways. The
consistency of interactions between active components and targets in these pathways was confirmed
through molecular docking. Moreover, the potential therapeutic effect of MT was verified
in vivo, demonstrating its ability to effectively relieve inflammation by regulating these targeted
genes and pathways.

Conclusion:
The present work suggests that the therapeutic effect of MT herb pair on RA may be
attributed to its ability to regulate the TNF signaling pathway and IL-17 signaling pathway.
Disulfidptosis-related Protein RPN1 may be a Novel Anti-osteoporosis
Target of Kaempferol
Authors: Pan Chengzhen , Zhang Chi , Lin Zonghan , Liang Zhou , Cui Yinhang , Shang Zhihao , Wei Yuanxun , Chen Feng 
Published: January 2024

Background:
Osteoporosis (OP) is an age-related skeletal disease. Kaempferol can
regulate bone mesenchymal stem cells (BMSCs) osteogenesis to improve OP, but its mechanism
related to disulfidptosis, a newly discovered cell death mechanism, remains unclear.

Objective:
The study aimed to investigate the biological function and immune mechanism of disulfidptosis-
related ribophorin I (RPN1) in OP and to experimentally confirm that RPN1 is the
target for the treatment of OP with kaempferol.

Methods:
Differential expression analysis was conducted on disulfide-related genes extracted
from the GSE56815 and GSE7158 datasets. Four machine learning algorithms identified disease
signature genes, with RPN1 identified as a significant risk factor for OP through the nomogram.
Validation of RPN1 differential expression in OP patients was performed using the GSE56116
dataset. The impact of RPN1 on immune alterations and biological processes was explored. Predictive
ceRNA regulatory networks associated with RPN1 were generated via miRanda, miRDB,
and TargetScan databases. Molecular docking estimated the binding model between kaempferol
and RPN1. The targeting mechanism of kaempferol on RPN1 was confirmed through pathological
HE staining and immunohistochemistry in ovariectomized (OVX) rats.

Results:
RPN1 was abnormally overexpressed in the OP cohort, associated with TNF signaling,
hematopoietic cell lineage, and NF-kappa B pathway. Immune infiltration analysis showed a
positive correlation between RPN1 expression and CD8+ T cells and resting NK cells, while a
negative correlation with CD4+ naive T cells, macrophage M1, T cell gamma delta, T cell follicular
helper cells, activated mast cells, NK cells, and dendritic cells, was found. Four miRNAs
and 17 lncRNAs associated with RPN1 were identified. Kaempferol exhibited high binding affinity
(-7.2 kcal/mol) and good stability towards the RPN1. The experimental results verified that
kaempferol could improve bone microstructure destruction and reverse the abnormally high expression
of RPN1 in the femur of ovariectomized rats.

Conclusion:
RPN1 may be a new diagnostic biomarker in patients with OP, and may serve as a
new target for kaempferol to improve OP.
Neuropharmacological Study on Capsaicin in Scopolamine-injected Mice
Authors: Tyagi Sakshi , Thakur Ajit Kumar 
Published: January 2024

Aim::
To evaluate the potential beneficial role of Capsaicin in cognitive dysfunction, mitochondrial
impairment, and oxidative damage induced by scopolamine in mice.

Background::
Capsaicin is the chief phenolic component present in red chili and is responsible for
its pungent and spicy flavor. It affects TRPV1 channels in nociceptive sensory neurons and is present
in the hippocampus, and hypothalamus of the brains of rodents and humans.

Objective::
The main objective is to investigate the effective role of capsaicin in attenuating cognitive
dysfunction, mitochondrial impairment, and oxidative damage induced by scopolamine in
mice and examine the feasible mechanisms.

Methods::
Various doses of capsaicin (5, 10, and 20 mg/kg) were given orally to mice daily for 7
consecutive days after the administration of scopolamine. Various behavioral tests (motor coordination,
locomotor counts, hole board test) and biochemical assay (Pro-inflammatory cytokines, catalase,
lipid peroxidation, nitrite, reduced glutathione, and superoxide dismutase), mitochondrial
complex (I, II, III, and IV) enzyme activities, and mitochondrial permeability transition were evaluated
in the distinct regions of the brain.

Results::
Scopolamine-treated mice showed a considerable reduction in the entries and duration in
the light zone as well as in open arms of the elevated plus maze. Interestingly, capsaicin at different
doses reversed the anxiety, depressive-like behaviors, and learning and memory impairment effects
of scopolamine. Scopolamine-administered mice demonstrated substantially increased pro-inflammatory
cytokines levels, impaired mitochondrial enzyme complex activities, and increased
oxidative damage compared to the normal control group. Capsaicin treatment reinstated the reduced
lipid peroxidation, nitric oxide, catalase, superoxide dismutase, reduced glutathione activity,
decreasing pro-inflammatory cytokines and restoring mitochondrial complex enzyme activities
(I, II, III, and IV) as well as mitochondrial permeability. Moreover, the IL-1β level was restored at
a dose of capsaicin (10 and 20 mg/kg) only. Capsaicin reduced the scopolamine-induced acetylcholinesterase
activity, thereby raising the acetylcholine concentration in the hippocampal tissues
of mice. Preservation of neuronal cell morphology was also confirmed by capsaicin in histological
studies. From the above experimental results, capsaicin at a dose of 10 mg/kg, p.o. for seven
consecutive days was found to be the most effective dose.

Conclusion::
The experiential neuroprotective effect of capsaicin through the restoration of mitochondrial
functions, antioxidant effects, and modulation of pro-inflammatory cytokines makes it a
promising candidate for further drug development through clinical setup.
Cardiac Radiofrequency Ablation Exacerbates Myocardial Injury through
Pro-Inflammatory Response and Pro-Oxidative Stress in Elderly Patients
with Persistent Atrial Fibrillation
Authors: Li Xia , Zhou Wenhang , Guo Dianxuan , Hu Youdong , Zhou Hualan , Chen Ying 
Published: January 2024

Background:
There is a need to assess myocardial damage after radiofrequency ablation of
the pulmonary veins (PV) for persistent atrial fibrillation (PAF) in elderly patients.

Objective:
To evaluate oxidative stress, inflammatory response and myocardial damage in elderly
patients with PAF after radiofrequency ablation of the PV.

Methods:
High-sensitivity troponin T (hsTnT), malondialdehyde-modified low-density lipoprotein
(MDA-LDL), acrolein (ACR), lipid hydroperoxide (LHP), toll-like receptor 4 (TLR4), soluble
growth stimulation expressed gene 2 (sST2), angiotensin II (Ang II) and myocardial blood flow
(MBF) were determined before ablation and at 1, 3 and 5 months after radiofrequency ablation.

Results:
The levels of hsTnT, MDA-LDL, ACR, LHP, TLR4, sST2 and Ang II were increased 3
months after ablations compared with before ablation and 1 month after ablation, respectively
(P<0.001); they were further increased at 5 months after ablation compared with the 1- and 3-month
groups, respectively (P<0.001). MBF was decreased in the 3 months group after ablations compared
with before ablation and 1-month after ablation, respectively (P<0.001), and was further decreased in
5-months after ablations compared with 1-month and 3-month groups, respectively (P<0.001). Patients
with epicardial monopolar radiofrequency ablation had higher levels of hsTnT, MDA-LDL,
ACR, LHP, TLR4, sST2, Ang II and lower MBF than patients with endocardial monopolar and bipolar
radiofrequency ablations, respectively (P<0.001).

Conclusion:
Monopolar radiofrequency ablation method could result in more myocardial injury than
bipolar radiofrequency ablation. Oxidative stress and inflammatory response may be involved in cardiac
radiofrequency ablation-induced myocardial injury, resulting in myocardial ischemia in elderly
patients with PAF.
Radiopharmaceuticals: A New Vista for Diagnosis and Treatment of
Thyroid Cancer
Authors: Vernekar Siddhi , Budha Roja Rani , Alavala Rajasekhar Reddy 
Published: January 2024

Abstract:
Radiopharmaceuticals are in the diagnosis and treatment of cancerous and noncancerous
diseases, and a hope for optimistic effort in the field of nuclear medicine. They play a
crucial role in clinical nuclear medicine by providing a tool to comprehend human disease and
create efficient treatments. A detailed analysis is provided regarding the crux of molecular
imaging including PET and SPECT overview for the detection of cancers. For a specified
understanding of radiation therapy, topics include ranging from the selection of radionuclide to
its development and manufacture, and dosage requirements to establishing the importance of I-
131 Radiotherapy in thyroid cancer. In this review, we also discussed the current state of the art
of nuclear medicine in thyroid cancer, including the role of radioiodine (RAI) therapeutic scans
in the diagnosis of differentiated thyroid cancer. In addition, we established a brief outlook into
the current status of the research in thyroid cancer and discussed the future directions in this
field.
Calpain Inhibitor Calpeptin Improves Pancreatic Fibrosis in Mice with Chronic
Pancreatitis by Inhibiting the Activation of Pancreatic Stellate Cells
Authors: Shen Jie , Xiao Wenqin , Zong Guanzhao , Song Pengli , Wang Chuanyang , Bao Jingpiao , Peng Qi , Mei Zhu , Wang Jingjing , Wang Ruiyan , Jiang Jing , Wan Rong , Ni Jianbo , Wang Xingpeng , Hu Guoyong 
Published: January 2024

Background::
Pancreatic fibrosis is a hallmark feature of chronic pancreatitis (CP), resulting in persistent damage to the pancreas. The sustained activation of
pancreatic stellate cells (PSCs) plays a pivotal role in the progression of pancreatic fibrosis and is a major source of extracellular matrix (ECM)
deposition during pancreatic injury.

Methods::
Calpain is a calcium-independent lysosomal neutral cysteine endopeptidase and was found to be correlated to various fibrotic diseases. Studies
have revealed that calpeptin, a calpain inhibitor, can improve the fibrosis process of multiple organs. This study investigated the effect of the
calpain inhibitor, calpeptin, on fibrosis in experimental CP and activation of cultured PSCs in mice. CP was induced in mice by repeated injections
of cerulein for four weeks in vivo, and the activation process of mouse PSCs was isolated and cultured in vitro. Then, the inhibitory effect of
calpeptin on pancreatic fibrosis was confirmed based on the histological damage of CP, the expression of α-smooth muscle actin (α-SMA) and
collagen-Iα1(Col1α1), and the decrease in mRNA levels of calpain-1 and calpain-2.

Results::
In addition, it was revealed that calpeptin can inhibit the activation process of PSCs and induce significant PSCs apoptosis by downregulating the
expression of calpain-1, calpain-2 and TGF-β1, and the expression and phosphorylation of smad3 in vitro.

Conclusion::
These results suggest that the calpain inhibitor, calpeptin, plays a key role in the regulation of PSC activation by inhibiting the TGF-β1/smad3
signaling pathway, which supports the potential of calpeptin as an inhibitor of pancreatic fibrosis in mice by interfering with calpain.
A Web-Based Intervention Based on Acceptance and Commitment Therapy for Family Caregivers of People With Dementia: Mixed Methods Feasibility Study
Authors: Atefi Golnaz. L , van Knippenberg Rosalia J M , Bartels Sara Laureen , Losada-Baltar Andrés , Márquez-González María , Verhey Frans R J , de Vugt Marjolein E 
Published: January 2024

Background
Acceptance and commitment therapy (ACT), as an empirically based third-wave cognitive behavioral therapy, has shown promise in enhancing well-being and functioning across diverse populations. However, in the context of caregiving, the effect size of available ACT interventions remains at best moderate, sometimes accompanied by high dropout rates, highlighting the need for more effective and feasible intervention designs.

Objective
The objective of our study was to evaluate the feasibility and acceptability of a fully online ACT program designed for family caregivers of people with dementia. This study aimed to boost psychological flexibility and support caregivers, enabling them to realize and prioritize their own life values alongside their caregiving responsibilities.

Methods
A mixed methods feasibility study using an uncontrolled pretest-posttest design was conducted. This intervention included a 9-week web-based self-help program based on ACT incorporating collaborative goal setting and weekly web-based motivational coaching for family caregivers of people with dementia. This study involved 30 informal caregivers recruited through memory clinics and social media platforms in the Netherlands and received approval from the Medical Ethics Committee of the Maastricht University Medical Center+ (NL77389.068.21/metc21-029).

Results
A total of 24 caregivers completed the postintervention assessment, indicating a high adherence rate (24/29, 83%). Caregivers reported positive feedback regarding collaborative goal setting, but some found challenges in implementing new skills due to their own habitual responses or the unpredictable context of dementia caregiving. Personalizing the intervention based on individual value preferences was highlighted as beneficial.

Conclusions
Compared to other web-based self-help ACT interventions for family caregivers, this intervention showed a high adherence and sufficient level of feasibility, which underscores the use of personalization in delivering web-based interventions. Moreover, the potential of this ACT-based intervention for family caregivers of people with dementia was demonstrated, suggesting that further research and a larger-scale controlled trial are warranted to validate its effectiveness.

International Registered Report Identifier (IRRID)
RR2-10.1136/bmjopen-2022-070499
ASSESSMENT OF PRESCRIPTION PATTERN IN HIGH-RISK PREGNANCY AT A TERTIARY CARE HOSPITAL
Authors: B. J. VINEEL , SINGH J. SURAJ KUMAR , ZAKIR MOHAMMED 
Published: January 2024

Objective: Pregnancy is a special physiological condition where drug treatment presents a special concern. The aim of the study is to evaluate the pattern of drug use and WHO prescribing indicators in high-risk pregnancies.
Methods: A prospective observational study was carried out for a period of six months. A self-designed data collection form was used to collect the data from the prescriptions. The collected data was entered and analyzed using Microsoft Excel.
Results: A total of 200 patients were included in this study. Preeclampsia (45, 22.5%) was the most frequently recorded complication, followed by eclampsia (43, 21.5%), anemia (34, 17%), and PIH (32, 16%). Antimicrobial agents (435, 32.5%) were the most frequently prescribed class of drug, followed by hematinics (194, 14.4%). A total of 1,338 drugs were prescribed in 200 patients. The average number of drugs per prescription was 6.69, the percentage of drugs prescribed by generic name was 88.04%, the percentage of drugs prescribed from EDL was 83.10%, the percentage of prescriptions with an antibiotic prescribed was 88%, and the percentage of prescriptions with an injection prescribed was 76%.
Conclusion: During pregnancy, as we see, every complication need treatment and different class of drugs in, which some drugs may cause serious side effect to both mother and fetus. The prescription pattern was suboptimal when compared to the WHO core prescribing indicators' suggested values. Studying drug prescribing patterns in high-risk pregnancies can help improve practices, leading to safer and more effective medication use and, ultimately better health outcomes for both mothers and fetuses.