bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aberrant palmitoylation caused by a ZDHHC21 mutation contributes to pathophysiology of Alzheimer’s disease
Authors: Li Wenwen , Pang Yana , Wang Yan , Mei Fan , Guo Mengmeng , Wei Yiping , Li Xinyue , Qin Wei , Wang Wei , Jia Longfei , Jia Jianping 
Published: June 2023

Abstract
Background
The identification of pathogenic mutations in Alzheimer’s disease (AD) causal genes led to a better understanding of the pathobiology of AD. Familial Alzheimer’s disease (FAD) is known to be associated with mutations in the APP, PSEN1, and PSEN2 genes involved in Aβ production; however, these genetic defects occur in only about 10–20% of FAD cases, and more genes and new mechanism causing FAD remain largely obscure.

Methods
We performed exome sequencing on family members with a FAD pedigree and identified gene variant ZDHHC21 p.T209S. A ZDHHC21T209S/T209S knock-in mouse model was then generated using CRISPR/Cas9. The Morris water navigation task was then used to examine spatial learning and memory. The involvement of aberrant palmitoylation of FYN tyrosine kinase and APP in AD pathology was evaluated using biochemical methods and immunostaining. Aβ and tau pathophysiology was evaluated using ELISA, biochemical methods, and immunostaining. Field recordings of synaptic long-term potentiation were obtained to examine synaptic plasticity. The density of synapses and dendritic branches was quantified using electron microscopy and Golgi staining.

Results
We identified a variant (c.999A > T, p.T209S) of ZDHHC21 gene in a Han Chinese family. The proband presented marked cognitive impairment at 55 years of age (Mini-Mental State Examination score = 5, Clinical Dementia Rating = 3). Considerable Aβ retention was observed in the bilateral frontal, parietal, and lateral temporal cortices. The novel heterozygous missense mutation (p.T209S) was detected in all family members with AD and was not present in those unaffected, indicating cosegregation. ZDHHC21T209S/T209S mice exhibited cognitive impairment and synaptic dysfunction, suggesting the strong pathogenicity of the mutation. The ZDHHC21 p.T209S mutation significantly enhanced FYN palmitoylation, causing overactivation of NMDAR2B, inducing increased neuronal sensitivity to excitotoxicity leading to further synaptic dysfunction and neuronal loss. The palmitoylation of APP was also increased in ZDHHC21T209S/T209S mice, possibly contributing to Aβ production. Palmitoyltransferase inhibitors reversed synaptic function impairment.

Conclusions
ZDHHC21 p.T209S is a novel, candidate causal gene mutation in a Chinese FAD pedigree. Our discoveries strongly suggest that aberrant protein palmitoylation mediated by ZDHHC21 mutations is a new pathogenic mechanism of AD, warranting further investigations for the development of therapeutic interventions.
The predictive value of atherogenic index of plasma for cardiovascular outcomes in patients with acute coronary syndrome undergoing percutaneous coronary intervention with LDL-C below 1.8mmol/L
Authors: Wang Yue , Wang Shen , Sun Shuaifeng , Li Fadong , Zhao Wenxin , Yang Hongxia , Wu Xiaofan 
Published: June 2023

Abstract
Background
The potential predictive significance of atherogenic index of plasma (AIP) for cardiovascular outcomes in patients with acute coronary syndrome (ACS) and who have undergone percutaneous coronary intervention (PCI), with low-density lipoprotein-cholesterol (LDL-C) below 1.8mmol/L, has not been well explored.

Methods
The retrospective cohort analysis included 1,133 patients with ACS and LDL-C levels below 1.8mmol/L who underwent PCI. AIP is calculated as log (triglyceride/high-density lipoprotein-cholesterol). Patients were divided into two groups according to the median value of AIP. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCEs), a composite of all-cause death, nonfatal myocardial infarction, ischemic stroke or unplanned repeat revascularization. The association between AIP and the prevalence of MACCE was evaluated using multivariable Cox proportional hazard models.

Results
Over a median follow-up of 26 months, the incidence of MACCE was higher in the high AIP group compared to the low AIP group (9.6% vs. 6.0%, P log-rank = 0.020), and the difference was mainly derived from an increased risk of unplanned repeat revascularization (7.6% vs. 4.6%, P log-rank = 0.028). After adjusting for multiple variables, elevated AIP was independently associated with an increased risk of MACCE, regardless of whether AIP was considered a nominal or continuous variable (hazard ratio [HR] 1.62, 95% confidence interval [CI] 1.04–2.53 or HR 2.01, 95% CI 1.09–3.73).

Conclusions
The present study demonstrates that AIP is a significant predictor of adverse outcomes in ACS patients undergoing PCI with LDL-C < 1.8mmol/L. These results suggest that AIP may offer supplementary prognostic information for ACS patients with optimally managed LDL-C levels.
Independent and joint associations between the triglyceride-glucose index and NT-proBNP with the risk of adverse cardiovascular events in patients with diabetes and acute coronary syndrome: a prospective cohort study
Authors: Wang Man , Zhou Li , Su Wen , Dang Wenxi , Li Hongwei , Chen Hui 
Published: June 2023

Abstract
Background
Elevated triglyceride-glucose (TyG) index and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are independently associated with increased risk of major adverse cardio-cerebral events (MACCEs) in diabetic patients with the acute coronary syndrome (ACS), but have not been evaluated jointly. We sought to investigate the independent and joint association of the TyG index and NT-proBNP with MACCEs risk.

Methods
Data from 5046 patients with diabetes and ACS were recorded in the Cardiovascular Center Beijing Friendship Hospital Database Bank between 2013 and 2021, including measurements of fasting triglycerides, plasma glucose, and NT-proBNP. The TyG index was calculated as Ln (fasting triglycerides [mg/dL] × fasting plasma glucose [mg/dL]/2). Associations of the TyG index and NT-proBNP with MACCEs risk were assessed using flexible parametric survival models.

Results
During 13589.9 person-years of follow-up, 985 incident MACCEs of the 5046 patients (65.6 years of age and 62.0% men) were observed. Elevated TyG index (HR: 1.18; 95% CI 1.05‒1.32 per 1 unit increase) and NT-proBNP categories (HR: 1.95; 95% CI: 1.50‒2.54 for > 729 pg/ml compared to < 129 pg/ml) were independently associated with MACCEs risk in the fully adjusted model. According to the joint categories of the TyG index and NT-proBNP, patients with the TyG index > 9.336 and NT-proBNP > 729 pg/ml were at the highest risk of MACCEs (HR: 2.45; 95% CI 1.64‒3.65) than the ones with TyG index < 8.746 and NT-proBNP < 129 pg/ml. The test for interaction was not significant (Pinteraction = 0.49). Incorporating these two biomarkers into the established clinical model, the Global Registry of Acute Coronary Events (GRACE) risk score, resulted in a significant improvement in risk stratification.

Conclusions
The TyG index and NT-proBNP were independently and jointly associated with the risk of MACCEs in patients with diabetes and ACS, suggesting that patients with both markers elevated should be aware of the higher risk in the future.
Predictors of mosquito bed net use among children under-fives in Ghana: a multilevel analysis of the 2019 malaria indicator survey
Authors: Aheto Justice Moses K. , Babah Rahmatu , Dzokoto Maxwell Kwame , Kwarah Williams , Alhassan Yakubu 
Published: June 2023

Abstract
Background
Morbidities and mortalities due to malaria can be prevented by the use of insecticide-treated mosquito bed nets (ITN), which has been proven for malaria control and elimination. The purpose of this study was to assess the critical factors that predict the use of ITN among children under-fives in Ghana.

Methods
The study utilized data from the 2019 Ghana Malaria Indicator Survey (GMIS). The outcome variable was mosquito bed net use among children under-fives. To determine critical factors that independently predict ITN use, multilevel multivariable logistic regression was employed using Stata version 16. Odds ratios and associated 95% confidence intervals and p-values were reported. A p < 0.05 was used to declare statistical significance.

Results
The overall prevalence of ITN usage was 57.4%. Utilization of bed nets was 66.6% in the rural areas and 43.5% in the urban areas, was highest in the Upper West region (80.6%) even when stratified to rural (82.9%) and urban areas (70.3%) whilst Greater Accra region (30.5%, rural = 41.7%, urban = 28.9%) had the least. The community level multilevel analysis showed that bed net utilization was higher among children in rural areas [AOR = 1.99, 95% CI 1.32–3.01, p = 0.001] and in household with wooden wall materials [AOR = 3.29, 95% CI 1.15–9.40, p = 0.027]. Bed net utilization was however, less for households with 3 + children under-five [AOR = 0.29, 95% CI 0.19–0.46, p < 0.001), 4 years old (AOR = 0.66, 95% CI 00.48–00.92, p = 0.014], without universal access to bed net [AOR = 0.52, 95% CI 0.37–0.73, p < 0.001], those in the Greater Accra [AOR = 0.26, 95% CI 0.13–0.51, p < 0.001], Eastern [AOR = 0.47, 95% CI 0.23–0.95, p = 0.036], Northern [AOR = 0.42, 95% CI 0.20–0.88, p = 0.022], middle [AOR = 0.57, 95% CI 0.35–0.94, p = 0.026] and rich/richest [AOR = 0.51, 95% CI 0.29–0.92, p = 0.025] household wealth quintile. Substantial unobserved household and community level differences in bed net use were found.

Conclusion
This study demonstrates the need to intensify promotion of ITN use to those in urban areas, Greater Accra, Eastern and Northern regions, houses without wooden wall materials, middle and rich/richest households. Interventions should be targeted at older children and households with more under-five children and to ensure full access and use of ITNs among all children under-fives in each household as part of the overall goal of achieving the health-related SDGs.
Identification of TIMP1 as an inflammatory biomarker associated with temporal lobe epilepsy based on integrated bioinformatics and experimental analyses
Authors: He Ya , Zhang Hongxia , Ma Limin , Li Jingang , Wang Fei , Zhou Hui , Zhang Guangliang , Wen Yuetao 
Published: June 2023

Abstract
Background
Epilepsy is the second most prevalent neurological disease. Although there are many antiseizure drugs, approximately 30% of cases are refractory to treatment. Temporal lobe epilepsy (TLE) is the most common epilepsy subtype, and previous studies have reported that hippocampal inflammation is an important mechanism associated with the occurrence and development of TLE. However, the inflammatory biomarkers associated with TLE are not well defined.

Methods
In our study, we merged human hippocampus datasets (GSE48350 and GSE63808) through batch correction and generally verified the diagnostic roles of inflammation-related genes (IRGs) and subtype classification according to IRGs in epilepsy through differential expression, random forest, support vector machine, nomogram, subtype classification, enrichment, protein‒protein interaction, immune cell infiltration, and immune function analyses. Finally, we detected the location and expression of inhibitor of metalloproteinase-1 (TIMP1) in epileptic patients and kainic acid-induced epileptic mice.

Results
According to the bioinformatics analysis, we identified TIMP1 as the most significant IRG associated with TLE, and we found that TIMP1 was mainly located in cortical neurons and scantly expressed in cortical gliocytes by immunofluorescence staining. We detected decreased expression of TIMP1 by quantitative real-time polymerase chain reaction and western blotting.

Conclusion
TIMP1, the most significant IRG associated with TLE, might be a novel and promising biomarker to study the mechanism of epilepsy and guide the discovery of new drugs for its treatment.
Application of platelet-rich plasma (PRP) in lips rejuvenation
Authors: Huang YuanYuan , Tang JunYi , He XiaoYing , Liu HongYun , Cheng HangHangLiu , Yang Yu , Cheng Biao , Tian Ju 
Published: June 2023

Abstract
Background
In recent years, minimally invasive and non-invasive rejuvenation methods have been welcomed. PRP has been used widely for skin rejuvenation, but there are few studies on PRP for lip rejuvenation.

Objective
The objective of this study was to investigate the preliminary effects of PRP for lip rejuvenation.

Methods
Between October 2018 and April 2023, 15 participants with lip aging (1 male, 14 females; range 27–58 years) were treated with PRP. The follow-up time was 3 to 24months. After 3 to 6 times treatments, beauty seekers and experienced physicians jointly evaluated effectiveness of treatment. The assessment included improvements in the colour, wrinkles, and skin texture of the lips before and after treatment.

Results
According to the beauty seekers and Surgeons ’evaluation, the aging characteristics of the lips of the 15 beauty seekers have been improved to varying degrees. The most obvious improvement was that the color of the lips which became more vivid. There was no swelling, bruising, scar hyperplasia and other complications. A participant was evaluated using the VISIA skin detector. The patient’s lip color and discoloration improved after treatment. Of the 15 participants treated. 3 participants experienced mild pain or discomfort during the injection process. There was no swelling, bruising, scar hyperplasia and other complications.

Conclusion
The results of this study revealed promising evidence of PRP as an effective option on lip rejuvenation. However, large, multi-center, controlled, long term, pilot studies are required to confirm the preliminary results of our study.
Correlation analysis of the vertebral compression degree and CT HU value in elderly patients with osteoporotic thoracolumbar fractures
Authors: Li Cheng , Lai Xing-ming , Liu Nian , Lin Yang , Hu Wei 
Published: June 2023

Abstract
Background
To explore the correlation of the vertebral compression degree and cancellous bone CT HU in elderly patients with osteoporotic thoracolumbar fractures.

Methods
Elderly patients with single-segment vertebral fragility fractures were retrospectively reviewed. All patients experienced a low-energy trauma and underwent thoracolumbar MRI. The consistency of measurement between two spine surgeons was evaluated. The average CT HU value of the adjacent vertebral body was used instead.

Results
A total of 54 patients were included in the final analysis. The patients’ average age was 70.39 ± 8.53 years, and the average CT HU value was 72.78 ± 29.75 HU. The average vertebral compression ratio was 0.57 ± 0.16. Measurements showed both good intrarater repeatability and good interrater reproducibility of the vertebral compression ratio (ICC = 0.978). The degree of vertebral compression in thoracolumbar osteoporotic fractures was strongly positively correlated with the cancellous bone CT HU value (P < 0.01).

Conclusions
The local bone quality as evaluated by the CT HU value is an important factor affecting the degree of compression in osteoporotic vertebral fractures. This study provides quantitative evidence that a greater compression ratio with thoracolumbar osteoporotic fractures was associated with lower bone density in elderly patients. Further longitudinal studies with larger cohorts are needed to verify this relationship.
Pituitary abscess: a case report and systematic review of 488 cases
Authors: Stringer Felicity , Foong Yi Chao , Tan Alanna , Hayman Sarah , Zajac Jeffrey D. , Grossmann Mathis , Zane Justin Ng Yau , Zhu Jasmine , Ayyappan Sujith 
Published: June 2023

Abstract
Background
Pituitary abscess (PA) is a rare condition and not well understood. We aimed to describe a case and perform a comprehensive systematic review to explore presenting symptoms, radiological findings, endocrine abnormalities and mortality.

Aim
To identify presenting symptoms, radiological findings, endocrinological abnormalities and predictors of mortality for PA.

Methods
We systematically reviewed the literature to identify all case reports of PA. Data regarding presentation, mortality, radiological findings, endocrinological abnormalities and treatment was extracted.

Results
We identified 488 patients from 218 articles meeting the inclusion criteria. Mortality was 5.1%, with days to presentation (OR 1.0005, 95% CI 1.0001–1.0008, p < 0.01) being the only identified independent predictor of mortality. Mortality rates have decreased over time, with cases published prior to 2000 having higher mortality rates (OR 6.92, 95% CI 2.80–17.90, p < 0.001). The most common symptom was headache (76.2%), followed by visual field defects (47.3%). Classical signs of infection were only present in 43%. The most common imaging feature on magnetic resonance imaging (MRI) was high T2 and low T1 signal of the pituitary gland with peripheral contrast enhancement. Over half (54.8%) were culture negative, with the most common bacterial organism being staphylococcus aureus (7.8%) and fungal organism being aspergillus (8.8%). The most common endocrine abnormality was hypopituitarism (41.1%), followed by diabetes insipidus (24.8%). Whilst symptoms resolved in most patients, persistent endocrine abnormalities were present in over half of patients (61.0%).

Conclusion
PA is associated with significant mortality, with delayed presentation increasing risk of mortality. Ongoing endocrinological abnormalities are common. Given the non-specific clinical presentation, the appearance of high T2, low T1 and peripheral contrast enhancement of the pituitary on MRI should prompt consideration of this rare disease.
Exosomal circRNA: emerging insights into cancer progression and clinical application potential
Authors: Zhang Fan , Jiang Jiajia , Qian Hui , Yan Yongmin , Xu Wenrong 
Published: June 2023

AbstractExosomal circRNA serves a novel genetic information molecule, facilitating communication between tumor cells and microenvironmental cells, such as immune cells, fibroblasts, and other components, thereby regulating critical aspects of cancer progression including immune escape, tumor angiogenesis, metabolism, drug resistance, proliferation and metastasis. Interestingly, microenvironment cells have new findings in influencing tumor progression and immune escape mediated by the release of exosomal circRNA. Given the intrinsic stability, abundance, and broad distribution of exosomal circRNAs, they represent excellent diagnostic and prognostic biomarkers for liquid biopsy. Moreover, artificially synthesized circRNAs may open up new possibilities for cancer therapy, potentially bolstered by nanoparticles or plant exosome delivery strategies. In this review, we summarize the functions and underlying mechanisms of tumor cell and non-tumor cell-derived exosomal circRNAs in cancer progression, with a special focus on their roles in tumor immunity and metabolism. Finally, we examine the potential application of exosomal circRNAs as diagnostic biomarkers and therapeutic targets, highlighting their promise for clinical use.
Safety and activity of the first-in-class locked nucleic acid (LNA) miR-221 selective inhibitor in refractory advanced cancer patients: a first-in-human, phase 1, open-label, dose-escalation study
Authors: Tassone Pierfrancesco , Di Martino Maria Teresa , Arbitrio Mariamena , Fiorillo Lucia , Staropoli Nicoletta , Ciliberto Domenico , Cordua Alessia , Scionti Francesca , Bertucci Bernardo , Salvino Angela , Lopreiato Mariangela , Thunarf Fredrik , Cuomo Onofrio , Zito Maria Cristina , De Fina Maria Rosanna , Brescia Amelia , Gualtieri Simona , Riillo Caterina , Manti Francesco , Caracciolo Daniele , Barbieri Vito , Di Paola Eugenio Donato , Di Francesco Adele Emanuela , Tagliaferri Pierosandro 
Published: June 2023

Abstract
Background
We developed a 13-mer locked nucleic acid (LNA) inhibitor of miR-221 (LNA-i-miR-221) with a full phosphorothioate (PS)-modified backbone. This agent downregulated miR-221, demonstrated anti-tumor activity against human xenografts in mice, and favorable toxicokinetics in rats and monkeys. Allometric interspecies scaling allowed us to define the first-in-class LNA-i-miR-221 safe starting dose for the clinical translation.

Methods
In this first-in-human, open-label, dose-escalation phase 1 trial, we enrolled progressive cancer patients (aged ≥ 18 years) with ECOG 0–2 into 5 cohorts. The treatment cycle was based on a 30-min IV infusion of LNA-i-miR-221 on 4 consecutive days. Three patients within the first cohort were treated with 2 cycles (8 infusions), while 14 patients were treated with a single course (4 infusions); all patients were evaluated for phase 1 primary endpoint. The study was approved by the Ethics Committee and Regulatory Authorities (EudraCT 2017-002615-33).

Results
Seventeen patients received the investigational treatment, and 16 were evaluable for response. LNA-i-miR-221 was well tolerated, with no grade 3–4 toxicity, and the MTD was not reached. We recorded stable disease (SD) in 8 (50.0%) patients and partial response (PR) in 1 (6.3%) colorectal cancer case (total SD + PR: 56.3%). Pharmacokinetics indicated non-linear drug concentration increase across the dose range. Pharmacodynamics demonstrated concentration-dependent downregulation of miR-221 and upregulation of its CDKN1B/p27 and PTEN canonical targets. Five mg/kg was defined as the recommended phase II dose.

Conclusions
The excellent safety profile, the promising bio-modulator, and the anti-tumor activity offer the rationale for further clinical investigation of LNA-i-miR-221 (ClinTrials.Gov: NCT04811898).
Characteristics of a trauma population in an ambulance organisation in Sweden: results from an observational study
Authors: Larsson Glenn , Axelsson Christer , Hagiwara Magnus Andersson , Herlitz Johan , Magnusson Carl 
Published: June 2023

AbstractBackgroundGlobally, injuries are a major health problem, and in Sweden, injuries are the second most common reason for ambulance dispatch. However, there is a knowledge gap regarding the epidemiology of injuries requiring assessment by emergency medical services (EMS) in Sweden. The aim of the present study was to describe the prehospital population with injuries that have been assessed and treated by EMS.MethodsA randomly selected retrospective sample was collected from 1 January through 31 December 2019 in a region in southwestern Sweden. Data were collected from ambulance and hospital medical records.ResultsAmong 153,724 primary assignments, 26,697 (17.4%) were caused by injuries. The study cohort consisted of 5,235 patients, of whom 50.5% were men, and the median age was 63 years. The most common cause of injury was low-energy fall (51.4%), and this was the cause in 77.8% of those aged > 63 years and in 26.7% of those aged ≤ 63 years. The injury mechanism was a motor vehicle in 8.0%, a motorcycle in 2.1% and a bicycle in 4.0%. The most common trauma location was the residential area (55.5% overall; 77.9% in the elderly and 34.0% in the younger group). In the prehospital setting, the most frequent clinical sign was a wound (33.2%), a closed fracture were seen in 18.9% and an open fracture in 1.0%. Pain was reported in 74.9% and 42.9% reported severe pain. Medication was given to 42.4% of patients before arrival in the hospital. The most frequent triage colour according to the RETTS was orange (46.7%), whereas only 4.4% were triaged red. Among all patients, 83.6% were transported to the hospital, and 27.8% received fracture treatment after hospital admission. The overall 30-day mortality rate was 3.4%.ConclusionAmong EMS assignments in southwestern Sweden, 17% were caused by injury equally distributed between women and men. More than half of these cases were caused by low-energy falls, and the most common trauma location was a residential area. The majority of the victims had pain upon arrival of the EMS, and a large proportion appeared to have severe pain.