bluuebunny/crossref_metadata_2025_split huggingface dataset:
SGLT2-inhibitors effects on the coronary fibrous cap thickness and MACEs in diabetic patients with inducible myocardial ischemia and multi vessels non-obstructive coronary artery stenosis
Authors: Sardu Celestino , Trotta Maria Consiglia , Sasso Ferdinando Carlo , Sacra Cosimo , Carpinella Gerardo , Mauro Ciro , Minicucci Fabio , Calabrò Paolo , D’ Amico Michele , D’ Ascenzo Fabrizio , De Filippo Ovidio , Iannaccone Mario , Pizzi Carmine , Paolisso Giuseppe , Marfella Raffaele 
Published: April 2023

Abstract
Background
Sodium–glucose transporter 2 inhibitors (SGLT2-I) could modulate atherosclerotic plaque progression, via down-regulation of inflammatory burden, and lead to reduction of major adverse cardiovascular events (MACEs) in type 2 diabetes mellitus (T2DM) patients with ischemic heart disease (IHD). T2DM patients with multivessel non-obstructive coronary stenosis (Mv-NOCS) have over-inflammation and over-lipids’ plaque accumulation. This could reduce fibrous cap thickness (FCT), favoring plaque rupture and MACEs. Despite this, there is not conclusive data about the effects of SGLT2-I on atherosclerotic plaque phenotype and MACEs in Mv-NOCS patients with T2DM. Thus, in the current study, we evaluated SGLT2-I effects on Mv-NOCS patients with T2DM in terms of FCT increase, reduction of systemic and coronary plaque inflammation, and MACEs at 1 year of follow-up.

Methods
In a multi-center study, we evaluated 369 T2DM patients with Mv-NOCS divided in 258 (69.9%) patients that did not receive the SGLT2-I therapy (Non-SGLT2-I users), and 111 (30.1%) patients that were treated with SGLT2-I therapy (SGLT2-I users) after percutaneous coronary intervention (PCI) and optical coherence tomography (OCT) evaluation. As the primary study endpoint, we evaluated the effects of SGLT2-I on FCT changes at 1 year of follow-up. As secondary endpoints, we evaluated at baseline and at 12 months follow-up the inflammatory systemic and plaque burden and rate of MACEs, and predictors of MACE through multivariable analysis.

Results
At 6 and 12 months of follow-up, SGLT2-I users vs. Non-SGLT2-I users showed lower body mass index (BMI), glycemia, glycated hemoglobin, B-type natriuretic peptide, and inflammatory cells/molecules values (p < 0.05). SGLT2-I users vs. Non-SGLT2-I users, as evaluated by OCT, evidenced the highest values of minimum FCT, and lowest values of lipid arc degree and macrophage grade (p < 0.05). At the follow-up end, SGLT2-I users vs. Non-SGLT2-I users had a lower rate of MACEs [n 12 (10.8%) vs. n 57 (22.1%); p < 0.05]. Finally, Hb1Ac values (1.930, [CI 95%: 1.149–2.176]), macrophage grade (1.188, [CI 95%: 1.073–1.315]), and SGLT2-I therapy (0.342, [CI 95%: 0.180–0.651]) were independent predictors of MACEs at 1 year of follow-up.

Conclusions
SGLT2-I therapy may reduce about 65% the risk to have MACEs at 1 year of follow-up, via ameliorative effects on glucose homeostasis, and by the reduction of systemic inflammatory burden, and local effects on the atherosclerotic plaque inflammation, lipids’ deposit, and FCT in Mv-NOCS patients with T2DM.
Can government subsidies and public mechanisms alleviate the physical and mental health vulnerability of China’s urban and rural residents?
Authors: Li Yali , Marquez Ronald 
Published: April 2023

Abstract
Background
Poverty vulnerability has been defined as the likelihood of a family falling into poverty in the upcoming months. Inequality is a major cause of poverty vulnerability in developing countries. There is evidence that establishing effective government subsidies and public service mechanisms significantly reduces health poverty vulnerability. One of the ways to study poverty vulnerability is by using empirical data such as income elasticity of demand to perform the analysis. Income elasticity refers to the extent to which changes in consumers’ income affect changes in demand for commodities or public goods. In this work, we assess health poverty vulnerability in rural and urban China. We provide two levels of evidence on the marginal effects of the design and implementation of government subsidies and public mechanisms in reducing health poverty vulnerability, before and after incorporating the income elasticity of demand for health.

Methods
Multidimensional physical and mental health poverty indexes, according to the Oxford Poverty & Human Development Initiative and the Andersen model, were implemented to measure health poverty vulnerability by using the 2018 China Family Panel Survey database (CFPS) as the data source for empirical analysis. The income elasticity of demand for health care was used as the key mediating variable of impact. Our assessment was conducted by a two-level multidimensional logistic regression using STATA16 software.

Results
The first level regression indicates that the marginal utility of public mechanism (PM) in reducing urban and rural vulnerability as expected poverty on physical and mental health (VEP-PH&MH) was insignificant. On the other hand, government subsidies (GS) policies had a positive suppression effect on VEP-PH&MH to a relatively low degree. The second level regression found that given the diversity of health needs across individual households, i.e., the income elasticity of demand (HE) for health care products, PM and GS policies have a significant effect in reducing VEP-PH&MH in rural and urban areas. Our analysis has verified the significant positive impact of enacting accurate GS and PM policies on effectively reducing VEP-PH&MH in rural as well as urban areas.

Conclusions
This study shows that implementing government subsidies and public mechanisms has a positive marginal effect on reducing VEP-PH&MH. Meanwhile, there are individual variations in health demands, urban-rural disparities, and regional disparities in the effects of GS and PM on inhibiting VEP-PH&MH. Therefore, special consideration needs to be given to the differences in the degree of health needs of individual residents among urban and rural areas and regions with varying economic development. Furthermore, considerations of this approach in the current worldwide scenario are analyzed.
Precise pancreatic cancer therapy through targeted degradation of mutant p53 protein by cerium oxide nanoparticles
Authors: Zhang Hao , Zhang Wang , Hu Bochuan , Qin Xiaohua , Yi Tianxiang , Ye Yayi , Huang Xiaowan , Song Yang , Yang Zhenyu , Qian Jieying , Zhang Yunjiao 
Published: April 2023

Abstract
Background
In a significant proportion of cancers, point mutations of TP53 gene occur within the DNA-binding domain, resulting in an abundance of mutant p53 proteins (mutp53) within cells, which possess tumor-promoting properties. A potential and straightforward strategy for addressing p53-mutated cancer involves the induction of autophagy or proteasomal degradation. Based on the previously reported findings, elevating oxidative state in the mutp53 cells represented a feasible approach for targeting mutp53. However, the nanoparticles previous reported lacked sufficient specificity of regulating ROS in tumor cells, consequently resulted in unfavorable toxicity in healthy cells.

Results
We here in showed that cerium oxide CeO2 nanoparticles (CeO2 NPs) exhibited an remarkable elevated level of ROS production in tumor cells, as compared to healthy cells, demonstrating that the unique property of CeO2 NPs in cancer cells provided a feasible solution to mutp53 degradation. CeO2 NPs elicited K48 ubiquitination-dependent degradation of wide-spectrum mutp53 proteins in a manner that was dependent on both the dissociation of mutp53 from the heat shock proteins Hsp90/70 and the increasing production of ROS. As expected, degradation of mutp53 by CeO2 NPs abrogated mutp53-manifested gain-of-function (GOF), leading to a reduction in cell proliferation and migration, and dramatically improved the therapeutic efficacy in a BxPC-3 mutp53 tumor model.

Conclusions
Overall, CeO2 NPs increasing ROS specifically in the mutp53 cancer cells displayed a specific therapeutic efficacy in mutp53 cancer and offered an effective solution to address the challenges posed by mutp53 degradation, as demonstrated in our present study.
Cost-effectiveness of COVID-19 vaccination in Latin America and the Caribbean: an analysis in Argentina, Brazil, Chile, Colombia, Costa Rica, Mexico, and Peru
Authors: Augustovski Federico , Bardach Ariel , Santoro Adrián , Rodriguez-Cairoli Federico , López-Osornio Alejandro , Argento Fernando , Havela Maissa , Blumenfeld Alejandro , Ballivian Jamile , Solioz Germán , Capula Analía , López Analía , Cejas Cintia , Savedoff William , Palacios Alfredo , Rubinstein Adolfo , Pichon-Riviere Andrés 
Published: April 2023

Abstract
Objective
Our study analyzes the cost-effectiveness of the COVID-19 vaccination campaigns in Argentina, Brazil, Chile, Colombia, Costa Rica, Mexico, and Peru.

Methods
Using a previously published SVEIR model, we analyzed the impact of a vaccination campaign (2021) from a national healthcare perspective. The primary outcomes were quality adjusted life years (QALYs) lost and total costs. Other outcomes included COVID-19 cases, hospitalizations, deaths, and life years. We applied a discount rate of 3% for health outcomes. We modeled a realistic vaccination campaign in each country (the realistic country-specific campaign). Additionally, we assessed a standard campaign (similar, “typical“ for all countries), and an optimized campaign (similar in all countries with higher but plausible population coverage). One-way deterministic sensitivity analyses were performed.

Findings
Vaccination was health improving as well as cost-saving in almost all countries and scenarios. Our analysis shows that vaccination in this group of countries prevented 573,141 deaths (508,826 standard; 685,442 optimized) and gained 5.07 million QALYs (4.53 standard; 6.03 optimized). Despite the incremental costs of vaccination campaigns, they had a total net cost saving to the health system of US$16.29 billion (US$16.47 standard; US$18.58 optimized). The realistic (base case) vaccination campaign in Chile was the only scenario, which was not cost saving, but it was still highly cost-effective with an ICER of US$22 per QALY gained. Main findings were robust in the sensitivity analyses.

Interpretation
The COVID-19 vaccination campaign in seven Latin American and Caribbean countries -that comprise nearly 80% of the region- was beneficial for population health and was also cost-saving or highly cost-effective.
Adiponectin deficiency accelerates brain aging via mitochondria-associated neuroinflammation
Authors: He Kaiwu , Nie Lulin , Ali Tahir , Liu Zizhen , Li Weifen , Gao Ruyan , Zhang Zena , Liu Jianjun , Dai Zhongliang , Xie Yongmei , Zhang Zaijun , Liu Gongping , Dong Ming , Yu Zhi-Jian , Li Shupeng , Yang Xifei 
Published: April 2023

Abstract
Background
A wide spectrum of changes occurs in the brain with age, from molecular to morphological aspects, and inflammation accompanied by mitochondria dysfunction is one of the significant factors associated with age. Adiponectin (APN), an essential adipokine in glucose and lipid metabolism, is involved in the aging; however, its role in brain aging has not been adequately explored. Here, we aimed to explore the relationship between APN deficiency and brain aging using multiple biochemical and pharmacological methods to probe APN in humans, KO mice, primary microglia, and BV2 cells.

Results
We found that declining APN levels in aged human subjects correlated with dysregulated cytokine levels, while APN KO mice exhibited accelerated aging accompanied by learning and memory deficits, anxiety-like behaviors, neuroinflammation, and immunosenescence. APN-deficient mice displayed aggravated mitochondrial dysfunction and HDAC1 upregulation. In BV2 cells, the APN receptor agonist AdipoRon alleviated the mitochondrial deficits and aging markers induced by rotenone or antimycin A. HDAC1 antagonism by Compound 60 (Cpd 60) improved mitochondrial dysfunction and age-related inflammation, as validated in D-galactose-treated APN KO mice.

Conclusion
These findings indicate that APN is a critical regulator of brain aging by preventing neuroinflammation associated with mitochondrial impairment via HDAC1 signaling.
Direct association with the vascular basement membrane is a frequent feature of myelinating oligodendrocytes in the neocortex
Authors: Palhol Justine S. C. , Balia Maddalena , Sánchez-Román Terán Fernando , Labarchède Mélody , Gontier Etienne , Battefeld Arne 
Published: April 2023

Abstract
Background
Oligodendrocyte lineage cells interact with the vasculature in the gray matter. Physical and functional interactions between blood vessels and oligodendrocyte precursor cells play an essential role in both the developing and adult brain. Oligodendrocyte precursor cells have been shown to migrate along the vasculature and subsequently detach from it during their differentiation to oligodendrocytes. However, the association of mature oligodendrocytes with blood vessels has been noted since the discovery of this glial cell type almost a century ago, but this interaction remains poorly explored.

Results
Here, we systematically investigated the extent of mature oligodendrocyte interaction with the vasculature in mouse brain. We found that ~ 17% of oligodendrocytes were in contact with blood vessels in the neocortex, the hippocampal CA1 region and the cerebellar cortex. Contacts were made mainly with capillaries and sparsely with larger arterioles or venules. By combining light and serial electron microscopy, we demonstrated that oligodendrocytes are in direct contact with the vascular basement membrane, raising the possibility of direct signaling pathways and metabolite exchange with endothelial cells. During experimental remyelination in the adult, oligodendrocytes were regenerated and associated with blood vessels in the same proportion compared to control cortex, suggesting a homeostatic regulation of the vasculature-associated oligodendrocyte population.

Conclusions
Based on their frequent and close association with blood vessels, we propose that vasculature-associated oligodendrocytes should be considered as an integral part of the brain vasculature microenvironment. This particular location could underlie specific functions of vasculature-associated oligodendrocytes, while contributing to the vulnerability of mature oligodendrocytes in neurological diseases.
Intraoperative electrical stimulation promotes the short-term recovery of patients with cubital tunnel syndrome after surgery
Authors: Zhang Xuelei , Xiu Xiaolei , Wang Ping , Han Yaxin , Chang Wenli , Zhao Jianyong 
Published: April 2023

Abstract
Background
This study was designed to investigate whether intraoperative electrical nerve stimulation has effects on the short-term recovery of cubital tunnel syndrome patients after ulnar nerve release.

Methods
Patients diagnosed as cubital tunnel syndrome were selected. At the same time, they received conventional surgery treatment. The patients were divided by a randomized digits table into two groups. The control group underwent conventional surgery, and the electrical stimulation (ES) group underwent intraoperative electrical stimulation. All the patients were tested for sensory and motor functions, grip strength, key pinch strength, motor conductivity velocity (MCV), and maximum compound muscle action potential (CMAP) before operation and 1 month and 6 months after operation.

Results
In patients treated with intraoperative ES, the sensory and motor functions and the strength of muscle were significantly improved after 1-month and 6-month follow-up than the control group. After the follow-up, the patients in the ES group had significantly higher grip strength and key pinch strength than the control group. After the follow-up, the patients in the ES group had significantly higher MCV and CMAP than the control group.

Conclusion
Intraoperative electrical stimulation of nerve muscle can significantly promote the short-term recovery of nerve and muscle functions after the surgery in cubital tunnel syndrome patients.
Molecular identification of the chitinase genes in Aedes albopictus and essential roles of AaCht10 in pupal-adult transition
Authors: An Sha , Liu Wenjuan , Fu Jingwen , Zhang Zhong , Zhang Ruiling 
Published: April 2023

Abstract
Background
Aedes albopictus is an increasingly serious threat in public health due to it is vector of multiple arboviruses that cause devastating human diseases, as well as its widening distribution in recent years. Insecticide resistance is a serious problem worldwide that limits the efficacy of chemical control strategies against Ae. albopictus. Chitinase genes have been widely recognized as attractive targets for the development of effective and environmentally safe insect management measures.

Methods
Chitinase genes of Ae. albopictus were identified and characterized on the basis of bioinformatics search of the referenced genome. Gene characterizations and phylogenetic relationships of chitinase genes were investigated, and spatio-temporal expression pattern of each chitinase gene was evaluated using qRT-PCR. RNA interference (RNAi) was used to suppress the expression of AaCht10, and the roles of AaCht10 were verified based on phynotype observations, chitin content analysis and hematoxylin and eosin (H&E) stain of epidermis and midgut.

Results
Altogether, 14 chitinase-related genes (12 chitinase genes and 2 IDGFs) encoding 17 proteins were identified. Phylogenetic analysis showed that all these AaChts were classified into seven groups, and most of them were gathered into group IX. Only AaCht5-1, AaCht10 and AaCht18 contained both catalytic and chitin-binding domains. Different AaChts displayed development- and tissue-specific expression profiling. Suppression of the expression of AaCht10 resulted in abnormal molting, increased mortality, decreased chitin content and thinning epicuticle, procuticle and midgut wall of pupa.

Conclusions
Findings of the present study will aid in determining the biological functions of AaChts and also contribute to using AaChts as potential target for mosquito management.

Graphical Abstract
Neuroglobin plays as tumor suppressor by disrupting the stability of GPR35 in colorectal cancer
Authors: Xiang Qin , Zhou Dishu , Xiang Xinni , Le Xin , Deng Chaoqun , Sun Ran , Li Chunhong , Pang Huayang , He Jin , Zheng Zeze , Tang Jun , Peng Weiyan , Peng Xi , He Xiaoqian , Wu Fan , Qiu Jingfu , Xu Yongzhu , Xiang Tingxiu 
Published: April 2023

Abstract
Background
The incidence of colorectal cancer (CRC) has increased in recent years. Identification of accurate tumor markers has become the focus of CRC research. Early and frequent DNA methylation tends to occur in cancer. Thus, identifying accurate methylation biomarkers would improve the efficacy of CRC treatment. Neuroglobin (NGB) is involved in neurological and oncological diseases. However, there are currently no reports on epigenetic regulation involvement of NGB in CRC.

Results
NGB was downregulated or silenced in majority CRC tissues and cell lines. The hypermethylation of NGB was detected in tumor tissue, but no or a very low methylation frequency in normal tissues. Overexpression of NGB induced G2/M phase arrest and apoptosis, suppressed proliferation, migration, invasion in vitro, and inhibited CRC tumor growth and angiogenesis in vivo. Isobaric tag for relative and absolute quantitation (Itraq)-based proteomics identified approximately 40% proteins related to cell–cell adhesion, invasion, and tumor vessel formation in the tumor microenvironment, among which GPR35 was proved critical for NGB-regulated tumor angiogenesis suppression in CRC.

Conclusions
NGB, an epigenetically silenced factor, inhibits metastasis through the GPR35 in CRC. It is expected to grow into a potential cancer risk assessment factor and a valuable biomarker for early diagnosis and prognosis assessment of CRC.
Opportunistic screening for osteoporosis by abdominal CT in a British population
Authors: Vadera Sonam , Osborne Timothy , Shah Vikas , Stephenson James A. 
Published: April 2023

Abstract
Background
It has previously been shown that CT scans performed for other indications can be used to identify patients with osteoporosis. This has not yet been tested in a British population. We sought to evaluate the use of vertebral CT attenuation measures for predicting osteoporosis in a British cohort, using dual-energy X-ray absorptiometry (DEXA) as a reference standard.

Methods
Patients who underwent abdominal CT in 2018 and concomitantly underwent DEXA within a six-month interval were retrospectively included. CT attenuation values in Hounsfield units (HU) were measured by placement of a region-of-interest at the central portion of the L1 vertebral body and then compared to their corresponding DEXA score. Receiver operating characteristic (ROC) curves were generated to evaluate the performance of a logistic regression model and to determine sensitivity and specificity thresholds.

Results
536 patients (394 females, mean age 65.8) were included, of which 174 had DEXA-defined osteoporosis. L1 attenuation measures were significantly different (p < 0.01) between the three DEXA-defined groups of osteoporosis (118 HU), osteopenia (143 HU) and normal bone density (178 HU). The area under the ROC curve was 0.74 (95% CI 0.69–0.78). A threshold of 169 HU was 90% sensitive, and a threshold of 104 HU was 90% specific for diagnosing osteoporosis.

Conclusions
Routine abdominal CT can be used to opportunistically screen for osteoporosis without additional cost or radiation exposure. The thresholds identified in this study are comparable with previous studies in other populations. We recommend radiologists engage with primary care and rheumatology providers to determine appropriate cut-off values for further investigation.
The added values of 18F-FDG PET/CT in differentiating cancer recurrence and osteoradionecrosis of mandible in patients with treated oral squamous cell carcinoma
Authors: Cheng Nai-Ming , Lin Chien-Yu , Liao Chun-Ta , Tsan Din-Li , Ng Shu-Hang , Yen Tzu-Chen 
Published: April 2023

Abstract
Background
Osteoradionecrosis (ORN) of the jaw requires a differential diagnosis to exclude cancer recurrence. Here, we sought to develop a scoring system comprising 18F-FDG PET/CT parameters for distinguishing between the two conditions in patients with oral squamous cell carcinoma (OSCC).

Methods
The study consisted of 103 OSCC patients with suspected ORN of the jaw. All participants underwent 18F-FDG PET/CT imaging within 6 months of diagnostic histopathology. Following extraction of PET parameters, we identified clinical and imaging predictors of mandibular recurrence-free survival (MRFS) using receiver operating characteristic curve analysis and multivariate Cox regression models.

Results
The results of histopathology revealed mandibular cancer recurrence in 24 patients (23.3%). Multivariate Cox regression analyses identified an age at diagnosis ≤ 52 years (P = 0.013), a location of the SUVmax voxel with soft tissue predominance (P = 0.019), and mandibular total lesion glycolysis (TLG) > 62.68 g (P < 0.001) as independent risk factors for MRFS. A scoring system was devised with scores from 0 (no risk factor) to 3 (presence of all three risk factors). High-risk patients with a score of 2–3 compared with score of 0–1 had a significantly higher likelihood of mandibular cancer recurrence (hazard ratio: 32.50, 95% confidence interval: 8.51–124.18, P < 0.001). The scoring system had a sensitivity of 87.50%, a specificity of 82.28%, and an accuracy of 83.50% for identifying mandibular cancer recurrence.

Conclusions
The scoring system of our study is clinically useful for identifying mandibular cancer recurrence in patients with suspected ORN of the jaw.