bluuebunny/crossref_metadata_2025 huggingface dataset:
One for All, All for One: A Close Look at In-Resin Fluorescence Protocols for CLEM
Authors: Heiligenstein Xavier , Lucas Miriam S.
Published: June 2022

Sample preparation is the novel bottleneck for high throughput correlative light and electron microscopy (CLEM). Protocols suitable for both imaging methods must therefore balance the requirements of each technique. For fluorescence light microscopy, a structure of interest can be targeted using: 1) staining, which is often structure or tissue specific rather than protein specific, 2) dye-coupled proteins or antibodies, or 3) genetically encoded fluorescent proteins. Each of these three methods has its own advantages. For ultrastructural investigation by electron microscopy (EM) resin embedding remains a significant sample preparation approach, as it stabilizes the sample such that it withstands the vacuum conditions of the EM, and enables long-term storage. Traditionally, samples are treated with heavy metal salts prior to resin embedding, in order to increase imaging contrast for EM. This is particularly important for volume EM (vEM) techniques. Yet, commonly used contrasting agents (e.g., osmium tetroxide, uranyl acetate) tend to impair fluorescence. The discovery that fluorescence can be preserved in resin-embedded specimens after mild heavy metal staining was a game changer for CLEM. These so-called in-resin fluorescence protocols present a significant leap forward for CLEM approaches towards high precision localization of a fluorescent signal in (volume) EM data. Integrated microscopy approaches, combining LM and EM detection into a single instrument certainly require such an “all in one” sample preparation. Preserving, or adding, dedicated fluorescence prior to resin embedding requires a compromise, which often comes at the expense of EM imaging contrast and membrane visibility. Especially vEM can be strongly hampered by a lack of heavy metal contrasting. This review critically reflects upon the fundamental aspects of resin embedding with regard to 1) specimen fixation and the physics and chemistry underlying the preservation of protein structure with respect to fluorescence and antigenicity, 2) optimization of EM contrast for transmission or scanning EM, and 3) the choice of embedding resin. On this basis, various existing workflows employing in-resin fluorescence are described, highlighting their common features, discussing advantages and disadvantages of the respective approach, and finally concluding with promising future developments for in-resin CLEM.
Regulatory Role of N6-Methyladenosine (m6A) Modification in Osteoarthritis
Authors: Zhai Ganggang , Xiao Likang , Jiang Chenyang , Yue Songkai , Zhang Meng , zheng Jia , Liu Zeming , Dong Yonghui
Published: June 2022

Osteoarthritis (OA) is the most common joint disease, usually occurring in middle-aged and elderly people. However, current treatment for OA in its early stages is ineffective, and drug therapy is often ineffective in slowing the progression of the disease. In fact, a deeper understanding of the underlying molecular mechanisms of OA could help us to better develop effective therapeutic measures. N6-methyladenosine (m6A) is a methylation that occurs at the adenosine N6-position, which is the most common internal modification on eukaryotic mRNAs. The role and mechanisms of m6A in mammalian gene regulation have been extensively studied. The “Writer”, “eraser”, and “reader” proteins are key proteins involved in the dynamic regulation of m6A modifications. Recent studies on post-transcriptional regulation alone have shown that m6a modification has an important role in the development of OA. This paper summarizes the specific regulatory processes of M6A in disease and reviews the role of m6A in OA, describing its pathophysiological role and molecular mechanisms, as well as its future research trends and potential clinical applications in OA.
Novel Coumarin–Pyridine Hybrids as Potent Multi-Target Directed Ligands Aiming at Symptoms of Alzheimer’s Disease
Authors: Babaei Elaheh , Küçükkılınç Tuba Tüylü , Jalili-Baleh Leili , Nadri Hamid , Öz Esin , Forootanfar Hamid , Hosseinzadeh Elaheh , Akbari Tayebeh , Ardestani Mehdi Shafiee , Firoozpour Loghman , Foroumadi Alireza , Sharifzadeh Mohammad , Mirjalili Bi Bi Fatemeh , Khoobi Mehdi
Published: June 2022

In this research, a series of coumarin-based scaffolds linked to pyridine derivatives via a flexible aliphatic linkage were synthesized and assessed as multifunctional anti-AD agents. All the compounds showed acceptable acetylcholinesterase (AChE) inhibition activity in the nanomolar range (IC50 = 2–144 nM) and remarkable butyrylcholinesterase (BuChE) inhibition property (IC50 = 9–123 nM) compared to donepezil as the standard drug (IC50 = 14 and 275 nM, respectively). Compound 3f as the best AChE inhibitor (IC50 = 2 nM) showed acceptable BuChE inhibition activity (IC50 = 24 nM), 100 times more active than the standard drug. Compound 3f could also significantly protect PC12 and SH-SY5Y cells against H2O2-induced cell death and amyloid toxicity, respectively, superior to the standard drugs. It could interestingly reduce β-amyloid self and AChE-induced aggregation, more potent than the standard drug. All the results suggest that compound 3f could be considered as a promising multi-target-directed ligand (MTDL) against AD.
Enhanced Anti-Inflammatory Effects of Silibinin and Capsaicin Combination in Lipopolysaccharide-Induced RAW264.7 Cells by Inhibiting NF-κB and MAPK Activation
Authors: Zheng Yingying , Chen Jie , Wu Xiaozheng , Zhang Xin , Hu Chunmei , Kang Yu , Lin Jing , Li Jiamin , Huang Yuechang , Zhang Xingmin , Li Chen
Published: June 2022

Silibinin and capsaicin both are natural product molecules with diverse biological activities. In this article, we investigated the anti-inflammatory effects of silibinin combined with capsaicin in lipopolysaccharide (LPS)-induced RAW264.7 cells. The results showed that silibinin combined with capsaicin strongly inhibited LPS-induced nitric oxide (NO), tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), and COX-2. Moreover, silibinin combined with capsaicin potently inhibited nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. The results of the present study indicate that silibinin combined with capsaicin effectively inhibits inflammation.
Selection and Identification of a DNA Aptamer for Multidrug-Resistant Acinetobacter baumannii Using an In-House Cell-SELEX Methodology
Authors: Farrel Côrtes Marina , Marli Bes Taniela , Ribeiro Deo Beatriz , Barbosa dos Anjos Beatriz , Jimenez Galisteo Andrés , Cerdeira Sabino Ester , Santos Carlos , Figueiredo Costa Silvia
Published: June 2022

Infections caused by multidrug-resistant A. baumannii are a worldwide health concern with high mortality rates. Rapid identification of this infectious agent is critical as it can easily spread with difficult or no options for treatment. In this context, the development of reliable and economically viable detection and therapeutic methodologies are still challenging. One of the promising solutions is the development of nucleic acid aptamers capable of interacting with bacteria. These aptamers can be used for specific recognition of infectious agents as well as for blocking their functions. Cell-SELEX technology currently allows the selection and identification of aptamers and is flexible enough to target molecules present in an entire bacterial cell without their prior knowledge. However, the aptamer technology is still facing many challenges, such as the complexity of the screening process. Here, we describe the selection and identification of a new aptamer A01, using an in-house whole-cell SELEX-based methodology, against multi-resistant Acinetobacter baumannii, with rapid execution and low cost. In addition, this protocol allowed the identification of the aptamer A01 with the whole A. baumannii cell as a target. The aptamer A01 demonstrated a binding preference to A. baumannii when compared to K. pneumoniae, C. albicans, and S. aureus in fluorescence assays. Although the time-kill assay did not show an effect on bacterial growth, the potential bactericidal or bacteriostatic cannot be totally discarded. The new categorized aptamer (A01) displayed a significant binding affinity to MDR A. baumannii.
Dental Materials for Oral Microbiota Dysbiosis: An Update
Authors: Zhu Jieyu , Chu Wenlin , Luo Jun , Yang Jiaojiao , He Libang , Li Jiyao
Published: June 2022

The balance or dysbiosis of the microbial community is a major factor in maintaining human health or causing disease. The unique microenvironment of the oral cavity provides optimal conditions for colonization and proliferation of microbiota, regulated through complex biological signaling systems and interactions with the host. Once the oral microbiota is out of balance, microorganisms produce virulence factors and metabolites, which will cause dental caries, periodontal disease, etc. Microbial metabolism and host immune response change the local microenvironment in turn and further promote the excessive proliferation of dominant microbes in dysbiosis. As the product of interdisciplinary development of materials science, stomatology, and biomedical engineering, oral biomaterials are playing an increasingly important role in regulating the balance of the oral microbiome and treating oral diseases. In this perspective, we discuss the mechanisms underlying the pathogenesis of oral microbiota dysbiosis and introduce emerging materials focusing on oral microbiota dysbiosis in recent years, including inorganic materials, organic materials, and some biomolecules. In addition, the limitations of the current study and possible research trends are also summarized. It is hoped that this review can provide reference and enlightenment for subsequent research on effective treatment strategies for diseases related to oral microbiota dysbiosis.
Comparative Profiling of Circulating Exosomal Small RNAs Derived From Peruvian Patients With Tuberculosis and Pulmonary Adenocarcinoma
Authors: Guio Heinner , Aliaga-Tobar Victor , Galarza Marco , Pellon-Cardenas Oscar , Capristano Silvia , Gomez Henry L. , Olivera Mivael , Sanchez Cesar , Maracaja-Coutinho Vinicius
Published: June 2022

Tuberculosis (TB) is one of the most fatal infectious diseases, caused by the aerobic bacteria Mycobacterium tuberculosis. It is estimated that one-third of the world’s population is infected with the latent (LTB) version of this disease, with only 5-10% of infected individuals developing its active (ATB) form. Pulmonary adenocarcinoma (PA) is the most common and diverse form of primary lung carcinoma. The simultaneous or sequential occurrence of TB and lung cancer in patients has been widely reported and is known to be an issue for diagnosis and surgical treatment. Raising evidence shows that patients cured of TB represent a group at risk for developing PA. In this work, using sRNA-sequencing, we evaluated the expression patterns of circulating small RNAs available in exosomes extracted from blood samples of Peruvian patients affected by latent tuberculosis, active tuberculosis, or pulmonary adenocarcinoma. Differential expression analysis revealed a set of 24 microRNAs perturbed in these diseases, revealing potential biomarker candidates for the Peruvian population. Most of these miRNAs are normally expressed in healthy lung tissue and are potential regulators of different shared and unique KEGG pathways related to cancers, infectious diseases, and immunology.
Role of the Complement System in the Modulation of T-Cell Responses in Chronic Chagas Disease
Authors: Caputo María Belén , Elias Josefina , Cesar Gonzalo , Alvarez María Gabriela , Laucella Susana Adriana , Albareda María Cecilia
Published: June 2022

Chagas disease, caused by the intracellular pathogen Trypanosoma cruzi, is the parasitic disease with the greatest impact in Latin America and the most common cause of infectious myocarditis in the world. The immune system plays a central role in the control of T. cruzi infection but at the same time needs to be controlled to prevent the development of pathology in the host. It has been shown that persistent infection with T. cruzi induces exhaustion of parasite-specific T cell responses in subjects with chronic Chagas disease. The continuous inflammatory reaction due to parasite persistence in the heart also leads to necrosis and fibrosis. The complement system is a key element of the innate immune system, but recent findings have also shown that the interaction between its components and immune cell receptors might modulate several functions of the adaptive immune system. Moreover, the findings that most of immune cells can produce complement proteins and express their receptors have led to the notion that the complement system also has non canonical functions in the T cell. During human infection by T. cruzi, complement activation might play a dual role in the acute and chronic phases of Chagas disease; it is initially crucial in controlling parasitemia and might later contributes to the development of symptomatic forms of Chagas disease due to its role in T-cell regulation. Herein, we will discuss the putative role of effector complement molecules on T-cell immune exhaustion during chronic human T. cruzi infection.
Proteomics Study of the Synergistic Killing of Tigecycline in Combination With Aminoglycosides Against Carbapenem-Resistant Klebsiella pneumoniae
Authors: Ma Xinqian , Fu Shining , Wang Yifan , Zhao Lili , Yu Wenyi , He Yukun , Ni Wentao , Gao Zhancheng
Published: June 2022

Co-administration of antibiotics with synergistic effects is one method to combat carbapenem-resistant organisms. Although the synergistic effects of tigecycline combined with aminoglycosides against carbapenem-resistant Klebsiella pneumoniae (CRKP) have been demonstrated in vitro and in animal models, the underlying mechanism remains elusive. Here we used proteomics analysis to assess the short-term bacterial responses to tigecycline and aminoglycosides alone or in combination. Emergence of tigecycline resistance during treatment and the susceptibility of tigecycline-resistant strains to aminoglycosides was further evaluated. The proteomic responses to tigecycline and aminoglycosides were divergent in monotherapy, with proteomic alterations to combination therapy dominated by tigecycline. Adaptive responses to tigecycline were associated with the upregulation of oxidative phosphorylation and translation-related proteins. These responses might confer CRKP hypersensitivity towards aminoglycosides by increasing the drug uptake and binding targets. Meanwhile, tigecycline might perturb adaptive responses to aminoglycosides through inhibition of heat shock response. Tigecycline-resistant strains could be isolated within 24 h exposure even in strains without heteroresistance, and the sensitivity to aminoglycosides significantly increased in resistant strains. Overall, these findings demonstrated that adaption to tigecycline in CRKP was a double-edged sword associated with the synergistic killing in tigecycline–aminoglycoside combination. Evolutionary hypersensitivity can provide novel insight into the mechanisms of antibiotic synergistic effects.
Inpatient Specialist Palliative Care in Patients With Left Ventricular Assist Devices (LVAD): A Retrospective Case Series
Authors: Tenge Theresa , Santer David , Schlieper Daniel , Schallenburger Manuela , Schwartz Jacqueline , Meier Stefan , Akhyari Payam , Pfister Otmar , Walter Silke , Eckstein Sandra , Eckstein Friedrich , Siegemund Martin , Gaertner Jan , Neukirchen Martin
Published: June 2022

Background

Repeat hospitalizations, complications, and psychosocial burdens are common in patients with left ventricular assist devices (LVAD). Specialist palliative care (sPC) involvement supports patients during decision-making until end-of-life. In the United States, guidelines recommend early specialist palliative care (esPC) involvement prior to implantation. Yet, data about sPC and esPC involvement in Europe are scarce.

Materials and Methods

This is a retrospective descriptive study of deceased LVAD patients who had received sPC during their LVAD-related admissions to two university hospitals in Duesseldorf, Germany and Basel, Switzerland from 2010 to 2021. The main objectives were to assess: To which extent have LVAD patients received sPC, how early is sPC involved? What are the characteristics of those, how did sPC take place and what are key challenges in end-of-life care?

Results

In total, 288 patients were implanted with a LVAD, including 31 who received sPC (11%). Twenty-two deceased LVAD patients (19 male) with sPC were included. Mean patient age at the time of implantation was 67 (range 49–79) years. Thirteen patients (59%) received LVAD as destination therapy, eight patients (36%) were implanted as bridge to transplantation (BTT), and one as an emergency LVAD after cardiogenic shock (5%). None of the eight BTT patients received a heart transplantation before dying. Most (n = 13) patients lived with their family and mean Eastern Cooperative Oncology Group (ECOG) performance status was three. Mean time between LVAD implantation and first sPC contact was 1.71 years, with a range of first sPC contact from 49 days prior to implantation to more than 6 years after. Two patients received esPC before implantation. In Duesseldorf, mean time between first sPC contact and in-hospital death was 10.2 (1–42) days. In Basel, patients died 16 (0.7–44) months after first sPC contact, only one died on the external sPC unit. Based on thorough examination of two case reports, we describe key challenges of sPC in LVAD patients including the necessity for sPC expertise, ethical and communicative issues as well as the available resources in this setting.

Conclusion

Despite unequivocal recommendations for sPC in LVAD patients, the integration of sPC for these patients is yet not well established.
Association Between the Use of Pre- and Post-thrombolysis Anticoagulation With All-Cause Mortality and Major Bleeding in Patients With Pulmonary Embolism
Authors: Tan Jiang-Shan , Liu Ningning , Hu Song , Wu Yan , Gao Xin , Guo Ting-Ting , Yan Xin-Xin , Peng Fu-Hua , Hua Lu
Published: June 2022

Objective

To explore the comparative clinical efficacy and safety outcomes of anticoagulation before (pre-) or following (post-) thrombolytic therapy in systemic thrombolytic therapy for pulmonary embolism (PE).

Methods

PubMed, the Cochrane Library, EMBASE, EBSCO, Web of Science, and CINAHL databases were searched from inception through 1 May 2021. All randomized clinical trials comparing systemic thrombolytic therapy vs. anticoagulation alone in patients with PE and those that were written in English were eligible. The primary efficacy and safety outcomes were all-cause mortality and major bleeding, respectively. Odds ratios (OR) estimates and associated 95% confidence intervals (CIs) were calculated. A Bayesian network analysis was performed using R studio software, and then the efficacy and safety rankings were derived.

Results

This network meta-analysis enrolled 15 trials randomizing 2,076 patients. According to the plot rankings, the anticoagulant therapy was the best in terms of major bleeding, and the post-thrombolysis anticoagulation was the best in terms of all-cause mortality. Taking major bleeding and all-cause mortality into consideration, the most safe–effective treatment was the post-thrombolysis anticoagulation in patients who needed thrombolytic therapy. The net clinical benefit analysis comparing associated ICH benefits vs. mortality risks of post-thrombolysis anticoagulation demonstrated a net clinical benefit of 1.74%.

Conclusion

The systemic thrombolysis followed by anticoagulation had a better advantage in all-cause mortality and major bleeding than the systemic thrombolysis before anticoagulation. The adjuvant anticoagulation treatment of systemic thrombolytic therapy should be optimized.
Integrated Analysis of circRNA-miRNA-mRNA-Mediated Network and Its Potential Function in Atrial Fibrillation
Authors: Wei Feiyu , Zhang Xi , Kuang Xiaohui , Gao Xiaolong , Wang Jing , Fan Jie
Published: June 2022

Background

Atrial fibrillation (AF) is one of the most prevalent arrhythmias, characterized by a high risk of heart failure and embolic stroke. Competing endogenous RNA network has been reported to play an important role in cardiovascular diseases. The main objective of the present study was to construct a circRNA–miRNA–mRNA-mediated network and explore the potential function in AF.

Methods

The microarray data of circRNA, miRNA, and mRNA in AF were downloaded from the Gene Expression Omnibus database. The RobustRankAggreg method was used to screen the different expression circRNAs(DECs). Then the circRNA–miRNA–mRNA-mediated network was constructed by using the CircInteractome database and the miRWalk online tool. A quantitative real-time polymerase chain reaction was used to detect the circRNA expression level in plasma. The left atrial fibrosis was evaluated with the left atrial low voltage area (LVA) by using left atrial voltage matrix mapping.

Results

Three DECs (hsa_circRNA_102461, hsa_circRNA_103693, and hsa_circRNA_059880) and 4 miRNAs were screened. Then a circRNA–miRNA–mRNA-mediated network was constructed, which included 2 circRNAs, 4 miRNAs, and 83 genes. Furthermore, the plasma’s hsa_circ_0070391 expression level was confirmed to be upregulated and positively correlated with left atrial fibrosis in AF (r = 0.88, P < 0.001), whereas hsa_circ_0003935 was downregulated. Moreover, the ROC curve analysis revealed hsa_circ_0070391 and hsa_circ_0003935 could differentiate AF from the healthy controls with an AUC of 0.95 (95% sensitivity and 90% specificity) and 0.86 (70% sensitivity and 75% specificity), respectively. Finally, the free of atrial tachyarrhythmia rate was dramatically lower in the hsa_circ_0070391 high expression group than in the low expression group post catheter ablation (70.0 vs. 90.0%, p = 0.04).

Conclusion

This study provides a novel insight to further understand the AF pathogenesis from the perspective of the circRNA–miRNA–mRNA network, suggesting that plasma circRNAs could serve as a novel atrial fibrosis and prognosis biomarker for AF.
Ferroptosis and Autophagy-Related Genes in the Pathogenesis of Ischemic Cardiomyopathy
Authors: Zheng Yue , Gao Wenqing , Zhang Qiang , Cheng Xian , Liu Yanwu , Qi Zhenchang , Li Tong
Published: June 2022

Background

Obesity plays an important role in type 2 diabetes mellitus (T2DM) and myocardial infarction (MI). Ferroptosis and ferritinophagy are related to metabolic pathways, such as fatty acid metabolism and mitochondrial respiration. We aimed to investigate the ferroptosis- and autophagy-related differentially expressed genes (DEGs) that might be potential targets for MI progression.

Methods

GSE116250 was analyzed to obtain DEGs. A Venn diagram was used to obtain the overlapping ferroptosis- and autophagy-related DEGs. The enrichment pathway analysis was performed and the hub genes were obtained. Pivotal miRNAs, transcription factors, and drugs with the hub genes interactions were also predicted. The MI mice model was constructed, and qPCR analysis and single-cell sequencing were used to validate the hub genes.

Results

Utilizing the limma package and the Venn diagram, 26 ferroptosis-related and 29 autophagy-related DEGs were obtained. The list of ferroptosis-related DEGs was analyzed, which were involved in the cellular response to a toxic substance, cellular oxidant detoxification, and the IL-17 signaling pathway. The list of autophagy-related DEGs was involved in the regulation of autophagy, the regulation of JAK-STAT signaling pathway, and the regulation of MAPK cascade. In the protein-protein interaction network, the hub DEGs, such as IL-6, PTGS2, JUN, NQO1, NOS3, LEPR, NAMPT, CDKN2A, CDKN1A, and Snai1, were obtained. After validation using qPCR analysis in the MI mice model and single-cell sequencing, the 10 hub genes can be the potential targets for MI deterioration.

Conclusion

The screened hub genes, IL-6, PTGS2, JUN, NQO1, NOS3, LEPR, NAMPT, CDKN2A, CDKN1A, and Snai1, may be therapeutic targets for patients with MI and may prevent adverse cardiovascular events.
Congenital Heart Diseases and Periodontal Diseases—Is There a Link?
Authors: Rughwani Roshan R. , Cholan Priyanka K. , Victor Dhayanand J.
Published: June 2022

An understanding in the field of periodontal medicine explains the fact that the oral cavity serves as a niche for numerous pathogenic microorganisms. When these microorganisms or their by-products disseminate to the various parts of the body, they are capable of triggering diseases characterized by an altered host immune-inflammatory response in the anatomically distinct organ. This mechanism is reported in the propagation of cardiovascular diseases with respect to periodontal medicine. Abundant amount of literature suggests an association between atherosclerotic cardiovascular disease and periodontal diseases. However, there is very less data available to highlight the association between periodontal disease and non-atherosclerotic cardiovascular disease, such as congenital anomalies of the heart. This review outlines the relationship between periodontal diseases and congenital heart diseases and also helps us understand whether the presence of periodontal disease can worsen the preexisting congenital cardiac disease.
Before Rice and the First Rice: Archaeobotanical Study in Ha Long Bay, Northern Vietnam
Authors: Wang Weiwei , Nguyen Kim Dung , Dang Le Hai , Zhao Chunguang , Carson Mike T. , Yang Xiaoyan , Hung Hsiao-chun
Published: June 2022

Mainland Southeast Asia experienced a long, sustained period of foraging economy before rice and millet farming spread into this area prior to 4,000 years BP. Although hundreds of individuals from dense cemeteries are found in several hunter-gatherer sites in Guangxi, Southern China, and Northern Vietnam, dating from the early to middle Holocene (ca. 9,000–4,500 years BP), so far, little has been known about food sources in these pre-farming contexts. In particular, plant food resources have been unclear, although they likely were crucial to supporting rather large populations of hunter-gatherers in this region. To investigate this issue, micro plant remains, including starches and phytoliths, were recovered from stone tools excavated at the Cai Beo site in Ha Long Bay of coastal Northeastern Vietnam, and those findings revealed new understanding of the ancient diet. Examinations of those residues indicated that the hunter-gatherers at Cai Beo as early as 7,000–6,000 years BP exploited a broad spectrum of plants, such as taros, yams, acorns, palms, and more. This study exemplifies how maritime hunter-gatherers interfaced with the local plants and generated population growth from about 7,000 to 4,500 years BP. The results help us to conceptualize the early exploitation, management, and potential cultivation of subtropical and tropical plants over the broad geography of Asia and the Pacific before the arrival of rice and millet farming. In particular, the result validates the significance of roots and tubers in the ancient subsistence economy of Southeast Asia. Moreover, from the archaeological context of 4,500 to 4,000 years BP, the rice discovered in this study represents one of the earliest known in Mainland Southeast Asia.
Pupils’ Adaptability at School, a Balance Between Demands and Resources?
Authors: Oger Marie , Broc Guillaume , Martin-Krumm Charles , Le Roux Fleur , Muller Anita , Tarquinio Cyril
Published: June 2022

School burnout is affecting more and more adolescents. In order to develop appropriate preventative measures, the problem more than ever requires a detailed understanding of the mechanisms operating on students’ capacity to adapt to circumstances rendered particularly difficult by the SARS-CoV-2 pandemic (COVID-19). In the absence of an explanatory framework in the field of school health, the JD-R model of work-related stress constitutes an original prism for reading the quality of pupils’ adaptation to their school environment. The aim of this research is on the one hand to observe the predictive links between the different variables operationalized in the school JD-R model and on the other, to test the adequacy of this model against the data in schools acutely affected by the COVID situation. A total of 470 middle school, high school and 1st year BTS students agreed to participate in the longitudinal study. They were administered six scales spread over three measurement periods. The results of the predictive path analyses reveal that the hypotheses assumed are to a good degree verified. However, even if the model as a whole does not fit the data well, in their essence, the results point to the importance of strengthening students’ own resources as well as those present within the school.
Integrated Digital Health Solutions in the Management of Growth Disorders in Pediatric Patients Receiving Growth Hormone Therapy: A Retrospective Analysis
Authors: Tornincasa Vincenzo , Dixon David , Le Masne Quentin , Martin Blaine , Arnaud Lilian , van Dommelen Paula , Koledova Ekaterina
Published: June 2022

Digital health has seen rapid advancements over the last few years in helping patients and their healthcare professionals better manage treatment for a variety of illnesses, including growth hormone (GH) therapy for growth disorders in children and adolescents. For children and adolescents requiring such therapy, as well as for their parents, the treatment is longitudinal and often involves daily injections plus close progress monitoring; a sometimes daunting task when young children are involved. Here, we describe our experience in offering devices and digital health tools to support GH therapy across some 40 countries. We also discuss how this ecosystem of care has evolved over the years based on learnings and advances in technology. Finally, we offer a glimpse of future planned enhancements and directions for digital health to play a bigger role in better managing conditions treated with GH therapy, as well as model development for adherence prediction. The continued aim of these technologies is to improve clinical decision making and support for GH-treated patients, leading to better outcomes.
Association of Metabolic Dysfunction-Associated Fatty Liver Disease and Liver Stiffness With Bone Mineral Density in American Adults
Authors: Li Hejun , Luo Hengcong , Zhang Ying , Liu Lisi , Lin Rong
Published: June 2022

Contest

The relationship between metabolic dysfunction-associated fatty liver disease (MAFLD) and liver stiffness and bone mineral density (BMD) remains unclear.

Objectives

We aimed to investigate the association between MAFLD and liver stiffness and BMD in the United States population.

Methods

A cross-sectional study among 2031 participants over 50 years old in the National Health and Nutrition Examination Survey (NHANES) 2017-2018 was performed. All patients underwent vibration controlled transient elastography (VCTE) and dual-energy x-ray absorptiometry (DXA). The linear and logistic regression model were used to analyze the association between the MAFLD and liver stiffness and osteoporosis, with adjustments for known covariates. Furthermore, the sensitive analyses were conducted to explore the relationship between MAFLD and liver stiffness and whole osteoporosis (include femoral and lumbar osteoporosis).

Results

MAFLD was prevalent in the study population, with a prevalence of 50.9% for men and 40.7% for women. The multiple linear models demonstrated positive associations between MAFLD and liver stiffness and total femur BMD, femur neck BMD, trochanter BMD, intertrochanter BMD. In multiple logistic regression models, both MAFLD and significant liver fibrosis were negatively associated with femoral osteoporosis (OR=0.41, 95% CI: 0.27 to 0.63; OR=0.67, 95% CI: 0.33-1.37, respectively). Nonetheless, when BMI was adjusted, the association between MAFLD and liver stiffness and osteoporosis became insignificant. Besides, as showed in the sensitive analyses, the relationship between MAFLD and liver stiffness and whole osteoporosis were stable.

Conclusions

These results suggest that MAFLD and liver stiffness were associated with higher femoral and lumbar bone mineral density in individuals aged over 50 years. But the results may be confounded by BMI.
Analysis of Intestinal Short-Chain Fatty Acid Metabolism Profile After Probiotics and GLP-1 Treatment for Type 2 Diabetes Mellitus
Authors: Min Qiuxia , Wang Yan , Jin TaiCheng , Zhu Lei , Wu XianYan , Li YiKun , Wang YanJiao , Xu Ning
Published: June 2022

Type 2 diabetes accounts for about 90% of diabetes patients, and the incidence of diabetes is on the rise as people’s lifestyles change. Compared with GLP-1 treatment, probiotic treatment can directly regulate homeostasis of the host gut microbe, and thus homeostasis of its metabolites. Currently, the regulatory role of probiotics on intestinal metabolites after treatment of type 2 diabetes mellitus remains unclear. The purpose of this study was to investigate the therapeutic effect of probiotics on type 2 diabetes mellitus and its regulatory effect on short-chain fatty acids, which are metabolites of intestinal microorganisms. I collected feces from 15 patients with diabetes before treatment and 15 patients with type 2 diabetes after treatment with GLP-1 and probiotics. The abundance of short-chain fatty acids in feces was determined by GC-MS. Results Both GLP-1 and probiotics could improve the levels of blood glucose, urine glucose and BMI in patients with type 2 diabetes. After glP-1 treatment, two short-chain fatty acids (butyric acid and valerate acid) in intestine were significantly changed. Propionic acid and isovalerate were significantly changed after probiotic treatment. At the same time, KEGG signal pathway enrichment results showed that probiotics intervention mainly achieved the purpose of treating type 2 diabetes through regulating protein and carbohydrate metabolism. Taken together, our study shows changes in intestinal short-chain fatty acids after probiotics or GLP-1 treatment of type 2 diabetes, which will provide us with new insights into the mechanism of probiotics treatment of type 2 diabetes, as well as potential intervention targets for diabetes treatment.
New Diagnostic Model for the Differentiation of Diabetic Nephropathy From Non-Diabetic Nephropathy in Chinese Patients
Authors: Zhang WeiGuang , Liu XiaoMin , Dong ZheYi , Wang Qian , Pei ZhiYong , Chen YiZhi , Zheng Ying , Wang Yong , Chen Pu , Feng Zhe , Sun XueFeng , Cai Guangyan , Chen XiangMei
Published: June 2022

Background

The disease pathology for diabetes mellitus patients with chronic kidney disease (CKD) may be diabetic nephropathy (DN), non-diabetic renal disease (NDRD), or DN combined with NDRD. Considering that the prognosis and treatment of DN and NDRD differ, their differential diagnosis is of significance. Renal pathological biopsy is the gold standard for diagnosing DN and NDRD. However, it is invasive and cannot be implemented in many patients due to contraindications. This article constructed a new noninvasive evaluation model for differentiating DN and NDRD.

Methods

We retrospectively screened 1,030 patients with type 2 diabetes who has undergone kidney biopsy from January 2005 to March 2017 in a single center. Variables were ranked according to importance, and the machine learning methods (random forest, RF, and support vector machine, SVM) were then used to construct the model. The final model was validated with an external group (338 patients, April 2017–April 2019).

Results

In total, 929 patients were assigned. Ten variables were selected for model development. The areas under the receiver operating characteristic curves (AUCROCs) for the RF and SVM methods were 0.953 and 0.947, respectively. Additionally, 329 patients were analyzed for external validation. The AUCROCs for the external validation of the RF and SVM methods were 0.920 and 0.911, respectively.

Conclusion

We successfully constructed a predictive model for DN and NDRD using machine learning methods, which were better than our regression methods.

Clinical Trial Registration

ClinicalTrial.gov, NCT03865914.
Treatment of Primary Aldosteronism and Reversal of Renin Suppression Improves Left Ventricular Systolic Function
Authors: Puar Troy H. , Cheong Chin Kai , Foo Roger S.Y. , Saffari Seyed Ehsan , Tu Tian Ming , Chee Min Ru , Zhang Meifen , Ng Keng Sin , Wong Kang Min , Wong Andrew , Ng Foo Cheong , Aw Tar Choon , Khoo Joan , Gani Linsey , King Thomas , Loh Wann Jia , Soh Shui Boon , Au Vanessa , Tay Tunn Lin , Tan Eberta , Mae Lily , Yew Jielin , Tan Yen Kheng , Tong Khim Leng , Lee Sheldon , Chai Siang Chew
Published: June 2022

Introduction

Primary aldosteronism (PA) is associated with increased risk of cardiovascular events. However, treatment of PA has not been shown to improve left ventricular (LV) systolic function using the conventional assessment with LV ejection fraction (LVEF). We aim to use speckle-tracking echocardiography to assess for improvement in subclinical systolic function after treatment of PA.

Methods

We prospectively recruited 57 patients with PA, who underwent 24-h ambulatory blood pressure (BP) measurements and echocardiography, including global longitudinal strain (GLS) assessment of left ventricle, at baseline and 12 months post-treatment.

Results

At baseline, GLS was low in 14 of 50 (28.0%) patients. On multivariable analysis, GLS was associated with diastolic BP (P = 0.038) and glomerular filtration rate (P = 0.026). GLS improved post-surgery by −2.3, 95% CI: −3.9 to −0.6, P = 0.010, and post-medications by −1.3, 95% CI: −2.6 to 0.03, P = 0.089, whereas there were no changes in LVEF in either group. Improvement in GLS was independently correlated with baseline GLS (P < 0.001) and increase in plasma renin activity (P = 0.007). Patients with post-treatment plasma renin activity ≥1 ng/ml/h had improvements in GLS (P = 0.0019), whereas patients with persistently suppressed renin had no improvement. Post-adrenalectomy, there were also improvements in LV mass index (P = 0.012), left atrial volume index (P = 0.002), and mitral E/e’ (P = 0.006), whereas it was not statistically significant in patients treated with medications.

Conclusion

Treatment of hyperaldosteronism is effective in improving subclinical LV systolic dysfunction. Elevation of renin levels after treatment, which reflects adequate reversal of sodium overload state, is associated with better systolic function after treatment.

Clinical Trial Registration

www.ClinicalTrials.gov, identifier: NCT03174847.
Efficacy and Safety of Lenvatinib in Anaplastic Thyroid Carcinoma: A Meta-Analysis
Authors: Huang Dongmei , Zhang Jinming , Zheng Xiangqian , Gao Ming
Published: June 2022

Background

Lenvatinib has shown promising efficacy in targeted therapies that have been tested to treat anaplastic thyroid carcinoma (ATC) in both preclinical and clinical studies. The aim of this study was to evaluate the efficacy and safety of lenvatinib in the treatment of patients with ATC.

Methods

PubMed, the Cochrane Library, Embase, and ClinicalTrials.gov were searched for potential eligible studies from inception to February 1, 2022. The outcomes included partial response (PR), stable disease (SD), disease control rate (DCR), median progression-free survival (mPFS), and median overall survival (mOS). Effect sizes for all pooled results were presented with 95% CIs with upper and lower limit.

Results

Ten studies met the inclusion criteria. The aggregated results showed that the pooled PR, SD, and DCR were 15.0%, 42.0%, and 63.0%, respectively. The pooled mPFS and mOS were 3.16 (2.18–5.60) months and 3.16 (2.17–5.64) months, respectively. Furthermore, PFS rate at 3 months (PFSR-3m), PFSR-6m, PFSR-9m, PFSR-12m, and PFSR-15m were 52.0%, 22.5%, 13.9%, 8.4%, and 2.5%, respectively. Meanwhile, the 3-month OS rate (OSR-3m), OSR-6m, OSR-9m, OSR-12m, and OSR-15m were 64.0%, 39.3%, 29.7%, 18.9%, and 14.2%, respectively. The most common adverse events (AEs) of lenvatinib were hypertension (56.6%), proteinuria (32.6%), and fatigue (32%).

Conclusions

This meta-analysis showed that lenvatinib has meaningful antitumor activity, but limited clinical efficacy in ATC.

Systematic Review Registration

PROSPERO [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42022308624].
Chinese Visceral Adiposity Index Is More Closely Associated With Hypertension and Prehypertension Than Traditional Adiposity Indices in Chinese Population: Results From the REACTION Study
Authors: Li Binqi , Wang Jie , Zhou Xin , Liu Yang , Wang Weiqing , Gao Zhengnan , Tang Xulei , Yan Li , Wan Qin , Luo Zuojie , Qin Guijun , Chen Lulu , Ning Guang , Mu Yiming
Published: June 2022

Purpose

The optimal adiposity index that is strongly associated with hypertension or prehypertension remains inconclusive in Chinese population. This study aimed to investigate the relationship between Chinese visceral adiposity index (CVAI) and hypertension and prehypertension, as well as to compare the discriminative power of CVAI, visceral adiposity index (VAI), body mass index (BMI), waist circumference (WC), waist to height ratio (WHtR), low-density lipoprotein cholesterol (LDL-C), and waist-to-hip ratio (WHR) with hypertension and prehypertension in Chinese general population.

Patients and Methods

A total of 34732 participants from REACTION study were recruited. Multiple logistic regression analyses were performed to detect the association between adiposity indices (CVAI, VAI, BMI, WC, WHtR, WHR, LDL-C) and hypertension and prehypertension.

Results

Multivariate logistic regression analysis showed that compared with other obesity indices, CVAI remained significantly associated with hypertension and prehypertension (Hypertension: odds ratio (OR) 3.475, 95% confidence interval (CI) 3.158-3.824, p<0.001 in total subjects; OR 2.762, 95% CI 2.369–3.221, p<0.001 in men; OR 3.935, 95% CI 3.465–4.469, p<0.001 in women, Prehypertension: OR 2.747, 95% CI 2.460-3.068, p<0.001 in total subjects; OR 2.605, 95% CI 2.176–3.119, p<0.001 in men; OR 2.854, 95% CI 2.465–3.304, p<0.001 in women).In a stratified analysis, CVAI was significantly associated with hypertension and prehypertension at any level of blood glucose, age or estimated glomerular filtration rate(eGFR).

Conclusion

CVAI is significantly associated with hypertension and prehypertension. CVAI shows the superior discriminative ability for hypertension and prehypertension compared with VAI, BMI, WC, WHtR, WHR and LDL-C in Chinese general population.
CD137 Regulates Bone Loss via the p53 Wnt/β-Catenin Signaling Pathways in Aged Mice
Authors: Han Jiyu , Wang Yanhong , Zhou Haichao , Zhang Yingqi , Wan Daqian
Published: June 2022

Senile osteoporosis is a chronic skeletal disease, leading to increased bone brittleness and risk of fragile fractures. With the acceleration of population aging, osteoporosis has gradually become one of the most serious and prevalent problems worldwide. Bone formation is highly dependent on the proper osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in the bone marrow microenvironment, which is generated by the functional relationship among different cell types, including osteoblasts, adipogenic cells, and bone marrow stromal cells in the bone marrow. It is still not clear how osteoporosis is caused by its molecular mechanism. With aging, bone marrow is able to restrain osteogenesis. Discovering the underlying signals that oppose BMSC osteogenic differentiation from the bone marrow microenvironment and identifying the unusual changes in BMSCs with aging is important to elucidate possible mechanisms of senile osteoporosis. We used 3 gene expression profiles (GSE35956, GSE35957, and GSE35959) associated with osteoporosis. And a protein-protein interaction (PPI) network was also built to identify the promising gene CD137. After that, we performed in vivo experiments to verify its function and mechanism. In this experiment, we found that significant bone loss was observed in aged (18-month-old) mice compared with young (6-month-old) mice. The adipose tissue in bone marrow cavity from aged mice reached above 10 times more than young mice. Combining bioinformatics analysis and vivo experiments, we inferred that CD137 might be involved in the p53 and canonical Wnt/β-catenin signaling pathways and thereby influenced bone mass through regulation of marrow adipogenesis. Importantly, osteoporosis can be rescued by blocking CD137 signaling in vivo. Our research will contribute to our understanding not only of the pathogenesis of age-related bone loss but also to the identification of new targets for treating senile osteoporosis.
Association of Serum 25 (OH) Vitamin D With Chronic Kidney Disease Progression in Type 2 Diabetes
Authors: Duan Suyan , Lu Fang , Wu Buyun , Zhang Chengning , Nie Guangyan , Sun Lianqin , Huang Zhimin , Guo Honglei , Zhang Bo , Xing Changying , Yuan Yanggang
Published: June 2022

Objectives

Growing evidence demonstrated that vitamin D levels had been linked to type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) in light of various extraskeletal effects. Therefore, the present study aimed to evaluate the association of 25-hydroxyvitamin D [25(OH)D] level with the clinicopathological features and CKD progression in T2DM.

Methods

A total of 182 patients with T2DM with CKD stages 1 through 4 (G1–G4) were retrospectively included. Identification of the serum 25(OH)D level associated with CKD progression was executed by Kaplan–Meier survival analysis and Cox proportional hazards models. We further performed sensitivity analyses with a time-weighted average (TWA) of the serum 25(OH)D level in 75 participants to reinforce the findings.

Results

The median serum 25(OH)D level was 26 (IQR, 14; 39) nmol/L in the study participants. Median follow-up time was 42 months, during which 70 (38%) patients confronted CKD progression. Cumulative kidney outcomes were significantly higher in the lowest tertile of the serum 25(OH)D level in Kaplan–Meier analyses (P < 0.001). Consistently, the analyses of Cox proportional hazards regression models indicated a significantly greater risk for CKD progression in the lowest tertile of the serum 25(OH)D level compared with the highest tertile of the serum 25(OH)D level (P = 0.03). These relationships remained robust with further sensitivity analysis of data with TWA of the serum 25(OH)D level, showing an independent association between lower TWA of the serum 25(OH)D level and an unfavorable renal outcome in patients with T2DM with CKD.

Conclusions

Our findings demonstrated that patients with T2DM with a decreased 25(OH)D level had deteriorated renal function. Both lower levels of baseline and TWA of serum 25(OH)D were associated with an increased risk of CKD progression in patients with T2DM, which suggested that the long-term maintenance of optimal vitamin D levels from early in life might be associated with reduced future risk of CKD development in T2DM.
Impedance Modeling and Stability-Oriented Parameter Optimization of Isolated Dual Active Bridge-Based Two-Stage AC-DC-DC Converter
Authors: Feng Fan , Fang Jingyang , Manandhar Ujjal , Gooi Hoay Beng , Wang Liguo
Published: June 2022

The isolated dual active bridge (DAB)-based two-stage AC-DC-DC converters have been widely applied in grid-connected power electronics systems. However, the impedance interactions between the DAB converter and the AC-DC rectifier can cause instability problems to the two-stage converter systems. The accurate terminal impedance characteristics of the DAB converters are still not clear due to the high frequency ac conversion stage. This makes it difficult to assess the impacts of the DAB circuit parameters on the stability of the two-stage converters. To address these issues, the impedance models of the DAB converters are originally derived in this paper. Based on the developed impedance models, the stability of the DAB-based two-stage AC-DC-DC converters is analyzed. The impacts of the DAB converter circuit parameters on the stability of the two-stage AC-DC-DC converters are comprehensively revealed by the Bode and Nyquist plots. The analysis results offer instructive implications to finetune the design rules of the DAB converters. The conclusions are validated by comprehensive simulation and experimental results.