bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lipid metabolism, BMI and the risk of nonalcoholic fatty liver disease in the general population: evidence from a mediation analysis
Authors: Lu Song , Xie Qiyang , Kuang Maobin , Hu Chong , Li Xinghui , Yang Huijian , Sheng Guotai , Xie Guobo , Zou Yang 
Published: March 2023

AbstractBackgroundBody mass index (BMI) and lipid parameters are the most commonly used anthropometric parameters and biomarkers for assessing nonalcoholic fatty liver disease (NAFLD) risk. This study aimed to assess and quantify the mediating role of traditional and non-traditional lipid parameters on the association between BMI and NAFLD.MethodUsing data from 14,251 subjects from the NAGALA (NAfld in the Gifu Area, Longitudinal Analysis) study, mediation analyses were performed to explore the roles of traditional [total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C)] and non-traditional [non-HDL-C, remnant cholesterol (RC), TC/HDL-C ratio, LDL-C/HDL-C ratio, TG/HDL-C ratio, non-HDL-C/HDL-C ratio, and RC/HDL-C ratio] lipid parameters in the association of BMI with NAFLD and quantify the mediation effect of these lipid parameters on the association of BMI with NAFLD using the percentage of mediation.ResultAfter fully adjusting for confounders, multivariate regression analysis showed that both BMI and lipid parameters were associated with NAFLD (AllP-value < 0.001). Mediation analysis showed that both traditional and non-traditional lipid parameters mediated the association between BMI and NAFLD (AllP-value of proportion mediate < 0.001), among which non-traditional lipid parameters such as RC, RC/HDL-C ratio, non-HDL-C/HDL-C ratio, and TC/HDL-C ratio accounted for a relatively large proportion, 11.4%, 10.8%, 10.2%, and 10.2%, respectively. Further stratified analysis according to sex, age, and BMI showed that this mediation effect only existed in normal-weight (18.5 kg/m2 ≤ BMI < 25 kg/m2) people and young and middle-aged (30–59 years old) people; moreover, the mediation effects of all lipid parameters except TC accounted for a higher proportion in women than in men.ConclusionThe new findings of this study showed that all lipid parameters were involved in and mediated the risk of BMI-related NAFLD, and the contribution of non-traditional lipid parameters to the mediation effect of this association was higher than that of traditional lipid parameters, especially RC, RC/HDL-C ratio, non-HDL-C/HDL-C ratio, and TC/HDL-C ratio. Based on these results, we suggest that we should focus on monitoring non-traditional lipid parameters, especially RC and RC/HDL-C ratio, when BMI intervention is needed in the process of preventing or treating NAFLD.
Multisystem ALK-positive histiocytosis: a multi-case study and literature review
Authors: Liu Wei , Liu Hong-jie , Wang Wei-ya , Tang Yuan , Zhao Sha , Zhang Wen-yan , Yan Jia-qi , Liu Wei-ping 
Published: March 2023

Abstract
Background
Anaplastic lymphoma kinase (ALK)-positive histiocytosis, a novel rare histiocytic proliferation, was first described in 2008; it occurs in early infancy with liver and hematopoietic involvement. The spectrum was subsequently broadened to include localized diseases in older children and young adults. However, its full clinicopathological features and molecular lineage have not been fully elucidated.

Results
Here, we report four cases of multisystem ALK-positive histiocytosis without hematopoietic involvement. Clinically, three patients were adults aged between 32 and 51 years. Two patients’, whose main manifestations were intracranial mass and numerous micronodules in the thoracoabdominal cavity organs and skin papules respectively, had a partial response to ALK inhibitors after surgery. One patient presented with mediastinal neoplasm without surgical treatment, and progressive disease occurred after two years of ALK inhibitor therapy. The fourth patient was a 17-month-old male with a large intracranial mass and presented with a poor response to ALK inhibitor and chemoradiotherapy; he died eight months after surgery. Pathologically, the histiocytes were large, with abundant eosinophilic cytoplasm, and mixed with variable numbers of foamy cells and Touton giant cells. Interstitial fibrosis was also observed. Histiocytes were positive for macrophage markers (CD68 and CD163) and ALK. KIF5B-ALK fusions were detected in two cases, EML4-ALK in one, and both DCTN1-ALK and VRK2-ALK fusions were detected in one case.

Conclusions
We observed that ALK inhibitors present robust and durable responses in adult patients but a poor response in young children with central nervous system involvement. There is no consensus on the optimal treatment regimen and long-term prognosis requires further observation. Moreover, every unusual histiocytic proliferative lesion, especially unresectable and multisystem involvement, should be routinely tested for ALK immunohistochemical staining to identify this rare disease.
Utilization of cervical cancer screening services and its associated factors in Iran: a case–control study
Authors: Dadipoor Sara , Alavi Azin , Kader Zainab , Eshaghi Sani Kakhaki Hadi , Mohseni Shokrollah , Shahabi Nahid 
Published: March 2023

Abstract
Background
Considering the high incidence rate of cervical cancer (CC) in Iran, screening is an effective way of reducing the impact of the disease due to early detection. Thus, the recognition of the factors affecting the use of cervical cancer screening (CCS) services is essential.The present study aimed to determine the associated factors of CCS in women living in the suburbs of Bandar Abbas in the south of Iran.

Methods
The present case–control study was conducted between January and March 2022 in the suburban areas of Bandar abbas. Two hundred participants were assigned to the case group and 400 participants were assigned to the control group. A self-constructed questionnaire was used to collect the data. This questionnaire contained demographic information, reproductive information, knowledge of CC, knowledge of CCS and access to the screening. Univariate and multivariate regression analyses were run to analyze the data. The data were analyzed in STATA 14.2 at a significance level of p < 0.05.

Results
The mean and standard deviation of participants’ age in the case group was 30.33 ± 4.892, and in the control group was 31.35 ± 6.149. The mean and standard deviation of knowledge in the case group was 10.21 ± 1.815 and in the control group was 7.24 ± 2.447. The mean and standard deviation of access was 43.72 ± 6.339 in the case and 37.17 ± 4.828 in the control group. The results of multivariate regression analysis showed the following factors increased the odds of CCS: knowledge (OR medium = 18.697, OR high = 13.413), access (OR medium = 4.028, OR high = 8.126), being married (OR = 3.193), being educated (OR diploma = 2.587, OR university degree = 1.432), middle and high SES (OR Middle = 6.078, OR Upper = 6.608), and not smoking (OR = 1.144). Also, women's reproductive status, including history of sexually transmitted diseases (OR = 2.612), use of oral contraceptives (OR = 1.579), sexual hygiene (OR = 8.718).

Conclusions
In the light of the present findings, it can be concluded that besides increasing suburban women’s knowledge, their access to screening facilities should be improved. The present findings showed the need to remove the barriers to CCS in women of low SES to increase the rate of CCS. The present findings contribute to a better understanding of factors involved in CCS.
Effect of olmesartan and amlodipine on serum angiotensin-(1–7) levels and kidney and vascular function in patients with type 2 diabetes and hypertension
Authors: Kim Kyuho , Moon Ji Hye , Ahn Chang Ho , Lim Soo 
Published: March 2023

Abstract
Background
Recent studies suggest that angiotensin-converting enzyme 2 (ACE2) and angiotensin-(1–7) [Ang-(1–7)] might have beneficial effects on the cardiovascular system. We investigated the effects of olmesartan on the changes in serum ACE2 and Ang-(1–7) levels as well as kidney and vascular function in patients with type 2 diabetes and hypertension.

Methods
This was a prospective, randomized, active comparator-controlled trial. Eighty participants with type 2 diabetes and hypertension were randomized to receive 20 mg of olmesartan (N = 40) or 5 mg of amlodipine (N = 40) once daily. The primary endpoint was changes of serum Ang-(1–7) from baseline to week 24.

Results
Both olmesartan and amlodipine treatment for 24 weeks decreased systolic and diastolic blood pressures significantly by > 18 mmHg and > 8 mmHg, respectively. Serum Ang-(1–7) levels were more significantly increased by olmesartan treatment (25.8 ± 34.5 pg/mL → 46.2 ± 59.4 pg/mL) than by amlodipine treatment (29.2 ± 38.9 pg/mL → 31.7 ± 26.0 pg/mL), resulting in significant between-group differences (P = 0.01). Serum ACE2 levels showed a similar pattern (6.31 ± 0.42 ng/mL → 6.74 ± 0.39 ng/mL by olmesartan treatment vs. 6.43 ± 0.23 ng/mL → 6.61 ± 0.42 ng/mL by amlodipine treatment; P < 0.05). The reduction in albuminuria was significantly associated with the increases in ACE2 and Ang-(1–7) levels (r =  − 0.252 and r =  − 0.299, respectively). The change in Ang-(1–7) levels was positively associated with improved microvascular function (r = 0.241, P < 0.05). Multivariate regression analyses showed that increases in serum Ang-(1–7) levels were an independent predictor of a reduction in albuminuria.

Conclusions
These findings suggest that the beneficial effects of olmesartan on albuminuria may be mediated by increased ACE2 and Ang-(1–7) levels. These novel biomarkers may be therapeutic targets for the prevention and treatment of diabetic kidney disease.
Trial registration: ClinicalTrials.gov NCT05189015.
Is anterior knee pain following anterior cruciate ligament reconstruction a consideration for graft choice, and the influence of COVID: a qualitative analysis in recreational athletes
Authors: Sanjevic Anastasia , Tourvas Evangelos , Cairns Mark A. , Alnuaimi Fahad , Theodoropoulos John , Dwyer Tim , Chahal Jas , Ogilvie-Harris Darrell 
Published: March 2023

Abstract
Background
We set out to investigate whether anterior knee pain following anterior cruciate ligament reconstruction has a significant effect on patients, and whether it should influence graft choice.

Methods
This was a qualitative analysis of a set of recreational athletes treated at a university hospital at about 1 year following anterior cruciate ligament reconstruction surgery. Participants were interviewed by an orthopaedic fellow and resident using structured, open-ended questions. Inductive theme analysis was used to code the data.

Results
There were 4 major themes: (1) Our hypothesis was that patients would be given adequate information to make an appropriate graft choice. This hypothesis was rejected. Discussion took place, but with little details or rationale for the graft choice. The predominant theme was that the surgeon made the decision, and there was a lack of reliable information for the patient to make a choice. (2) The overall theme was that most patients had no anterior knee pain, and it did not interfere with activities of daily living. (3) One theme was that patients were able to resume all sports without restriction, but in some, the anterior knee pain interfered with the more demanding activities such as impact, cutting, and pivoting. A separate theme was that fear was a major impediment to return to sports and was not related to the anterior knee pain. (4) The overriding theme was that the generalized closures associated with the COVID-19 pandemic slowed the rehabilitation process. Although virtual care was available in general, it was not particularly satisfactory. Patients indicated that they had not been able to return to the gym or to their sporting activities as a result.

Conclusions
Amongst non-competitive athletes, anterior knee pain post-anterior cruciate ligament reconstruction surgery does not significantly affect activities of daily living. Although there is a minor effect on sporting activities, the inability to return to sports is related to factors such as the COVID-19 pandemic, fear, or insufficient rehabilitation, rather than anterior knee pain. Overall, anterior knee pain is not a significant factor that plays a role in determining graft choice.
A systematic evaluation of normalization methods and probe replicability using infinium EPIC methylation data
Authors: Welsh H. , Batalha C. M. P. F. , Li W. , Mpye K. L. , Souza-Pinto N. C. , Naslavsky M. S. , Parra E. J. 
Published: March 2023

Abstract
Background
The Infinium EPIC array measures the methylation status of > 850,000 CpG sites. The EPIC BeadChip uses a two-array design: Infinium Type I and Type II probes. These probe types exhibit different technical characteristics which may confound analyses. Numerous normalization and pre-processing methods have been developed to reduce probe type bias as well as other issues such as background and dye bias.

Methods
This study evaluates the performance of various normalization methods using 16 replicated samples and three metrics: absolute beta-value difference, overlap of non-replicated CpGs between replicate pairs, and effect on beta-value distributions. Additionally, we carried out Pearson’s correlation and intraclass correlation coefficient (ICC) analyses using both raw and SeSAMe 2 normalized data.

Results
The method we define as SeSAMe 2, which consists of the application of the regular SeSAMe pipeline with an additional round of QC, pOOBAH masking, was found to be the best performing normalization method, while quantile-based methods were found to be the worst performing methods. Whole-array Pearson’s correlations were found to be high. However, in agreement with previous studies, a substantial proportion of the probes on the EPIC array showed poor reproducibility (ICC < 0.50). The majority of poor performing probes have beta values close to either 0 or 1, and relatively low standard deviations. These results suggest that probe reliability is largely the result of limited biological variation rather than technical measurement variation. Importantly, normalizing the data with SeSAMe 2 dramatically improved ICC estimates, with the proportion of probes with ICC values > 0.50 increasing from 45.18% (raw data) to 61.35% (SeSAMe 2).
Injection of an improperly stored proprotein convertase subtilisin/kexin type 9 monoclonal antibody in a patient with secondary dyslipidemia from nephrotic syndrome: a case report
Authors: Kongmalai Tanawan , Chuanchaiyakul Nalinee , Srinoulprasert Yuttana , Thongtang Nuntakorn 
Published: March 2023

Abstract
Background
Elevated plasma cholesterol and/or plasma triglyceride levels in nephrotic syndrome patients are the result of impaired lipoprotein clearance and a compensatory increase in hepatic lipoprotein synthesis. Plasma proprotein convertase subtilisin/kexin type 9 levels directly correlate to the amount of proteinuria in nephrotic syndrome patients. Proprotein convertase subtilisin/kexin type 9 monoclonal antibody has been used to treat dyslipidemia in some refractory nephrotic syndrome cases. As a therapeutic protein, proprotein convertase subtilisin/kexin type 9 monoclonal antibody simply deteriorates if stored in inappropriate temperatures or conditions.

Case presentation
In this article, we present the case of a 16-year-old Thai female with severe combined dyslipidemia secondary to refractory nephrotic syndrome. She received proprotein convertase subtilisin/kexin type 9 monoclonal antibody (alirocumab) treatment. However, the drugs were mistakenly frozen in a freezer for up to 17 hours before being stored at 4 °C. After using two frozen devices, serum total cholesterol, free proprotein convertase subtilisin/kexin type 9, and lipoprotein(a) significantly decreased. Nonetheless, the patient developed a skin rash 2 weeks after the second injection and the lesion spontaneously resolved without any treatment approximately 1 month later.

Conclusions
The effectiveness of proprotein convertase subtilisin/kexin type 9 monoclonal antibody seems to be stable after being stored under freeze–thaw conditions. However, improperly stored drugs should be discarded to avoid any potential undesirable side effects.
Single-cell analyses reveal distinct expression patterns and roles of long non-coding RNAs during hESC differentiation into pancreatic progenitors
Authors: Luo Hai-Tao , He Qian , Yang Wei , He Fei , Dong Jun , Hu Chao-Feng , Yang Xiao-Fei , Li Ning , Li Fu-Rong 
Published: March 2023

AbstractBackgroundDeep understanding the differentiation process of human embryonic stem cells (hESCs) is essential for developing cell-based therapeutic strategy. Substantial efforts have been made to investigate protein-coding genes, yet it remains lacking comprehensive characterization of long non-coding RNAs (lncRNAs) during this process.MethodshESCs were passaged every 5–6 days and had maintained stable karyotype even until the 50th generation. Pancreatic progenitor specification of in vitro differentiation from hESCs was performed and modified. The nuclei were stained with 4,6-Diamidino-2-phenylindole (DAPI). Droplet-based platform (10X Genomics) was applied to generate the single-cell RNA sequencing (scRNA-seq) data. The quality of the filtered read pairs was evaluated by using FastQC. Batch effects were removed using the size factor method. Dimension reduction and unsupervised clustering analyses were performed using Seurat R package. The Monocle 2 and MetaCell algorithms were used to order single cells on a pseudotime course and partition the scRNA-seq data into metacells, respectively. Co-expression network was constructed using WGCNA. Module- and hub-based methods were adopted to predict the functions of lncRNAs.ResultsA total of 77,382 cells during the differentiation process of hESCs toward pancreatic progenitors were sequenced. According to the single-cell map, the cells from different time points were authenticated to constitute a relatively homogeneous population, in which a total of 7382 lncRNAs could be detected. Through further analyzing the time course data, conserved and specific expression features of lncRNAs during hESC differentiation were revealed. Based upon pseudotime analysis, 52 pseudotime-associated lncRNAs that grouped into three distinct expression patterns were identified. We also implemented MetaCell algorithm and network-based methods to explore the functional mechanisms of these lncRNAs. Totally, 464 lncRNAs, including 49 pseudotime-associated lncRNAs were functionally annotated by either module-based or hub-based methods. Most importantly, we demonstrated that the lncRNAHOTAIRM1, which co-localized and co-expressed with severalHOXgenes, may play crucial role in the generation of pancreatic progenitors through regulation of exocytosis and retinoic acid receptor signaling pathway.ConclusionsOur single-cell analyses provide valuable data resources for biological researchers and novel insights into hESC differentiation processes, which will guide future endeavors to further elucidate the roles of lncRNAs.
Alleviating the unwanted effects of oxidative stress on Aβ clearance: a review of related concepts and strategies for the development of computational modelling
Authors: Somin Sarawoot , Kulasiri Don , Samarasinghe Sandhya 
Published: March 2023

AbstractTreatment for Alzheimer’s disease (AD) can be more effective in the early stages. Although we do not completely understand the aetiology of the early stages of AD, potential pathological factors (amyloid beta [Aβ] and tau) and other co-factors have been identified as causes of AD, which may indicate some of the mechanism at work in the early stages of AD. Today, one of the primary techniques used to help delay or prevent AD in the early stages involves alleviating the unwanted effects of oxidative stress on Aβ clearance. 4-Hydroxynonenal (HNE), a product of lipid peroxidation caused by oxidative stress, plays a key role in the adduction of the degrading proteases. This HNE employs a mechanism which decreases catalytic activity. This process ultimately impairs Aβ clearance. The degradation of HNE-modified proteins helps to alleviate the unwanted effects of oxidative stress. Having a clear understanding of the mechanisms associated with the degradation of the HNE-modified proteins is essential for the development of strategies and for alleviating the unwanted effects of oxidative stress. The strategies which could be employed to decrease the effects of oxidative stress include enhancing antioxidant activity, as well as the use of nanozymes and/or specific inhibitors. One area which shows promise in reducing oxidative stress is protein design. However, more research is needed to improve the effectiveness and accuracy of this technique. This paper discusses the interplay of potential pathological factors and AD. In particular, it focuses on the effect of oxidative stress on the expression of the Aβ-degrading proteases through adduction of the degrading proteases caused by HNE. The paper also elucidates other strategies that can be used to alleviate the unwanted effects of oxidative stress on Aβ clearance. To improve the effectiveness and accuracy of protein design, we explain the application of quantum mechanical/molecular mechanical approach.
Eating disorders during lockdown: the transcultural influence on eating and mood disturbances in Ibero-Brazilian population
Authors: Baenas Isabel , Neufeld Carmem Beatriz , Ramos Rita , Munguía Lucero , Pessa Rosane P. , Rodrigues Tânia , Jiménez-Murcia Susana , Gonçalves Sónia , Teodoro Marília C. , Pinto-Bastos Ana , Almeida Nazaré O. , Granero Roser , Etxandi Mikel , Soares Shauana R. S. , Fernández-Aranda Fernando , Machado Paulo P. P. 
Published: March 2023

AbstractBackgroundCOVID-19 pandemic has implied exceptional restrictive measures to contain its widespread, with adverse consequences on mental health, especially for those people with a background of mental illness, such as eating disorders (EDs). In this population, the influence of socio-cultural aspects on mental health has been still underexplored. Then, the main aim of this study was to assess changes in eating and general psychopathology in people with EDs during lockdown regarding the ED subtype, age, and provenance, and considering socio-cultural aspects (e.g., socioeconomical factors such as work and financial losses, social support, restrictive measures, or health accessibility, among others).MethodsThe clinical sample was composed of 264 female participants with EDs (74 anorexia nervosa (AN), 44 bulimia nervosa (BN), 81 binge eating disorder (BED), and 65 other specified feeding and eating disorder (OSFED)), with a mean age of 33.49 years old (SD = 12.54), from specialized ED units in Brazil, Portugal, and Spain. The participants were evaluated using the COVID-19 Isolation Eating Scale (CIES).ResultsA global impairment in mood symptoms and emotion regulation was reported in all the ED subtypes, groups of age, and countries. Spanish and Portuguese individuals seemed more resilient than Brazilian ones (p < .05), who reported a more adverse socio-cultural context (i.e., physical health, socio-familial, occupational, and economic status) (p < .001). A global trend to eating symptoms worsening during lockdown was observed, regardless of the ED subtype, group of age, and country, but without reaching statistical significance. However, the AN and BED groups described the highest worsening of the eating habits during lockdown. Moreover, individuals with BED significantly increased their weight and body mass index, similarly to BN, and in contrast to the AN and OSFED groups. Finally, we failed to find significant differences between groups of age although the younger group described a significant worsening of the eating symptoms during lockdown.ConclusionsThis study reports a psychopathological impairment in patients with EDs during lockdown, being socio-cultural aspects potential modulatory factors. Individualized approaches to detect special vulnerable groups and long-term follow-ups are still needed.