bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activity-to-sedentary ratio provides novel insight into mortality reduction among male survivors of cardiovascular disease in the United States: national health and nutrition examination survey, 2007–2014
Authors: Ding Yuanyuan , Chen Jiahao , Niu Mengying , Xiao Qi , Zhao Hongqin , Pan Xudong , Zhu Xiaoyan 
Published: January 2023

Abstract
Background
Lower physical activity and sedentary behavior have been identified as modifiable risk factors for cardiovascular disease (CVD). However, the quantitative, dose-response association between activity-to-sedentary ratio (ASR) and mortality is unknown.

Methods
Prospective cohort studies with participants 50 to 80 years that reported the association between recreational physical activity, sedentary behavior, and all-cause mortality were included from the 2007 to 2014 United States National Health and Nutrition Examination Survey (NHANES) and followed through December 31, 2015. Cox or Weibull regression models and restricted cubic splines were used to determine the association between ASR and all-cause mortality.

Results
Sixty deaths occurred among 498 CVD survivors, with a median of 56 months of follow-up. After accounting for all covariates, CVD survivors with an ASR between 0.21 and 0.57 (hazard ratio [HR], 0.47; 95% confidence interval [CI], 0.25–0.87) and those with an ASR more than 0.57 (HR, 0.40; 95% CI, 0.20–0.81) were at significantly lower risk for mortality than participants with an ASR <  0.21. Moreover, a nonlinear negative association and an L-shaped association were observed for the level of ASR with risk of mortality among CVD survivors (P for nonlinearity = 0.004). What’s more, adjusting for covariates, a statistically significant interaction (P for interaction = 0.016) between sex and ASR, an increase of ASR more than and equal to 0.18 was associated with a lower risk of mortality among males (HR, 0.23; 95% CI, 0.12–0.46).

Conclusions
An negative correlation between ASR and mortality in CVD survivors, especially in males when ASR is more than 0.18. Our novel findings provide further insights into easing the global burden of deaths.
Alterations of SOCS1 and SOCS3 transcript levels, but not promoter methylation levels in subcutaneous adipose tissues in obese women
Authors: Emamgholipour Solaleh , Esmaeili Fataneh , Shabani Maryam , Hasanpour Seyedeh Zahra , Pilehvari Mahsa , Zabihi-Mahmoudabadi Hossein , Motevasseli Meysam , Shanaki Mehrnoosh 
Published: January 2023

Abstract
Background
Animal model studies suggest that change in the members of the suppressor of the cytokine signaling (SOCS) family (mainly SOCS1 and SOCS3) is linked to the pathogenesis of obesity-related metabolic disorders. Moreover, epigenetic modification is involved in the transcriptional regulation of the SOCS gene family. Here, we aimed to evaluate the mRNA expression as well as gene promoter methylation of SOCS1 and SOCS3 in subcutaneous adipose tissue (SAT) from obese women compared to normal-weight subjects. We also intend to identify the possible association of SOCS1 and SOCS3 transcript levels with metabolic parameters in the context of obesity.

Methods
This study was conducted on women with obesity (n = 24) [body mass index (BMI) ≥ 30 kg/m 2] and women with normal-weight (n = 22) (BMI < 25 kg/m 2). Transcript levels of SOCS1 and SOCS3 were evaluated by real-time PCR in SAT from all participants. After bisulfite treatment of DNA, methylation-specific PCR was used to assess the putative methylation of 10 CpG sites in the promoter of SOCS1 and 13 CpG sites in SOCS3 in SAT from women with obesity and normal weight.

Results
It was found that unlike SOCS3, which disclosed an elevating expression pattern, the expression level of SOCS1 was lower in the women with obesity as compared with their non‐obese counterparts (P-value = 0.03 for SOCS1 transcript level and P-value = 0.011 for SOCS3 transcript level). As for the analysis of promoter methylation, it was found that SOCS1 and SOCS3 methylation were not significantly different between the individuals with obesity and normal weight (P-value = 0.45 and P-value = 0.89). Correlation analysis indicated that the transcript level of SOCS1 mRNA expression had an inverse correlation with BMI, hs-CRP levels, HOMA-IR, and insulin levels. However, the SOCS3 transcript level showed a positive correlation with BMI, waist-to-height ratio, waist circumference, hip circumference, hs-CRP, HOMA-IR, insulin, fasting blood glucose, and total cholesterol. Interestingly, HOMA-IR is the predictor of the transcript level of SOCS1 (β =  − 0.448, P-value = 0.003) and SOCS3 (β = 0.465, P-value = 0.002) in SAT of all participants.

Conclusions
Our findings point to alterations of SOCS1 and SOCS3 transcript levels, but not promoter methylation levels in subcutaneous adipose tissues from women with obesity. Moreover, mRNA expression of SOCS1 and SOCS3 in SAT was associated with known obesity indices, insulin resistance, and hs-CRP, suggesting the contribution of SOCS1 and SOCS3 in the pathogenesis of obesity-related metabolic abnormalities. However, further studies are required to establish this concept.
Clinical practice guideline adaptation for risk-based caries management in 18–55 year-old Iranian adults
Authors: Pakdaman A. , Gholizadeh N. , Kharazifard M. J. , Eshrati M. 
Published: January 2023

Abstract
Purpose
To adapt an evidence-based clinical practice guideline (CPG) for risk-based management of caries in 18–55 year-old Iranian adults.

Methods
A multidisciplinary adaptation team reviewed evidence-based guidelines such as the NICE, SIGN, and ADA according to the defined clinical questions. In addition, databases such as the PubMed and Google Scholar were searched and CPGs were screened and appraised using the AGREE II (Appraisal of Guidelines for Research and Evaluation II) tool. Clinical scenarios were developed and their level of evidence, clinical advantage and adaptability were assessed. Following a two-round ranking by experts, the final recommendations were selected using the RAND-UCLA appropriateness method.

Results
Of 17 CPGs, 5 were selected as the source guidelines for adaptation. To assess the risk of caries in the adult population, reduced Cariogram (without saliva tests) and CAMBRA were suggested as diagnostic tools. In addition, 53 risk-based recommendations on the preventive care (including the use of fluoride toothpaste, fluoride, and chlorhexidine mouthwash, at home and in-office fluoride gel, fluoride varnish, mouth buffering, and sealant), operative intervention threshold, and follow-up interval were adapted for Iranian adults.

Conclusions
A guideline was adapted for risk-based management of dental caries in Iranian adults. This helps local dentists in decision making and promoting oral health of adults. Further research is needed to assess the external validity and feasibility of the adapted guideline in the Iranian population.
High porosity 3D printed titanium mesh allows better bone regeneration
Authors: Ma Rui , Liu Qian , Zhou Libo , Wang Lingxiao 
Published: January 2023

AbstractBackgroundMost patients with insufficient bone mass suffer from severe horizontal or vertical bone defects in oral implant surgery. The purpose of this study was to compare the bone regeneration effects of titanium meshes with different porosity in the treatment of bone defects.MethodsNine beagle dogs were equally divided into three groups based on execution time. Three months after the extraction of the first to fourth premolars of the mandible, three bone defects were randomly made in the mandible. Bone particles and three kinds of three-dimensional (3D) printed titanium nets with different porosities (low porosity group (LP), 55%; medium porosity group (MP), 62%; and high porosity group (HP), 68%) were replanted in situ. The beagles were killed 4, 8, and 12 weeks after surgery. Formalin-fixed specimens were embedded in acrylic resin. The specimens were stained with micro-CT, basic fuchsin staining, and toluidine blue staining.ResultsMicro-CT analysis showed that the trabecular thickness, trabecular number, and bone volume fraction of the HP group were higher than those of the other two groups. Moreover, the trabecular separation of the HP group decreased slightly and was lower than that of the MP and LP groups. Histological staining analysis showed that the trabecular number in the HP group was higher than in the other two groups at 8 and 12 weeks, and the bone volume fraction of the HP was higher than that in the other two groups at 12 weeks. Moreover, the trabecular thickness of the MP was higher than that of the LP group at 12 weeks and the trabecular separation was lower in the HP group at 4 and 8 weeks. The differences were statistically significant (p < 0.05).ConclusionA 3D printed titanium mesh with HP in a certain range may have more advantages than a titanium mesh with LP in repairing large bone defects.
Predicting decompression surgery by applying multimodal deep learning to patients’ structured and unstructured health data
Authors: Jujjavarapu Chethan , Suri Pradeep , Pejaver Vikas , Friedly Janna , Gold Laura S. , Meier Eric , Cohen Trevor , Mooney Sean D. , Heagerty Patrick J. , Jarvik Jeffrey G. 
Published: January 2023

AbstractBackgroundLow back pain (LBP) is a common condition made up of a variety of anatomic and clinical subtypes. Lumbar disc herniation (LDH) and lumbar spinal stenosis (LSS) are two subtypes highly associated with LBP. Patients with LDH/LSS are often started with non-surgical treatments and if those are not effective then go on to have decompression surgery. However, recommendation of surgery is complicated as the outcome may depend on the patient’s health characteristics. We developed a deep learning (DL) model to predict decompression surgery for patients with LDH/LSS.Materials and methodWe used datasets of 8387 and 8620 patients from a prospective study that collected data from four healthcare systems to predict early (within 2 months) and late surgery (within 12 months after a 2 month gap), respectively. We developed a DL model to use patients’ demographics, diagnosis and procedure codes, drug names, and diagnostic imaging reports to predict surgery. For each prediction task, we evaluated the model’s performance using classical and generalizability evaluation. For classical evaluation, we split the data into training (80%) and testing (20%). For generalizability evaluation, we split the data based on the healthcare system. We used the area under the curve (AUC) to assess performance for each evaluation. We compared results to a benchmark model (i.e. LASSO logistic regression).ResultsFor classical performance, the DL model outperformed the benchmark model for early surgery with an AUC of 0.725 compared to 0.597. For late surgery, the DL model outperformed the benchmark model with an AUC of 0.655 compared to 0.635. For generalizability performance, the DL model outperformed the benchmark model for early surgery. For late surgery, the benchmark model outperformed the DL model.ConclusionsFor early surgery, the DL model was preferred for classical and generalizability evaluation. However, for late surgery, the benchmark and DL model had comparable performance. Depending on the prediction task, the balance of performance may shift between DL and a conventional ML method. As a result, thorough assessment is needed to quantify the value of DL, a relatively computationally expensive, time-consuming and less interpretable method.
Applying value-based strategies to accelerate access to novel cancer medications: guidance from the Oncology Health Economics Expert Panel in Qatar (Q-OHEP)
Authors: Hamad Anas , Elazzazy Shereen , Bujassoum Salha , Rasul Kakil , Gaziev Javid , Cherif Honar , Al-Boloshi Zakiya , Hanssens Yolande , Saleh Ayman , Rasheed Hadi Abu , Al-Badriyeh Daoud , Babiker Ahmed , Hmaidan Amid Abu , Al-Hail Moza 
Published: January 2023

Abstract
Background
In line with global trends, cancer incidence and mortality may have decreased for specific types of cancer in Qatar. However, the cancer-related burden on patients, healthcare systems, and the economy is expected to expand; thus, cancer remains a significant public healthcare issue in Qatar. Qatar’s free access to cancer care represents a considerable economic burden. Ensuring the best utilization of financial resources in the healthcare sector is important to provide unified and fair access to cancer care for all patients. Experts from the Qatar Oncology Health Economics Expert Panel (Q-OHEP) aimed to establish a consistent and robust base for evaluating oncology/hematology medications; involve patients’ insights to accelerate access to cutting-edge medications; increase the value of cancer care; and reach a consensus for using cost-effective strategies and efficient methodologies in cancer treatment.

Methods
The Q-OHEP convened on 30 November 2021 for a 3-hour meeting to discuss cancer management, therapeutics, and health economics in Qatar, focusing on four domains: (1) regulatory, (2) procurement, (3) treatment, and (4) patients. Discussions, guided by a moderator, focused on a list of suggested open-ended questions.

Results
Some of the salient recommendations included the development of a formal, fast-track, preliminary approval pathway for drugs needed by patients with severe disease or in critical condition; and encouraging and promoting the conduct of local clinical trials and real-world observational studies using existing registry data. The Q-OHEP also recommended implementing a forecast system using treatment center data based on the supply/demand of formulary oncology drugs to detect treatment patterns, estimate needs, expedite procurement, and prevent shortages/delays. Furthermore, the panel discussed the needs to define value concerning cancer treatment in Qatar, implement value-based models for reimbursement decision-making such as health technology assessment and multiple-criteria decision analysis, and promote patient education and involvement/feedback in developing and implementing cancer management guidelines.

Conclusion
Herein, we summarize the first Q-OHEP consensus recommendations, which aim to provide a solid basis for evaluating, registering, and approving new cancer medications to accelerate patient access to novel cancer treatments in Qatar; promote/facilitate the adoption and collection of patient-reported outcomes; and implement value-based cancer care in Qatar.
Nonribosomal antibacterial peptides isolated from Streptomyces agglomeratus 5-1-3 in the Qinghai-Tibet Plateau
Authors: Jiang Kan , Chen Ximing , Zhang Wei , Guo Yehong , Liu Guangxiu 
Published: January 2023

Abstract
Background
New antibiotics are urgently needed in clinical treatment of superdrug-resistant bacteria. Nonribosomal peptides (NRPs) are a major source of antibiotics because they exhibit structural diversity, and unique antibacterial mechanisms and resistance. Analysis of gene clusters of S. agglomeratus 5-1-3 showed that Clusters 3, 6, 12, 21, and 28 were used to synthesize NRPs. Here, we examined secondary metabolites of S. agglomeratus 5-1-3 isolated from soils in the Qinghai-Tibet Plateau, China, for NRPs with antibacterial activity.

Results
We isolated a total of 36 Streptomyces strains with distinct colony morphological characteristics from 7 soil samples. We screened 8 Streptomyces strains resistant to methicillin-resistant Staphylococcus aureus (MRSA). We then selected S. agglomeratus 5-1-3 for further study based on results of an antibacterial activity test. Here, we isolated three compounds from S. agglomeratus 5-1-3 and characterized their properties. The crude extract was extracted with ethyl acetate and purified with column chromatography and semipreparative high-performance liquid chromatography (HPLC). We characterized the three compounds using NMR analyses as echinomycin (1), 5,7,4ʹ-trihydroxy-3.3′,5′-trimethoxy flavone (2), and 2,6,2′, 6′-tetramethoxy-4,4-bis(2,3-epoxy-1-hydroxypropyl)-biphenyl (3). We tested the antibacterial activity of pure compounds from strain 5-1-3 with the Oxford cup method. NRP echinomycin (1) showed excellent anti-MRSA activity with a minimum inhibitory concentration (MIC) of 2.0 μg/mL. Meanwhile, MIC of compound 2 and 3 was 128.0 μg/mL for both. In addition, 203 mg of echinomycin was isolated from 10 L of the crude extract broth of strain 5-1-3.

Conclusion
In this study, S. agglomeratus 5-1-3 with strong resistance to MRSA was isolated from the soils in the Qinghai-Tibet Plateau. Strain 5-1-3 had a high yield of echinomycin (1) an NRP with a MIC of 2 μg/mL against MRSA. We propose that echinomycin derived from S. agglomeratus 5-1-3 may be a potent antibacterial agent for pharmaceutical use.
Treatment escalation patterns to start biologics in refractory moderate juvenile dermatomyositis among members of the Childhood Arthritis and Rheumatology Research Alliance
Authors: Sherman Matthew A. , Kim Hanna , Banschbach Katelyn , Brown Amanda , Gewanter Harry L. , Lang Bianca , Perron Megan , Robinson Angela Byun , Spitznagle Jacob , Stingl Cory , Syverson Grant , Tory Heather O. , Spencer Charles H. , Tarvin Stacey E. 
Published: January 2023

AbstractBackgroundDespite new and better treatments for juvenile dermatomyositis (JDM), not all patients with moderate severity disease respond adequately to first-line therapy. Those with refractory disease remain at higher risk for disease and glucocorticoid-related complications. Biologic disease-modifying antirheumatic drugs (DMARDs) have become part of the arsenal of treatments for JDM. However, prospective comparative studies of commonly used biologics are lacking.MethodsThe Childhood Arthritis and Rheumatology Research Alliance (CARRA) JDM biologics workgroup met in 2019 and produced a survey assessing current treatment escalation practices for JDM, including preferences regarding use of biologic treatments. The cases and questions were developed using a consensus framework, requiring 80% agreement for consensus. The survey was completed online in 2020 by CARRA members interested in JDM. Survey results were analyzed among all respondents and according to years of experience. Chi-square or Fisher’s exact test was used to compare the distribution of responses to each survey question.ResultsOne hundred twenty-one CARRA members responded to the survey (denominators vary for each question). Of the respondents, 88% were pediatric rheumatologists, 85% practiced in the United States, and 43% had over 10 years of experience. For a patient with moderately severe JDM refractory to methotrexate, glucocorticoids, and IVIG, approximately 80% of respondents indicated that they would initiate a biologic after failing 1–2 non-biologic DMARDs. Trials of methotrexate and mycophenolate were considered necessary by 96% and 60% of respondents, respectively, before initiating a biologic. By weighed average, rituximab was the preferred biologic over abatacept, tocilizumab, and infliximab. Over 50% of respondents would start a biologic by 4 months from diagnosis for patients with refractory moderately severe JDM. There were no notable differences in treatment practices between respondents by years of experience.ConclusionMost respondents favored starting a biologic earlier in disease course after trialing up to two conventional DMARDs, specifically including methotrexate. There was a clear preference for rituximab. However, there remains a dearth of prospective data comparing biologics in refractory JDM. These findings underscore the need for biologic consensus treatment plans (CTPs) for refractory JDM, which will ultimately facilitate comparative effectiveness studies and inform treatment practices.
Protein kinase B (AKT) upregulation and Thy-1-αvβ3 integrin-induced phosphorylation of Connexin43 by activated AKT in astrogliosis
Authors: Pérez-Núñez Ramón , Chamorro Alejandro , González María Fernanda , Contreras Pamela , Artigas Rocío , Corvalán Alejandro H. , van Zundert Brigitte , Reyes Christopher , Moya Pablo R. , Avalos Ana María , Schneider Pascal , Quest Andrew F. G. , Leyton Lisette 
Published: January 2023

Abstract
Background
In response to brain injury or inflammation, astrocytes undergo hypertrophy, proliferate, and migrate to the damaged zone. These changes, collectively known as "astrogliosis", initially protect the brain; however, astrogliosis can also cause neuronal dysfunction. Additionally, these astrocytes undergo intracellular changes involving alterations in the expression and localization of many proteins, including αvβ3 integrin. Our previous reports indicate that Thy-1, a neuronal glycoprotein, binds to this integrin inducing Connexin43 (Cx43) hemichannel (HC) opening, ATP release, and astrocyte migration. Despite such insight, important links and molecular events leading to astrogliosis remain to be defined.

Methods
Using bioinformatics approaches, we analyzed different Gene Expression Omnibus datasets to identify changes occurring in reactive astrocytes as compared to astrocytes from the normal mouse brain. In silico analysis was validated by both qRT-PCR and immunoblotting using reactive astrocyte cultures from the normal rat brain treated with TNF and from the brain of a hSOD1G93A transgenic mouse model. We evaluated the phosphorylation of Cx43 serine residue 373 (S373) by AKT and ATP release as a functional assay for HC opening. In vivo experiments were also performed with an AKT inhibitor (AKTi).

Results
The bioinformatics analysis revealed that genes of the PI3K/AKT signaling pathway were among the most significantly altered in reactive astrocytes. mRNA and protein levels of PI3K, AKT, as well as Cx43, were elevated in reactive astrocytes from normal rats and from hSOD1G93A transgenic mice, as compared to controls. In vitro, reactive astrocytes stimulated with Thy-1 responded by activating AKT, which phosphorylated S373Cx43. Increased pS373Cx43 augmented the release of ATP to the extracellular medium and AKTi inhibited these Thy-1-induced responses. Furthermore, in an in vivo model of inflammation (brain damage), AKTi decreased the levels of astrocyte reactivity markers and S373Cx43 phosphorylation.

Conclusions
Here, we identify changes in the PI3K/AKT molecular signaling network and show how they participate in astrogliosis by regulating the HC protein Cx43. Moreover, because HC opening and ATP release are important in astrocyte reactivity, the phosphorylation of Cx43 by AKT and the associated increase in ATP release identify a potential therapeutic window of opportunity to limit the adverse effects of astrogliosis.