bluuebunny/crossref_metadata_2025 huggingface dataset:
Large gap between attitude and action in tuberculosis preventive treatment among tuberculosis-related healthcare workers in eastern China
Authors: Wang Fei , Ren Yanli , Liu Kui , Peng Ying , Chen Xinyi , Chen Bin , Jiang Jianmin
Published: October 2022

Healthcare workers (HCWs) are at a high risk for latent tuberculosis infection (LTBI) because of occupational exposure, and the attitudes and behaviors of frontline tuberculosis (TB)-related HCWs toward preventive treatment of LTBI in eastern China remain unknown. This study aimed to explore the attitudes and actual behaviors of TB-related HCWs toward TB preventive treatment (TPT) and to analyze the relevant factors influencing the attitudes of HCWs. A stratified random sample of 28 TB-designated hospitals was selected in Zhejiang Province, China. All TB-related HCWs in the selected hospitals were recruited to answer questionnaires and were tested for LTBI by the TB interferon gamma release assay. TPT use was assessed two years after the survey. Univariate analysis and binary logistic regression models were used to analyze the factors influencing the TPT intention of HCWs. A total of 318 TB-related HCWs were recruited from 28 TB-designated hospitals; 62.3% of them showed positive attitudes toward TPT, while the rest were reluctant to treat positive LTBI prophylactically. binary logistic regression analysis revealed that the factors influencing the attitudes of HCWs were mainly education level, household income, history of alcohol consumption, and workplace. The IGRA test found that 35.2% (112/318) of HCWs tested positive for LTBI. Most people refused treatment because of drug side effects, followed by the belief that treatment was ineffective, wanting to wait until the onset of the disease, and that it was too much trouble to take the medication. According to the results of a follow-up survey, only one of these HCWs underwent TPT, and the consistency rate of attitudes and behaviors was 36.6% (41/112). This study reveals different attitudes toward TPT among TB-associated HCWs in eastern China and a large gap between attitudes and actual action. The management of HCWs with LTBI still needs further strengthening.
Assessment of absolute risk of life-threatening cardiac events in long QT syndrome patients
Authors: Wang Meng , Peterson Derick R. , Pagan Eleonora , Bagnardi Vincenzo , Mazzanti Andrea , McNitt Scott , Rich David Q. , Seplaki Christopher L. , Kutyifa Valentina , Polonsky Bronislava , Barsheshet Alon , Kukavica Deni , Rosero Spencer , Goldenberg Ilan , Priori Silvia , Zareba Wojciech
Published: October 2022

Background

Risk stratification in long QT syndrome (LQTS) patients is important for optimizing patient care and informing clinical decision making. We developed a risk prediction algorithm with prediction of 5-year absolute risk of the first life-threatening arrhythmic event [defined as aborted cardiac arrest, sudden cardiac death, or appropriate implantable cardioverter defibrillator (ICD) shock] in LQTS patients, accounting for individual risk factors and their changes over time.

Methods

Rochester-based LQTS Registry included the phenotypic cohort consisting of 1,509 LQTS patients with a QTc ≥ 470 ms, and the genotypic cohort including 1,288 patients with single LQT1, LQT2, or LQT3 mutation. We developed two separate risk prediction models which included pre-specified time-dependent covariates of beta-blocker use, syncope (never, syncope while off beta blockers, and syncope while on beta blockers), and sex by age < and ≥13 years, baseline QTc, and genotype (for the genotypic cohort only). Follow-up started from enrollment in the registry and was censored at patients’ 50s birthday, date of death due to reasons other than sudden cardiac death, or last contact, whichever occurred first. The predictive models were externally validated in an independent cohort of 1,481 LQTS patients from Pavia, Italy.

Results

In Rochester dataset, there were 77 endpoints in the phenotypic cohort during a median follow-up of 9.0 years, and 47 endpoints in the genotypic cohort during a median follow-up of 9.8 years. The time-dependent extension of Harrell’s generalized C-statistics for the phenotypic model and genotypic model were 0.784 (95% CI: 0.740–0.827) and 0.785 (95% CI: 0.721–0.849), respectively, in the Rochester cohort. The C-statistics obtained from external validation in the Pavia cohort were 0.700 (95% CI: 0.610–0.790) and 0.711 (95% CI: 0.631–0.792) for the two models, respectively. Based on the above models, an online risk calculator estimating a 5-year risk of life-threatening arrhythmic events was developed.

Conclusion

This study developed two risk prediction algorithms for phenotype and genotype positive LQTS patients separately. The estimated 5-year absolute risk can be used to quantify a LQTS patient’s risk of developing life-threatening arrhythmic events and thus assisting in clinical decision making regarding prophylactic ICD therapy.
Sustainability assessment of coupled human and natural systems from the perspective of the supply and demand of ecosystem services
Authors: Liu Haimeng , Xing Lu , Wang Chengxin , Zhang Haiyan
Published: October 2022

The sustainability of coupled human and natural systems (CHANS), linked to several of the United Nation’s Sustainable Development Goals, affects both global sustainable development and human wellbeing. However, few studies have explored the relationship between the whole human system and the natural system from the perspective of supply and demand. Based on ecosystem service concept and Maslow’s hierarchy of needs, we constructed an ecosystem services supply index (ESSI) and a human demand index (HMDI) and then analyzed the spatial mismatch of the ESSI and HMDI in 338 prefecture cities in China. We propose a supply-demand balance index inspired by the doughnut theory and demonstrate the conflicts and synergies between ecosystems and human systems. Our results show that the ESSI decreased from 2000 to 2010, but remained almost unchanged from 2010 to 2020. The low ESSI values were mainly distributed over the North China Plain, the Yangtze River Delta, and the Sichuan Basin. The HMDI increased from 2000 to 2020, but the rate of increase has slowed since 2010. The high HMDI values were mainly distributed over the east coast of China, Inner Mongolia, and part of Xinjiang province. From 2000 to 2020, the cities with spatial mismatches of the ESSI and HMDI showed a significant increase and spatial agglomeration. The sustainability of most regions showed a decreasing trend, and the higher the value of the supply-demand balance index, the faster the speed of decrease. Overall, there were more regions in a state of conflict between the natural ecosystem and humans than in a synergistic state, although this number has decreased since 2010. Urban agglomerations and western regions should receive more attention for their ecological health. This study provides a new methodology to assess the sustainability of CHANS that could be applied to other locations. Our findings could support the Chinese government in regional ecosystem governance and territorial space planning.
Obesity in adolescents may be associated with limitations in daily activities and an increased level of anxiety in patients and their parents – preliminary results of a pilot study
Authors: Wójcik Małgorzata , Goncerz Dawid , Piasny Marta , Surówka Anna , Mazurek Edyta , Drożdż Dorota , Kozioł-Kozakowska Agnieszka , Starzyk Jerzy B. , Makara-Studzińska Marta
Published: October 2022

Obesity is a chronic disease, that in adolescents may lead to serious consequences affecting somatic and mental health. This study aimed to assess the prevalence of depressive symptoms and anxiety in adolescents with obesity and their parents. The relationships between depressive and anxiety symptoms and the somatic consequences of obesity were also analyzed. 

Material and Methods

19 patients with obesity (BMI Z-SCORE 2.1-5.5), at the age 16-17, and their parents answered validated questionnaires (Children’s Depression Inventory 2, The State-Trait Anxiety Inventory), and a survey assessing everyday functioning. 

Results

There were no significant differences in the occurrence of symptoms of depression in children and their parents: for the overall scale score of T-score (p=0.331), for the emotional problems (p=0.281) subscale, and the functional problems (p=0.147) subscale. The comparison of the results between boys and girls revealed no significant differences. A significantly higher level of anxiety was found in parents of children who gained weight in the year preceding the study (p = 0.046), and both in children and parents of children with metabolic-associated fatty liver disease – MAFLD (p=0.022 and p=0.007). According to adolescents, obesity affects the most leisure activities.

Conclusion

Obesity, like any chronic disease, can have a significant impact on the emotional state of children and adolescents as well as the possibility of realizing interests and spending free time. Much more important than depressive disorders are anxiety disorders concerning both patients and their parents.
Identification of compositional and structural changes in the nucleus pulposus of patients with cervical disc herniation by Raman spectroscopy
Authors: Wang Zhiqi , Xue Tao , Zhang Tongxing , Wang Xuehui , Zhang Hui , Gao Zhongyu , Zhou Qiang , Gao Erke , Zhang Tao , Li Zhaoyang
Published: October 2022

Purpose

Cervical disc herniation (CDH) is one of the most common spinal diseases in modern society; intervertebral disc degeneration (IVDD) has long been considered as its primary cause. However, the mechanism of intervertebral disc degeneration is still unclear. The aim of the study is to examine the components and structures of proteoglycan and collagen in cervical disc herniated nucleus pulposus (NP) using a validated and convenient Raman spectra technique and histological methods to further elucidate the mechanism of IVDD at the microscopic level.

Methods

Our study used a burgeoning technique of Raman spectroscopy combined with in vitro intervertebral disc NP to characterize the above mentioned research purposes. Firstly, we collected cervical disc NP samples and imaging data by certain inclusion and exclusion criteria. Then, we graded the NP of the responsible segment according to the patient’s preoperative cervical magnetic resonance imaging (MRI) T2-weighted images by Pfirrmann grading criteria while measuring the T2 signal intensity value of NP. In addition, the structure of the NP samples was evaluated by histological staining (H&E staining and Safranin-O staining). Finally, the samples were scanned and analyzed by Raman spectroscopy.

Results

A total of 28 NP tissues from 26 patients (two of these patients were cases that involved two segments) with CDH were included in this study. According to the Raman spectroscopy scan, the relative content of proteoglycans which is characterized by the ratio of the two peaks (I1,064/I1,004) in the NP showed a significantly negative correlation with Pfirrmann grade (P < 0.001), while the collagen content and the NP intensity value showed a positive correlation (P < 0.001). For the microstructural characterization of collagen, we found that it may have an essential role in the degenerative process of the intervertebral disc. Moreover, histological staining (H&E staining and Safranin-O staining) showed the general structure of the NP and the distribution of macromolecules.

Conclusion

The present study demonstrated the possibility of characterizing the macromolecular substances inside the cervical disc NP tissue by Raman spectroscopy. It also confirmed that macromolecular substances such as proteoglycans and collagen have some degree of alteration in content and structure during degeneration, which has a further positive significance for the elucidation of CDH’s mechanism.
Preoperative prognostic risk stratification model for papillary thyroid carcinoma based on clinical and ultrasound characteristics
Authors: Shen Keyu , Xiao Siqi , Wu Xianji , Zhang Guang
Published: October 2022

Background

The preoperative risk stratification for patients with papillary thyroid carcinoma (PTC) plays a crucial role in guiding individualized treatment. We aim to construct a predictive model that aids in distinguishing between patients with low-risk and high-risk PTC based on preoperative clinical and ultrasound characteristics.

Materials and methods

Patients who underwent open surgery and were diagnosed with PTC via a postoperative pathological report between January 2020 and December 2020 were retrospectively reviewed. Data including basic information, preoperative ultrasound characteristics, thyroid function, and postoperative pathology characteristics were obtained. Univariate logistic regression analysis and least absolute shrinkage and selection operator regression analysis were performed to screen candidate variables. Finally, the preoperative predictive model for PTC was established based on the results of the multivariate logistic regression analysis.

Results

A total of 1,875 patients with PTC were enrolled. Eight variables (sex, age, number of foci, maximum tumor diameter on ultrasound, calcification, capsule, lymph node status on ultrasound, and thyroid peroxidase (TPO) antibody level) significantly associated with risk stratification were included in the predictive model. A nomogram was constructed for clinical utility. The model showed good discrimination, and the area under the curve was 0.777 [95% confidence interval (CI): 0.752–0.803] and 0.769 (95% CI: 0.729–0.809) in the training set and validation set, respectively. The calibration curve exhibited a rather good consistency with the perfect prediction. Furthermore, decision curve analysis and clinical impact curve showed that the model had good efficacy in predicting the prognostic risk of PTC.

Conclusions

The nomogram model based on preoperative indicators for predicting the prognostic stratification of PTC showed a good predictive value. This could aid surgeons in deciding on individualized precision treatments.
Lower bile acids as an independent risk factor for renal outcomes in patients with type 2 diabetes mellitus and biopsy-proven diabetic kidney disease
Authors: Xiao Xiang , Zhang Junlin , Ji Shuming , Qin Chunmei , Wu Yucheng , Zou Yutong , Yang Jia , Zhao Yuancheng , Yang Qin , Liu Fang
Published: October 2022

Aims

Abnormalities of glucolipid metabolism are critical mechanisms involved in the progression of diabetic kidney disease (DKD). Bile acids have an essential role in regulating glucolipid metabolism. This study investigated the clinicopathological characteristics of DKD patients with different bile acid levels and explored the relationship between bile acids and renal outcomes of DKD patients.

Methods

We retrospectively reviewed and evaluated the histopathological features and clinical features of our cohort of 184 patients with type 2 diabetes mellitus and biopsy-proven DKD. Patients were divided into the lower bile acids group (≤2.8 mmol/L) and higher bile acids group (>2.8 mmol/L) based on the cutoff value of bile acids obtained using the time-dependent receiver-operating characteristic curve. Renal outcomes were defined as end-stage renal disease (ESRD). The influence of bile acids on renal outcomes and correlations between bile acids and clinicopathological indicators were evaluated.

Results

Bile acids were positively correlated with age (r = 0.152; P = 0.040) and serum albumin (r = 0.148; P = 0.045) and negatively correlated with total cholesterol (r = -0.151; P = 0.041) and glomerular class (r = -0.164; P =0.027). During follow-up, 64 of 184 patients (34.78%) experienced progression to ESRD. Lower levels of proteinuria, serum albumin, and bile acids were independently associated with an increased risk of ESRD (hazard ratio, R=5.319; 95% confidence interval, 1.208–23.425).

Conclusions

Bile acids are an independent risk factor for adverse renal outcomes of DKD patients. The serum level of bile acids should be maintained at more than 2.8 mmol/L in DKD patients. Bile acid analogs or their downstream signaling pathway agonists may offer a promising strategy for treating DKD.
Association between body fat distribution and kidney stones: Evidence from a US population
Authors: Li Guoxiang , Liang Hu , Hao Yunwu , Huang Qingfeng , Shen Xudong , Chen Yang , Chen Mingwei , Xi Junhua , Hao Zongyao
Published: October 2022

Objectives

We aimed to evaluate the relationship between the proportion of Android to Gynoid ratio and the incidence of kidney stones among US adults.

Methods

Participants aged 20-59 years from the 2011-2018 National Health and Nutrition Examination Survey (NHANES) database were selected to assess the association between Android to Gynoid ratio and kidney stone prevalence using logistic regression analysis, subgroup analysis and calculation of dose-response curves.

Results

This study ultimately included 10858 participants, of whom 859 self-reported a history of kidney stones. And after adjusting for all confounders, an increased Android to Gynoid ratio was associated with an increased prevalence of kidney stones (OR=2.75, 95% CI:1.62-4.88). And subgroup analysis showed an increased prevalence of kidney stones in women (OR=3.55, 95% CI: 1.54-8.22), non-diabetic (OR=2.59, 95% CI: 1.45-4.60), 60 > age ≥ 40 years (OR=3.51, 95% CI: 1.83-6.71), Mexican-American (OR=4.35, 95% CI: 1.40- 13.53) and white (OR=3.86, 95% CI: 1.82-8.18) groups, there was a significant positive association between A/G ratio and kidney stones. In contrast, in the hypertensive subgroup, the A/G ratio was associated with kidney stones in all groups.

Conclusions

Higher Android to Gynoid ratio is associated with a high prevalence of kidney stone disease.
Are the determinants of the progression to type 2 diabetes and regression to normoglycemia in the populations with pre-diabetes the same?
Authors: Alizadeh Zeinab , Baradaran Hamid Reza , Kohansal Karim , Hadaegh Farzad , Azizi Fereidoun , Khalili Davood
Published: October 2022

Background

We aimed to determine the predictors of regression to normoglycemia and progression to diabetes among subjects with pre-diabetes in a single model concurrently.

Methods

The present study included 1329 participants aged 20 to 70 years with prediabetes from the population-based cohort of the Tehran Lipid and Glucose Study, with a 10-year follow-up. Glycemic status at follow-up was categorized as regression to normoglycemia: fasting plasma glucose [FPG] of <5.55 and 2h-plasma glucose [PG] of <7.77 mmol/L, and not taking antidiabetic medications. Glycemic status at follow-up was categorized as progression to diabetes: FPG ≥7 or 2h-PG of ≥11.1 mmol/L, or taking antidiabetic medications. Glycemic status determined whether the patients remained in prediabetes category (isolated impaired fasting glycaemia [iIFG] [(5.55≤FPG<7 and 2h-PG<7.77 mmol/L); isolated impared glucose tolarence [iIGT] (7.77 ≤ 2h-PG<11.1 and FGP<5.55 mmol/L)]. With prediabetes as a reference, multinomial logistic regression was utilized to identify the determinants of glycemic changes.

Results

Approximately 40% of participants returned to normoglycemia (n = 578), and similar percentage of participants progressed to diabetes (n = 518). Based on the multivariable multinomial model, regression to normoglycemia was associated with age (relative risk ratio [RRR] = 0.97; 95% CI, 0.95-0.99), female sex (RRR = 1.72; 95% CI, 1.18-2.50), high education level of ≥12 years (RRR = 2.10; 95% CI, 1.19-3.70), and combined IFG/impaired glucose tolerance (IGT) versus IFG (RRR = 0.45; 95% CI, 0.29-0.70). The risk of progression to diabetes increased with body mass index (RRR = 1.10; 95% CI, 1.05-1.15), waist circumference (RRR = 0.97; 95% CI, 0.96-0.99), positive familial history of diabetes (RRR = 1.62; 95% CI, 1.07-2.45), and combined IFG/IGT versus IFG (RRR = 2.54; 95% CI, 1.71-3.77).

Conclusion

A small percentage of patients with prediabetes remain in this condition, but the majority go on to develop diabetes or regress to normoglycemia. Both directions had distinct predictors.
Gestational diabetes is associated with alteration on pelvic floor muscle activation pattern during pregnancy and postpartum: Prospective cohort using electromyography assessment
Authors: Prudencio Caroline Baldini , Nunes Sthefanie Kenickel , Pinheiro Fabiane Affonso , Sartorão Filho Carlos Izaias , Nava Guilherme Thomaz de Aquino , Salomoni Sauro Emerick , Pedroni Cristiane Rodrigues , Rudge Marilza Vieira Cunha , Barbosa Angélica Mércia Pascon ,   Diamater Study Group
Published: October 2022

Background and objective

Gestational diabetes mellitus (GDM) is a comorbidity which may cause acute and lifelong disorders to mother and child. Alterations in muscular and connective tissues have been associated with GDM in translation studies, characterizing gestational diabetic myopathy. Pregnancy-specific urinary incontinence and sexual disabilities, disorders that depend on the pelvic floor muscle (PFM) integrity, are also associated with GDM both during and after pregnancy. The aim was to compare PFM activation patterns between GDM and non-GDM women from 24–30 gestational weeks to 18–24 months postpartum during a standard clinical test during gestation and postpartum.

Methods

We conducted a prospective three-time-point cohort study from gestation (24–30 weeks—T1, and 36–38 weeks—T2) to 18–24 months postpartum (T3). PFM electromyography was recorded in primigravida or primiparous women with one previous elective c-section with or without the diagnosis of GDM according to the American Diabetes Association criteria. A careful explanation of the muscle anatomy and functionality of the PFM was given to participants before EMG assessment. The outcome measures were PFM activation patterns assessed during pregnancy and postpartum, comparing intra and between groups. PFM activation patterns were assessed by normalized electromyography signal at rest and during 1-second (sec) phasic, 10-sec hold, and 60-sec sustained contractions.

Results

Demographic and obstetric data showed homogeneity between groups. The GDM group achieved peak PFM EMG amplitudes similarly to the non-GDM group, but they took longer to return to baseline levels during the ~1-sec contraction (flicks). During 10-sec hold contractions, the GDM group sustained lower levels of PFM activation than the non-GDM group at both 36–38 weeks of gestation and 18–24 months postpartum when compared to the non-GDM group.

Conclusion

The results suggest that GDM impaired PFM control mainly on 1-sec flicks and 10-sec hold contraction, which appears to develop during late pregnancy and extends long-term postpartum. This motor behavior may play a role on pelvic floor dysfunctions.
Impact of admission and early persistent stress hyperglycaemia on clinical outcomes in acute pancreatitis
Authors: Yang Xinmin , Shi Na , Yao Linbo , He Wenhua , Zhu Ping , Li Sheyu , Li Lan , Li Yuying , Liu Shiyu , Deng Lihui , Jin Tao , Liu Tingting , Lu Nonghua , Windsor John A. , Sutton Robert , Zhu Yin , Xia Qing , Huang Wei
Published: October 2022

Background

To determine the impact of glucose levels at admission and during first week (early phase) on clinical outcomes in patients with acute pancreatitis (AP) and to investigate the relationship between stress hyperglycaemia (SHG) and hypertriglyceridaemia (HTG).

Methods

Two independent and prospective databases were retrospectively analysed (n = 1792). Patients admitted with pain of less than 48 hours and confirmed AP were included. SHG was defined as admission blood glucose ≥ 10.00 mmol/L (non-diabetic) or ≥ 16.67 mmol/L (diabetic). Blood glucose records for the first week were inspected to determine whether SHG lasted ≥ 48 hours (persistent) or < 48 hours (transient). Clinical outcomes were compared between designated patient groups using multivariate and trend analyses. The correlation between SHG and HTG (serum triglyceride ≥ 5.65 mmol/L) was also analysed.

Results

On admission, SHG was present in 27.8% (499/1792) patients; during the first 48 hours of admission, transient and persistent SHG was found in 31% (556/1792) and 8.0% (144/1792) patients, respectively. Admission SHG was associated with higher incidence of persistent organ failure, acute necrotic collection, major infection, and mortality as well as prolonged length of hospital stay (all P < 0.05). Duration of SHG was also associated with worsened clinical outcomes (all P < 0.05). In HTG-AP patients, more severe clinical outcomes were observed in those who concomitantly had SHG (P < 0.05).

Conclusions

Admission and persistent SHG during the first week of admission worsens clinical outcomes of AP patients. These effects are more pronounced when admission HTG co-existed.
Study on coupling coordination of the human settlement environment and tourism industry in the yellow river basin
Authors: Yu Xiao , Chen Hanxue
Published: October 2022

The human settlement environment is the basic space where people live, produce and live. The tourism industry is one of the industries closest to the development goal of the human settlement environment. The coordinated development of the human settlement environment and the tourism industry provides vital support for high-quality sustainable development in the region, but the related research is relatively insufficient. Based on the panel data from 2010 to 2019, this study takes the Yellow Basin as the research object, using comprehensive evaluation, coupling degree, and coupling coordination models. The study aims to comprehensively measure the development level of the human settlement environment and tourism industry in nine provinces of the Yellow River Basin and analyzes the spatio-temporal differentiation characteristics of the coupling coordination between the human settlement environment and tourism industry in the Yellow River Basin. The results demonstrate an interactive coupling relationship between the human settlement environment and the tourism industry. We observe an upward fluctuation in the development level of the two systems in the Yellow River Basin and converging development trends between the two; however, the tourism industry in the region is far behind in driving the construction of the human settlement environment. Regarding the spatial and temporal evolution of the coupling coordination of the two systems, in the time dimension, the coupling degree of the nine provinces in the Yellow River Basin was relatively stable from 2010 to 2019 and maintained a high level. The coupling coordination degree was on the rise, evolving from near-disorder to elementary coordination. The two systems in the Basin still showed a pattern of “high coupling-low coordination.” Nevertheless, in the spatial dimension, the coupling and coupling coordination degrees of the two systems in the Yellow River Basin showed an unbalanced development pattern of “high in the southeast and low in the northwest.” The regions with a low coordination level demonstrated that the development of the tourism industry lags behind in the construction of the human settlement environment. Findings in this study provide references for increasing the resonance between the human settlement environment and the tourism industry and promoting the overall coordinated, balanced and sustainable development of the Yellow River Basin.
Social cost of carbon: A revisit from a systems analysis perspective
Authors: Khabarov Nikolay , Smirnov Alexey , Obersteiner Michael
Published: October 2022

The social cost of carbon (SCC) is estimated by integrated assessment models (IAMs) and is widely used by government agencies to value climate policy impacts. Although there is an ongoing debate about obtained numerical estimates and related uncertainties, little attention has been paid so far to the SCC calculation method itself. This work attempts to fill the gap by providing the theoretical background and economic interpretation of the SCC calculation approach implemented in the DICE (Dynamic Integrated Climate-Economy) IAM. Our analysis indicates that the present calculation method is unable to reflect the linkages between two key IAM components—complex interconnected systems—climate and economy, both influenced by emission abatement policies. Within the modeling framework of DICE, the presently estimated SCC valuates emissions, which are beyond policy control, against consumption of products, which cannot be produced by the economy. This makes the SCC irrelevant for application in climate-economic policies and, therefore, calls for a replacement by a more appropriate indicator. An apparent SCC alternative, which can be considered for policy formulation, is the direct output of the DICE model, the socially optimal marginal abatement cost (SMAC), which corresponds to technological possibilities at the optimal level of carbon emissions abatement. In policymaking, because of the revealed SCC deficiency, great attention needs to be paid to the use of estimates obtained earlier.
Development of a joint diagnostic model of thyroid papillary carcinoma with artificial neural network and random forest
Authors: Wang Shoufei , Liu Wenfei , Ye Ziheng , Xia Xiaotian , Guo Minggao
Published: October 2022

Objective: Papillary thyroid carcinoma (PTC) accounts for 80% of thyroid malignancy, and the occurrence of PTC is increasing rapidly. The present study was conducted with the purpose of identifying novel and important gene panels and developing an early diagnostic model for PTC by combining artificial neural network (ANN) and random forest (RF).

Methods and results: Samples were searched from the Gene Expression Omnibus (GEO) database, and gene expression datasets (GSE27155, GSE60542, and GSE33630) were collected and processed. GSE27155 and GSE60542 were merged into the training set, and GSE33630 was defined as the validation set. Differentially expressed genes (DEGs) in the training set were obtained by “limma” of R software. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis as well as immune cell infiltration analysis were conducted based on DEGs. Important genes were identified from the DEGs by random forest. Finally, an artificial neural network was used to develop a diagnostic model. Also, the diagnostic model was validated by the validation set, and the area under the receiver operating characteristic curve (AUC) value was satisfactory.

Conclusion: A diagnostic model was established by a joint of random forest and artificial neural network based on a novel gene panel. The AUC showed that the diagnostic model had significantly excellent performance.
Identification of five genetic variants with differential effects on obesity-related traits based on age
Authors: Chung Ju Yeon , Jung Hae-Un , Kim Dong Jun , Baek Eun Ju , Kim Han Kyul , Kang Ji-One , Lim Ji Eun , Oh Bermseok
Published: October 2022

Obesity is a major public health concern, and its prevalence generally increases with age. As the number of elderly people is increasing in the aging population, the age-dependent increase in obesity has raised interest in the underlying mechanism. To understand the genetic basis of age-related increase in obesity, we identified genetic variants showing age-dependent differential effects on obesity. We conducted stratified analyses between young and old groups using genome-wide association studies of 355,335 United Kingom Biobank participants for five obesity-related phenotypes, including body mass index, body fat percentage, waist-hip ratio, waist circumference, and hip circumference. Using t-statistic, we identified five significant lead single nucleotide polymorphisms: rs2258461 with body mass index, rs9861311 and rs429358 with body fat percentage, rs2870099 with waist-hip ratio, and rs145500243 with waist circumference. Among these single nucleotide polymorphisms, rs429358, located in APOE gene was associated with diverse age-related diseases, such as Alzheimer’s disease, coronary artery disease, age-related degenerative macular diseases, and cognitive decline. The C allele of rs429358 gradually decreases body fat percentage as one grows older in the range of 40–69 years. In conclusion, we identified five genetic variants with differential effects on obesity-related phenotypes based on age using a stratified analysis between young and old groups, which may help to elucidate the mechanisms by which age influences the development of obesity.
Evidence for a genetic contribution to the ossification of spinal ligaments in Ossification of Posterior Longitudinal Ligament and Diffuse idiopathic skeletal hyperostosis: A narrative review
Authors: Couto Ana Rita , Parreira Bruna , Power Deborah M. , Pinheiro Luís , Madruga Dias João , Novofastovski Irina , Eshed Iris , Sarzi-Puttini Piercarlo , Pappone Nicola , Atzeni Fabiola , Verlaan Jorrit-Jan , Kuperus Jonneke , Bieber Amir , Ambrosino Pasquale , Kiefer David , Khan Muhammad Asim , Mader Reuven , Baraliakos Xenofon , Bruges-Armas Jácome
Published: October 2022

Diffuse Idiopathic Skeletal Hyperostosis (DISH) and Ossification of the Posterior Longitudinal Ligament (OPLL) are common disorders characterized by the ossification of spinal ligaments. The cause for this ossification is currently unknown but a genetic contribution has been hypothesized. Over the last decade, many studies on the genetics of ectopic calcification disorders have been performed, mainly on OPLL. Most of these studies were based on linkage analysis and case control association studies. Animal models have provided some clues but so far, the involvement of the identified genes has not been confirmed in human cases. In the last few years, many common variants in several genes have been associated with OPLL. However, these associations have not been at definitive levels of significance and evidence of functional significance is generally modest. The current evidence suggests a multifactorial aetiopathogenesis for DISH and OPLL with a subset of cases showing a stronger genetic component.
3D printed Ti-5Cu alloy accelerates osteogenic differentiation of MC3T3-E1 cells by stimulating the M2 phenotype polarization of macrophages
Authors: Zhao Xin , Zhou Xing , Sun Hui , Shi Huixin , Song Yiping , Wang Qiang , Zhang Guangping , Xu Dake
Published: October 2022

Ti-5Cu alloy has been proved to have excellent mechanical properties and cell compatibility and has certain antibacterial properties due to the addition of Cu. However, there are few studies on the effects of Ti-5Cu alloy on macrophage polarization and immune-related bone formation. In this study, we prepared Ti-5Cu alloy by three-dimensional printing technology and found that Ti-5Cu alloy presented a much smoother surface compared with Ti. In addition, the CCK-8 results indicated the Ti-5Cu alloy had no cytotoxicity to RAW264.7 cells by co-culture. The results of inductively coupled plasma mass spectrometry showed that the concentration of Cu2+ was 0.133 mg/L after 7 days of co-culture, and the CCK-8 results proved that Cu2+ had no cytotoxicity to RAW264.7 at this concentration. Then, we studied the effects of Ti-5Cu alloy on macrophage polarization; it was shown that the Ti-5Cu alloy is more prone to modulate the RAW264.7 polarization towards the M2 phenotype and the conditioned medium derived from Ti-5Cu alloy significantly promoted the proliferation and osteogenic differentiation of MC3T3-E1 cells. However, when the expression of Oncostatin M (OSM) gene of RAW264.7 was knocked down, the osteogenic differentiation of MC3T3-E1 cells was decreased. This suggests that the OSM secreted by RAW264.7 co-cultured with Ti-5Cu alloy could accelerate the osteogenic differentiation of MC3T3-E1 cells by acting on OSMR/gp130 receptors.
Buprenorphine reverses neurocognitive impairment in EcoHIV infected mice: A potential therapy for HIV-NCI
Authors: Murphy Aniella J. , Kelschenbach Jennifer , He Hongxia , Chao Wei , Kim Boe-Hyun , Volsky David J. , Berman Joan W.
Published: October 2022

Thirty-eight million people worldwide are living with HIV, PWH, a major public health problem. Antiretroviral therapy (ART) revolutionized HIV treatment and significantly increased the lifespan of PWH. However, approximately 15-50% of PWH develop HIV associated neurocognitive disorders (HIV-NCI), a spectrum of cognitive deficits, that negatively impact quality of life. Many PWH also have opioid use disorder (OUD), and studies in animal models of HIV infection as well as in PWH suggest that OUD can contribute to HIV-NCI. The synthetic opioid agonist, buprenorphine, treats OUD but its effects on HIV-NCI are unclear. We reported that human mature inflammatory monocytes express the opioid receptors MOR and KOR, and that buprenorphine reduces important steps in monocyte transmigration. Monocytes also serve as HIV reservoirs despite effective ART, enter the brain, and contribute to HIV brain disease. Using EcoHIV infected mice, an established model of HIV infection and HIV-NCI, we previously showed that pretreatment of mice prior to EcoHIV infection reduces mouse monocyte entry into the brain and prevents NCI. Here we show that buprenorphine treatment of EcoHIV infected mice with already established chronic NCI completely reverses the disease. Disease reversal was associated with a significant reduction in brain inflammatory monocytes and reversal of dendritic injury in the cortex and hippocampus. These results suggest that HIV-NCI persistence may require a continuing influx of inflammatory monocytes into the brain. Thus, we recommend buprenorphine as a potential therapy for mitigation of HIV brain disease in PWH with or without OUD.
Preoperative sarcopenia and systemic immune-inflammation index can predict response to intravesical Bacillus Calmette-Guerin instillation in patients with non-muscle invasive bladder cancer
Authors: Liu Peng , Chen Shouzhen , Gao Xingzhe , Liang Hao , Sun Daqian , Shi Benkang , Zhang Qiujie , Guo Hu
Published: October 2022

Background

To explore the prognostic significance of sarcopenia and systemic immune-inflammation index (SII) for response to intravesical Bacillus Calmette-Guerin (BCG) in patients with intermediate-, and high-risk non-muscle invasive bladder cancer (NMIBC).

Methods

We retrospectively analyzed 183 consecutive patients treated in Qilu hospital of Shandong University for a first diagnosis of intermediate and high risk NMIBC. Using computed tomography scans at the third lumbar vertebra level, we calculated skeletal muscle index (SMI). Sarcopenia was defined as SMI <43 cm2/m2 for males with BMI < 25 kg/m2, <53 cm2/m2 for males with BMI ≥ 25 kg/m2, and <41 cm2/m2 for females. The response to intravesical BCG immunotherapy and relapse-free survival (RFS) were analyzed.

Results

Compared with BCG responders, BCG non-responders were associated with sarcopenia (P < 0.001), carcinoma in situ (P < 0.001), T1 stage (P < 0.001), multiple tumor (P < 0.001), tumor diameter >=3cm (P < 0.001), and have a significant increase of neutrophil-to-lymphocyte ratio (NLR) (P < 0.001), platelet to lymphocyte ratio (PLR) (P = 0.004), SII (P < 0.001). The area under the ROC curve (AUC) of the BMI, NLR, PLR, and SII for response to intravesical BCG immunotherapy were 0.425, 0.693, 0.631, and 0.702 respectively. Logistic regression analysis demonstrated that sarcopenia and SII were predictors of response to intravesical BCG immunotherapy. The Kaplan-Meier survival analysis showed that the RFS of patients with BCG response, lower SII and no sarcopenia was significantly increased compared with that of patients with BCG non-response, higher SII and sarcopenia, respectively. Subgroup analysis demonstrated that the RFS of patients with high SII and sarcopenia was significantly decreased compared with those with low SII and no sarcopenia in Ta stage subgroup, T1 stage subgroup, non-Cis subgroup, multiple tumor subgroup, single tumor subgroup, tumor diameter≥3cm subgroup and tumor diameter<3cm subgroup, respectively (P < 0.05). However, there was no significant difference in RFS for patients in CIS subgroup (P > 0.05). Multivariate Cox analysis shown that sarcopenia (p=0.005) and high SII (p = 0.003) were significantly associated with poor RFS.

Conclusions

Both sarcopenia and high SII are useful predictors of response to intravesical BCG in intermediate- and high-risk NMIBC patients. Patients with intermediate- and high-risk NMIBC that had sarcopenia or high SII at diagnosis were associated with poor RFS, and the combination of sarcopenia and SII may be a better predictor of RFS.
Changes in the urinary proteome before and after quadrivalent influenza vaccine and COVID-19 vaccination
Authors: Pan Xuanzhen , Liu Yongtao , Bao Yijin , Wei Lilong , Gao Youhe
Published: October 2022

The proteome of urine samples from quadrivalent influenza vaccine cohort were analyzed with self-contrasted method. Significantly changed urine protein at 24 hours after vaccination was enriched in immune-related pathways, although each person’s specific pathways varied. We speculate that this may be because different people have different immunological backgrounds associated with influenza. Then, urine samples were collected from several uninfected SARS-CoV-2 young people before and after the first, second, and third doses of the COVID-19 vaccine. The differential proteins compared between after the second dose (24h) and before the second dose were enriched in pathways involving in multicellular organismal process, regulated exocytosis and immune-related pathways, indicating no first exposure to antigen. Surprisingly, the pathways enriched by the differential urinary protein before and after the first dose were similar to those before and after the second dose. It is inferred that although the volunteers were not infected with SARS-CoV-2, they might have been exposed to other coimmunogenic coronaviruses. Two to four hours after the third vaccination, the differentially expressed protein were also enriched in multicellular organismal process, regulated exocytosis and immune-related pathways, indicating that the immune response has been triggered in a short time after vaccination. Multicellular organismal process and regulated exocytosis after vaccination may be a new indicator to evaluate the immune effect of vaccines. Urinary proteome is a terrific window to monitor the changes in human immune function.
Two novel mollusk short-form ApeC-containing proteins act as pattern recognition proteins for peptidoglycan
Authors: Li Jin , Liu Shumin , Zhang Yang , Huang Qiuyun , Zhang Hao , OuYang Jihua , Mao Fan , Fan Huiping , Yi Wenjie , Dong Meiling , Xu Anlong , Huang Shengfeng
Published: October 2022

The Apextrin C-terminal (ApeC) domain is a new protein domain largely specific to aquatic invertebrates. In amphioxus, a short-form ApeC-containing protein (ACP) family is capable of binding peptidoglycan (PGN) and agglutinating bacteria via its ApeC domain. However, the functions of ApeC in other phyla remain unknown. Here we examined 130 ACPs from gastropods and bivalves, the first and second biggest mollusk classes. They were classified into nine groups based on their phylogenetics and architectures, including three groups of short-form ACPs, one group of apextrins and two groups of ACPs of complex architectures. No groups have orthologs in other phyla and only four groups have members in both gastropods and bivalves, suggesting that mollusk ACPs are highly diversified. We selected one bivalve ACP (CgACP1; from the oyster Crossostrea gigas) and one gastropod ACP (BgACP1; from the snail Biomphalaria glabrata) for functional experiments. Both are highly-expressed, secreted short-form ACPs and hence comparable to the amphioxus ACPs previously reported. We found that recombinant CgACP1 and BgACP1 bound with yeasts and several bacteria with different affinities. They also agglutinated these microbes, but showed no inhibiting or killing effects. Further analyses show that both ACPs had high affinities to the Lys-type PGN from S. aureus but weak or no affinities to the DAP-type PGN from Bacillus subtilis. Both recombinant ACPs displayed weak or no affinities to other microbial cell wall components, including lipopolysaccharide (LPS), lipoteichoic acid (LTA), zymosan A, chitin, chitosan and cellulose, as well as to several PGN moieties, including muramyl dipeptide (MDP), N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc). Besides, CgACP1 had the highest expression in the gill and could be greatly up-regulated quickly after bacterial challenge. This is reminiscent of the amphioxus ACP1/2 which serve as essential mucus lectins in the gill. Taken together, the current findings from mollusk and amphioxus ACPs suggest several basic common traits for the ApeC domains, including the high affinity to Lys-type PGN, the bacterial binding and agglutinating capacity, and the role as mucus proteins to protect the mucosal surface.
Immunogenicity and protective efficacy of the recombinant Pasteurella multocida lipoproteins VacJ and PlpE, and outer membrane protein H from P. multocida A:1 in ducks
Authors: Li Yajuan , Xiao Junfang , Chang Yung-Fu , Zhang Hui , Teng Yutao , Lin Wencheng , Li Hongxin , Chen Weiguo , Zhang Xinheng , Xie Qingmei
Published: October 2022

Duck cholera (duck hemorrhagic septicemia) is a highly contagious disease caused by Pasteurella multocida, and is one of the major bacterial diseases currently affecting the duck industry. Type A is the predominant pathogenic serotype. In this study, the genes encoding the lipoproteins VacJ, PlpE, and the outer membrane protein OmpH of P. multocida strain PMWSG-4 were cloned and expressed as proteins in E. coli. The recombinant VacJ (84.4 kDa), PlpE (94.8 kDa), and OmpH (96.7 kDa) proteins were purified, and subunit vaccines were formulated with a single water-in-oil adjuvant, while killed vaccines were prepared using a single oil-coated adjuvant. Antibody responses in ducks vaccinated with recombinant VacJ, PlpE, and OmpH proteins formulated with adjuvants were significantly antigenic (p<0.005). Protectivity of the vaccines was evaluated via the intraperitoneal challenge of ducks with 20 LD50 doses of P. multocida A: 1. The vaccine formulation consisting of rVacJ, rPlpE, rOmpH, and adjuvant provided 33.3%, 83.33%, and 83.33% protection, respectively, the vaccine formulation consisting of three recombinant proteins, rVacJ, rPlpE, rOmpH and adjuvant, was 100% protective, and the killed vaccine was 50% protective. In addition, it was shown through histopathological examination and tissue bacterial load detection that all vaccines could reduce tissue damage and bacterial colonization to varying (p<0.001). These findings indicated that recombinant PlpE or OmpH fusion proteins formulated with oil adjuvants have the potential to be used as vaccine candidates against duck cholera subunits.