bluuebunny/crossref_metadata_2025_split huggingface dataset:
The association of lipid ratios with hyperuricemia in a rural Chinese hypertensive population
Authors: Yu Yu , Lan Tian , Wang Dandan , Fang Wangsheng , Tao Yu , Li Minghui , Huang Xiao , Zhou Wei , Wang Tao , Zhu Lingjuan , Bao Huihui , Cheng Xiaoshu 
Published: September 2021

Abstract
Background
Current studies support lipid ratios [the total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio; the triglyceride (TG)/HDL-C ratio; the low-density lipoprotein cholesterol (LDL -C)/HDL-C ratio; and non-HDL-C] as reliable indicators of cardiovascular disease, stroke, and diabetes. However, whether lipid ratios could serve as markers for hyperuricemia (HUA) remains unclear due to limited research. This study aimed to explore the association between lipid ratios and HUA in hypertensive patients.

Methods
The data from 14,227 Chinese hypertensive individuals in the study were analyzed. Multiple logistic regression analysis and smooth curve fitting models examined the relationship between lipid ratios and HUA.

Results
The results showed positive associations between the lipid ratios and HUA (all P < 0.001). Furthermore, lipid ratios were converted from continuous variables to tertiles. Compared to the lowest tertile, the fully adjusted ORs (95 % CI) of the TC/HDL-C ratio, the TG/HDL-C ratio, the LDL-C/HDL-C ratio, and non-HDL-C in the highest tertile were 1.79 (1.62, 1.99), 2.09 (1.88, 2.32), 1.67 (1.51, 1.86), and 1.93 (1.74, 2.13), respectively (all P < 0.001).

Conclusions
The study suggested that high lipid ratios (TC/HDL-C ratio, TG/HDL-C ratio, LDL-C/HDL-C ratio, and non-HDL-C) are associated with HUA in a Chinese hypertensive population. This study’s findings further expand the scope of the application of lipid ratios. These novel and essential results suggest that lipid ratio profiles might be potential and valuable markers for HUA.

Trial registration
No. ChiCTR1800017274. Registered July 20, 2018.
Utility of non-HDL-C in predicting proteinuria remission of idiopathic membranous nephropathy: a retrospective cohort study
Authors: Dong Lei , Wei Wang , Han Min , Xu Gang 
Published: September 2021

Abstract
Background
Idiopathic membranous nephropathy (IMN) may have various clinical outcomes. Hyperlipidemia is quite common in IMN. However, the utility of the lipid profile in predicting outcomes remains unknown. This study aimed to explore the correlation between hyperlipidemia and proteinuria remission in IMN.

Methods
256 patients who diagnosed with IMN confirmed by renal biopsy in Wuhan Tongji Hospital from January 2016 to October 2020 were included in this study. The end point was defined as a combination of partial and complete remission. Cox proportional-hazards regression analysis and Kaplan–Meier curve were applied to assess the prognostic value of the lipid profile for proteinuria remission.

Results
A total of 153 (59.8%) patients achieved remission and 103 (40.2%) did not. The levels of total cholesterol, low-density lipoprotein, and non-high-density lipoprotein were significantly lower in the remission group than in the non-remission group. Non-high-density lipoprotein level revealed the strongest correlation with proteinuria (Spearman’s rho = 0.42; P < 0.001). The multivariate analysis demonstrated that serum total cholesterol [hazard ratio (HR): 0.883; 95% confidence interval (CI): 0.813–0.958; P = 0.003] and non-high-density lipoprotein cholesterol (HR: 0.892; 95% CI: 0.820–0.970; P = 0.007) levels were independent markers to predict proteinuria remission in IMN.

Conclusions
Among the lipid profile, the non-high-density lipoprotein level exhibited the strongest correlation with proteinuria in IMN. Moreover, elevated serum cholesterol and non-high-density lipoprotein cholesterol concentrations at baseline predicted probability of proteinuria non-remission in IMN.
Behavioral effects of different contraceptive methods and HIV acquisition: an ancillary study of the ECHO randomized trial
Authors: Singata-Madliki Mandisa , Lawrie Theresa A. , Balakrishna Yusentha , d’Hellencourt Florence Carayon-Lefebvre , Hofmeyr G. Justus 
Published: September 2021

Abstract
Background
The ECHO trial randomised 7829 women to depot medroxyprogesterone acetate (DMPA-IM), the copper intrauterine device (IUD) and the levonorgestrel (LNG) implant (1:1:1) and found no clear difference in HIV incidence between these three groups. We have previously hypothesized that oligo-amenorrhoea induced by DMPA-IM may have a protective effect on HIV acquisition. The aim of this ancillary study was to assess the effects of DMPA-IM, the IUD and the LNG implant on menstrual symptoms and sexual behavior and to correlate these with HIV acquisition.

Methods
At the Effective Care Research Unit (ECRU) in South Africa, of 615 women already randomised to DMPA-IM, the copper IUD and the LNG implant (1:1:1) 552 agreed to participate. Participants completed a 28-day symptom and behavior diary following their one-month ECHO trial visit and returning it at their 3-month follow-up visit. HIV acquisition data were retrieved from ECHO trial records.

Results
Of 552 women enrolled on the ancillary study, 390 (70.6%) completed their daily diary; 130, 133, and 127 received DMPA-IM, IUD, and LNG implant, respectively. Thirty-three (5.9%) of these women acquired HIV. Women on the progestin-only contraceptives were more likely to experience amenorrhoea, as expected, and were less likely to have intra-menstrual coitus than IUD users (p < 0.001 for DMPA-IM vs IUD and p = 0.002 for implant vs IUD). Overall coital frequency was highest and condom usage lowest among DMPA-IM users. Intra-menstrual coitus correlated positively, and duration of menstruation correlated negatively, with HIV acquisition, although these effects were not statistically significant (p = 0.09 and p = 0.079, respectively).

Conclusions
Findings support the hypothesis that oligo-amenorrhoea and the associated reduced intra-menstrual coitus may mitigate the potential for an increased biological risk of HIV acquisition with DMPA-IM but more evidence is needed.
Study registration number PACTR201706001651380
Identification and functional analysis of novel SLC25A19 variants causing thiamine metabolism dysfunction syndrome 4
Authors: Chen Yuanying , Fang Boliang , Hu Xuyun , Guo Ruolan , Guo Jun , Fang Kenan , Ni Jingwen , Li Wei , Qian Suyun , Hao Chanjuan 
Published: September 2021

Abstract
Background
Thiamine metabolism dysfunction syndrome 4 (THMD4, OMIM #613710) is an autosomal recessive inherited disease caused by the deficiency of SLC25A19 that encodes the mitochondrial thiamine pyrophosphate (TPP) transporter. This disorder is characterized by bilateral striatal degradation and progressive polyneuropathy with the onset of fever of unknown origin. The limited number of reported cases and lack of functional annotation of related gene variants continue to limit diagnosis.

Results
We report three cases of encephalopathy from two unrelated pedigrees with basal ganglia signal changes after fever of unknown origin. To distinguish this from other types of encephalopathy, such as acute necrotizing encephalopathy, exome sequencing was performed, and four novel heterozygous variations, namely, c.169G>A (p.Ala57Thr), c.383C>T (p.Ala128Val), c.76G>A (p.Gly26Arg), and c.745T>A (p.Phe249Ile), were identified in SLC25A19. All variants were confirmed using Sanger sequencing. To determine the pathogenicity of these variants, functional studies were performed. We found that mitochondrial TPP levels were significantly decreased in the presence of SLC25A19 variants, indicating that TPP transport activities of mutated SLC25A19 proteins were impaired. Thus, combining clinical phenotype, genetic analysis, and functional studies, these variants were deemed as likely pathogenic.

Conclusions
Exome sequencing analysis enables molecular diagnosis as well as provides potential etiology. Further studies will enable the elucidation of SLC25A19 protein function. Our investigation supplied key molecular evidence for the precise diagnosis of and clinical decision-making for a rare disease.
Cytogenetic and molecular analysis of distal 4q duplication with distinctive phenotype using single-nucleotide polymorphism array
Authors: Zhuang Jianlong , Zhang Na , Fu Wanyu , Yao Jianfeng , Li Yanqing , Zeng Shuhong , Wang Yuanbai , Xie Yingjun , Jiang Yuying 
Published: September 2021

Abstract
Aims
There is little knowledge about partial trisomy 4q and the genotype–phenotype correlation. In this study, we presented the detail of two Chinese families with partial distal 4q duplication in an attempt to clarify the correlation between the genotype and the phenotype.

Methods
Two pedigrees with distal 4q duplication were enrolled in this study. Karyotype analysis and single-nucleotide polymorphism (SNP) array detection were performed for prenatal diagnosis. Fluorescence in situ hybridization analysis. (FISH) was conducted to verify the copy number variants.

Results
Two families with partial trisomy 4q were identified. The fetus in pedigree 1 exhibited multiple ultrasound anomalies including intrauterine growth restriction and an atrioventricular septal defect who had a duplication of 4q28.3-qter associate with 6p25.2-p25.3 deletion, which resulted from balanced translocation carried by his father t(4;6)(q28.3;p25.2). The fetus in pedigree 2 had a distal 4q28.3-qter duplication combined with monosomy of Xp21.3-p22.3, and the karyotype was described as 46,X,der(X)t(X;4)(p21.3;q28.3)mat, which originally inherited from the pregnant woman who exhibited a mild clinical phenotype limited to short stature.

Conclusions
In our study, we for the first time identified the partial trisomy 4q associate with 6p or Xp deletion. In addition, our finding further strengthens that mild clinical phenotype in 4q duplication case may be due to the spreading of X inactivation to the autosomal in derivation of chromosome X.
Targeting INMT and interrupting its methylation pathway for the treatment of castration resistant prostate cancer
Authors: Zhong Shangwei , Jeong Ji-Hak , Huang Changhao , Chen Xueyan , Dickinson Shohreh Iravani , Dhillon Jasreman , Yang Li , Luo Jun-Li 
Published: September 2021

Abstract
Background
Castration-resistant prostate cancer (CRPC) is associated with a very poor prognosis, and the treatment of which remains a serious clinical challenge.

Methods
RNA-seq, qPCR, western blot and immunohistochemistry were employed to identify and confirm the high expression of indolethylamine N-methyltransferase (INMT) in CRPC and the clinical relevance. Chip assay was used to identify Histone-Lysine N-Methyltransferase (SMYD3) as a major epigenetic regulator of INMT. LC-MS/MS were used to identify new substrates of INMT methylation in CRPC tissues. Gene knockdown/overexpression, MTT and mouse cancer models were used to examine the role of INMT as well as the anticancer efficacy of INMT inhibitor N,N-dimethyltryptamine (DMT), the SMYD3 inhibitor BCl-12, the selenium compounds methaneseleninic acid (MSA) and Se-(Methyl)selenocysteine hydrochloride (MSC), and the newly identified endogenous INMT substrate Bis(7)-tacrine.

Results
We found that the expression of INMT was highly increased in CRPC and was correlated with poor prognosis of clinical prostate cancer (PCa). INMT promoted PCa castration resistance via detoxification of anticancer metabolites. Knockdown of INMT or treatment with INMT inhibitor N,N-dimethyltryptamine (DMT) significantly suppressed CRPC development. Histone-Lysine N-Methyltransferase SMYD3 was a major epigenetic regulator of INMT expression, treatment with SMYD3 inhibitor BCl-121 suppressed INMT expression and inhibits CRPC development. Importantly, INMT knockdown significantly increased the anticancer effect of the exogenous selenium compounds methaneseleninic acid (MSA) and Se-(Methyl)selenocysteine hydrochloride (MSC) as well as the endogenous metabolite Bis(7)-tacrine.

Conclusions
Our study suggests that INMT drives PCa castration resistance through detoxification of anticancer metabolites, targeting INMT or its regulator SMYD3 or/and its methylation metabolites represents an effective therapeutic avenue for CRPC treatment.
Design, synthesis, and biological evaluation of symmetrical azine derivatives as novel tyrosinase inhibitors
Authors: Karimian Somaye , Kazemi Fatemeh , Attarroshan Mahshid , Gholampour Maryam , Hemmati Shiva , Sakhteman Amirhossein , Behzadipour Yasaman , Kabiri Maryam , Iraji Aida , Khoshneviszadeh Mehdi 
Published: September 2021

AbstractA series of symmetrical azine derivatives containing different substituted benzyl moieties were designed, synthesized, and evaluated for their inhibitory activity against tyrosinase. The results showed that compounds 3e, 3f, 3h, 3i, 3j, and 3k possess effective tyrosinase inhibition with IC50 values ranging from 7.30 μM to 62.60 μM. Particularly, compounds 3f displayed around three-fold improvement in the potency (IC50 = 7.30 ± 1.15 μM) compared to that of kojic acid (IC50 = 20.24 ± 2.28 μM) as the positive control. Kinetic study of compound 3f confirmed uncompetitive inhibitory activity towards tyrosinase indicating that it can bind to enzyme–substrate complex. Next, molecular docking analysis was performed to study the interactions and binding mode of the most potent compound 3f in the tyrosinase active site. Besides, the cytotoxicity of 3f, as well as its potency to reduce the melanin content were also measured on invasive melanoma B16F10 cell line. Also, 3f exhibited above 82% cell viability in the A375 cell line at 10 µM. Consequently, compounds 3f could be introduced as a potent tyrosinase inhibitor that might be a promising candidate in the cosmetics, medicine, and food industry.
In vivo quantitative assessment of therapeutic response to bortezomib therapy in disseminated animal models of multiple myeloma with [18F]FDG and [64Cu]Cu-LLP2A PET
Authors: Ghai Anchal , Fettig Nikki , Fontana Francesca , DiPersio John , Rettig Mike , Neal Julie O. , Achilefu Samuel , Shoghi Kooresh I. , Shokeen Monica 
Published: September 2021

Abstract
Background
Multiple myeloma (MM) is a disease of cancerous plasma cells in the bone marrow. Imaging-based timely determination of therapeutic response is critical for improving outcomes in MM patients. Very late antigen-4 (VLA4, CD49d/CD29) is overexpressed in MM cells. Here, we evaluated [18F]FDG and VLA4 targeted [64Cu]Cu-LLP2A for quantitative PET imaging in disseminated MM models of variable VLA4 expression, following bortezomib therapy.

Methods
In vitro and ex vivo VLA4 expression was evaluated by flow cytometry. Human MM cells, MM.1S-CG and U266-CG (C: luciferase and G: green fluorescent protein), were injected intravenously in NOD-SCID gamma mice. Tumor progression was monitored by bioluminescence imaging (BLI). Treatment group received bortezomib (1 mg/kg, twice/week) intraperitoneally. All cohorts (treated, untreated and no tumor) were longitudinally imaged with [18F]FDG (7.4–8.0 MBq) and [64Cu]Cu-LLP2A (2–3 MBq; Molar Activity: 44.14 ± 1.40 MBq/nmol) PET, respectively.

Results
Flow cytometry confirmed high expression of CD49d in U266 cells (> 99%) and moderate expression in MM.1S cells (~ 52%). BLI showed decrease in total body flux in treated mice. In MM.1S-CG untreated versus treated mice, [64Cu]Cu-LLP2A localized with a significantly higher SUVmean in spine (0.58 versus 0.31, p < 0.01) and femur (0.72 versus 0.39, p < 0.05) at week 4 post-tumor inoculation. There was a four-fold higher uptake of [64Cu]Cu-LLP2A (SUVmean) in untreated U266-CG mice compared to treated mice at 3 weeks post-treatment. Compared to [64Cu]Cu-LLP2A, [18F]FDG PET detected treatment-related changes at later time points.

Conclusion
[64Cu]Cu-LLP2A is a promising tracer for timely in vivo assessment of therapeutic response in disseminated models of MM.
Food system resilience: ontology development and impossible trinities
Authors: van Wassenaer Lan , Oosterkamp Elsje , van Asseldonk Marcel , Ryan Mark 
Published: September 2021

Abstract
Background
Given the polysemy of the concept resilience, is it possible to have a unified conceptualisation of food system resilience? This paper provides a multidisciplinary evaluation of the literature to identify common themes that prevail in food system resilience debates and the challenges to reach a unified conceptualisation. The aim is to provide insights into some of the main issues and tensions that we identified during our research which will then allow academics and policymakers to identify the most significant themes and topics for discussion in the debate. While we only focus on one application of resilience, namely, food system resilience during extreme events, we believe that our approach and findings could be integrated and applied to other areas of resilience, as well.

Results
Our ontological exploration shows that ‘resilience’ is a rich concept that has an important bearing on many themes and topics in the domain of food systems. This makes it highly relevant to develop and apply the concept of ‘food system resilience’. The application of the concept in research and practice, however, faces many challenges that are rooted in ontological and epistemological differences among different disciplines and practices. While posing serious challenges in interdisciplinary collaboration and communication, these challenges also foster new research opportunities as knowledge gaps are discovered. We propose that there is a need to critically investigate the social, environmental, and economic trade-offs implied in policy strategies towards resilience at various levels of food systems and among different actors or groups of actors.

Conclusion
Interdisciplinary communication between different fields can be difficult and divisive. The ambition to unify the theory may be counterproductive in addressing practical problems that often require multidisciplinary collaboration. The challenge is to identify context-specific challenges and policy options using the ‘resilience lens’ and translating the concept into measurable indicators. Our research identifies some of these challenges and aims to provide a way to improve dialogue between different actors, through discussions about tensions and issues within their research. The ontological differences and debates are unlikely to be resolved anytime soon, nor should it be a priority to resolve these differences. A pragmatic case-specific approach can be adopted to address the problem while considering ontological differences. Our research will provide food system resilience researchers with some guidance about challenges in their research, as well as those working on developing ontologies.
Effect of thinning intensity on the stem CO2 efflux of Larix principis-rupprechtii Mayr
Authors: Zhao Kuangji , Fahey Timothy J. , Wang Xiangzhen , Wang Jie , He Fang , Fan Chuan , Jia Zhongkui , Li Xianwei 
Published: September 2021

Abstract
Background
Stem CO2 efflux (ES) plays a critical role in the carbon budget of forest ecosystems. Thinning is a core practice for sustainable management of plantations. It is therefore necessary and urgent to study the effect and mechanism of thinning intensity (TI) on ES.

Methods
In this study, five TIs were applied in Larix principis-rupprechtii Mayr 21-, 25-, and 41-year-old stands in North China in 2010. Portable infrared gas analyzer (Li-8100 A) was used to measure ES and its association with environmental factors at monthly intervals from May to October in 2013 to 2015. In addition, nutrients, wood structure and nonstructural carbon (NSC) data were measured in August 2016.

Results
The results show that ES increased with increasing TI. The maximum ES values occurred at a TI of 35 % (3.29, 4.57 and 2.98 µmol∙m-2∙s-1) and were 1.54-, 1.94- and 2.89-fold greater than the minimum ES value in the CK stands (2.14, 2.35 and 1.03 µmol∙m-2∙s-1) in July for the 21-, 25- and 41-year-old forests, respectively. The ES of the trees in low-density stands was more sensitive to temperature than that of the trees in high-density stands. Soluble sugars (SS) and temperature are the main factors affecting ES. When the stand density is low enough as 41-year-old L. principis-rupprechtii forests with TI 35 %, bark thickness (BT) and humidity should be considered in addition to air temperature (Ta), wood temperature (Tw), sapwood width (SW), nitrogen concentration (N) and SS in the evaluation of ES. If a change in stand density is ignored, the CO2 released from individual 21-, 25- and 41-year-old trees could be underestimated by 168.89 %, 101.94 % and 200.49 %, respectively. CO2 release was estimated based on the stem equation in combination with the factors influencing ES for reference.

Conclusions
We suggest that it is not sufficient to conventional models which quantify ES only by temperature and that incorporating the associated drivers (e.g. density, SS, SW and N) based on stand density into conventional models can improve the accuracy of ES estimates.
Closing the know-do gap for child health: UNICEF’s experiences from embedding implementation research in child health and nutrition programming
Authors: Jackson Debra , Shahabuddin A. S. M. , Sharkey Alyssa B. , Källander Karin , Muñiz Maria , Mwamba Remy , Nyankesha Elevanie , Scherpbier Robert W. , Hasman Andreas , Balarajan Yarlini , Albright Kerry , Idele Priscilla , Peterson Stefan Swartling 
Published: September 2021

AbstractUNICEF operates in 190 countries and territories, where it advocates for the protection of children’s rights and helps meet children’s basic needs to reach their full potential. Embedded implementation research (IR) is an approach to health systems strengthening in which (a) generation and use of research is led by decision-makers and implementers; (b) local context, priorities, and system complexity are taken into account; and (c) research is an integrated and systematic part of decision-making and implementation. By addressing research questions of direct relevance to programs, embedded IR increases the likelihood of evidence-informed policies and programs, with the ultimate goal of improving child health and nutrition.This paper presents UNICEF’s embedded IR approach, describes its application to challenges and lessons learned, and considers implications for future work.From 2015, UNICEF has collaborated with global development partners (e.g. WHO, USAID), governments and research institutions to conduct embedded IR studies in over 25 high burden countries. These studies focused on a variety of programs, including immunization, prevention of mother-to-child transmission of HIV, birth registration, nutrition, and newborn and child health services in emergency settings. The studies also used a variety of methods, including quantitative, qualitative and mixed-methods.UNICEF has found that this systematically embedding research in programs to identify implementation barriers can address concerns of implementers in country programs and support action to improve implementation. In addition, it can be used to test innovations, in particular applicability of approaches for introduction and scaling of programs across different contexts (e.g., geographic, political, physical environment, social, economic, etc.). UNICEF aims to generate evidence as to what implementation strategies will lead to more effective programs and better outcomes for children, accounting for local context and complexity, and as prioritized by local service providers. The adaptation of implementation research theory and practice within a large, multi-sectoral program has shown positive results in UNICEF-supported programs for children and taking them to scale.