bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of evolocumab in individuals with type 2 diabetes with and without atherogenic dyslipidemia: An analysis from BANTING and BERSON
Authors: Lorenzatti Alberto J. , Monsalvo Maria Laura , López J. Antonio G. , Wang Huei , Rosenson Robert S. 
Published: May 2021

Abstract
Background
Atherogenic dyslipidemia (AD), characterized by increased concentrations of apolipoprotein B (ApoB)-containing particles, is often present in individuals with type 2 diabetes mellitus (T2DM). Non-high-density lipoprotein cholesterol (non-HDL-C), cholesterol transported by apolipoprotein B (ApoB)-containing particles), and total apoB are considered secondary goals of lipid-lowering therapy to guide treatment of residual cardiovascular risk. The BANTING and BERSON studies demonstrated that evolocumab added to statin therapy reduced atherogenic lipid and lipoproteins concentrations in patients with T2DM.

Methods
This post-hoc analysis combined data from two randomized, placebo-controlled trials, BANTING and BERSON, to investigate the effect of evolocumab (140 mg every two weeks [Q2W] or 420 mg monthly [QM]) on atherogenic lipid (LDL-C, non-HDL-C, VLDL-C, remnant cholesterol) and lipoproteins (ApoB, lipoprotein(a) (Lp[a])), and achievement of 2019 European Society of Cardiology/European Atherosclerosis Society lipid treatment goals in individuals with and without AD.

Results
In individuals with high TGs with (n = 389) and without (n = 196) AD receiving background statin therapy, evolocumab, compared with placebo, substantially reduced the cholesterol levels from all ApoB atherogenic lipoproteins (least squares (LS) mean LDL-C by 66.7% to 74.3%, non-HDL-C by 53.4% to 65.8%, median remnant cholesterol by 28.9% to 34.2%, VLDL-C by 16.1% to 19.6%) and median TGs levels (by 17.5% to 19.6%) at the mean of weeks 10 and 12. LS mean ApoB was significantly reduced by 41.5% to 56.6% at week 12. Results were consistent in diabetic individuals with normal TGs (n = 519). Evolocumab was also associated with a significant reduction in median Lp(a) by 35.0% to 53.9% at the mean of weeks 10 and 12. A majority (74.7% to 79.8%) of evolocumab-treated individuals achieved the goal of both an LDL-C < 1.4 mmol/L and an LDL-C reduction of at least 50%, > 75% achieved non-HDL-C < 2.2 mmol/L at the mean of weeks 10 and 12, and > 67% achieved ApoB < 65 mg/dL at week 12.

Conclusions
Evolocumab effectively reduced LDL-C, non-HDL-C, ApoB, Lp(a), and remnant cholesterol in individuals with T2DM with and without AD. Evolocumab Q2W or QM enabled most individuals at high/very-high cardiovascular disease risk to achieve their LDL-C, non-HDL-C, and ApoB recommended goals.
Exosomal proteomic signatures correlate with drug resistance and carboplatin treatment outcome in a spontaneous model of canine osteosarcoma
Authors: Weinman Marcus A. , Ramsey Stephen A. , Leeper Haley J. , Brady Jacqueline V. , Schlueter Andrew , Stanisheuski Stanislau , Maier Claudia S. , Miller Tasha , Ruby Carl E. , Bracha Shay 
Published: May 2021

Abstract
Background
Osteosarcoma patients often experience poor outcomes despite chemotherapy treatment, likely due in part to various mechanisms of tumor cell innate and/or acquired drug resistance. Exosomes, microvesicles secreted by cells, have been shown to play a role in drug resistance, but a comprehensive protein signature relating to osteosarcoma carboplatin resistance has not been fully characterized.

Methods
In this study, cell lysates and exosomes from two derivatives (HMPOS-2.5R and HMPOS-10R) of the HMPOS osteosarcoma cell line generated by repeated carboplatin treatment and recovery, were characterized proteomically by mass spectrometry. Protein cargos of circulating serum exosomes from dogs with naturally occurring osteosarcoma, were also assessed by mass spectrometry, to identify biomarkers that discriminate between good and poor responders to carboplatin therapy.

Results
Both cell lysates and exosomes exhibited distinct protein signatures related to drug resistance. Furthermore, exosomes from the resistant HMPOS-2.5R cell line were found to transfer drug resistance to drug-sensitive HMPOS cells. The comparison of serum exosomes from dogs with a favorable disease-free interval [DFI] of > 300 days, and dogs with < 100 days DFI revealed a proteomic signature that could discriminate between the two cohorts with high accuracy. Furthermore, when the patient’s exosomes were compared to exosomes isolated from carboplatin resistant cell lines, several putative biomarkers were found to be shared.

Conclusions
The findings of this study highlight the significance of exosomes in the potential transfer of drug resistance, and the discovery of novel biomarkers for the development of liquid biopsies to better guide personalized chemotherapy treatment.
Knockdown of MCM8 inhibits development and progression of bladder cancer in vitro and in vivo
Authors: Zhu Wei , Gao Fei , Zhou Hongyi , Jin Ke , Shao Jianfeng , Xu Zhuoqun 
Published: April 2021

Abstract
Background
Bladder cancer is a frequently diagnosed urinary system tumor, whose mortality remains rising. Minichromosome maintenance eight homologous recombination repair factor (MCM8), a newly discovered MCM family member, has been shown to be required for DNA replication. Unfortunately, little is known concerning the roles of MCM8 in bladder cancer.

Methods
The present study, we aimed at probing into the impacts and detailed mechanisms of MCM8 in bladder cancer progression. In this study, MCM8 expression level was detected through immunohistochemistry staining (IHC), qRT-PCR and Western blot assay. Silenced MCM8 cell models were constructed by lentivirus transfection. In vitro, the cell proliferation was evaluated by the MTT assay. The wound-healing assay and the transwell assay were utilized to assess the cell migration. Also, the cell apoptosis and the cell cycle were determined by flow cytometry. Moreover, the Human Apoptosis Antibody Array assay was performed to analyze the alterations of apoptosis-related proteins. The in vivo experiments were conducted to verify the effects of MCM8 knockdown on the tumor growth of bladder cancer.

Results
The results demonstrated that compared with normal adjacent tissues, MCM8 expression in bladder cancer tissues was strongly up-regulated. The up-regulation of MCM8 expression in bladder cancer may be a valuable independent prognostic indicator. Of note, MCM8 inhibition modulated the malignant phenotypes of bladder cancer cells. In terms of mechanism, it was validated that MCM8 knockdown made Akt, P-Akt, CCND1 and CDK6 levels down-regulated, as well as MAPK9 up-regulated.

Conclusions
Taken together, our study demonstrated an important role of MCM8 in bladder cancer and created a rationale for the therapeutic potential of MCM8 inhibition in human bladder cancer therapy.
Dual effects of targeting S100A11 on suppressing cellular metastatic properties and sensitizing drug response in gastric cancer
Authors: Cui Yuxin , Li Liting , Li Zhilei , Yin Jie , Lane Jane , Ji Jiafu , Jiang Wen G. 
Published: April 2021

AbstractBackgroundS100A11 is a member of the S100 family of proteins containing two EF-hand calcium-binding motifs. The dysregulated expression of the S100A11 gene has been implicated in tumour metastasis. However, the role of S100A11 protein in tumour cell response to chemotherapeutic drugs has not been characterised.MethodsTranscript levels of S100A11 in gastric cancer were evaluated using an in-house patient cohort. Protein expression of S100A11 in gastric cancer was estimated by immunohistochemistry of a tissue microarray. The stable gastric cancer cell lines were established using lentiviral shRNA vectors. The knockdown of S100A11 was validated by qRT-PCR, PCR, and Western blot. The cellular function of S100A11 was estimated by assays of cell adhesion, migration, and invasion. The cell cytotoxic assay was performed to investigate the response to chemotherapeutic drugs. An unsupervised hierarchical clustering and principal component analysis (HCPC) was applied to unveil the dimensional role of S100A11 among all S100 family members in gastric cancer.ResultsHigh expression of S100A11 is associated with poor survival of gastric cancer patients (p < 0.001, HR = 1.85) and is an independent prognostic factor of gastric cancer. We demonstrate that S100A11 plays its role as a tumour promoter through regulating the MMP activity and the epithelial-mesenchymal transition (EMT) process. The stable knockdown of S100A11 suppresses the metastatic properties of gastric cancer cells, which include enhancing cell adhesion, but decelerating cell migration and invasion. Furthermore, the knockdown of S100A11 gene expression dramatically induces the cellular response of gastric cancer cells to the first-line chemotherapeutic drugs fluoropyrimidine 5-fluorouracil (5-FU) and cisplatin.ConclusionThe present study identifies S100A11 as a tumour promoter in gastric cancer. More importantly, the S100A11-specific targeting potentially presents dual therapeutic benefits by not only controlling tumour progression but also sensitising chemotherapeutic cytotoxic response.
Asymptomatic malaria and anaemia among pregnant women during high and low malaria transmission seasons in Burkina Faso: household-based cross-sectional surveys in Burkina Faso, 2013 and 2017
Authors: Rouamba Toussaint , Samadoulougou Sékou , Ouédraogo Mady , Hien Hervé , Tinto Halidou , Kirakoya-Samadoulougou Fati 
Published: May 2021

Abstract
Background
Malaria in endemic countries is often asymptomatic during pregnancy, but it has substantial consequences for both the mother and her unborn baby. During pregnancy, anaemia is an important consequence of malaria infection. In Burkina Faso, the intensity of malaria varies according to the season, albeit the prevalence of malaria and anaemia as well as their risk factors, during high and low malaria transmission seasons is underexplored at the household level.

Methods
Data of 1751 pregnant women from October 2013 to March 2014 and 1931 pregnant women from April 2017 to June 2017 were drawn from two cross-sectional household surveys conducted in 24 health districts of Burkina Faso. Pregnant women were tested for malaria in their household after consenting. Asymptomatic carriage was defined as a positive result from malaria rapid diagnostic tests in the absence of clinical symptoms of malaria. Anaemia was defined as haemoglobin level less than 11 g/dL in the first and third trimester and less than 10.5 g/dL in the second trimester of pregnancy.

Results
Prevalence of asymptomatic malaria in pregnancy was estimated at 23.9% (95% CI 20.2–28.0) during the high transmission season (October–November) in 2013. During the low transmission season, it was 12.7% (95% CI 10.9–14.7) between December and March in 2013–2014 and halved (6.4%; 95% CI 5.3–7.6) between April and June 2017. Anaemia prevalence was estimated at 59.4% (95% CI 54.8–63.8) during the high transmission season in 2013. During the low transmission season, it was 50.6% (95% CI 47.7–53.4) between December and March 2013–2014 and 65.0% (95% CI 62.8–67.2) between April and June, 2017.

Conclusion
This study revealed that the prevalence of malaria asymptomatic carriage and anaemia among pregnant women at the community level remain high throughout the year. Thus, more efforts are needed to increase prevention measures such as IPTp–SP coverage in order to reduce anaemia and contribute to preventing low birth weight and poor pregnancy outcomes.
Molecular surveillance of anti-malarial resistance pfcrt, pfmdr1, and pfk13 polymorphisms in African Plasmodium falciparum imported parasites to Wuhan, China
Authors: Cheng Weijia , Song Xiaonan , Tan Huabing , Wu Kai , Li Jian 
Published: May 2021

Abstract
Background
Imported malaria parasites with anti-malarial drug resistance (ADR) from Africa is a serious public health challenge in non-malarial regions, including Wuhan, China. It is crucial to assess the ADR status in African Plasmodium falciparum isolates from imported malaria cases, as this will provide valuable information for rational medication and malaria control.

Methods
During 2017–2019, a cross-sectional study was carried out in Wuhan, China. Peripheral blood 3 ml of returned migrant workers from Africa was collected. The target fragments from pfcrt, pfmdr1, and k13 propeller (pfk13) genes were amplified, sequenced, and analysed.

Results
In total, 106 samples were collected. Subsequently, 98.11% (104/106), 100% (106/106), and 86.79% (92/106) of these samples were successfully amplified and sequenced for the pfcrt (72–76), pfmdr1, and pfk13 genes, respectively. The prevalence of the pfcrt 76 T, pfmdr1 86Y, and pfmdr1 184F mutations was 9.62, 4.72, and 47.17%, respectively. At codons 72–76, the pfcrt locus displayed three haplotypes, CVMNK (wild-type), CVIET (mutation type), CV M/I N/E K/T (mixed type), with 87.50%, 9.62%, and 2.88% prevalence, respectively. For the pfmdr1 gene, NY (wild type), NF and YF (mutant type), N Y/F, Y Y/F, and N/Y Y/F (mixed type) accounted for 34.91, 43.40, 3.77, 15.09, 0.94, and 1.89% of the haplotypes, respectively. A total of 83 isolates with six unique haplotypes were found in pfcrt and pfmdr1 combined haplotypes, of which NY-CVMNK and NF-CVMNK accounted for 40.96% (34/83) and 43.37% (36/83), respectively. Furthermore, 90 cases were successfully sequenced (84.91%, 90/106) at loci 93, 97, 101, and 145, and 78 cases were successfully sequenced (73.58%, 78/106) at loci 343, 353, and 356 for pfcrt. However, the mutation was observed only in locus 356 with 6.41%. For pfk13, mutations reported in Southeast Asia (at loci 474, 476, 493, 508, 527, 533, 537, 539, 543, 553, 568, 574, 578, and 580) and Africa (at loci 550, 561, 575, 579, and 589) were not observed.

Conclusions
The present data from pfcrt and pfmdr1 demonstrate that anti-malarial drugs including chloroquine, amodiaquine, and mefloquine, remain effective against malaria treatment in Africa. The new mutations in pfcrt related to piperaquine resistance remain at relatively low levels. Another source of concern is the artemether-lumefantrine resistance-related profiles of N86 and 184F of pfmdr1. Although no mutation in pfk13 is detected, molecular surveillance must continue.
A multi-center longitudinal study on responsive breastfeeding in China from the perspective of health equity: research protocol
Authors: Shu Wen , Li Menglong , Amaerjiang Nubiya , Fan Xin , Lin Shunna , Segura-Pérez Sofia , Pérez-Escamilla Rafael , Hu Yifei 
Published: May 2021

Abstract
Background
Socio-economic inequities can strongly influence suboptimal infant feeding outcomes. Factors such as lack of knowledge about breastfeeding, low family income, low educational attainment, social and economic status, cultural norms and ethnicity may negatively affect success with offering breastfeeding following a responsive feeding approach (ie. responsive breastfeeding). Such inequities can indeed shorten breastfeeding duration, and negatively affect behavioral and cognitive infant outcomes. In China, there is a dearth of studies focusing on breastfeeding from the responsive and health equity perspective.

Objective
The aim of this article is to present a protocol of an ongoing longitudinal cohort study investigating factors associated with responsive breastfeeding behaviors, and the child’s behavioral and cognitive development from birth to12 months post-partum in five centers in China. The study seeks to identify breastfeeding barriers and facilitators from a health equity perspective.

Methods
We are enrolling 700 women and their singleton full term infants in Chongqing, Huizhou and Guangzhou urban and rural areas. The study questionnaires will be administrated within 72 h, 30 days, 3, 6, 9, and 12 months post-partum during the baby’s vaccination visits. We will investigate the difference between urban and rural areas sociodemographic characteristics, breastfeeding knowledge, attitudes and practice, postnatal depression, maternal emotion regulation and parenting stress, and anthropometric and cognitive development indicators of the infants at each time-point.

Conclusion
Our article illustrates how a cohort study can be designed to understand the barriers and facilitators of responsive breastfeeding taking equity principles into account to help promote infants’ growth and development in China.
Innovations in the national household random sampling in Brazilian National Health Survey: results from Starfield and Shi’s adult primary care assessment tool (PCAT)
Authors: Pinto Luiz Felipe , D’Avila Otavio Pereira , Hauser Lisiane , Harzheim Erno 
Published: May 2021

Abstract
Background
Several middle and upper income countries carry out household surveys that seek to trace the profile of access and use of health services. Probably one of the most ambitious examples is Brazil, with its National Health Survey (PNS-2019). We evaluated PNS-2019, presenting in an unprecedented way, one of its innovations, which refer to Starfield and Shi’s adult Primary Care Assessment Tool (PCAT).

Methods
Based on a cross-sectional study, we evaluated Module H of the PNS-2019, which interviewed a probabilistic sample of about 10,000 adults in 2019 in all 27 Brazilian states. According to the PCAT methodology, an average score equal to or above 6.6 indicates a greater orientation and quality of the evaluated primary care services.

Results
Brazilian overall PCAT score [5, 9] reveals the need to improve primary health care services across the country. There were no statistically significant differences in the scores by sex (men and women, 5.9), and race (whites 5.9 [5.7; 6.0] and brown / black 5.9 [5.8; 6.0]). On the other hand, there was a difference in terms of age. The elderly evaluated the services in a more positive way (score = 6.1 [6.0; 6.2]), when compared to those aged 40–59 years (5.9 [5.7; 6.0]) and 18 to 39 years (5.6 [5.5; 5.8]). First results of PNS-2019 show that the population that most needs primary care services in SUS is the one with the best perception and the most positive evaluation of the actions and procedures offered in health facilities.

Discussion
During 2019, Brazil undertook important structural reforms in PHC based on a new financing model with the aim of inducing an improvement in efficiency and strengthening its attributes. It is essential that countries with universal health coverage (UHC) guarantee access to their population and, especially, the most vulnerable, seek better efficiency of these services and regularly assess PHC based on the population’s perception, through an independent methodology that monitor the quality of services and the strength of PHC, generating value for public resources applied to health services.
Feelings of safety during daytime walking: associations with mental health, physical activity and cardiometabolic health in high vacancy, low-income neighborhoods in Detroit, Michigan
Authors: Pearson Amber L. , Clevenger Kimberly A. , Horton Teresa H. , Gardiner Joseph C. , Asana Ventra , Dougherty Benjamin V. , Pfeiffer Karin A. 
Published: May 2021

Abstract
Introduction
Individuals living in low-income neighborhoods have disproportionately high rates of obesity, Type-2 diabetes, and cardiometabolic conditions. Perceived safety in one’s neighborhood may influence stress and physical activity, with cascading effects on cardiometabolic health.

Methods
In this study, we examined relationships among feelings of safety while walking during the day and mental health [perceived stress (PSS), depression score], moderate-to-vigorous physical activity (PA), Body Mass Index (BMI), and hemoglobin A1C (A1C) in low-income, high-vacancy neighborhoods in Detroit, Michigan. We recruited 69 adults who wore accelerometers for one week and completed a survey on demographics, mental health, and neighborhood perceptions. Anthropometrics were collected and A1C was measured using A1CNow test strips. We compiled spatial data on vacant buildings and lots across the city. We fitted conventional and multilevel regression models to predict each outcome, using perceived safety during daytime walking as the independent variable of interest and individual or both individual and neighborhood-level covariates (e.g., number of vacant lots). Last, we examined trends in neighborhood features according to perceived safety.

Results
In this predominantly African American sample (91%), 47% felt unsafe during daytime walking. Feelings of perceived safety significantly predicted PSS (β = − 2.34, p = 0.017), depression scores (β = − 4.22, p = 0.006), and BMI (β = − 2.87, p = 0.01), after full adjustment. For PA, we detected a significant association for sex only. For A1C we detected significant associations with blighted lots near the home. Those feeling unsafe lived in neighborhoods with higher park area and number of blighted lots.

Conclusion
Future research is needed to assess a critical pathway through which neighborhood features, including vacant or poor-quality green spaces, may affect obesity—via stress reduction and concomitant effects on cardiometabolic health.
Paradigm shift: the primary function of the “Adiponectin Receptors” is to regulate cell membrane composition
Authors: Pilon Marc 
Published: April 2021

AbstractThe ADIPOR1 and ADIPOR2 proteins (ADIPORs) are generally considered as adiponectin receptors with anti-diabetic properties. However, studies on the yeast and C. elegans homologs of the mammalian ADIPORs, and of the ADIPORs themselves in various mammalian cell models, support an updated/different view. Based on findings in these experimental models, the ADIPORs are now emerging as evolutionarily conserved regulators of membrane homeostasis that do not require adiponectin to act as membrane fluidity sensors and regulate phospholipid composition. More specifically, membrane rigidification activates ADIPOR signaling to promote fatty acid desaturation and incorporation of polyunsaturated fatty acids into membrane phospholipids until fluidity is restored. The present review summarizes the evidence supporting this new view of the ADIPORs, and briefly examines physiological consequences.
Influence of uric acid on the correlation between waist circumference and triglyceride glucose index: an analysis from CHARLS
Authors: Zheng Jia , Jiang Min , Xie Yanxia 
Published: April 2021

Abstract
Background
Waist circumference (WC) and uric acid (UA) are significantly related. Still, their temporal sequence and how the sequence works on future risk of triglyceride glucose (TyG) are unknown, especially in the Chinese population.

Methods
Cross-lagged panel model was used to analyze the reciprocal, longitudinal relationships among a set of interrelated variables. The mediation model was constructed to test the effect of the relationship between WC and UA on TyG.

Results
A total of 5727 subjects were enrolled in our study population, of which 53.5% were women, and the mean age was 59.0 (standard deviation, 8.62) years. After adjusting for traditional confounding factors, the results showed that a higher level of baseline WC was significantly associated with a higher level of follow-up UA (β = 0.003, P = 0.031) and follow-up TyG (β = 0.003, P < 0.001);. Simultaneously, there was no statistical association between the level of baseline UA and the level of follow-up WC (β = − 0.009, P = 0.951). The mediation effects of UA on WC-TyG were estimated to be 18.1% in adults, and 36.2% in women.

Conclusions
The current study demonstrated that higher baseline level of WC probably preceded UA’ level in general population. In addition, UA mediated the relationship of WC to TyG, especially in females. And the possible mechanism would require further clarification.