bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of RhoC in cancer cell migration
Authors: Lou Yingyue , Jiang Yuhan , Liang Zhen , Liu Bingzhang , Li Tian , Zhang Duo 
Published: October 2021

AbstractMigration is one of the five major behaviors of cells. Although RhoC—a classic member of the Rho gene family—was first identified in 1985, functional RhoC data have only been widely reported in recent years. Cell migration involves highly complex signaling mechanisms, in which RhoC plays an essential role. Cell migration regulated by RhoC—of which the most well-known function is its role in cancer metastasis—has been widely reported in breast, gastric, colon, bladder, prostate, lung, pancreatic, liver, and other cancers. Our review describes the role of RhoC in various types of cell migration. The classic two-dimensional cell migration cycle constitutes cell polarization, adhesion regulation, cell contraction and tail retraction, most of which are modulated by RhoC. In the three-dimensional cell migration model, amoeboid migration is the most classic and well-studied model. Here, RhoC modulates the formation of membrane vesicles by regulating myosin II, thereby affecting the rate and persistence of amoeba-like migration. To the best of our knowledge, this review is the first to describe the role of RhoC in all cell migration processes. We believe that understanding the detail of RhoC-regulated migration processes will help us better comprehend the mechanism of cancer metastasis. This will contribute to the study of anti-metastatic treatment approaches, aiding in the identification of new intervention targets for therapeutic or genetic transformational purposes.
Safety monitoring experience of single-low dose primaquine co-administered with artemether–lumefantrine among providers and patients in routine healthcare practice: a qualitative study in Eastern Tanzania
Authors: Mosha Dominic , Kakolwa Mwaka A. , Mahende Muhidin K. , Masanja Honorati , Abdulla Salim , Drakeley Chris , Gosling Roland , Wamoyi Joyce 
Published: October 2021

AbstractBackgroundPrimaquine is a gametocytocidal drug recommended by the World Health Organization (WHO) in a single-low dose combined with artemisinin-based combination therapy (ACT) for the treatment and prevention ofPlasmodium falciparummalaria transmission. Safety monitoring concerns and the lack of a universal validated and approved primaquine pharmacovigilance tool is a challenge for a national rollout in many countries. This study aimed to explore the acceptance, reliability and perceived effectiveness of the primaquine roll out monitoring pharmacovigilance tool (PROMPT).MethodsThis study was conducted in three dispensaries in the Coastal region of Eastern Tanzania. The study held six in-depth interviews with healthcare providers and six participatory focus group discussions with malaria patients (3) and parents/guardians of sick children (3). Participants were purposively sampled. Thematic analysis was conducted with the aid of NVivo qualitative analysis software.ResultsThe respondents’ general acceptance and perceived effectiveness of the single-low dose primaquine and PROMPT was good. Screening procedure for treatment eligibility and explaining to patients about the possible adverse events was considered very useful for safety reasons. Crushing and dissolving of primaquine tablet to get the appropriate dose, particularly in children, was reported by all providers to be challenging. Transport costs and poor access to the health facility were the main reasons for a patient failing to return to the clinic for a scheduled follow-up visit. Treatment was perceived to be safe by both providers and patients and reported no case of a severe adverse event. Some providers were concerned with the haemoglobin drop observed on day 7.ConclusionSingle-low dose primaquine was perceived to be safe and acceptable among providers and patients. PROMPT demonstrated to be a reliable and user-friendly tool among providers. Further validation of the tool by involving the National Malaria Control Programme is pivotal to addressing key challenges and facilitating primaquine adoption in the national policy.
Risk factors associated with house entry of malaria vectors in an area of Burkina Faso with high, persistent malaria transmission and high insecticide resistance
Authors: Yaro Jean Baptiste , Tiono Alfred B. , Sanou Antoine , Toe Hyacinthe K. , Bradley John , Ouedraogo Alphonse , Ouedraogo Z. Amidou , Guelbeogo Moussa W. , Agboraw Efundem , Worrall Eve , Sagnon N.’Fale , Lindsay Steven W. , Wilson Anne L. 
Published: October 2021

Abstract
Background
In rural Burkina Faso, the primary malaria vector Anopheles gambiae sensu lato (s.l.) primarily feeds indoors at night. Identification of factors which influence mosquito house entry could lead to development of novel malaria vector control interventions. A study was therefore carried out to identify risk factors associated with house entry of An. gambiae s.l. in south-west Burkina Faso, an area of high insecticide resistance.

Methods
Mosquitoes were sampled monthly during the malaria transmission season using CDC light traps in 252 houses from 10 villages, each house sleeping at least one child aged five to 15 years old. Potential risk factors for house entry of An. gambiae s.l. were measured, including socio-economic status, caregiver’s education and occupation, number of people sleeping in the same part of the house as the child, use of anti-mosquito measures, house construction and fittings, proximity of anopheline aquatic habitats and presence of animals near the house. Mosquito counts were compared using a generalized linear mixed-effect model with negative binomial and log link function, adjusting for repeated collections.

Results
20,929 mosquitoes were caught, of which 16,270 (77.7%) were An. gambiae s.l. Of the 6691 An. gambiae s.l. identified to species, 4101 (61.3%) were An. gambiae sensu stricto and 2590 (38.7%) Anopheles coluzzii. Having a metal-roof on the child’s sleeping space (IRR = 0.55, 95% CI 0.32–0.95, p = 0.03) was associated with fewer malaria vectors inside the home.

Conclusion
This study demonstrated that the rate of An. gambiae s.l. was 45% lower in sleeping spaces with a metal roof, compared to those with thatch roofs. Improvements in house construction, including installation of metal roofs, should be considered in endemic areas of Africa to reduce the burden of malaria.
Genetic variation of Plasmodium falciparum histidine-rich protein 2 and 3 in Assosa zone, Ethiopia: its impact on the performance of malaria rapid diagnostic tests
Authors: Alemayehu Gezahegn Solomon , Messele Alebachew , Blackburn Kayla , Lopez Karen , Lo Eugenia , Janies Daniel , Golassa Lemu 
Published: October 2021

Abstract
Background
Rapid diagnostic tests (RDT) are commonly used for the diagnosis of malaria caused by Plasmodium falciparum. However, false negative results of RDT caused by genetic variation of P. falciparum histidine-rich protein 2 and 3 genes (pfhrp2/3) threaten existing malaria case management and control efforts. The main objective of this study was to investigate the genetic variations of the pfhrp2/3 genes.

Methods
A cross-sectional study was conducted from malaria symptomatic individuals in 2018 in Assosa zone, Ethiopia. Finger-prick blood samples were collected for RDT and microscopic examination of thick and thin blood films. Dried blood spots (DBS) were used for genomic parasite DNA extraction and molecular detection. Amplification of parasite DNA was made by quantitative PCR. DNA amplicons of pfhrp2/3 were purified and sequenced.

Results
The PfHRP2 amino acid repeat type isolates were less conserved compared to the PfHRP3 repeat type. Eleven and eight previously characterized PfHRP2 and PfHRP3 amino acid repeat types were identified, respectively. Type 1, 4 and 7 repeats were shared by PfHRP2 and PfHRP3 proteins. Type 2 repeats were found only in PfHRP2, while types 16 and 17 were found only in PfHRP3 with a high frequency in all isolates. 18 novel repeat types were found in PfHRP2 and 13 novel repeat types were found in PfHRP3 in single or multiple copies per isolate. The positivity rate for PfHRP2 RDT was high, 82.9% in PfHRP2 and 84.3% in PfHRP3 sequence isolates at parasitaemia levels > 250 parasites/µl. Using the Baker model, 100% of the isolates in group A (If product of types 2 × type 7 repeats ≥ 100) and 73.7% of the isolates in group B (If product of types 2 × type 7 repeats 50–99) were predicted to be detected by PfHRP2 RDT at parasitaemia level > 250 parasite/μl.

Conclusion
The findings of this study indicate the presence of different PfHRP2 and PfHRP3 amino acid repeat including novel repeats in P. falciparum from Ethiopia. These results indicate that there is a need to closely monitor the performance of PfHRP2 RDT associated with the genetic variation of the pfhrp2 and pfhrp3 gene in P. falciparum isolates at the country-wide level.
Multiple overlapping stent-assisted coiling improves efficacy and safety of treatment for complex intracranial aneurysms: a randomized trial
Authors: You Lingtong , Huang Jiaxin , Zhang Jinning , Jiang Zhixian 
Published: October 2021

AbstractBackgroundIntracranial aneurysm rupture is the main cause of subarachnoid hemorrhage, leading to high disability and mortality. This study aimed to evaluate the clinical treatment effects of multiple overlapping stent-assisted coiling for complex intracranial aneurysms.MethodsWe conducted a randomized, controlled, single-blinded clinical trial among 168 patients diagnosed with complex intracranial aneurysms. Treatment allocation to either single stent (SS) group or multiple stent (MS) group was randomized at 1:1 ratio using a Web-based platform. The O’Kelly–Marotta (OKM) grading scale was used to evaluate the degree of aneurysm occlusion after operation and during follow-up. Good aneurysm occlusion was defined as OKM grade C–D. The modified Rankin Scale (mRS) was used to evaluate the neurological status and the clinical outcome of patients.ResultsEfficacy comparative analysis demonstrated that major recurrence of aneurysms was significantly reduced in the MS group (P = 0.012). In addition, the MS group displayed significantly reduced number of patients with mRS between 3 and 6 (P = 0.007) and increased number of patients with mRS between 0 and 1 (P = 0.034). Furthermore, the MS group showed increased percentage of patients with OKM grade C–D (P = 0.041). Compared with the SS group, the MS group exhibited decreased mortality (P = 0.037) and morbidity (P = 0.035).ConclusionsMultiple overlapping stent-assisted coiling significantly improved the clinical treatment effects and provided a new method for complex intracranial aneurysms.
Comparison of obesity-related indices for identifying nonalcoholic fatty liver disease: a population-based cross-sectional study in China
Authors: Xie Fangfei , Pei Yuyu , Zhou Quan , Cao Deli , Wang Yun 
Published: October 2021

Abstract
Background
The relationship between nonalcoholic fatty liver disease (NAFLD) and obesity-related indices has been analyzed separately thus far, and evidence comparing these indices together is still lacking, especially in China. This study aimed to comprehensively evaluate the predictive performance of anthropometric and metabolic indices to identify NAFLD in Chinese adults.

Methods
This study recruited a total of 1748 participants who were 18 years or older in southeastern China. The systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), total cholesterol (TC), triglycerides (TGs), low-density lipoprotein (LDL), waist circumference (WC), a body shape index (ABSI), atherogenic index of plasma (AIP), abdominal volume index (AVI), body adiposity index (BAI), body mass index (BMI), body roundness index (BRI), conicity index (CI), triglyceride glucose (TyG), waist hip ratio (WHR), and waist height ratio (WHtR) were measured. The association between these indices and NAFLD was analyzed via logistic analyses with odds ratios (ORs). Receiver operating characteristic (ROC) curves and areas under the curve (AUCs) were used to compare the predictive performance of these indices to identify NAFLD.

Results
BMI had the greatest total AUC (AUC = 0.841) in the ROC curve analysis. However, BRI and BMI both had the best diagnostic ability in males (AUC = 0.812), and BRI had the best diagnostic ability in females (AUC = 0.849). Furthermore, AVI had the greatest AUC for patients who were ~ 20 (AUC = 0.892) and ~ 40 years old (AUC = 0.831), while TyG showed a higher predictive ability than AVI in those who were ~ 60 years old (AUC = 0.766).

Conclusion
This study identified sex- and age-specific indices for predicting NAFLD in Chinese subjects. Compared with indices for all age groups, sex- and age-specific indices can provide more accurate assistance for clinical diagnosis and treatment.
Accumulation of cholesterol, triglycerides and ceramides in hepatocellular carcinomas of diethylnitrosamine injected mice
Authors: Haberl Elisabeth M. , Pohl Rebekka , Rein-Fischboeck Lisa , Höring Marcus , Krautbauer Sabrina , Liebisch Gerhard , Buechler Christa 
Published: October 2021

Abstract
Background
Dysregulated lipid metabolism is critically involved in the development of hepatocellular carcinoma (HCC). The respective metabolic pathways affected in HCC can be identified using suitable experimental models. Mice injected with diethylnitrosamine (DEN) and fed a normal chow develop HCC. For the analysis of the pathophysiology of HCC in this model a comprehensive lipidomic analysis was performed.

Methods
Lipids were measured in tumor and non-tumorous tissues by direct flow injection analysis. Proteins with a role in lipid metabolism were analysed by immunoblot. Mann-Whitney U-test or paired Student´s t-test were used for data analysis.

Results
Intra-tumor lipid deposition is a characteristic of HCCs, and di- and triglycerides accumulated in the tumor tissues of the mice. Peroxisome proliferator-activated receptor gamma coactivator 1 alpha, lipoprotein lipase and hepatic lipase protein were low in the tumors whereas proteins involved in de novo lipogenesis were not changed. Higher rates of de novo lipogenesis cause a shift towards saturated acyl chains, which did not occur in the murine HCC model. Besides, LDL-receptor protein and cholesteryl ester levels were higher in the murine HCC tissues. Ceramides are cytotoxic lipids and are low in human HCCs. Notably, ceramide levels increased in the murine tumors, and the simultaneous decline of sphingomyelins suggests that sphingomyelinases were involved herein. DEN is well described to induce the tumor suppressor protein p53 in the liver, and p53 was additionally upregulated in the tumors.

Conclusions
Ceramides mediate the anti-cancer effects of different chemotherapeutic drugs and restoration of ceramide levels was effective against HCC. High ceramide levels in the tumors makes the DEN injected mice an unsuitable model to study therapies targeting ceramide metabolism. This model is useful for investigating how tumors evade the cytotoxic effects of ceramides.
Association of lipid accumulation product with chronic kidney disease in Chinese community adults: a report from the REACTION study
Authors: Yan Pijun , Xu Yong , Miao Ying , Tang Qian , Wu Yuru , Bai Xue , Zhang Zhihong , Li Qian , Wan Qin 
Published: October 2021

Abstract
Background
Limited studies regarding the correlation of lipid accumulation product (LAP) with a decreased estimated glomerular filtration rate (eGFR) have yielded conflicting findings, and no report has demonstrated the relationship of LAP with chronic kidney disease (CKD), defined as the presence of albuminuria and/or a decreased eGFR. The purpose of this study was to estimate the possible correlation of LAP with CKD prevalence in Chinese community adults.

Method
In this cross-sectional study, LAP level of 7202 participants (age ≥ 40 years) was determined, and its possible association with CKD was evaluated by a multiple logistic regression model.

Results
Compared with subjects with non-CKD, non-albuminuria, and high eGFR, LAP levels significantly increased in female not male subjects with CKD, albuminuria, and low eGFR, respectively (all P < 0.001). The univariate logistic regression analysis revealed that LAP level of female not male subjects were significantly and positively associated with the prevalence of CKD (P < 0.001). The multivariate logistic regression analysis showed that the risk of CKD prevalence in female not male subjects progressively increased across LAP quartiles (P for trend < 0.01), and the risk of CKD prevalence of subjects in Q4 significantly increased compared to those in Q1 after adjustment for potential confounding factors in Models 4 (odds ratio [OR]: 1.382, 95% confidence intervals [CI] 1.002–1.906, P < 0.05). Stratified analysis revealed positive associations of LAP quartiles with risk of CKD prevalence in people with the following characteristics: women, older, overweight, with hypertension, normal glucose tolerance, appropriate low-density lipoprotein cholesterol, nonsmokers, nondrinkers, and no cardiovascular disease events.

Conclusions
High LAP levels might be significantly associated with risk of CKD prevalence in community-dwelling Chinese female adults, which may inform both public health recommendations and clinical practice.
Investigating the response scale of the EORTC QLQ-C30 in German cancer patients and a population survey
Authors: Koller Michael , Müller Karolina , Nolte Sandra , Schmidt Heike , Harvey Christina , Mölle Ulrike , Boehm Andreas , Engeler Daniel , Metzger Jürg , Sztankay Monika , Holzner Bernhard , Groenvold Mogens , Kuliś Dagmara , Bottomley Andrew ,   the EORTC Quality of Life Group
Published: October 2021

Abstract
Background
The European Organization for research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30) scales are scored on a 4-point response scale, ranging from not at all to very much. Previous studies have shown that the German translation of the response option quite a bit as mäßig violates interval scale assumptions, and that ziemlich is a more appropriate translation. The present studies investigated differences between the two questionnaire versions.

Methods
The first study employed a balanced cross-over design and included 450 patients with different types of cancer from three German-speaking countries. The second study was a representative survey in Germany including 2033 respondents. The main analyses included compared the ziemlich and mäßig version of the questionnaire using analyses of covariance adjusted for sex, age, and health burden.

Results
In accordance with our hypothesis, the adjusted summary score was lower in the mäßig than in the ziemlich version; Study 1: − 4.5 (95% CI − 7.8 to − 1.3), p = 0.006, Study 2: − 3.1 (95% CI − 4.6 to − 1.5), p < 0.001. In both studies, this effect was pronounced in respondents with a higher health burden; Study 1: − 6.8 (95% CI − 12.2 to − 1.4), p = 0.013; Study 2: − 4.5 (95% CI − 7.3 to − 1.7), p = 0.002.

Conclusions
We found subtle but consistent differences between the two questionnaire versions. We recommend to use the optimized response option for the EORTC QLQ-C30 as well as for all other German modules.
Trial registration: The study was retrospectively registered on the German Registry for Clinical Studies (reference number DRKS00012759, 04th August 2017, https://www.drks.de/DRKS00012759).
Regional brain tissue changes in patients with cystic fibrosis
Authors: Roy Bhaswati , Woo Marlyn S. , Vacas Susana , Eshaghian Patricia , Rao Adupa P. , Kumar Rajesh 
Published: October 2021

Abstract
Background
Cystic fibrosis (CF) patients present with a variety of symptoms, including mood and cognition deficits, in addition to classical respiratory, and autonomic issues. This suggests that brain injury, which can be examined with non-invasive magnetic resonance imaging (MRI), is a manifestation of this condition. However, brain tissue integrity in sites that regulate cognitive, autonomic, respiratory, and mood functions in CF patients is unclear. Our aim was to assess regional brain changes using high-resolution T1-weighted images based gray matter (GM) density and T2-relaxometry procedures in CF over control subjects.

Methods
We acquired high-resolution T1-weighted images and proton-density (PD) and T2-weighted images from 5 CF and 15 control subjects using a 3.0-Tesla MRI. High-resolution T1-weighted images were partitioned to GM-tissue type, normalized to a common space, and smoothed. Using PD- and T2-weighted images, whole-brain T2-relaxation maps were calculated, normalized, and smoothed. The smoothed GM-density and T2-relaxation maps were compared voxel-by-voxel between groups using analysis of covariance (covariates, age and sex; SPM12, p < 0.001).

Results
Significantly increased GM-density, indicating tissues injury, emerged in multiple brain regions, including the cerebellum, hippocampus, amygdala, basal forebrain, insula, and frontal and prefrontal cortices. Various brain areas showed significantly reduced T2-relaxation values in CF subjects, indicating predominant acute tissue changes, in the cerebellum, cerebellar tonsil, prefrontal and frontal cortices, insula, and corpus callosum.

Conclusions
Cystic fibrosis subjects show predominant acute tissue changes in areas that control mood, cognition, respiratory, and autonomic functions and suggests that tissue changes may contribute to symptoms resulting from ongoing hypoxia accompanying the condition.
Vaccination of older adults: Influenza, pneumococcal disease, herpes zoster, COVID-19 and beyond
Authors: Weinberger Birgit 
Published: October 2021

AbstractPreserving good health in old age is of utmost importance to alleviate societal, economic and health care-related challenges caused by an aging society. The prevalence and severity of many infectious diseases is higher in older adults, and in addition to the acute disease, long-term sequelae, such as exacerbation of underlying chronic disease, onset of frailty or increased long-term care dependency, are frequent. Prevention of infections e.g. by vaccination is therefore an important measure to ensure healthy aging and preserve quality of life. Several vaccines are specifically recommended for older adults in many countries, and in the current SARS-CoV-2 pandemic older adults were among the first target groups for vaccination due to their high risk for severe disease. This review highlights clinical data on the influenza,Streptococcus pneumoniaeand herpes zoster vaccines, summarizes recent developments to improve vaccine efficacy, such as the use of adjuvants or higher antigen dose for influenza, and gives an overview of SARS-CoV-2 vaccine development for older adults. Substantial research is ongoing to further improve vaccines, e.g. by developing universal influenza and pneumococcal vaccines to overcome the limitations of the current strain-specific vaccines, and to develop novel vaccines against pathogens, which cause considerable morbidity and mortality in older adults, but for which no vaccines are currently available. In addition, we need to improve uptake of the existing vaccines and increase awareness for life-long vaccination in order to provide optimal protection for the vulnerable older age group.