bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bioinformatics prediction and experimental verification identify MAD2L1 and CCNB2 as diagnostic biomarkers of rhabdomyosarcoma
Authors: Xia Tian , Meng Lian , Zhao Zhijuan , Li Yujun , Wen Hao , Sun Hao , Zhang Tiantian , Wei Jingxian , Li Feng , Liu Chunxia 
Published: November 2021

Abstract
Background
Rhabdomyosarcoma (RMS) is a malignant soft-tissue tumour. In recent years, the tumour microenvironment (TME) has been reported to be associated with the development of tumours. However, the relationship between the occurrence and development of RMS and TME is unclear. The purpose of this study is to identify potential tumor microenvironment-related biomarkers in rhabdomyosarcoma and analyze their molecular mechanisms, diagnostic and prognostic significance.

Methods
We first applied bioinformatics method to analyse the tumour samples of 125 patients with rhabdomyosarcoma (RMS) from the Gene Expression Omnibus database (GEO). Differential genes (DEGs) that significantly correlate with TME and the clinical staging of tumors were extracted. Immunohistochemistry (IHC) was applied to validate the expression of mitotic arrest deficient 2 like 1 (MAD2L1) and cyclin B2 (CCNB2) in RMS tissue. Then, we used cell function and molecular biology techniques to study the influence of MAD2L1 and CCNB2 expression levels on the progression of RMS.

Results
Bioinformatics results show that the RMS TME key genes were screened, and a TME-related tumour clinical staging model was constructed. The top 10 hub genes were screened through the establishment of a protein–protein interaction (PPI) network, and then Gene Expression Profiling Interactive Analysis (GEPIA) was conducted to measure the overall survival (OS) of the 10 hub genes in the sarcoma cases in The Cancer Genome Atlas (TCGA). Six DEGs of statistical significance were acquired. The relationship between these six differential genes and the clinical stage of RMS was analysed. Further analysis revealed that the OS of RMS patients with high expression of MAD2L1 and CCNB2 was worse and the expression of MAD2L1 and CCNB2 was related to the clinical stage of RMS patients. Gene set enrichment analysis (GSEA) revealed that the genes in MAD2L1 and CCNB2 groups with high expression were mainly related to the mechanism of tumour metastasis and recurrence. In the low-expression MAD2L1 and CCNB2 groups, the genes were enriched in the metabolic and immune pathways. Immunohistochemical results also confirmed that the expression levels of MAD2L1 (30/33, 87.5%) and CCNB2 (33/33, 100%) were remarkably higher in RMS group than in normal control group (0/11, 0%). Moreover, the expression of CCNB2 was related to tumour size. Downregulation of MAD2L1 and CCNB2 suppressed the growth, invasion, migration, and cell cycling of RMS cells and promoted their apoptosis. The CIBERSORT immune cell fraction analysis indicated that the expression levels of MAD2L1 and CCNB2 affected the immune status in the TME.

Conclusions
The expression levels of MAD2L1 and CCNB2 are potential indicators of TME status changes in RMS, which may help guide the prognosis of patients with RMS and the clinical staging of tumours.
High prevalence of malaria in a non-endemic setting among febrile episodes in travellers and migrants coming from endemic areas: a retrospective analysis of a 2013–2018 cohort
Authors: Garcia-Ruiz de Morales Alejandro , Morcate Covadonga , Isaba-Ares Elena , Perez-Tanoira Ramon , Perez-Molina Jose A. 
Published: November 2021

Abstract
Background
The study aimed to analyse the likelihood of imported malaria in people with a suggestive clinical picture and its distinctive characteristics in a hospital in the south of Madrid, Spain.

Methods
Observational retrospective study that consisted of a review of all medical files of patients with any malaria test registered at Móstoles University Hospital between April 2013 and April 2018. All suspected malaria cases were confirmed by Plasmodium spp. polymerase chain reaction (PCR).

Results
Of the 328 patients with suspected malaria (53.7% migrant-travellers; 38.7% visitors; 7.6% travellers), 108 cases were confirmed (101 by Plasmodium falciparum), accounting for a 33% positive sample rate. Sixteen cases were diagnosed only by PCR. Patients with malaria, compared to those without, presented predominantly with fever (84% vs. 65%), were older (34 vs. 24 years), sought medical attention earlier (17d vs. 32d), had a greater number of previous malaria episodes (74% vs. 60%), lower levels of platelets (110,500µL vs. 250,000µL), and higher of bilirubin (0.6 mg/dL vs. 0.5 mg/dL). Severe malaria was present in 13 cases; no deaths were recorded. Malaria diagnosis showed a bimodal distribution with two peaks: June to September and November to January.

Conclusions
Malaria is still a common diagnosis among febrile patients coming from the tropics specially among migrant travellers. Fever, thrombocytopenia, and/or high bilirubin levels should raise suspicion for this parasitic infection. Prompt diagnosis is crucial to avoid severe cases and deaths.
Assessing health-seeking behaviour and malaria prevention practices among communities in four districts of the Volta Region of Ghana
Authors: Orish Verner N. , Maalman Raymond Saa-Eru , Donkor Otchere Y. , Ceruantes Barbara Yordanis Henandez , Osei Eric , Amu Hubert , Appiah Prince Kubi , Konlan Kennedy Diema , Mumuni Hadiru , Kim Eunji , Kim Siwoo , Jung Hajun , Ofori-Amoah Jones , Kofie Philip , Adjuik Martin , Alhassan Robert Kaba , Donkor Ernestina Safoa , Zottor Francis Bruno , Kweku Margaret , Amuna Paul , Kim So Yoo , Gyapong John Owusu ,   the UHAS-Yonsei Project Team
Published: November 2021

Abstract
Background
Malaria is a preventable disease that causes huge morbidity and mortality in malaria-endemic areas, especially among children and pregnant women. The malaria control programme focuses on the prevention of mosquito bites using insecticide-treated nets (ITNs) and mosquito aerosol sprays and coils, as well as prevention of severe disease among those infected through prompt and adequate treatment. The success of the malaria control programme in Ghana is dependent on the malaria prevention practices of people in the community. Therefore, this study evaluated the malaria prevention practices of participants in four districts of the Volta Region of Ghana.

Methods
This was a cross-sectional study conducted in Ketu South, Nkwanta South, Hohoe Municipality and Ho West districts of the Volta Region of Ghana. Questionnaire were administered to adults who consented to each household visited. Questions were asked on the socio-demographics and malaria prevention practices of the households. Data analysis was done using SPSS version 23 with frequency distribution done for all the variables. Pearson chi-square was used to determine the significant association between socio-demographics and malaria prevention practices, and Multivariate nominal logistic regression analysis was used to model the relationship between dichotomous dependent variables (ITN ownership and usage) and independent variables.

Results
Out of the 2493 participants; 2234 (89.6%) owned ITN and 1528 (68.4%) used ITN a night before this study, 768 (30.8%) used mosquito aerosol spray and 368 (15%) used mosquito coil. More females significantly owned ITN than males (1293, 92.4%, p ≤ 0.001). Participants from Ketu South had 1.5 times higher odds of owning an ITN compared to Ho West whose odds are not different from Nkwanta South or Hohoe (AOR, 1.56 [95% 1.09–2.22]; p = 0.01). In terms of ITN usage, participants in Nkwanta South were less likely to use ITN compared to the other districts; AOR, 0.434 [95% CI 0.31–0.62, p < 0.001]. Also, of the 668 participants that had a fever within the past 3 days, 268 (40.1%) visited a patent medicine store and 156 (23.4%) visited health facilities.

Conclusion
There is high ownership of ITNs, but relatively low utilization among the community members. Education on malaria prevention practices should be intensified and continuous among the population of the Volta Region to ensure the success of malaria control in the region.
Long-term training on sand changes lower limb muscle activities during running in runners with over-pronated feet
Authors: Jafarnezhadgero AmirAli , Fatollahi Amir , Sheykholeslami Ali , Dionisio Valdeci Carlos , Akrami Mohammad 
Published: November 2021

Abstract
Background
Running on sand could be a promising exercise intervention for the treatment of over-pronated feet. However, there is a lack of knowledge about the effects of running on sand on muscle activities. Therefore, this study aims to evaluate the long-term effects of running on sand on the activities of selected lower limb muscles in individuals with OPF compared with healthy controls.

Methods
Sixty recreational adult male runners with over-pronated feet (foot posture index > 10) were divided into two equal groups (intervention and control). Participants ran barefoot at a pre-defined speed (⁓3.3 m/s) over level stable ground both before and after long-term training on the sand. Muscle activities were recorded using a surface bipolar electromyography system.

Results
For the intervention group, we found a reduced foot posture index (p < 0.001; d = 2.00) and significant group-by-time interactions for gluteus medius activity during the mid-stance phase (p < 0.028; d = 0.59). Significantly higher gluteus medius activity (p = 0.028, d = 0.569) was found during the post-test. We also observed significant group-by-time interactions for medial gastrocnemius activity during the push-off phase (p < 0.041; d = 0.54). Significantly larger medial gastrocnemius activity (p = 0.041; d = 0.636) was found during the post-test compared to the pre-test.

Conclusions
Long-term running on sand resulted in reduced pronation, increased medial gastrocnemius activity, and improved frontal plane pelvic stability due to higher gluteus medius activity.
Trial registration: IRCT20191211045704N1. Registered 25 February 2020. Retrospectively registered.
Effect of limb rotation on radiographic alignment measurement in mal-aligned knees
Authors: Sun Xiaoshu , Yang Bin , Xiao Shengzhao , Yan Yichen , Liu Zifan , Yuan Liang , Wang Xiaohua , Sun Bin , Yao Jie , Fan Yubo 
Published: November 2021

Abstract
Purpose
Long-leg-radiography (LLR) is commonly used for the measurement of lower limb alignment. However, limb rotations during radiography may interfere with the alignment measurement. This study examines the effect of limb rotation on the accuracy of measurements based on the mechanical and anatomical axes of the femur and tibia, with variations in knee flexion and coronal deformity.

Methods
Forty-five lower limbs of 30 patients were scanned with CT. Virtual LLRs simulating five rotational positions (neutral, ± 10$$^{\circ }$$

∘

, and ± 20$$^{\circ }$$

∘

internal rotation) were generated from the CT images. Changes in the hip–knee–ankle angle (HKA) and the femorotibial angle (FTA) were measured on each image with respect to neutral values. These changes were related to knee flexion and coronal deformity under both weight- and non-weight-bearing conditions.

Results
The measurement errors of the HKA and FTA derived from limb rotation were up to 4.84 ± 0.66$$^{\circ }$$

∘

and 7.35 ± 0.88$$^{\circ }$$

∘

, respectively, and were correlated with knee flexion (p < 0.001) and severe coronal deformity (p < 0.001). Compared with the non-weight-bearing position, the coronal deformity measured in the weight-bearing condition was 2.62$$^{\circ }$$

∘

greater, the correlation coefficients between the coronal deformity and the deviation ranges of HKA and FTA were also greater.

Conclusions
Flexion and severe coronal deformity have a significant influence on the measurement error of lower limb alignment. Errors can be amplified in the weight-bearing condition compared with the non-weight-bearing condition. When using HKA and FTA to represent the mechanical axis and the anatomical axis on LLR, limb rotation impacts the anatomic axis more than the mechanical axis in patients with severe deformities. Considering LLR as the gold standard image modality, attention should be paid to the measurement of knee alignment. Especially for the possible errors derived from weight-bearing long-leg radiographs of patients with severe knee deformities.
Dysregulation of alternative splicing is associated with the pathogenesis of ulcerative colitis
Authors: Li Daowei , Tan Yue 
Published: November 2021

Abstract
Background
Although numerous risk loci for ulcerative colitis (UC) have been identified in the human genome, the pathogenesis of UC remains unclear. Recently, multiple transcriptomic analyses have shown that aberrant gene expression in the colon tissues of UC patients is associated with disease progression. A pioneering study also demonstrated that altered post-transcriptional regulation is involved in the progression of UC. Here, we provide a genome-wide analysis of alternative splicing (AS) signatures in UC patients. We analyzed three datasets containing 74 tissue samples from UC patients and identified over 2000 significant AS events.

Results
Skipped exon and alternative first exon were the two most significantly altered AS events in UC patients. The immune response-related pathways were remarkably enriched in the UC-related AS events. Genes with significant AS events were more likely to be dysregulated at the expression level.

Conclusions
We present a genomic landscape of AS events in UC patients based on a combined analysis of two cohorts. Our results indicate that dysregulation of AS may have a pivotal role in determining the pathogenesis of UC. In addition, our study uncovers genes with potential therapeutic implications for UC treatment.
Prenatal ambient air pollution and maternal depression at 12 months postpartum in the MADRES pregnancy cohort
Authors: Bastain Theresa M. , Chavez Thomas , Habre Rima , Hernandez-Castro Ixel , Grubbs Brendan , Toledo-Corral Claudia M. , Farzan Shohreh F. , Lurvey Nathana , Lerner Deborah , Eckel Sandrah P. , Lurmann Fred , Lagomasino Isabel , Breton Carrie 
Published: November 2021

Abstract
Background
Depression is the leading cause of mental health-related morbidity and affects twice as many women as men. Hispanic/Latina women in the US have unique risk factors for depression and they have lower utilization of mental health care services. Identifying modifiable risk factors for maternal depression, such as ambient air pollution, is an urgent public health priority. We aimed to determine whether prenatal exposure to ambient air pollutants was associated with maternal depression at 12 months after childbirth.

Methods
One hundred eighty predominantly low-income Hispanic/Latina women participating in the ongoing MADRES cohort study in Los Angeles, CA were followed from early pregnancy through 12 months postpartum through a series of phone questionnaires and in-person study visits. Daily prenatal ambient pollutant estimates of nitrogen dioxide (NO2), ozone (O3), and particulate matter (PM10 and PM2.5) were assigned to participant residences using inverse-distance squared spatial interpolation from ambient monitoring data. Exposures were averaged for each trimester and across pregnancy. The primary outcome measure was maternal depression at 12 months postpartum, as reported on the 20-item Center for Epidemiologic Studies-Depression (CES-D) scale. We classified each participant as depressed (n = 29) or not depressed (n = 151) based on the suggested cutoff of 16 or above (possible scores range from 0 to 60) and fitted logistic regression models, adjusting for potential confounders.

Results
We found over a two-fold increased odds of depression at 12 months postpartum associated with second trimester NO2 exposure (OR = 2.63, 95% CI: 1.41–4.89) and pregnancy average NO2 (OR = 2.04, 95% CI: 1.13–3.69). Higher second trimester PM2.5 exposure also was associated with increased depression at 12 months postpartum (OR = 1.56, 95% CI: 1.01–2.42). The effect for second trimester PM10 was similar and was borderline significant (OR = 1.58, 95% CI: 0.97–2.56).

Conclusions
In a low-income cohort consisting of primarily Hispanic/Latina women in urban Los Angeles, we found that prenatal ambient air pollution, especially mid-pregnancy NO2 and PM2.5, increased the risk of depression at 12 months after childbirth. These results underscore the need to better understand the contribution of modifiable environmental risk factors during potentially critical exposure periods.
A new phenotypic classification system for dyslipidemias based on the standard lipid panel
Authors: Sampson Maureen , Ballout Rami A. , Soffer Daniel , Wolska Anna , Wilson Sierra , Meeusen Jeff , Donato Leslie J. , Fatica Erica , Otvos James D. , Brinton Eliot A. , Rosenson Robert S. , Wilson Peter , Amar Marcelo , Shamburek Robert , Karathanasis Sotirios K. , Remaley Alan T. 
Published: November 2021

Abstract
Background
Dyslipoproteinemias can be classified by their distinct lipoprotein patterns, which helps determine atherosclerotic cardiovascular disease (ASCVD) risk and directs lipid management but this has required advanced laboratory testing.

Objective
To develop a new algorithm for classifying lipoprotein disorders that only relies on the standard lipid panel.

Methods
Lipid thresholds for defining the different lipoprotein phenotypes were derived for Non-High-Density Lipoprotein-Cholesterol (NonHDL-C) and Triglycerides (TG) to be concordant when possible with the current US Multi-Society guidelines for blood cholesterol management.

Results
The new classification method categorizes patients into all the classical Fredrickson-like phenotypes except for Type III dysbetalipoproteinemia. In addition, a new hypolipidemic phenotype (Type VI) due to genetic mutations in apoB-metabolism is described. The validity of the new algorithm was confirmed by lipid analysis by NMR (N = 11,365) and by concordance with classification by agarose gel electrophoresis/beta-quantification (N = 5504). Furthermore, based on the Atherosclerosis Risk in Communities (ARIC) cohort (N = 14,742), the lipoprotein phenotypes differ in their association with ASCVD (TypeV>IIb > IVb > IIa > IVa > normolipidemic) and can be used prognostically as risk enhancer conditions in the management of patients.

Conclusions
We describe a clinically useful lipoprotein phenotyping system that is only dependent upon the standard lipid panel. It, therefore, can be easily implemented for increasing compliance with current guidelines and for improving the care of patients at risk for ASCVD.
Associations of visit-to-visit variabilities and trajectories of serum lipids with the future probability of type 2 diabetes mellitus
Authors: Sun Qian , Liu Jingchao , Wu Lei , Sun Yue , Jin Jianrong , Wang Sudan , Wu Jing , Jing Yang , Zhou Hui , Dong Chen 
Published: November 2021

Abstract
Background
Serum lipid abnormalities are generally considered as a major risk factor for type 2 diabetes mellitus (T2DM). However, evidence for the effect of long-term serum lipid fluctuations on future T2DM probability remains limited.

Methods
A total of 4475 nondiabetic participants who underwent annual health examinations between 2010 and 2013 were followed for the subsequent 5-year risk of T2DM. The Cox proportional hazards model was performed to evaluate the associations of visit-to-visit variabilities and trajectories of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c) with T2DM probability.

Results
During the five-year follow-up, 223 newly developed T2DM cases were identified. Compared with the “Low” TG trajectory, “Moderate” and “Moderate-High” TG trajectories were significantly associated with T2DM incidence, with adjusted hazard ratios (HRs) and 95 % confidence intervals (CIs) of 1.51 (1.12-2.03) and 2.55 (1.62-4.03), respectively. Additionally, participants in the third and fourth quartiles of TG/standard deviation (SD) were associated with increased T2DM probability when compared with those in the lowest quartile. After excluding individuals with prediabetes, participants with “Moderate-High” TG trajectory still had a 2.43-fold greater risk of T2DM compared with those with “Low” TG trajectory (95 % CI: 1.28-4.63). In addition, compared with participants in “Low” HDL-c trajectory, the future T2DM probability was significantly reduced in those with “Moderate” and “High” HDL-c trajectories, with HR (95 % CI) of 0.52 (0.37-0.72) and 0.38 (0.18-0.80), respectively. After excluding individuals with prediabetes, the “Moderate” HDL-c trajectory remained associated with decreased T2DM probability when compared with “Low” HDL-c trajectory (HR: 0.55, 95 % CI: 0.35-0.88). However, the incidence of T2DM was not associated with the long-term fluctuations of TC and LDL-c.

Conclusions
Long-term visit-to-visit variability of TG, and the change trajectories of TG and HDL-c were significantly associated with future T2DM probability. Moreover, these associations were not affected after excluding individuals with prediabetes.
Application of nanotechnology in the diagnosis and treatment of bladder cancer
Authors: Xu Yadong , Luo Cheng , Wang Jieqiong , Chen Lingwu , Chen Junxing , Chen Tianfeng , Zeng Qinsong 
Published: November 2021

AbstractBladder cancer (BC) is a common malignancy in the genitourinary system and the current theranostic approaches are unsatisfactory. Sensitivity and specificity of current diagnosis methods are not ideal and high recurrence and progression rates after initial treatment indicate the urgent need for management improvements in clinic. Nanotechnology has been proposed as an effective method to improve theranosis efficiency for both non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC). For example, gold nanoparticles (AuNPs) have been developed for simple, fast and sensitive urinary sample test for bladder cancer diagnosis. Nanoparticles targeting bladder cancers can facilitate to distinguish the normal and abnormal bladder tissues during cystoscopy and thus help with the complete removal of malignant lesions. Both intravenous and intravesical agents can be modified by nanotechnology for targeted delivery, high anti-tumor efficiency and excellent tolerability, exhibiting encouraging potential in bladder cancer treatment. Photosensitizers and biological agents can also be delivered by nanotechnology, intermediating phototherapy and targeted therapy. The management of bladder cancer remained almost unchanged for decades with unsatisfactory effect. However, it is likely to change with the fast-developed nanotechnology. Herein we summarized the current utility of nanotechnology in bladder cancer diagnosis and treatment, providing insights for the future designing and discovering novel nanoparticles for bladder cancer management.
Graphical Abstract