bluuebunny/crossref_metadata_2025_split huggingface dataset:
STAT3 pathway as a molecular target for resveratrol in breast cancer treatment
Authors: Kohandel Zeynab , Farkhondeh Tahereh , Aschner Michael , Pourbagher-Shahri Ali Mohammad , Samarghandian Saeed 
Published: September 2021

AbstractSignal transducer and activator of transcription 3 (STAT3) induces breast cancer malignancy. Recent clinical and preclinical studies have demonstrated an association between overexpressed and activated STAT3 and breast cancer progression, proliferation, metastasis, and chemoresistance. Resveratrol (RES), a naturally occurring phytoalexin, has demonstrated anti-cancer activity in several disease models. Furthermore, RES has also been shown to regulate the STAT3 signaling cascade via its anti-oxidant and anti-inflammatory effects. In the present review, we describe the STAT3 cascade signaling pathway and address the therapeutic targeting of STAT3 by RES as a tool to mitigate breast cancer.
Recombinant immunotoxins development for HER2-based targeted cancer therapies
Authors: Mahmoudi Reza , Dianat-Moghadam Hassan , Poorebrahim Mansour , Siapoush Samaneh , Poortahmasebi Vahdat , Salahlou Reza , Rahmati Mohammad 
Published: September 2021

AbstractUnderstanding the molecular mechanisms of cancer biology introduces targeted therapy as a complementary method along with other conventional therapies. Recombinant immunotoxins are tumor specific antibodies that their recognizing fragment is utilized for delivering modified toxins into tumor cells. These molecules have been considered as a targeted strategy in the treatment of human cancers. HER2 tumor biomarker is a transmembrane tyrosine kinase receptor that can be used for targeted therapies in the forms of anti-HER2 monoclonal antibodies, antibody–drug conjugates and immunotoxins. There have been many studies on HER2-based immunotoxins in recent years, however, little progress has been made in the clinical field which demanded more improvements. Here, we summarized the HER2 signaling and it’s targeting using immunotherapeutic agents in human cancers. Then, we specifically reviewed anti-HER2 immunotoxins, and their strengths and drawbacks to highlight their promising clinical impact.
Risk factors for Plasmodium falciparum infection in pregnant women in Burkina Faso: a community-based cross-sectional survey
Authors: Yaro Jean Baptiste , Ouedraogo Alphonse , Diarra Amidou , Sombié Salif , Ouedraogo Z. Amidou , Nébié Issa , Drakeley Chris , Sirima Sodiomon B. , Tiono Alfred B. , Lindsay Steven W. , Wilson Anne L. 
Published: September 2021

Abstract
Background
Malaria in pregnancy remains a public health problem in sub-Saharan Africa. Identifying risk factors for malaria in pregnancy could assist in developing interventions to reduce the risk of malaria in Burkina Faso and other countries in the region.

Methods
Two cross-sectional surveys were carried out to measure Plasmodium falciparum infection using microscopy in pregnant women in Saponé Health District, central Burkina Faso. Data were collected on individual, household and environmental variables and their association with P. falciparum infection assessed using multivariable analysis.

Results
A total of 356 pregnant women were enrolled in the surveys, 174 during the dry season and 182 during the wet season. The mean number of doses of sulfadoxine–pyrimethamine for Intermittent Preventive Treatment in pregnancy (IPTp-SP) was 0.4 doses during the first trimester, 1.1 doses at the second and 2.3 doses at the third. Overall prevalence of P. falciparum infection by microscopy was 15.7%; 17.8% in the dry season and 13.7% in the wet season. 88.2% of pregnant women reported sleeping under an insecticide-treated net (ITN) on the previous night. The odds of P. falciparum infection was 65% lower in women who reported using an ITN compared to those that did not use an ITN (Odds ratio, OR = 0.35, 95% CI 0.14–0.86, p = 0.02). IPTp-SP was also associated with reduced P. falciparum infection, with each additional dose of IPTp-SP reducing the odds of infection by 44% (OR = 0.56, 95% CI 0.39–0.79, p = 0.001). Literate women had a 2.54 times higher odds of P. falciparum infection compared to illiterate women (95% CI 1.31–4.91, p = 0.006).

Conclusions
The prevalence of P. falciparum infection among pregnant women remains high in Burkina Faso, although use of IPTp-SP and ITNs were found to reduce the odds of infection. Despite this, compliance with IPTp-SP remains far from that recommended by the National Malaria Control Programme and World Health Organization. Behaviour change communication should be strengthened to encourage compliance with protective malaria control tools during pregnancy.
The association between physical activity, sedentary time and health-related quality of life in cancer survivors
Authors: Yan Rui , Che Beibei , Lv Binghui , Wu Peng , Lu Xinyuan , Zhang Yaxuan , Wang Jiwei , Yu Jinming 
Published: September 2021

Abstract
Background
Although physical activity (PA) and sedentary time in cancer survivors (CSs) were associated with health-related quality of life (HRQOL), it was not clear whether their associations were similar among CSs with different number of comorbid chronic diseases (CCDs). This study aimed to investigate the associations between PA, sedentary time and HRQOL in CSs with different number of CCDs.

Methods
A cross-sectional study was conducted among 1546 CSs between June and September 2018 in Shanghai, China. Data were collected with a self-reported questionnaire including sociodemographic characteristics, CCDs, PA, sedentary time and HRQOL. International Physical Activity Questionnaire and Cancer Quality of Life Questionnaire-Core30 were respectively used to measure PA and HRQOL of CSs. Associations of PA and sedentary time with HRQOL among CSs with different number of CCDs were evaluated by using logistic regression, adjusted for confounding factors.

Results
About seventy-five percent CSs had at least one CCD. Approximately three fifths CSs had high PA level and < 4 h/day sedentary time. Moderate PA level and high PA level were shown to be associated with better HRQOL among all participants. In CSs with ≤ 2 CCDs, high PA level was significantly associated with higher scores of physical function and lower scores of nausea and vomiting, appetite loss. However, there was a positive association between high PA level and constipation score among CSs with ≥ 3 CCDs. CSs with shorter sedentary time had better HRQOL in those with CCDs.

Conclusions
High PA level and long sedentary time have significant association with worse HRQOL of CSs with ≥ 3 CCDs, while high PA level is positively associated with HRQOL in CSs with ≤ 2 CCDs. Our findings may support further studies of the causal association between PA, sedentary times and HRQOL to provide targeted proposal to improve the HRQOL of CSs according to their number of CCDs.
Validation of the German version of the needs assessment tool: progressive disease-heart failure
Authors: Gonzalez-Jaramillo Valentina , Guyer Jelena , Luethi Nora , Sobanski Piotr , Zbinden Rut , Rodriguez Eveline , Hunziker Lukas , Eychmüller Steffen , Maessen Maud 
Published: September 2021

Abstract
Background
The Needs Assessment Tool: Progressive Disease-Heart Failure (NAT: PD-HF) is a tool created to assess the needs of people living with heart failure and their informal caregivers to assist delivering care in a more comprehensive way that addresses actual needs that are unmet, and to improve quality of life. In this study, we aimed to (1) Translate the tool into German and culturally adapt it. (2) Assess internal consistency, inter-rater reliability, and test–retest reliability of the German NAT: PD-HF. (3) Evaluate whether and how patients and health care personnel understand the tool and its utility. (4) Assess the tool’s face validity, applicability, relevance, and acceptability among health care personnel.

Methods
Single-center validation study. The tool was translated from English into German using a forward–backward translation. To assess internal consistency, we used Cronbach´s alpha. To assess inter-rater reliability and test–retest reliability, we used Cohen´s kappa, and to assess validity we used face validity.

Results
The translated tool showed good internal consistency. Raters were in substantial agreement on a majority of the questions, and agreement was almost perfect for all the questions in the test–retest analysis. Face validity was rated high by health care personnel.

Conclusion
The German NAT: PD-HF is a reliable, valid, and internally consistent tool that is well accepted by both patients and health care personnel. However, it is important to keep in mind that effective use of the tool requires training of health care personnel.
Interferon regulatory factor family influences tumor immunity and prognosis of patients with colorectal cancer
Authors: Chen Yan-Jie , Luo Shu-Neng , Dong Ling , Liu Tao-Tao , Shen Xi-Zhong , Zhang Ning-Ping , Liang Li 
Published: September 2021

AbstractBackgroundSince interferon regulatory factor (IRF) family functions in immune response to viral infection, its role in colorectal cancer (CRC) has not been inspected before. This study tries to investigate members of IRF family using bioinformatics approaches in aspect of differential expressions, biological function, tumor immune infiltration and clinical prognostic value for patients with CRC.MethodsTranscriptome profiles data, somatic mutations and clinical information of CRC were obtained from COAD/READ dataset of The Cancer Genome Atlas (TCGA) as a training set. Gene expression data (GSE17536 and GSE39582) were downloaded from the Gene Expression Omnibus as a validating set. A random forest algorithm was used to score the risk for every case. Analyzing gene and function enrichment, constructing protein–protein interaction and noncoding RNA network, identifying hub-gene, characterizing tumor immune infiltration, evaluating differences in tumor mutational burden (TMB) and sensitivity to chemotherapeutics or immunotherapy were performed by a series of online tools and R packages. Immunohistochemical (IHC) examinations were carried out validation in tissue samples.ResultsPrincipal-component analysis (PCA) suggested that the transcript expression levels of nine members of IRF family differed between normal colorectum and CRC. The risk score constructed by IRF family not only acted as an independent factor for predicting survival in CRC patients with different biological processes, signaling pathways and TMB, but also indicated different immunotherapy response with diverse immune and stromal cells infiltration. IRF3 and IRF7 were upregulated in CRC and suggested a shorter survival time in patients with CRC. Differentially expressed members of IRF family exhibited varying degrees of immune cell infiltration. IHC analysis showed a positive association between IRF3 and IRF7 expression and tumor-infiltrating immune cells, including CD4+T cell and CD68+macrophages.ConclusionsOn account of differential expression, IRF family members can help to predict both response to immunotherapy and clinical prognosis of patients with CRC. Our bioinformatic investigation not only gives a preliminary picture of the genetic features as well as tumor microenvironment, but it may provide a clue for further experimental exploration and verification on IRF family members in CRC.
Increased Tc17 cell levels and imbalance of naïve/effector immune response in Parkinson’s disease patients in a two-year follow-up: a case control study
Authors: Álvarez-Luquín Diana D. , Guevara-Salinas Adrián , Arce-Sillas Asiel , Espinosa-Cárdenas Raquel , Leyva-Hernández Jaquelín , Montes-Moratilla Esteban U. , Adalid-Peralta Laura 
Published: September 2021

AbstractBackgroundNeuroinflammation has been proved to play a role in dopaminergic neuronal death in Parkinson’s disease (PD). This link highlights the relevance of the immune response in the progression of the disease. However, little is known about the impact of peripheral immune response on the disease. This study is aimed to evaluate how immune cell populations change in untreated PD patients followed-up for 2 years.MethodsThirty-two patients with no previous treatment (PD-0 yr) and twenty-two healthy subjects (controls) were included in the study. PD patients were sampled 1 and 2 years after the start of the treatment. CD4 T cells (naïve/central memory, effector, and activated), CD8 T cells (activated, central memory, effector memory, NKT, Tc1, Tc2, and Tc17), and B cells (activated, plasma, and Lip-AP) were characterized by flow cytometry.ResultsWe observed decreased levels of naïve/central memory CD4 and CD8 T cells, Tc1, Tc2, NKT, and plasma cells, and increased levels of effector T cells, activated T cells, and Tc17.ConclusionsPD patients treated for 2 years showed an imbalance in the naive/effector immune response. Naïve and effector cell levels were associated with clinical deterioration. These populations are also correlated to aging. On the other hand, higher Tc17 levels suggest an increased inflammatory response, which may impact the progression of the disease. Our results highlight the relevant effect of treatment on the immune response, which could improve our management of the disease.
Utilisation of quality antenatal, delivery and postnatal care services in Nepal: An analysis of Service Provision Assessment
Authors: Khatri Resham B. , Durham Jo , Assefa Yibeltal 
Published: September 2021

Abstract
Background
Nepal has improved access and utilisation of routine maternal and newborn health (MNH) services. Despite improved access to routine MNH services such as antenatal care (ANC), and delivery and postnatal care (PNC) services, the burden of maternal and neonatal deaths in Nepal remains high. Most of those deaths could be prevented by improving utilisation of evidence-informed clinical MNH interventions. However, little is known on determinants of utilisation of such clinical MNH interventions in health facilities (HFs). This study investigated the determinants of utilisation of technical quality MNH services in Nepal.

Methods
This study used data from the 2015 Nepal Services Provision Assessment. A total of 523 pregnant and 309 postpartum women were included for the analysis of utilisation of technical quality of ANC, and delivery and PNC services, respectively. Outcome variables were utilisation of better quality i) ANC services, and ii) delivery and PNC services while independent variables included features of HFs and health workers, and demographic characteristics of pregnant and postpartum women. Binomial logistic regression was conducted to identify the determinants associated with utilisation of quality MNH services. The odds ratio with 95% confidence interval (CIs) were reported at the significance level of p < 0.05 (two-tailed).

Results
Women utilised quality ANC services if they attended facilities with better HF capacity (aOR = 2.12;95% CI: 1.03, 4.35). Women utilised better quality delivery and PNC services from private HFs compared to public HFs (aOR = 2.63; 95% CI: 1.14, 6.08). Women utilised better technical quality ANC provided by nursing staff compared to physicians (adjusted odds ratio (aOR) =2.89; 95% CI: 1.33, 6.29), and from staff supervised by a higher authority compared to those not supervised (aOR = 1.71; 95% CI: 1.01, 2.92). However, compared to province one, women utilised poor quality delivery and PNC services from HFs in province two (aOR = 0.15; 95% CI: 0.03, 0.63).

Conclusions
Women utilised quality MNH services at facilities with better HF capacity, service provided by nursing staff, and attended at supervised HFs/health workers. Provincial and municipal governments require strengthening HF capacities (e.g., supply equipment, medicines, supplies), recruiting trained nurse-midwives, and supervising health workers.
A dosimetric and radiobiological evaluation of VMAT following mastectomy for patients with left-sided breast cancer
Authors: Zhang Yun , Huang Yuling , Ding Shenggou , Yuan Xingxing , Shu Yuxian , Liang Jinhui , Mao Qingfeng , Jiang Chunling , Li Jingao 
Published: September 2021

Abstract
Background
To compare the dosimetric, normal tissue complication probability (NTCP), secondary cancer complication probabilities (SCCP), and excess absolute risk (EAR) differences of volumetric modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT) for left-sided breast cancer after mastectomy.

Methods and materials
Thirty patients with left-sided breast cancer treated with post-mastectomy radiation therapy (PMRT) were randomly enrolled in this study. Both IMRT and VMAT treatment plans were created for each patient. Planning target volume (PTV) doses for the chest wall and internal mammary nodes, PTV1, and PTV of the supraclavicular nodes, PTV2, of 50 Gy were prescribed in 25 fractions. The plans were evaluated based on PTV1 and PTV2 coverage, homogeneity index (HI), conformity index, conformity number (CN), dose to organs at risk, NTCP, SCCP, EAR, number of monitors units, and beam delivery time.

Results
VMAT resulted in more homogeneous chest wall coverage than did IMRT. The percent volume of PTV1 that received the prescribed dose of VMRT and IMRT was 95.9 ± 1.2% and 94.5 ± 1.6%, respectively (p < 0.001). The HI was 0.11 ± 0.01 for VMAT and 0.12 ± 0.02 for IMRT, respectively (p = 0.001). The VMAT plan had better conformity (CN: 0.84 ± 0.02 vs. 0.78 ± 0.04, p < 0.001) in PTV compared with IMRT. As opposed to IMRT plans, VMAT delivered a lower mean dose to the ipsilateral lung (11.5 Gy vs 12.6 Gy) and heart (5.2 Gy vs 6.0 Gy) and significantly reduced the V5, V10, V20, V30, and V40 of the ipsilateral lung and heart; only the differences in V5 of the ipsilateral lung did not reach statistical significance (p = 0.409). Although the volume of the ipsilateral lung and heart encompassed by the 2.5 Gy isodose line (V2.5) was increased by 6.7% and 7.7% (p < 0.001, p = 0.002), the NTCP was decreased by 0.8% and 0.6%, and SCCP and EAR were decreased by 1.9% and 0.1% for the ipsilateral lung. No significant differences were observed in the contralateral lung/breast V2.5, V5, V10, V20, mean dose, SCCP, and EAR. Finally, VMAT reduced the number of monitor units by 31.5% and the treatment time by 71.4%, as compared with IMRT.

Conclusions
Compared with IMRT, VMAT is the optimal technique for PMRT patients with left-sided breast cancer due to better target coverage, a lower dose delivered, NTCP, SCCP, and EAR to the ipsilateral lung and heart, similar doses delivered to the contralateral lung and breast, fewer monitor units and a shorter delivery time.
Left coronary button aneurysm presenting with progressive enlargement after aortic root replacement
Authors: Kobayashi Kimihiro , Kuroda Yoshinori , Mizumoto Masahiro , Yamashita Atsushi , Ohba Eiichi , Nakai Shingo , Ochiai Tomonori , Uchida Tetsuro 
Published: September 2021

Abstract
Background
Aneurysmal degeneration of the coronary button after aortic root replacement using the button technique is a rare but potentially life-threatening complication. However, the appropriate management of this complication, including the indications for conservative and surgical treatment, is still unknown.

Case presentation
Here we present a 38-year-old woman who successfully underwent surgical repair of a left coronary button aneurysm using the graft interposition technique 24 years after aortic root replacement. Because follow-up computed tomography after aortic root replacement showed a progressively enlarging left coronary button aneurysm, the patient was judged an acceptable candidate for surgical treatment, considering the potential risk of aneurysmal rupture and subsequent myocardial infarction. The postoperative recovery was uneventful. The patient is doing well 1 year after the surgery.

Conclusions
We believe that serial follow-up using computed tomography is mandatory for coronary button aneurysms, and surgical intervention may be considered if progressive enlargement of the aneurysm is observed, especially in younger patients.
Analytic Pearson residuals for normalization of single-cell RNA-seq UMI data
Authors: Lause Jan , Berens Philipp , Kobak Dmitry 
Published: September 2021

Abstract
Background
Standard preprocessing of single-cell RNA-seq UMI data includes normalization by sequencing depth to remove this technical variability, and nonlinear transformation to stabilize the variance across genes with different expression levels. Instead, two recent papers propose to use statistical count models for these tasks: Hafemeister and Satija (Genome Biol 20:296, 2019) recommend using Pearson residuals from negative binomial regression, while Townes et al. (Genome Biol 20:295, 2019) recommend fitting a generalized PCA model. Here, we investigate the connection between these approaches theoretically and empirically, and compare their effects on downstream processing.

Results
We show that the model of Hafemeister and Satija produces noisy parameter estimates because it is overspecified, which is why the original paper employs post hoc smoothing. When specified more parsimoniously, it has a simple analytic solution equivalent to the rank-one Poisson GLM-PCA of Townes et al. Further, our analysis indicates that per-gene overdispersion estimates in Hafemeister and Satija are biased, and that the data are in fact consistent with the overdispersion parameter being independent of gene expression. We then use negative control data without biological variability to estimate the technical overdispersion of UMI counts, and find that across several different experimental protocols, the data are close to Poisson and suggest very moderate overdispersion. Finally, we perform a benchmark to compare the performance of Pearson residuals, variance-stabilizing transformations, and GLM-PCA on scRNA-seq datasets with known ground truth.

Conclusions
We demonstrate that analytic Pearson residuals strongly outperform other methods for identifying biologically variable genes, and capture more of the biologically meaningful variation when used for dimensionality reduction.
PUMAS: fine-tuning polygenic risk scores with GWAS summary statistics
Authors: Zhao Zijie , Yi Yanyao , Song Jie , Wu Yuchang , Zhong Xiaoyuan , Lin Yupei , Hohman Timothy J. , Fletcher Jason , Lu Qiongshi 
Published: September 2021

AbstractPolygenic risk scores (PRSs) have wide applications in human genetics research, but often include tuning parameters which are difficult to optimize in practice due to limited access to individual-level data. Here, we introduce PUMAS, a novel method to fine-tune PRS models using summary statistics from genome-wide association studies (GWASs). Through extensive simulations, external validations, and analysis of 65 traits, we demonstrate that PUMAS can perform various model-tuning procedures using GWAS summary statistics and effectively benchmark and optimize PRS models under diverse genetic architecture. Furthermore, we show that fine-tuned PRSs will significantly improve statistical power in downstream association analysis.