bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discrimination between healthy and patients with Parkinson’s disease from hand resting activity using inertial measurement unit
Authors: Peres Luciano Brinck , Calil Bruno Coelho , da Silva Ana Paula Sousa Paixão Barroso , Dionísio Valdeci Carlos , Vieira Marcus Fraga , de Oliveira Andrade Adriano , Pereira Adriano Alves 
Published: May 2021

Abstract
Background
Parkinson’s disease (PD) is a neurological disease that affects the motor system. The associated motor symptoms are muscle rigidity or stiffness, bradykinesia, tremors, and gait disturbances. The correct diagnosis, especially in the initial stages, is fundamental to the life quality of the individual with PD. However, the methods used for diagnosis of PD are still based on subjective criteria. As a result, the objective of this study is the proposal of a method for the discrimination of individuals with PD (in the initial stages of the disease) from healthy groups, based on the inertial sensor recordings.

Methods
A total of 27 participants were selected, 15 individuals previously diagnosed with PD and 12 healthy individuals. The data collection was performed using inertial sensors (positioned on the back of the hand and on the back of the forearm). Different numbers of features were used to compare the values of sensitivity, specificity, precision, and accuracy of the classifiers. For group classification, 4 classifiers were used and compared, those being [Random Forest (RF), Support Vector Machine (SVM), K-Nearest Neighbor (KNN), and Naive Bayes (NB)].

Results
When all individuals with PD were analyzed, the best performance for sensitivity and accuracy (0.875 and 0.800, respectively) was found in the SVM classifier, fed with 20% and 10% of the features, respectively, while the best performance for specificity and precision (0.933 and 0.917, respectively) was associated with the RF classifier fed with 20% of all the features. When only individuals with PD and score 1 on the Hoehn and Yahr scale (HY) were analyzed, the best performances for sensitivity, precision and accuracy (0.933, 0.778 and 0.848, respectively) were from the SVM classifier, fed with 40% of all features, and the best result for precision (0.800) was connected to the NB classifier, fed with 20% of all features.

Conclusion
Through an analysis of all individuals in this study with PD, the best classifier for the detection of PD (sensitivity) was the SVM fed with 20% of the features and the best classifier for ruling out PD (specificity) was the RF classifier fed with 20% of the features. When analyzing individuals with PD and score HY = 1, the SVM classifier was superior across the sensitivity, precision, and accuracy, and the NB classifier was superior in the specificity. The obtained result indicates that objective methods can be applied to help in the evaluation of PD.
Associations between blood cadmium and endocrine features related to PCOS-phenotypes in healthy women of reproductive age: a prospective cohort study
Authors: Kim Keewan , Pollack Anna Z. , Nobles Carrie J. , Sjaarda Lindsey A. , Zolton Jessica R. , Radoc Jeannie G. , Schisterman Enrique F. , Mumford Sunni L. 
Published: May 2021

Abstract
Background
Cadmium is an endocrine disrupting chemical that affects the hypothalamic-pituitary-gonadal axis. Though evidence suggests its potential role in altering androgen synthesis and metabolic pathways that are characteristic of polycystic ovary syndrome (PCOS), its relation in healthy women of reproductive age is largely unknown. As women with mild sub-clinical features of PCOS who do not meet the diagnostic criteria of PCOS may still experience reduced fecundability, investigating associations between cadmium and PCOS-phenotypes among healthy women may provide unique insight into the reproductive implications for many on the PCOS spectrum. Therefore, the objective of this study was to evaluate associations between cadmium and androgens, anti-Müllerian hormone (AMH), and metabolic markers in women of reproductive age.

Methods
This was a prospective cohort study of 251 healthy premenopausal women without self-reported PCOS (mean age 27.3 years and BMI 24.1 kg/m2). Cadmium was measured in blood collected at baseline. Reproductive hormones and metabolic markers were measured in fasting serum 8 times per menstrual cycle for 2 cycles. Linear mixed models and Poisson regression with a robust error variance were used to examine associations between cadmium and reproductive hormones and metabolic markers and anovulation, respectively.

Results
Median (interquartile range) blood cadmium concentrations at baseline were 0.30 (0.19–0.43) µg/L. Higher levels of testosterone (2.2 %, 95 % confidence interval [CI] 0.4, 4.1), sex hormone-binding globulin (2.9 %, 95 % CI 0.5, 5.5), and AMH (7.7 %, 95 % CI 1.1, 14.9) were observed per 0.1 µg/L increase in cadmium concentrations. An 18 % higher probability of a mild PCOS-phenotype (95 % CI 1.06, 1.31), defined by a menstrual cycle being in the highest quartile of cycle-averaged testosterone and AMH levels, was also found per 0.1 µg/L increase in cadmium levels. No associations were observed for insulin and glucose. These findings were consistent even after analyses were restricted to non-smokers or further adjusted for dietary factors to account for potential sources of exposure.

Conclusions
Overall, among healthy reproductive-aged women, cadmium was associated with endocrine features central to PCOS, but not with metabolic markers. These suggest its potential role in the hormonal milieu associated with PCOS even at low levels of exposure.
Comparative evaluation of six nucleic acid amplification kits for SARS-CoV-2 RNA detection
Authors: Wu Shuang , Shi Xiaolu , Chen Qiongcheng , Jiang Yixiang , Zuo Le , Wang Lei , Jiang Min , Lin Yiman , Fang Shisong , Peng Bo , Wu Weihua , Liu Hui , Zhang Renli , Kwan Patrick S. L. , Hu Qinghua 
Published: May 2021

Abstract
Background
SARS-CoV-2 is a newly emerged coronavirus, causing the coronavirus disease 2019 (COVID-19) outbreak in December, 2019. As drugs and vaccines of COVID-19 remain in development, accurate virus detection plays a crucial role in the current public health crisis. Quantitative real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) kits have been reliably used for detection of SARS-CoV-2 RNA since the beginning of the COVID-19 outbreak, whereas isothermal nucleic acid amplification-based point-of-care automated kits have also been considered as a simpler and rapid alternative. However, as these kits have only been developed and applied clinically within a short timeframe, their clinical performance has not been adequately evaluated to date. We describe a comparative study between a newly developed cross-priming isothermal amplification (CPA) kit (Kit A) and five RT-qPCR kits (Kits B–F) to evaluate their sensitivity, specificity, predictive values and accuracy.

Methods
Fifty-two clinical samples were used including throat swabs (n = 30), nasal swabs (n = 7), nasopharyngeal swabs (n = 7) and sputum specimens (n = 8), comprising confirmed (n = 26) and negative cases (n = 26). SARS-CoV-2 detection was simultaneously performed on each sample using six nucleic acid amplification kits. The sensitivity, specificity, positive/negative predictive values (PPV/NPV) and the accuracy for each kit were assessed using clinical manifestation and molecular diagnoses as the reference standard. Reproducibility for RT-qPCR kits was evaluated in triplicate by three different operators using a SARS-CoV-2 RNA-positive sample. On the basis of the six kits’ evaluation results, CPA kit (Kit A) and two RT-qPCR Kits (Kit B and F) were applied to the SARS-CoV-2 detection in close-contacts of COVID-19 patients.

Results
For Kit A, the sensitivity, specificity, PPV/NPV and accuracy were 100%. Among the five RT-qPCR kits, Kits B, C and F had good agreement with the clinical diagnostic reports (Kappa ≥ 0.75); Kits D and E were less congruent (0.4 ≤ Kappa < 0.75). Differences between all kits were statistically significant (P < 0.001). The reproducibility of RT-qPCR kits was determined using a coefficients of variation (CV) between 0.95% and 2.57%, indicating good reproducibility.

Conclusions
This is the first comparative study to evaluate CPA and RT-qPCR kits’ specificity and sensitivity for SARS-CoV-2 detection, and could serve as a reference for clinical laboratories, thus informing testing protocols amid the rapidly progressing COVID-19 pandemic.
RETRACTED ARTICLE: VEGF as a potential molecular target in periodontitis: a meta-analysis and microarray data validation
Authors: Ren Bo , Feng Que , He Shan , Li Yanfeng , Fan Jiadong , Chai Guangquan , Liu Le , Liu Haiyun , Yang Chunhao , Wang Yingdi , Liu Huihui , Liu Huanyue , Song Yafan 
Published: May 2021

Abstract
Background
Anti-vascular endothelial growth factor (VEGF) has been used as a therapeutic drug for the treatment of some human diseases. However, no systematic evidence is performed for assessing the role of VEGF in periodontitis. We carried out a comprehensive analysis to explore the role of VEGF in patients with periodontitis.

Methods
Multiple databases were searched for eligible studies. The pooled standardized mean difference (SMD) and odds ratio (OR) with the corresponding 95% confidence interval (CI) were applied to evaluate the effect sizes. Clinical data validation from microarray analysis was used. Pathway and process enrichment analysis were also investigated.

Results
Finally, 16 studies were included in this analysis. Overall, there was a significantly higher level of VEGF expression in periodontitis than in healthy control groups (OR = 16.64, 95% CI = 6.01–46.06, P < 0.001; SMD = 2.25, 95% CI = 1.25–3.24, P < 0.001). Subgroup analysis of ethnicity showed that VEGF expression was still correlated with periodontitis in the Asian and European populations. No correlation was observed between VEGF expression and age, gender, and pathological type. A large clinical sample data (427 periodontitis patients and 136 healthy controls) further validated that VEGF expression was higher in periodontitis than in healthy control groups (P = 0.023). VEGF was involved in many functions such as blood vessel development, response to growth factor, cell proliferation, and cell adhesion.

Conclusions
High levels of VEGF were credible implications for the development of periodontitis. Anti-VEGF therapy may be valuable for the treatment of periodontitis in clinical management.
Extracellular vesicles-based pre-targeting strategy enables multi-modal imaging of orthotopic colon cancer and image-guided surgery
Authors: Jing Boping , Qian Ruijie , Jiang Dawei , Gai Yongkang , Liu Zhen , Guo Feng , Ren Sen , Gao Yu , Lan Xiaoli , An Rui 
Published: May 2021

Abstract
Backgroud
Colon cancer contributes to high mortality rates as the result of incomplete resection in tumor surgery. Multimodal imaging can provide preoperative evaluation and intraoperative image-guiding. As biocompatible nanocarriers, extracellular vesicles hold great promise for multimodal imaging. In this study, we aim to synthesized an extracellular vesicles-based nanoprobe to visualize colon cancer with positron-emission tomography/computed tomography (PET/CT) and near-infrared fluorescence (NIRF) imaging, and investigated its utility in image-guided surgery of colon cancer in animal models.

Results
Extracellular vesicles were successfully isolated from adipose-derived stem cells (ADSCs), and their membrane vesicles were observed under TEM. DLS detected that the hydrodynamic diameters of the extracellular vesicles were approximately 140 nm and the zeta potential was − 7.93 ± 0.24 mV. Confocal microscopy showed that extracellular vesicles had a strong binding ability to tumor cells. A click chemistry-based pre-targeting strategy was used to achieve PET imaging in vivo. PET images and the biodistribution results showed that the best pre-targeting time was 20 h, and the best imaging time was 2 h after the injection of 68 Ga-L-NETA-DBCO. The NIRF images showed that the tumor had clear images at all time points after administration of nanoparticles and the Tumor/Muscle ratio peaked at 20 h after injection. Our data also showed that both PET/CT and NIRF imaging clearly visualized the orthotopic colon cancer models, providing preoperative evaluation. Under real-time NIRF imaging, the tumor location and tumor boundary could be clearly observed.

Conclusions
In brief, this novel nanoprobe may be useful for multi-modal imaging of colon cancer and NIRF image-guided surgery. More importantly, this study provides a new possibility for clinical application of extracellular vesicles as nanocarriers.

Graphic Abstract
pH-activated, mitochondria-targeted, and redox-responsive delivery of paclitaxel nanomicelles to overcome drug resistance and suppress metastasis in lung cancer
Authors: Wang He , Shi Wenwen , Zeng Danning , Huang Qiudi , Xie Jiacui , Wen Huaying , Li Jinfang , Yu Xiyong , Qin Linghao , Zhou Yi 
Published: May 2021

Abstract
Background
Mitochondria play a role in the occurrence, development, drug resistance, metastasis, and other functions of cancer and thus are a drug target. An acid-activated mitochondria-targeting drug nanocarrier with redox-responsive function was constructed in the present study. However, whether this vector can precisely delivery paclitaxel (PTX) to enhance therapeutic efficacy in drug-resistant lung cancer is unknown.

Results
Acid-cleavable dimethylmaleic anhydride (DA) was used to modify pluronic P85-conjugated mitochondria-targeting triphenylphosphonium (TPP) using disulfide bonds as intermediate linkers (DA-P85-SS-TPP and DA-P-SS-T). The constructed nanocarriers demonstrated enhanced cellular uptake and selective mitochondrial targeting at extracellular pH characteristic for a tumor (6.5) and were characterized by extended circulation in the blood. TPP promoted the targeting of the DA-P-SS-T/PTX nanomicelles to the mitochondrial outer membrane to decrease the membrane potential and ATP level, resulting in inhibition of P-glycoprotein and suppression of drug resistance and cancer metastasis. PTX was also rapidly released in the presence of high glutathione (GSH) levels and directly diffused into the mitochondria, resulting in apoptosis of drug-resistant lung cancer cells.

Conclusions
These promising results indicated that acid-activated mitochondria-targeting and redox-responsive nanomicelles potentially represent a significant advancement in cancer treatment.

Graphic Abstarct
Age-specific cut-off levels of anti-Müllerian hormone can be used as diagnostic markers for polycystic ovary syndrome
Authors: Ramezani Tehrani Fahimeh , Rahmati Maryam , Mahboobifard Fatemeh , Firouzi Faezeh , Hashemi Nazanin , Azizi Fereidoun 
Published: May 2021

AbstractBackgroundThe majority of available studies on the AMH thresholds were not age-specific and performed the receiver operating characteristic curve (ROC) analysis, based on variations in sensitivity and specificity rather than positive and negative predictive values (PPV and NPV, respectively), which are more clinically applicable. Moreover, all of these studies used a pre-specified age categorization to report the age-specific cut-off values of AMH.MethodsA total of 803 women, including 303 PCOS patients and 500 eumenorrheic non-hirsute control women, were enrolled in the present study. The PCOS group included PCOS women, aged 20–40 years, who were referred to the Reproductive Endocrinology Research Center, Tehran, Iran. The Rotterdam consensus criteria were used for diagnosis of PCOS. The control group was selected among women, aged 20–40 years, who participated in Tehran Lipid and Glucose cohort Study (TLGS). Generalized additive models (GAMs) were used to identify the optimal cut-off points for various age categories. The cut-off levels of AMH in different age categories were estimated, using the Bayesian method.Main results and the role of chanceTwo optimal cut-off levels of AMH (ng/ml) were identified at the age of 27 and 35 years, based on GAMs. The cut-off levels for the prediction of PCOS in the age categories of 20–27, 27–35, and 35–40 years were 5.7 (95 % CI: 5.48–6.19), 4.55 (95 % CI: 4.52–4.64), and 3.72 (95 % CI: 3.55–3.80), respectively. Based on the Bayesian method, the PPV and NPV of these cut-off levels were as follows: PPV = 0.98 (95 % CI: 0.96–0.99) and NPV = 0.40 (95 % CI: 0.30–0.51) for the age group of 20–27 years; PPV = 0.96 (95 % CI: 0.91–0.99) and NPV = 0.82 (95 % CI: 0.78–0.86) for the age group of 27–35 years; and PPV = 0.86 (95 % CI: 0.80–0.94) and NPV = 0.96 (95 % CI: 0.93–0.98) for the age group of 35–40 years.ConclusionsApplication of age-specific cut-off levels of AMH, according to the GAMs and Bayesian method, could elegantly assess the value of AMH in discriminating PCOS patients in all age categories.
Prioritizing guideline recommendations for implementation: a systematic, consumer-inclusive process with a case study using the Australian Clinical Guidelines for Stroke Management
Authors: Lynch Elizabeth A. , Lassig Chris , Turner Tari , Churilov Leonid , Hill Kelvin , Shrubsole Kirstine 
Published: May 2021

Abstract
Background
Implementation of evidence-based care remains a key challenge in clinical practice. Determining “what” to implement can guide implementation efforts. This paper describes a process developed to identify priority recommendations from clinical guidelines for implementation, incorporating the perspectives of both consumers and health professionals. A case study is presented where the process was used to prioritize recommendations for implementation from the Australian Stroke Clinical Guidelines.

Methods
The process was developed by a multidisciplinary group of researchers following consultation with experts in the field of implementation and stroke care in Australia. Use of the process incorporated surveys and facilitated workshops. Survey data were analysed descriptively; responses to ranking exercises were analysed via a graph theory-based voting system.

Results
The four-step process to identify high-priority recommendations for implementation comprised the following: (1) identifying key implementation criteria, which included (a) reliability of the evidence underpinning the recommendation, (b) capacity to measure change in practice, (c) a recommendation–practice gap, (d) clinical importance and (e) feasibility of making the recommended changes; (2) shortlisting recommendations; (3) ranking shortlisted recommendations and (4) reaching consensus on top priorities.
The process was applied to the Australian Stroke Clinical Guidelines between February 2019 and February 2020. Seventy-five health professionals and 16 consumers participated. Use of the process was feasible. Three recommendations were identified as priorities for implementation from over 400 recommendations.

Conclusion
It is possible to implement a robust process which involves consumers, clinicians and researchers to systematically prioritize guideline recommendations for implementation. The process is generalizable and could be applied in clinical areas other than stroke and in different geographical regions to identify implementation priorities. The identification of three clear priority recommendations for implementation from the Australian Stroke Clinical Guidelines will directly inform the development and delivery of national implementation strategies.
Role of the ABL tyrosine kinases in the epithelial–mesenchymal transition and the metastatic cascade
Authors: Luttman Jillian Hattaway , Colemon Ashley , Mayro Benjamin , Pendergast Ann Marie 
Published: May 2021

AbstractThe ABL kinases, ABL1 and ABL2, promote tumor progression and metastasis in various solid tumors. Recent reports have shown that ABL kinases have increased expression and/or activity in solid tumors and that ABL inactivation impairs metastasis. The therapeutic effects of ABL inactivation are due in part to ABL-dependent regulation of diverse cellular processes related to the epithelial to mesenchymal transition and subsequent steps in the metastatic cascade. ABL kinases target multiple signaling pathways required for promoting one or more steps in the metastatic cascade. These findings highlight the potential utility of specific ABL kinase inhibitors as a novel treatment paradigm for patients with advanced metastatic disease.
Annexin A1 protects against cerebral ischemia–reperfusion injury by modulating microglia/macrophage polarization via FPR2/ALX-dependent AMPK-mTOR pathway
Authors: Xu Xin , Gao Weiwei , Li Lei , Hao Jiheng , Yang Bin , Wang Tao , Li Long , Bai Xuesong , Li Fanjian , Ren Honglei , Zhang Meng , Zhang Liyong , Wang Jiyue , Wang Dong , Zhang Jianning , Jiao Liqun 
Published: May 2021

Abstract
Background
Cerebral ischemia–reperfusion (I/R) injury is a major cause of early complications and unfavorable outcomes after endovascular thrombectomy (EVT) therapy in patients with acute ischemic stroke (AIS). Recent studies indicate that modulating microglia/macrophage polarization and subsequent inflammatory response may be a potential adjunct therapy to recanalization. Annexin A1 (ANXA1) exerts potent anti-inflammatory and pro-resolving properties in models of cerebral I/R injury. However, whether ANXA1 modulates post-I/R-induced microglia/macrophage polarization has not yet been fully elucidated.

Methods
We retrospectively collected blood samples from AIS patients who underwent successful recanalization by EVT and analyzed ANXA1 levels longitudinally before and after EVT and correlation between ANXA1 levels and 3-month clinical outcomes. We also established a C57BL/6J mouse model of transient middle cerebral artery occlusion/reperfusion (tMCAO/R) and an in vitro model of oxygen–glucose deprivation and reoxygenation (OGD/R) in BV2 microglia and HT22 neurons to explore the role of Ac2-26, a pharmacophore N-terminal peptide of ANXA1, in regulating the I/R-induced microglia/macrophage activation and polarization.

Results
The baseline levels of ANXA1 pre-EVT were significantly lower in 23 AIS patients, as compared with those of healthy controls. They were significantly increased to the levels found in controls 2–3 days post-EVT. The increased post-EVT levels of ANXA1 were positively correlated with 3-month clinical outcomes. In the mouse model, we then found that Ac2-26 administered at the start of reperfusion shifted microglia/macrophage polarization toward anti-inflammatory M2-phenotype in ischemic penumbra, thus alleviating blood–brain barrier leakage and neuronal apoptosis and improving outcomes at 3 days post-tMCAO/R. The protection was abrogated when mice received Ac2-26 together with WRW4, which is a specific antagonist of formyl peptide receptor type 2/lipoxin A4 receptor (FPR2/ALX). Furthermore, the interaction between Ac2-26 and FPR2/ALX receptor activated the 5’ adenosine monophosphate-activated protein kinase (AMPK) and inhibited the downstream mammalian target of rapamycin (mTOR). These in vivo findings were validated through in vitro experiments.

Conclusions
Ac2-26 modulates microglial/macrophage polarization and alleviates subsequent cerebral inflammation by regulating the FPR2/ALX-dependent AMPK-mTOR pathway. It may be investigated as an adjunct strategy for clinical prevention and treatment of cerebral I/R injury after recanalization. Plasma ANXA1 may be a potential biomarker for outcomes of AIS patients receiving EVT.