Miracle-dz/UniFAR-FTUs huggingface dataset:
circGFRA1 Enhances NSCLC Progression by Sponging miR-188-3p

Background Lung cancer continues to be one of the most dangerous tumors around the world. It is an urgency to explore the molecular mechanism of non-small cell lung cancer (NSCLC) progression for developing novel therapeutic approaches. Circular RNA (circRNA) is a novel type of non-coding RNA with a stable closed loop structure. Abnormally expressed circRNAs have been found in many kinds of cancer including NSCLC. Methods and Results The expression of circGFRA1 and miR-188-3p was detected in NSCLC tissues by RT-qPCR and it was found that circGFRA1 was highly expressed and miR-183-3p was lowly expressed in NSCLC tissues. In NSCLC cell lines, we confirmed that circGFRA1 acted as an miR-188-3p sponge using dual-luciferase reporter assay and RNA immunoprecipitation (RIP) analysis. Overexpression of cirGFRA1 enhanced NSCLC progression while miR-188-3p overexpression inhibited it by CCK8 and colony formation analysis. In vivo tumor xenograft model, circGFRA1 and miR-188-3p synergistically regulated the proliferation of NSCLC tumors. Mechanistic study indicated that circGFRA1 and miR-188-3p regulated the proliferation of NSCLC cells at least through PI3K/AKT signaling pathway. Conclusion Our study elaborated a novel circGFRA-miR-188-3p-PI3K/AKT regulatory pathway, providing a potential diagnostic biomarker and therapeutic target for NSCLC.
Multi-morbidities are Not a Driving Factor for an Increase of COPD-Related 30-Day Readmission Risk

Background and Objective Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States. COPD is expensive to treat, whereas the quality of care is difficult to evaluate due to the high prevalence of multi-morbidity among COPD patients. In the US, the Hospital Readmissions Reduction Program (HRRP) was initiated by the Centers for Medicare and Medicaid Services to penalize hospitals for excessive 30-day readmission rates for six diseases, including COPD. This study examines the difference in 30-day readmission risk between COPD patients with and without comorbidities. Methods In this retrospective cohort study, we used Cox regression to estimate the hazard ratio of 30-day readmission rates for COPD patients who had no comorbidity and those who had one, two or three, or four or more comorbidities. We controlled for individual, hospital and geographic factors. Data came from three sources: Healthcare Cost and Utilization Project (HCUP) State Inpatient Databases (SID), Area Health Resources Files (AHRF) and the American Hospital Association’s (AHA's) annual survey database for the year of 2013. Results COPD patients with comorbidities were less likely to be readmitted within 30 days relative to patients without comorbidities (aHR from 0.84 to 0.87, p < 0.05). In a stratified analysis, female patients with one comorbidity had a lower risk of 30-day readmission compared to female patients without comorbidity (aHR = 0.80, p < 0.05). Patients with public insurance who had comorbidities were less likely to be readmitted within 30 days in comparison with those who had no comorbidity (aHR from 0.79 to 0.84, p < 0.05). Conclusion COPD patients with comorbidities had a lower risk of 30-day readmission compared with patients without comorbidity. Future research could use a different study design to identify the effectiveness of the HRRP.
Ethnic Differences in the Prevalence of Type 2 Diabetes Diagnoses in the UK: Cross-Sectional Analysis of the Health Improvement Network Primary Care Database

Aims/Hypothesis Type 2 diabetes mellitus is associated with high levels of disease burden, including increased mortality risk and significant long-term morbidity. The prevalence of diabetes differs substantially among ethnic groups. We examined the prevalence of type 2 diabetes diagnoses in the UK primary care setting. Methods We analysed data from 404,318 individuals in The Health Improvement Network database, aged 0–99 years and permanently registered with general practices in London. The association between ethnicity and the prevalence of type 2 diabetes diagnoses in 2013 was estimated using a logistic regression model, adjusting for effect of age group, sex, and social deprivation. A multiple imputation approach utilising population-level information about ethnicity from the UK census was used for imputing missing data. Results Compared with those of White ethnicity (5.04%, 95% CI 4.95 to 5.13), the crude percentage prevalence of type 2 diabetes was higher in the Asian (7.69%, 95% CI 7.46 to 7.92) and Black (5.58%, 95% CI 5.35 to 5.81) ethnic groups, while lower in the Mixed/Other group (3.42%, 95% CI 3.19 to 3.66). After adjusting for differences in age group, sex, and social deprivation, all minority ethnic groups were more likely to have a diagnosis of type 2 diabetes compared with the White group (OR Asian versus White 2.36, 95% CI 2.26 to 2.47; OR Black versus White 1.65, 95% CI 1.56 to 1.73; OR Mixed/Other versus White 1.17, 95% CI 1.08 to 1.27). Conclusion The prevalence of type 2 diabetes was higher in the Asian and Black ethnic groups, compared with the White group. Accurate estimates of ethnic prevalence of type 2 diabetes based on large datasets are important for facilitating appropriate allocation of public health resources, and for allowing population-level research to be undertaken examining disease trajectories among minority ethnic groups, that might help reduce inequalities.
Learning unsupervised contextual representations for medical synonym discovery

Abstract Objectives An important component of processing medical texts is the identification of synonymous words or phrases. Synonyms can inform learned representations of patients or improve linking mentioned concepts to medical ontologies. However, medical synonyms can be lexically similar (“dilated RA” and “dilated RV”) or dissimilar (“cerebrovascular accident” and “stroke”); contextual information can determine if 2 strings are synonymous. Medical professionals utilize extensive variation of medical terminology, often not evidenced in structured medical resources. Therefore, the ability to discover synonyms, especially without reliance on training data, is an important component in processing training notes. The ability to discover synonyms from models trained on large amounts of unannotated data removes the need to rely on annotated pairs of similar words. Models relying solely on non-annotated data can be trained on a wider variety of texts without the cost of annotation, and thus may capture a broader variety of language. Materials and Methods Recent contextualized deep learning representation models, such as ELMo (Peters et al., 2019) and BERT, (Devlin et al. 2019) have shown strong improvements over previous approaches in a broad variety of tasks. We leverage these contextualized deep learning models to build representations of synonyms, which integrate the context of surrounding sentence and use character-level models to alleviate out-of-vocabulary issues. Using these models, we perform unsupervised discovery of likely synonym matches, which reduces the reliance on expensive training data. Results We use the ShARe/CLEF eHealth Evaluation Lab 2013 Task 1b data to evaluate our synonym discovery method. Comparing our proposed contextualized deep learning representations to previous non-neural representations, we find that the contextualized representations show consistent improvement over non-contextualized models in all metrics. Conclusions Our results show that contextualized models produce effective representations for synonym discovery. We expect that the use of these representations in other tasks would produce similar gains in performance.
Quercetin Enhanced Paclitaxel Therapeutic Effects Towards PC-3 Prostate Cancer Through ER Stress Induction and ROS Production

Introduction Prostate cancer is one of the most common cancers threatening public health worldwide. Although chemotherapy plays an important role in treating prostate cancer, it leads to many adverse effects and is prone to drug resistance. Quercetin, a natural product, is used in traditional Chinese medicine because of its strong antitumor activity and few side effects. Methods In this study, we combined quercetin and paclitaxel to kill prostate cancer cells in vivo and in vitro, and we investigated the relevant mechanism of this combination treatment. After the cancer cells were treated with quercetin or/and paclitaxel, cell growth inhibition, apoptosis, the cell cycle, reactive oxygen species (ROS) generation, and several endoplasmic reticulum (ER) stress signaling pathway related gene expressions were evaluated. Results The combined treatment with quercetin and paclitaxel significantly inhibited cell proliferation, increased apoptosis, arrested the cell cycle at the G2/M phase, inhibited cell migration, dramatically induced ER stress to occur, and increased ROS generation. In a PC-3 cancer-bearing murine model, this combination treatment exerted the most beneficial therapeutic effects, and quercetin increased the cancer cell-killing effects of paclitaxel, with nearly no side effects compared with the single paclitaxel treatment group. Conclusion Combination treatment possessed enhanced anti-cancer effects, and these results will provide a basis for treating prostate cancer using a combination of quercetin and paclitaxel.
Machine Learning to Predict the 1-Year Mortality Rate After Acute Anterior Myocardial Infarction in Chinese Patients

Abstract A formal risk assessment for identifying high-risk patients is essential in clinical practice and promoted in guidelines for the management of anterior acute myocardial infarction. In this study, we sought to evaluate the performance of different machine learning models in predicting the 1-year mortality rate of anterior ST-segment elevation myocardial infarction (STEMI) patients and to compare the utility of these models to the conventional Global Registry of Acute Coronary Events (GRACE) risk scores. We enrolled all of the patients aged >18 years with discharge diagnoses of anterior STEMI in the Western China Hospital, Sichuan University, from January 2011 to January 2017. A total of 1244 patients were included in this study. The mean patient age was 63.8±12.9 years, and the proportion of males was 78.4%. The majority (75.18%) received revascularization therapy. In the prediction of the 1-year mortality rate, the areas under the curve (AUCs) of the receiver operating characteristic curves (ROCs) of the six models ranged from 0.709 to 0.942. Among all models, XGBoost achieved the highest accuracy (92%), specificity (99%) and f1 score (0.72) for predictions with the full variable model. After feature selection, XGBoost still obtained the highest accuracy (93%), specificity (99%) and f1 score (0.73). In conclusion, machine learning algorithms can accurately predict the rate of death after a 1-year follow-up of anterior STEMI, especially the XGBoost model.
Patient Perspective in the Development of Electronic Patient-Reported Outcomes (ePROs) in Seizure Disorders: A Patient-Centric Approach

Background Patient-centered outcomes research (PCOR) emphasizes the patient perspective and input to inform the research process with the aim to improve the quality of care. Given PCOR’s emphasis on the patient perspective, methods to incorporate patient-reported outcomes (PROs) are important. Electronic PROs (ePROs) have been implemented successfully in many populations; however, many of these measurements do not incorporate patient perspective in the development of ePROs. For epilepsy and seizure disorders, user perspectives are key to developing measurements that capture real-time data, as seizures are not timed events; therefore, patients can wait days or even weeks and then try to recall their experience which can lead to variations in recall. ePRO can provide the necessary assurance that data were entered by the patient at the time the episode occurs. The aim of the present study was to assess patient perceptions of completing ePROs, expectations of ePRO devices for PCOR and on-site clinical visit in order to guide the development of successful ePRO deployment in seizure-related disorders. Methods This study used a naturalistic cohort design. A sample of 713 persons completed an online survey which consisted of 11 situational questions. Of the 713 individuals, results from 640 participants were included. Results were compared using a Wilcoxon signed-rank test. Results Most participants (71.9%) were able to accurately identify a seizure and 86.3% of participants felt it would be beneficial to have a short training on seizure symptoms prior to completing a daily seizure diary, and seizures should be reasonably reported within 10 mins (n = 426, 66.6%). Participants endorsed that repetitive movements and loss of consciousness as the most predominant symptoms they would look for in an ePRO. A majority of participants, 67.0% indicated that they regularly use accessibility features on using smartphones and tablets, and 38.6% indicated they would like to see more than one item per screen but only if they are related and to see all text in a larger size with scrolling features using fingers (n = 246; 38.4%). Conclusion This study has demonstrated the importance of developing ePROs that satisfy the needs of the participants and caregivers without compromising the scientific and clinical aspects of the disease construct. Developing tools using participant needs, observations, characteristics and input is essential to putting the participant perspective in patient-centered outcomes research.
Childhood Maltreatment, Negative Self-Referential Processing, and Depressive Symptoms During Stress

Introduction Researchers have documented that the impact of childhood maltreatment on later symptoms of depression differs depending on the type(s) of maltreatment experienced, with emotional abuse and neglect being more likely than other forms of childhood maltreatment to increase the risk for depression. It is possible that emotional abuse and neglect are more likely to increase the risk for depression because they promote the development of negative self-referential processing (SRP), but this has not yet been tested empirically. The current study was designed to examine whether negative SRP mediated the association between different forms of childhood maltreatment and symptoms of depression during a time of stress. Methods We assessed the experience of different forms of childhood maltreatment (ie, emotional neglect, physical neglect, emotional abuse, physical abuse, and sexual abuse) and negatively biased self-schemas early on in the university semester, among a sample of undergraduate students. We then assessed levels of depressive symptoms 2 months later during a naturalistic stressor (ie, university students’ first final exams). Results As expected, negative SRP mediated the relation between both neglect and emotional abuse, but not physical and sexual abuse, and later symptoms of depression. Discussion This is the first study to examine SRP as a mechanism underlying the association between forms of childhood maltreatment and symptoms of depression during a time of stress. Results suggest that the development of negative SRP biases may explain why some types of childhood maltreatment are more likely than others to increase an individual’s risk for depression during stressful developmental periods.
Unilateral Spatial Neglect After Stroke: Current Insights

Introduction Unilateral spatial neglect (USN) is a disorder of contralesional space awareness which often follows unilateral brain lesion. Since USN impairs awareness of contralesional space/body and often of concomitant motor disorders, its presence represents a negative prognostic factor of functional recovery. Thus, the disorder needs to be carefully diagnosed and treated. Here, we attempted to present a clear and concise picture of current insights in the comprehension and rehabilitation of USN. Methods We first provided an updated overview of USN clinical and neuroanatomical features and then highlighted recent progresses in the diagnosis and rehabilitation of the disease. In relation to USN rehabilitation, we conducted a MEDLINE literature research on three of the most promising interventions for USN rehabilitation: prismatic adaptation (PA), non-invasive brain stimulation (NIBS), and virtual reality (VR). The identified studies were classified according to the strength of their methods. Results The last years have witnessed a relative decrement of interest in the study of neuropsychological disorders of spatial awareness in USN, but a relative increase in the study of potential interventions for its rehabilitation. Although optimal protocols still need to be defined, high-quality studies have demonstrated the efficacy of PA, TMS and tDCS interventions for the treatment of USN. In addition, preliminary investigations are suggesting the potentials of GVS and VR approaches for USN rehabilitation. Conclusion Advancing neuropsychological and neuroscience tools to investigate USN pathophysiology is a necessary step to identify effective rehabilitation treatments and to foster our understanding of neurofunctional bases of spatial cognition in the healthy brain.
Efficiency and Tolerability of Induction and Consolidation Therapy with Arsenic Trioxide/Bortezomib/Ascorbic Acid/Dexamethasone (ABCD) Regimen Compared to Bortezomib/Dexamethasone (BD) Regimen in Newly Diagnosed Myeloma Patients

Purpose This study was aimed at comparing the efficacy and tolerability of an arsenic trioxide/bortezomib/ascorbic acid/dexamethasone (ABCD) regimen with efficacy and tolerability of a bortezomib/dexamethasone (BD) regimen in patients with newly diagnosed myeloma. Patients and Methods Fifty-seven and sixty-four patients were treated with the ABCD and BD regimens, respectively. Eligible and agreeable patients received autologous hematopoietic stem cell transplantation followed by consolidation. Results The response rates (above VGPR) were 74.1% and 32.8% in the ABCD- and BD-treated groups, respectively (P = 0.000). Compared to BD regimen, ABCD regimen significantly improved PFS (P = 0.026) and OS (P = 0.000) in newly diagnosed patients. Patients with a high tumor burden, low or standard risk, and without auto-HSCT seemed to especially benefit compared to the same group with BD regimen. ABCD also showed better tolerability with lower bone marrow suppression (P = 0.026). Furthermore, complete response or near CR after induction therapy was a good prognostic factor for ABCD-associated OS and PFS. Conclusion ABCD is an effective and tolerable regimen compared with BD regimen in newly diagnosed myeloma patients. ABCD regimen could be an economical, effective, and tolerable choice in low- and standard-risk patients.
Retinal Nerve Fiber Layer Thickness and Total Macular Volume in Multiple Sclerosis Subtypes and Their Relationship with Severity of Disease, a Cross-Sectional Study

Background Optic neuritis (ON) is an inflammatory demyelinating lesion in the optic nerve, which is strongly associated with multiple sclerosis (MS). Optical coherence tomography (OCT) is a noninvasive technique for the evaluation of the retinal layers. Our aim was to examine OCT metrics including retinal nerve fiber layer thickness (RNFLT), and total macular volume (TMV), in MS subtypes and their relationship with duration, first manifestation, and severity of disease. Material and Methods In this cross-sectional study, patients with a definite diagnosis of MS underwent complete ophthalmic and neurologic examination. OCT parameters including TMV and RNFLT were compared between MS subtypes and different first manifestations of MS. Their relationships were also studied with the duration and severity of disease based on the Expanded Disability Status Scale (EDSS) score. Results A total of 240 eyes were examined in 120 enrolled MS patients. The differences in RNFLT were not analytically meaningful between the subtypes of MS, but the differences in TMV values were statistically significant between the subtypes of MS (P: 0.39 and P: 0.04, respectively). The differences between RNFLT and TMV of eyes with and without ON were statistically significant between these two groups (P<0.001 and P<0.001). There was also an inverse correlation between EDSS disability score and RNFLT and TMV values (P: 0.00, r: −0.33 and P: 0.034, r: −0.11, respectively) and a significant inverse correlation between the duration of MS and RNFLT (P: 0.00, r: −0.47). The differences in RNFLT and TMV values were analytically meaningful between the categories of first manifestations of MS (P: 0.000 and P: 0.027, respectively). Conclusion RNFLT and TMV represent noninvasive parameters for assessment of neuroaxonal degeneration in the anterior visual pathway that correlate with the severity and duration of multiple sclerosis. The lowest RNFLT and TMV values were also seen in the perceptual category between the first manifestations of MS. Therefore, they may be useful in the evaluation of MS patients.
Apixaban: An Update of the Evidence for Its Place in the Prevention of Stroke in Patients with Atrial Fibrillation

Abstract Oral anticoagulant therapy for stroke prevention in atrial fibrillation patients has been remarkably changed by the introduction of non-vitamin k oral anticoagulants (NOAC). Apixaban was the third NOAC introduced to clinical practice. Aim was to outline the current evidence for Apixaban in stroke prevention in atrial fibrillation patients in the randomized trials and real-world data. Apixaban has been shown to be superior to warfarin in preventing stroke and systemic embolism and causes significantly less major bleeding based on large randomized trials. These data are confirmed in real-world studies. Apixaban has been shown to be safe and effective in atrial fibrillation patients in acute coronary syndrome or undergoing PCI in combination with a P2Y12 inhibitor. Regarding expanded use of apixaban also in valvular heart disease patients, there is still missing knowledge in relation to the safety and efficacy of apixaban which is being addressed by ongoing randomized clinical trials.
Reliability and Validity of Self-Screening Tool for Hearing Loss in Older Adults

Objective The present study aimed to identify the reliability and validity of a screening tool for the elderly who wish to check their level of hearing loss by themselves. Design A total of 170 older adults with different hearing levels participated. The Self-Assessment for Hearing Screening of the Elderly-Revised (SHSE-R) consisted of 20 questions measured on a 5-point scale and developed in terms of characteristics of age-related hearing loss. For reliability, the subjects responded to SHSE-R twice with a three-week interval. They also took various subjective and objective hearing tests and a working memory test and filled out two other questionnaires for validation. Results SHSE-R showed a high internal consistency and a high reliability when comparing test–retest scores. Its content validity was as high as 0.88–1. Convergent validity supported SHSE-R and its subcategories while showing either a positive or negative correlation with pure-tone average, word recognition scores, and otoacoustic emission tests. Construct validity was proved by a moderate negative correlation with the tests of speech in noise, speech with fast speed, and working memory. In criterion validity, a strong positive correlation existed between SHSE-R and the other questionnaires, except for a group with severe hearing loss. The factor analysis showed similar results to the original version of SHSE having three factors, although some items were interchanged. Conclusion We confirmed that SHSE-R was well developed with both excellent internal consistency and test–retest reliability and valuable convergent, construct, and criterion validities, consequently making SHSE-R useful for self-checking hearing loss in the elderly.