Miracle-dz/UniFAR-FTUs huggingface dataset:
Real-World Prevalence of Direct Oral Anticoagulant Off-Label Doses in Atrial Fibrillation: An Epidemiological Meta-Analysis

Background: The use of direct oral anticoagulant (DOAC) off-label doses in atrial fibrillation (AF) patients may result in poor clinical outcomes. However, the true prevalence remains scarce. This study aims at estimating the prevalence of DOAC off-label doses in AF patients. Methods: Databases of MEDLINE, EMBASE, and COCHRANE were searched from inception through February 2020 for real-world studies that reported the off-label definition and prevalence data of AF patients using DOACs. The primacy outcomes were the overall prevalence of DOAC off-label doses and the corresponding underdose and overdose. The random-effects model was used for data synthesis. Variations on individual DOAC and different regions were examined by subgroup analyses. Results: A total of 23 studies involving 162,474 AF patients were finally included. The overall prevalence of DOAC off-label doses was 24% (95% CI, 19–28%), with 18% for dabigatran, 27% for rivaroxaban, 24% for apixaban, and 26% for edoxaban. The prevalence of underdosed DOACs was 20% (95% CI, 16–24%) with significant difference among individual anticoagulants (13% for dabigatran, 22% for rivaroxaban, 22% for apixaban, and 18% for edoxaban; P interaction =0.02). The prevalence of overdosed DOACs was 5% (95% CI, 3–7%), with the lowest prevalence observed in apixaban (2%). Subgroup analyses by regions demonstrated that the prevalence of DOAC off-label doses was higher in Asia (32%) than in North America (14%) and in Europe (22%), with underdose being predominant. Regardless of different regions, the prevalence of overdose was relatively low (4–6%). Conclusion: This study provides an estimation of DOAC off-label doses in the real-world setting. The prevalence rate of DOAC off-label doses in AF patients was relatively high, with underdose being predominant. Clinicians in Asia preferred to prescribe underdose of DOACs to AF patients. More evidence about the appropriateness of DOAC off-label doses in AF patients is urgently needed. Education programs concerning the appropriate prescription of DOACs within the drug labels and accepted guidelines are necessary to DOAC prescribers to ensure the safety and effectiveness of anticoagulation therapy for patients with AF.
NaHS or Lovastatin Attenuates Cyclosporine A–Induced Hypertension in Rats by Inhibiting Epithelial Sodium Channels

The use of cyclosporine A (CsA) in transplant recipients is limited due to its side effects of causing severe hypertension. We have previously shown that CsA increases the activity of the epithelial sodium channel (ENaC) in cultured distal nephron cells. However, it remains unknown whether ENaC mediates CsA-induced hypertension and how we could prevent hypertension. Our data show that the open probability of ENaC in principal cells of split-open cortical collecting ducts was significantly increased after treatment of rats with CsA; the increase was attenuated by lovastatin. Moreover, CsA also elevated the levels of intracellular cholesterol (Cho), intracellular reactive oxygen species (ROS) via activation of NADPH oxidase p47phox, serum- and glucocorticoid-induced kinase isoform 1 (Sgk1), and phosphorylated neural precursor cell–expressed developmentally downregulated protein 4–2 (p-Nedd4-2) in the kidney cortex. Lovastatin also abolished CsA-induced elevation of α-, ß-, and γ-ENaC expressions. CsA elevated systolic blood pressure in rats; the elevation was completely reversed by lovastatin (an inhibitor of cholesterol synthesis), NaHS (a donor of H2S which ameliorated CsA-induced elevation of reactive oxygen species), or amiloride (a potent ENaC blocker). These results suggest that CsA elevates blood pressure by increasing ENaC activity via a signaling cascade associated with elevation of intracellular ROS, activation of Sgk1, and inactivation of Nedd4-2 in an intracellular cholesterol-dependent manner. Our data also show that NaHS ameliorates CsA-induced hypertension by inhibition of oxidative stress.
Tumor Inhibitory Effect of Long Non-coding RNA LOC100505817 on Gastric Cancer

Gastric cancer (GC) is one of the major malignancies worldwide. Emerging evidence has revealed the potential involvement of long noncoding RNA (lncRNA) in human genetic disorders and cancer, but the role of LOC100505817 remains unknown. Thus, in this study, we isolated tissues from GC patients to characterize the functional importance of LOC100505817 in GC tumorigenesis. We also proposed a hypothesis that the regulation of Wnt/β-catenin pathway by LOC100505817 was regulated by miR-20a-mediated WT1. After the collection of cancer tissues and adjacent tissues were obtained from GC patients, expression of LOC100505817, Wnt/β-catenin pathway- and EMT-related genes was quantified. Ectopic expression and knockdown experiments were applied in order to investigate the protective role of LOC100505817 in the progression of GC. Subsequently, cell viability, flow cytometry for apoptosis and cell cycle were detected via CCK-8, while migration and invasion were determined using scratch test and Transwell assay respectively. Then interactions among LOC100505817, miR-20a and WT1 were explored by dual luciferase reporter gene assay, RNA pull down assay and RNA binding protein immunoprecipitation (RIP) assay. The results found poor expression LOC100505817 was poorly expressed in GC cells and tissues. Overexpressed LOC100505817 resulted in the significant reduction of cell proliferation, migration and invasion as well as the expression of Wnt2b, β-catenin, CyclinD1, N-cadherin, Vimentin and snail, while increased cell apoptosis along with the expression of E-cadherin. Wnt/β-catenin pathway and EMT in GC cells were suppressed by LOC100505817 through miR-20a-inhibted WT1. In summary, our results provided evidence suggesting that LOC100505817 inhibits GC through LOC100505817-mediated inhibition of Wnt/β-catenin pathway, that leads to the overall restraining of GC cell proliferation, migration and invasion through miR-20a-reduced WT1.
Coping With the Experiences of Intimate Partner Violence Among South African Women: Systematic Review and Meta-Synthesis

Background: Intimate partner violence (IPV) continues to be a serious problem worldwide. South Africa has a high prevalence of women experiencing IPV. Although much research reports on the prevalence rates, risk factors, and consequences of IPV, fewer studies report on how women deal with the experiences of IPV. Objective: This systematic review of the empirical literature aimed to identify and synthesize the best available evidence on women's experiences of coping with IPV in South Africa. Methods: A four-level search and retrieval strategy using PRISMA and JBI guidelines was conducted, which included critical appraisal, study selection, data extraction, and data synthesis. Ten studies met the eligibility criteria and were included in the review. They were assessed to meet a set threshold (7/10) based on the JBI Critical Appraisal Checklist for Qualitative Research. All studies were conducted between 2010 and 2020, conducted in South Africa, and used qualitative methodologies to accomplish the overall aim of investigating IPV experiences of women and their responses to it. Results: The total number of women included in the studies was 159. The data extraction yielded 49 findings of which 47 were aggregated into 14 categories and three themes: (1) help- and support-seeking coping, (2) emotional regulation coping, and (3) problem avoidance and distraction coping. Help- and support-seeking coping refers to women's responses when they seek instrumental aid, advice, comfort, and/or understanding from others. Emotional regulation includes responses of women in which their emotions were expressed or regulated. Problem avoidance and distraction coping represent responses of women in which they take efforts to avoid thinking about the problem situation and rather reshift their focus. Conclusion: Overall, this review found that a variety of coping responses are used by South African women experiencing IPV. The findings point to the need for understanding IPV and responses to it within a broader social context rather than just at the personal level. Approaching IPV at many levels may lead to a change in societal norms, better access to and delivery of services to IPV survivors, more functional family affairs, and personal well-being and improved quality of life.
An Optical Coherence Tomography-Based Deep Learning Algorithm for Visual Acuity Prediction of Highly Myopic Eyes After Cataract Surgery

Background Due to complicated and variable fundus status of highly myopic eyes, their visual benefit from cataract surgery remains hard to be determined preoperatively. We therefore aimed to develop an optical coherence tomography (OCT)-based deep learning algorithms to predict the postoperative visual acuity of highly myopic eyes after cataract surgery. Materials and Methods The internal dataset consisted of 1,415 highly myopic eyes having cataract surgeries in our hospital. Another external dataset consisted of 161 highly myopic eyes from Heping Eye Hospital. Preoperative macular OCT images were set as the only feature. The best corrected visual acuity (BCVA) at 4 weeks after surgery was set as the ground truth. Five different deep learning algorithms, namely ResNet-18, ResNet-34, ResNet-50, ResNet-101, and Inception-v3, were used to develop the model aiming at predicting the postoperative BCVA, and an ensemble learning was further developed. The model was further evaluated in the internal and external test datasets. Results The ensemble learning showed the lowest mean absolute error (MAE) of 0.1566 logMAR and the lowest root mean square error (RMSE) of 0.2433 logMAR in the validation dataset. Promising outcomes in the internal and external test datasets were revealed with MAEs of 0.1524 and 0.1602 logMAR and RMSEs of 0.2612 and 0.2020 logMAR, respectively. Considerable sensitivity and precision were achieved in the BCVA < 0.30 logMAR group, with 90.32 and 75.34% in the internal test dataset and 81.75 and 89.60% in the external test dataset, respectively. The percentages of the prediction errors within ± 0.30 logMAR were 89.01% in the internal and 88.82% in the external test dataset. Conclusion Promising prediction outcomes of postoperative BCVA were achieved by the novel OCT-trained deep learning model, which will be helpful for the surgical planning of highly myopic cataract patients.
Soil Fungal Community Structure in Boreal Pine Forests: From Southern to Subarctic Areas of Finland

The boreal forest environment plays an important role in the global C cycle due to its high carbon storage capacity. However, relatively little is known about the forest fungal community at a regional scale in boreal forests. In the present study, we have re-analyzed the data from our previous studies and highlighted the core fungal community composition and potential functional groups in three forests dominated by Scots pine (Pinus sylvestris L.) in Finland, and identified the fungal generalists that appear across geographic locations despite differences in local conditions. The three forests represent subarctic, northern and southern boreal forest, and are all in an un-managed state without human interference or management. The subarctic and northern areas are subject to reindeer grazing. The results showed that the three locations formed distinct fungal community structures (P < 0.05). Compared to the two northern locations, the southern boreal forest harbored a greater abundance of Zygomycota, Lactarius, Mortierella Umbelopsis, and Tylospora, in which aspect there were no differences between the two northern forests. Cortinarius, Piloderma, and Suillus were the core fungal genera in the boreal Scots pine forest. Functionally, the southern boreal forest harbored a greater abundance of saprotroph, endophytes and fungal parasite-lichen, whereas a greater abundance of ectomycorrhizal fungi was observed in the northern boreal forests. Moreover, the pathotroph and wood saprotrophs were commonly present in these three regions. The three locations formed two distinct fungal community functional structures, by which the southern forest was clearly separated from the two northern forests, suggesting a distance–decay relationship via geographic location. This study provides useful information for better understanding the common fungal communities and functions in boreal forests in different geographical locations.
The Effect of the Deformity Genetic Background of the Breeders on the Spawning Quality of Gilthead Seabream (Sparus aurata L.)

Fish egg quality is strongly related with the ability of the egg to be fertilized and develop a normal embryo with good survival and a lack of abnormalities. Large variations in the spawning quantity or quality impact directly in the competitiveness and sustainability of hatcheries, which create an overly large broodstock in order to satisfy the on-growing companies’ demand for undeformed fry. The present study reports, for the first time in relation to gilthead seabream, the effect of the genetic background of breeders for presence or absence of deformity on their spawning quality and the importance of considering this when creating broodstock. The spawning quality of crosses of breeders with genetic background for presence or absence of deformity (EBVdef), were evaluated during a whole spawning season, through study of the following traits: oocyte yield, fertilization rate, viability rate, hatching rate, larval survival rate, fertilized eggs, viable eggs, hatched eggs, and number of alive larvae. Breeders with a genetic background for deformity and a normal phenotype had shorter spawning periods, lower oocyte yield and, consequently, produced a lower number of alive larvae. In these two traits, the genetic background of breeders was of greater importance during intermediate spawning periods, when spawning is generally considered optimal for the industry, while environmental factors were more important at the beginning and end of the spawning season. In conclusion, these results demonstrate the importance of controlling the breeders’ genetics when creating broodstock.
Smiles as a Signal of Prosocial Behaviors Toward the Robot in the Therapeutic Setting for Children With Autism Spectrum Disorder

We explored how robot-assisted therapy based on smile analysis may facilitate the prosocial behaviors of children with autism spectrum disorder. Prosocial behaviors, which are actions for the benefit of others, are required to belong to society and increase the quality of life. As smiling is a candidate for predicting prosocial behaviors in robot-assisted therapy, we measured smiles by annotating behaviors that were recorded with video cameras and by classifying facial muscle activities recorded with a wearable device. While interacting with a robot, the participants experienced two situations where participants' prosocial behaviors are expected, which were supporting the robot to walk and helping the robot from falling. We first explored the overall smiles at specific timings and prosocial behaviors. Then, we explored the smiles triggered by a robot and behavior changes before engaging in prosocial behaviors. The results show that the specific timing of smiles and prosocial behaviors increased in the second session of children with autism spectrum disorder. Additionally, a smile was followed by a series of behaviors before prosocial behavior. With a proposed Bayesian model, smiling, or heading predicted prosocial behaviors with higher accuracy compared to other variables. Particularly, voluntary prosocial behaviors were observed after smiling. The findings of this exploratory study imply that smiles might be a signal of prosocial behaviors. We also suggest a probabilistic model for predicting prosocial behaviors based on smile analysis, which could be applied to personalized robot-assisted therapy by controlling a robot's movements to arouse smiles and increase the probability that a child with autism spectrum disorder will engage in prosocial behaviors.
Influence of Spawning Ground Dynamics on the Long-Term Abundance of Japanese Flying Squid (Todarodes pacificus) Winter Cohort

Japanese flying squid (Todarodes pacificus) is one of the most commercially important resources in the Pacific Ocean and its abundance is largely affected by environmental conditions. We examined the influence of environmental factors in potential spawning grounds of the winter cohort, approximated from Japanese and South Korean catch and catch per unit effort (CPUE) data of Japanese flying squid. Annual spawning ground dynamics were constructed using sea surface temperature (SST), submarine elevation and mean Kuroshio axis data from 1979 to 2018. Based on these information, we generated a suite of spawning ground indices including suitability SST-weighted area of potential spawning ground (SSWA), mean values (January–April) of suitable SST (MVSS), and the meridional position (MP) of SST isolines (18–24°C). Comparable interannual-decadal variability patterns were detected between the squid abundance and spawning ground indices, with abrupt shifts around 1990/1991 and in recent decades. In particular, the Pacific Decadal Oscillation is negatively correlated with spawning ground indices, suggesting its role in regulating the environmental dynamics in the area. Further, the gradient forest model underpinned the importance of SSWA, SSWA_Lag1 and MVSS_Lag1 on squid abundance. The CPUE is also shown to be a better abundance index than the annual catch in modeling the species’ response to environmental variability in its spawning grounds. Our findings suggest that it is imperative to pay more and timely attention to the relationship between the abundance of Japanese flying squid and environmental changes, especially under adverse environmental conditions.
Quantification of Osteoclasts in Culture, Powered by Machine Learning

In vitro osteoclastogenesis is a central assay in bone biology to study the effect of genetic and pharmacologic cues on the differentiation of bone resorbing osteoclasts. To date, identification of TRAP+ multinucleated cells and measurements of osteoclast number and surface rely on a manual tracing requiring specially trained lab personnel. This task is tedious, time-consuming, and prone to operator bias. Here, we propose to replace this laborious manual task with a completely automatic process using algorithms developed for computer vision. To this end, we manually annotated full cultures by contouring each cell, and trained a machine learning algorithm to detect and classify cells into preosteoclast (TRAP+ cells with 1–2 nuclei), osteoclast type I (cells with more than 3 nuclei and less than 15 nuclei), and osteoclast type II (cells with more than 15 nuclei). The training usually requires thousands of annotated samples and we developed an approach to minimize this requirement. Our novel strategy was to train the algorithm by working at “patch-level” instead of on the full culture, thus amplifying by >20-fold the number of patches to train on. To assess the accuracy of our algorithm, we asked whether our model measures osteoclast number and area at least as well as any two trained human annotators. The results indicated that for osteoclast type I cells, our new model achieves a Pearson correlation (r) of 0.916 to 0.951 with human annotators in the estimation of osteoclast number, and 0.773 to 0.879 for estimating the osteoclast area. Because the correlation between 3 different trained annotators ranged between 0.948 and 0.958 for the cell count and between 0.915 and 0.936 for the area, we can conclude that our trained model is in good agreement with trained lab personnel, with a correlation that is similar to inter-annotator correlation. Automation of osteoclast culture quantification is a useful labor-saving and unbiased technique, and we suggest that a similar machine-learning approach may prove beneficial for other morphometrical analyses.
Arterial Infusion Chemotherapy for Neoplastic Esophagogastric Anastomotic Strictures After Esophagectomy

Background Neoplastic esophagogastric anastomotic strictures after resection of esophageal cancer is a very difficult problem in clinical practice. We aim at to investigate the safety and feasibility of arterial infusion chemotherapy in treatment of neoplastic esophagogastric anastomotic strictures after esophagectomy. Methods From October 2014 to December 2019, 50 patients with Neoplastic esophagogastric anastomotic strictures after resection of esophageal cancer were assessed retrospectively. Preoperative dysphagia was grade III in 34 cases and grade IV in 16 cases. Thirty-eight patients had different degrees of dyspnea before surgery Twenty-five patients had intolerable (grade IV) dyspnea and airway stenting was undertaken before surgery. Thirteen patients had tolerable dyspnea that did not require airway stenting, and preoperative dyspnea was grade III. Results All patients were successfully treated with arterial infusion chemotherapy, no paraplegia or death occurred. The dysphagia grade of 50 patients after AIC was compared: one case had grade I, 40 cases had grade II, and nine cases had grade III. Thirteen patients had tolerable dyspnea that did not necessitate airway stenting. Dyspnea was classified as grade I in five cases and grade II in eight cases. After 1–3 courses of AIC, 50 patients were followed up for a complete response (eight cases), partial response (28) and stable disease (14 cases). Total objective effective rate (complete response+ partial response) and disease control rate(complete response + partial response + stable disease)were 72.0% and 100.0%, respectively. The median duration of follow-up was 8.5 months. One-year survival was 46.0%. Conclusion Arterial infusion chemotherapy is safe and efficacious treatment for Neoplastic esophagogastric anastomotic strictures after esophagectomy.
Chess Not Checkers: Complexities Within the Myeloid Response to the Acute Kidney Injury Syndrome

Immune dysregulation in acute kidney injury (AKI) is an area of intense interest which promises to enhance our understanding of the disease and how to manage it. Macrophages are a heterogeneous and dynamic population of immune cells that carry out multiple functions in tissue, ranging from maintenance to inflammation. As key sentinels of their environment and the major immune population in the uninjured kidney, macrophages are poised to play an important role in the establishment and pathogenesis of AKI. These cells have a profound capacity to orchestrate downstream immune responses and likely participate in skewing the kidney environment toward either pathogenic inflammation or injury resolution. A clear understanding of macrophage and myeloid cell dynamics in the development of AKI will provide valuable insight into disease pathogenesis and options for intervention. This review considers evidence in the literature that speaks to the role and regulation of macrophages and myeloid cells in AKI. We also highlight barriers or knowledge gaps that need to be addressed as the field advances.