Miracle-dz/UniFAR-FTUs huggingface dataset:
Retinopathy of Prematurity Trends in Taiwan: A 10-Year Nationwide Population Study.

Purpose To investigate the 10-year epidemiology and risk factors of retinopathy of prematurity (ROP) in Taiwan using the National Health Insurance Research Database. Methods All premature infants (n = 34,192) from 2002 to 2011 were screened, and those with length of stay (LOS) longer than 28 days who survived after the initial discharge were enrolled (n = 11,180). The annual incidence of ROP and the risk factors associated with it were analyzed. Results A total of 4096 ROP infants, 36.6% of premature babies with LOS longer than 28 days, were identified. The numbers of newborns, premature infants, and cases with ROP decreased over time, but the proportion of extremely low birth weight infants increased over time (P < 0.01 for test of trend in number). Also, the proportion of ROP infants receiving treatment increased over time (P < 0.01 for test of trend in number). However, the incidence of ROP was steady throughout the study period. Multivariable analysis revealed that low birth weight, male sex (odds ratio [OR] = 1.12, P = 0.007), and multiparity (OR = 1.17, P = 0.002) were positively associated with ROP, whereas necrotizing enterocolitis (OR = 0.72, P = 0.002) had a negative association with ROP. Conclusions The average incidence of ROP from 2002 to 2011 in Taiwan showed no significant change over the 10-year period. Proportion of treatment-requiring ROP increased. Low birth weight, multiparity, and male sex were independent risk factors of ROP.
OsDER1 Is an ER-Associated Protein Degradation Factor That Responds to ER Stress1

Overexpression or suppression of OsDER1 in rice leads to an unfolded protein response and ER stress hypersensitivity, and suppression results in floury, shrunken seeds. Endoplasmic reticulum-associated protein degradation (ERAD) plays an important role in endoplasmic reticulum (ER) quality control. To date, little is known about the retrotranslocation machinery in the plant ERAD pathway. We obtained a DERLIN-like protein (OsDER1) through a SWATH-based quantitative proteomic analysis of ER membrane proteins extracted from ER-stressed rice (Oryza sativa) seeds. OsDER1, a homolog of yeast and mammal DER1, is localized in the ER and accumulates significantly under ER stress. Overexpression or suppression of OsDER1 in rice leads to activation of the unfolded protein response and hypersensitivity to ER stress, and suppression results in floury, shrunken seeds. In addition, the expression levels of polyubiquitinated proteins increased markedly in OsDER1 overexpression or suppression transgenic rice. Coimmunoprecipitation experiments demonstrated that OsDER1 interacted with OsHRD1, OsHRD3, and OsCDC48, the essential components of the canonical ERAD pathway. Furthermore, OsDER1 associated with the signal peptide peptidase, a homolog of a component of the alternative ERAD pathway identified recently in yeast and mammals. Our data suggest that OsDER1 is linked to the ERAD pathway.
Factor Structure and Incremental Utility of the Distress Tolerance Scale: A Bifactor Analysis

The Distress Tolerance Scale (DTS) is a self-report measure of perceived capacity to withstand aversive emotions. Initial factor analysis of this measure suggested a structure comprising one higher-order factor and four lower-order domain-specific factors. However, there is limited evidence in support of the DTS’s purported multidimensionality, and despite use of the DTS subscales, research has yet to assess their incremental utility. The current investigation sought to rectify the paucity of evidence in support of the DTS’s factor structure and independent use of DTS subscales via bifactor analysis. In the present study (N = 826 community adults), a bifactor model of the DTS provided the best fit to the data. However, an examination of statistical indices associated with bifactor modeling, as well as results from an examination of incremental utility, suggest that the domain-specific factors are largely redundant with the general factor and do not provide incremental utility in predicting relevant clinical constructs beyond the general factor. Measurement invariance between sexes was confirmed. Taken together, results support use of a DTS total score, but not subscale scores.
Impact of Implant Number on Mandibular Implant-Supported Profile Prostheses: A Systematic Review.

PURPOSE To assess studies on edentulous patients rehabilitated using mandibular implant-supported profile prostheses and analyze the impact of different numbers of implants used on the implant survival rate, peri-implant bone loss, and prosthesis survival rate. MATERIALS AND METHODS This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement and was registered on PROSPERO. The PubMed/MEDLINE database was searched for articles published before July 18, 2016. The study attempted to answer the following PICO question: In edentulous patients, do full-arch fixed prostheses supported by three implants have a satisfactory implant survival rate, marginal bone loss, and prosthesis survival rate compared with those supported by different numbers of implants? Evidence levels of each study were evaluated using the Oxford Centre for Evidence-Based Medicine (OCEBM); methodologic quality was evaluated using the Methodological Index for Nonrandomized Studies (MINORS) scale and Cochrane Risk of Bias Tool. Descriptive statistics were performed when applicable. Implant survival curves were constructed using the Kaplan-Meier method, and marginal bone loss was analyzed using the Kruskal-Wallis, Dunn's, and Mann-Whitney tests. RESULTS This analysis included 21 published studies of 4,712 implants and 1,245 mandibular implant-supported profile prostheses in 1,245 patients. The patients were grouped by the number of implants used: group 1 (three implants) had an implant survival rate of 90%; group 2 (four implants) had a rate of 95%; and group 3 (five implants) had the lowest rate, 74%. Groups 1 and 3 had the lowest first-year bone losses (median: 0.73 and 0.70 mm, respectively), and were significantly different from group 2 (median: 1.31 mm; P < .001). CONCLUSION Despite the limitations in the studies with low levels of evidence and the methodology of MeSH term research, it was concluded that the implant survival rate and first-year bone loss of full-arch fixed prostheses supported by three implants were satisfactory. However, the prosthesis survival rate was inferior to that of other groups, which suggests a longer follow-up of these rehabilitations.
Mathematics anxiety factors as predictors of mathematics self-efficacy and achievement among freshmen science and engineering students

The main purpose of this study was to determine the direct and indirect effects of mathematics anxiety on achievement in mathematics of first year science and engineering students. Data were obtained from a descriptive survey from 245 (201 male, 44 female) students from five departments of two faculties. Instruments used for data collection were standard scales of mathematics self-efficacy and mathematics anxiety adopted from MSES-R and RMARS for self-efficacy and anxiety, respectively. Factor analysis was used for data reduction and Cronbach’s α was obtained to check reliability of each factors. The independent samples t-test was conducted to compare means. Finally, path analyses were done to determine the direct and indirect effects of anxiety factors on mathematics achievement. The results indicate that the anxiety and self-efficacy scales yielded three factors each; the level of prevalence of mathematics anxiety among the gender groups was high for testand task-related anxieties and moderate for course-related anxiety; no significant gender difference in anxiety was observed; gender difference was significant in only mathematics capability and engagement in mathematics self-efficacy; all the anxiety factors and only two of the selfefficacy factors have significant direct effects on mathematics achievement; and the mathematics test anxiety has significant indirect effect as well through mathematics capability self-efficacy. Recommendations were forwarded that mathematics instructors should support female and mathematics test-anxious students by decreasing mathematics test anxiety and enhancing mathematics self-efficacy to do test. Specifically, teachers can cut students’ test anxiety in test taking situations through planned strategies of both teaching as well as preparing students for tests.
Regeneration of nerve crush injury using adipose‐derived stem cells: A multimodal comparison

Introduction: To restore full function following nerve crush injuries is critical but challenging. In an attempt to develop a viable therapy, we evaluated the effect of rat adipose‐derived stem cells (rASC) in 2 different settings of a sciatic crush injury model. Methods: In the first group, after 14 days of nerve crush injury, rASCs were injected distal to the lesion under ultrasound guidance. In the other group, alleviation of compression through clip removal (CR) was combined with epineural injection of rASCs. Gait analyses, MRI, gastrocnemius muscle weight ratio (MWR), and histomorphometry were performed for outcome analysis. Results: CR combined with rASC injection resulted in less muscle atrophy, as evidenced by MWR. These findings are further supported by better functional and anatomical outcomes. Discussion: Animals treated with CR and epineural stem cell injection showed enhanced anatomical and functional recovery. Muscle Nerve 58: 566–572, 2018
A Prospective Multicenter Study on Radiographic Crestal Bone Changes Around Dental Implants Placed at Crestal or Subcrestal Level: One-Year Findings.

PURPOSE To compare the peri-implant radiographic crestal bone changes around implants placed at the subcrestal or crestal level. MATERIALS AND METHODS Systemically healthy patients with at least two missing teeth requiring implant-supported fixed prosthetic restorations were enrolled in the study. Implants were randomly placed either 1 mm subcrestally or at the bone crest level. Radiographic examination was performed using the long-cone parallel technique and customized film holders. Digital periapical radiographs were obtained at the time of implant placement (T0), at the time of prosthesis delivery (T1), and 12 months (T2) after prosthetic loading. Marginal bone levels were measured at the mesial and distal aspects of each implant with digital image software. RESULTS A total of 54 implants were present for the radiographic analysis at the 12-month follow-up. No implant showed mechanical or biologic complications throughout the follow-up period. The implant survival percentage was 100%. After 1 year, the mean bone loss was 0.711 ± 0.721 mm in the subcrestal group and 0.224 ± 0.418 mm in the crestal group. Furthermore, only the subcrestal group showed statistically significant radiographic bone resorption at the end of the follow-up. CONCLUSION Within the limitations of this study, implants placed at the crestal level showed greater peri-implant bone stability during the 1-year follow-up. Studies with larger samples and longer follow-up are needed to confirm the results of this investigation.
Contactin‐associated protein‐like 2, a protein of the neurexin family involved in several human diseases

Contactin‐associated protein‐like 2 (CASPR2) is a cell adhesion protein of the neurexin family. Proteins of this family have been shown to play a role in the development of the nervous system, in synaptic functions, and in neurological diseases. Over recent years, CASPR2 function has gained an increasing interest as demonstrated by the growing number of publications. Here, we gather published data to comprehensively review CASPR2 functions within the nervous system in relation to CASPR2‐related diseases in humans. On the one hand, studies on Cntnap2 (coding for CASPR2) knockout mice revealed its role during development, especially, in setting‐up the inhibitory network. Consistent with this result, mutations in the CNTNAP2 gene coding for CASPR2 in human have been identified in neurodevelopmental disorders such as autism, intellectual disability, and epilepsy. On the other hand, CASPR2 was shown to play a role beyond development, in the localization of voltage‐gated potassium channel (VGKC) complex that is composed of TAG‐1, Kv1.1, and Kv1.2. This complex was found in several subcellular compartments essential for action potential propagation: the node of Ranvier, the axon initial segment, and the synapse. In line with a role of CASPR2 in the mature nervous system, neurological autoimmune diseases have been described in patients without neurodevelopmental disorders but with antibodies directed against CASPR2. These autoimmune diseases were of two types: central with memory disorders and temporal lobe seizures, or peripheral with muscular hyperactivity. Overall, we review the up‐to‐date knowledge on CASPR2 function and pinpoint confused or lacking information that will need further investigation.
The Two-Arm Coordination Test: Maturation of Bimanual Coordination in Typically Developing Children and Deficits in Children with Unilateral Cerebral Palsy

ABSTRACT Background: Tools to assess bimanual coordination are scant. We aimed to: 1) provide normative data of maturation of bimanual coordination in tipically developing (TD) children measured by the Two Arm Coordination Test (TACT), and 2) validate the TACT as an instrument to specifically discriminate impairment of bimanual coordination in children with unilateral cerebral palsy (UCP). Procedure: Cross-sectional observational study. 252 TD children and 26 children with UCP performed 8 trials of TACT (following a star pattern with a pointer steered by coordinated movements of both arms). Number of errors and time were combined in a performance index of motor learning.Results: In TD children, bimanual coordination improved with age (F(7,244)=36.888, p<. 001). Children with UCP had a poorer bimanual coordination than TD children (all t>24.25, all p<.01). TACT scores were correlated moderately to manual dexterity and manual ability (all r>-.452, all p<.039), showing the capacity of the TACT to provide information on different aspects of hand function. Conclusion: TACT is a valid instrument to assess bimanual coordination.
Detection of Somatic Structural Variants Enables Quantification and Characterization of Circulating Tumor DNA in Children With Solid Tumors.

Objective Liquid biopsies are being rapidly used in adult cancers as new biomarkers of disease. Circulating tumor DNA (ctDNA) levels have been reported to be proportional to disease burden, correlate with treatment response, and predict relapse. However, little is known about how frequently ctDNA is detectable in pediatric patients with solid tumors. Therefore, we developed a next-generation sequencing approach to detect and quantify ctDNA in the blood of patients with the most common pediatric solid tumors. Methods Detection of ctDNA requires assays sensitive to somatic events typically observed in the cancer type being studied. In pediatric solid tumors, structural variants are more common than recurrent point mutations. We adapted an ultralow passage whole-genome sequencing approach to capture copy number variants and a hybrid capture sequencing assay to detect translocations in liquid biopsy samples from pediatric patients. Results Copy number changes seen by ultralow passage whole-genome sequencing enabled detection of ctDNA in patients with osteosarcoma, neuroblastoma, alveolar rhabdomyosarcoma, and Wilms tumor. In Ewing sarcoma, detection of the EWSR1 translocation was a more sensitive approach. For patients with samples collected at multiple time points, changes in ctDNA levels corresponded to treatment response. We also found that disease-specific genomic biomarkers of prognosis were detectable in ctDNA. Conclusion This study demonstrates that liquid biopsy approaches that detect somatic structural variants are well suited to pediatric solid tumors. We show that children with the most common solid tumor malignancies have detectable levels of ctDNA, which may be used to track disease response and identify genomic subclassifiers of disease. Efforts to profile larger collections of clinically annotated specimens are under way to validate the clinical use of these assays.
Distinct immune signatures in directly treated and distant tumors result from TLR adjuvants and focal ablation

Both adjuvants and focal ablation can alter the local innate immune system and trigger a highly effective systemic response. Our goal is to determine the impact of these treatments on directly treated and distant disease and the mechanisms for the enhanced response obtained by combinatorial treatments. Methods: We combined RNA-sequencing, flow cytometry and TCR-sequencing to dissect the impact of immunotherapy and of immunotherapy combined with ablation on local and systemic immune components. Results: With administration of a toll-like receptor agonist agonist (CpG) alone or CpG combined with same-site ablation, we found dramatic differences between the local and distant tumor environments, where the directly treated tumors were skewed to high expression of F4/80, Cd11b and Tnf and the distant tumors to enhanced Cd11c, Cd3 and Ifng. When ablation was added to immunotherapy, 100% (n=20/20) of directly treated tumors and 90% (n=18/20) of distant tumors were responsive. Comparing the combined ablation-immunotherapy treatment to immunotherapy alone, we find three major mechanistic differences. First, while ablation alone enhanced intratumoral antigen cross-presentation (up to ~8% of CD45+ cells), systemic cross-presentation of tumor antigen remained low. Combining same-site ablation with CpG amplified cross-presentation in the draining lymph node (~16% of CD45+ cells) compared to the ablation-only (~0.1% of CD45+ cells) and immunotherapy-only cohorts (~10% of CD45+ cells). Macrophages and DCs process and present this antigen to CD8+ T-cells, increasing the number of unique T-cell receptor rearrangements in distant tumors. Second, type I interferon (IFN) release from tumor cells increased with the ablation-immunotherapy treatment as compared with ablation or immunotherapy alone. Type I IFN release is synergistic with toll-like receptor activation in enhancing cytokine and chemokine expression. Expression of genes associated with T-cell activation and stimulation (Eomes, Prf1 and Icos) was 27, 56 and 89-fold higher with ablation-immunotherapy treatment as compared to the no-treatment controls (and 12, 32 and 60-fold higher for immunotherapy-only treatment as compared to the no-treatment controls). Third, we found that the ablation-immunotherapy treatment polarized macrophages and dendritic cells towards a CD169 subset systemically, where CD169+ macrophages are an IFN-enhanced subpopulation associated with dead-cell antigen presentation. Conclusion: While the local and distant responses are distinct, CpG combined with ablative focal therapy drives a highly effective systemic immune response.
The influence of MTHFR genetic polymorphisms on adverse reactions after methotrexate in patients with hematological malignancies: a meta-analysis

ABSTRACT Objectives: The effect of methotrexate (MTX)-related adverse reaction on hematologic neoplasms patients is controversial. We performed this meta-analysis to assess the association between methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C polymorphism and the adverse reaction after MTX using. Methods: We searched for qualified studies according to PubMed, the Cochrane Library, and the Web of Science. The meta-analysis was performed by Review Manager 5.3. The analysis was conducted to compare risk ratios (RRs) with the corresponding 95% confidence interval (95% CI) to evaluate the relationship between different toxicity reactions and the genotype of MTHFR. Results: We included 17 studies which satisfied with the criteria in this meta-analysis. The results of our statistical analysis showed that no significant correlation between MTHFR C677T/A1298C genetic polymorphism and patients’ toxicity or the relapse and survival associated with MTX chemotherapy (P > .05). But we observed that a tendency toward increased risk of hepatotoxicity was also present for acute lymphoblastic leukemia in the mutation model (CT/TT vs. CC: RR: 1.92, 95% CI: 1.01–3.67; P = .05). Conclusion: The polymorphism of MTHFR C677T/A1298C may not be an important indicator for the accurate detection of side effects of chemotherapy after using MTX. More relative research is needed.
End of Life, Withdrawal, and Palliative Care Utilization among Patients Receiving Maintenance Hemodialysis Therapy.

BACKGROUND AND OBJECTIVES Withdrawal from maintenance hemodialysis before death has become more common because of high disease and treatment burden. The study objective was to identify patient factors and examine the terminal course associated with hemodialysis withdrawal, and assess patterns of palliative care involvement before death among patients on maintenance hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We designed an observational cohort study of adult patients on incident hemodialysis in a midwestern United States tertiary center, from January 2001 to November 2013, with death events through to November 2015. Logistic regression models evaluated associations between patient characteristics and withdrawal status and palliative care service utilization. RESULTS Among 1226 patients, 536 died and 262 (49% of 536) withdrew. A random sample (10%; 52 out of 536) review of Death Notification Forms revealed 73% sensitivity for withdrawal. Risk factors for withdrawal before death included older age, white race, palliative care consultation within 6 months, hospitalization within 30 days, cerebrovascular disease, and no coronary artery disease. Most withdrawal decisions were made by patients (60%) or a family member (33%; surrogates). The majority withdrew either because of acute medical complications (51%) or failure to thrive/frailty (22%). After withdrawal, median time to death was 7 days (interquartile range, 4-11). In-hospital deaths were less common in the withdrawal group (34% versus 46% nonwithdrawal, P=0.003). A third (34%; 90 out of 262) of those that withdrew received palliative care services. Palliative care consultation in the withdrawal group was associated with longer hemodialysis duration (odds ratio, 1.19 per year; 95% confidence interval, 1.10 to 1.3; P<0.001), hospitalization within 30 days of death (odds ratio, 5.78; 95% confidence interval, 2.62 to 12.73; P<0.001), and death in hospital (odds ratio, 1.92; 95% confidence interval, 1.13 to 3.27; P=0.02). CONCLUSIONS In this single-center study, the rate of hemodialysis withdrawals were twice the frequency previously described. Acute medical complications and frailty appeared to be driving factors. However, palliative care services were used in only a minority of patients.