Miracle-dz/UniFAR-FTUs huggingface dataset:
In-Vitro and In-Vivo Establishment and Characterization of Bioluminescent Orthotopic Chemotherapy-Resistant Human Osteosarcoma Models in NSG Mice

Osteosarcoma, the most common bone malignancy with a peak incidence at adolescence, had no survival improvement since decades. Persistent problems are chemo-resistance and metastatic spread. We developed in-vitro osteosarcoma models resistant to chemotherapy and in-vivo bioluminescent orthotopic cell-derived-xenografts (CDX). Continuous increasing drug concentration cultures in-vitro resulted in five methotrexate (MTX)-resistant and one doxorubicin (DOXO)-resistant cell lines. Resistance persisted after drug removal except for MG-63. Different resistance mechanisms were identified, affecting drug transport and action mechanisms specific to methotrexate (RFC/SCL19A1 decrease, DHFR up-regulation) for MTX-resistant lines, or a multi-drug phenomenon (PgP up-regulation) for HOS-R/DOXO. Differential analysis of copy number abnormalities (aCGH) and gene expression (RNAseq) revealed changes of several chromosomic regions translated at transcriptomic level depending on drug and cell line, as well as different pathways implicated in invasive and metastatic potential (e.g., Fas, Metalloproteinases) and immunity (enrichment in HLA cluster genes in 6p21.3) in HOS-R/DOXO. Resistant-CDX models (HOS-R/MTX, HOS-R/DOXO and Saos-2-B-R/MTX) injected intratibially into NSG mice behaved as their parental counterpart at primary tumor site; however, they exhibited a slower growth rate and lower metastatic spread, although they retained resistance and CGH main characteristics without drug pressure. These models represent valuable tools to explore resistance mechanisms and new therapies in osteosarcoma.
Root morphology of mandibular molars : a CBCT study Canals anatomy of mandibular molars

Background: To assess the number and anatomical classification of roots and root canals of first and second mandibular molars using cone beam computed tomography (CBCT) in a Chilean population. Materials and methods: This study evaluated the CBCT scans of 289 patients aged between 14 and 86 years, obtaining a sample of 1022 mandibular first and second molars. The number of roots and root canals was evaluated according to the anatomical classification proposed by Ahmed in 2016. Data were analyzed using Pearson’s chisquared test and ANOVA. Results: 951 molars had two roots (93.05%), while the remaining 71 molars (6.95%) had one root. The most frequent root and root canal morphologies found were: MM M D (29,65%), MM M D (22,3%) and MM M D (13,4%), with a total of 32 different anatomical distributions. C-shaped canals were present in 56 second molars and were more frequently found in women than in men (7.1% vs. 3.88%) (p = 0.024). Conclusions: The analysis of internal anatomy using CBCT revealed a highly variable distribution of root canals. The most frequent morphology found in mandibular molars in a Chilean population was two roots and three canals.
Midlife Forgetfulness and Risk of Dementia in Old Age: Results from the Danish Working Environment Cohort Study

Background: Despite the current evidence of a high prevalence of forgetfulness in middle-aged individuals, and the evidence of a link between midlife memory complaints and biological changes in the brain, no previous study has yet investigated midlife forgetfulness in relation to risk of dementia in old age. Aims: We investigated whether midlife forgetfulness was an indicator of an increased risk of dementia in old age. Methods: We used data from 3,136 employed men and women who participated in the Danish Work Environment Cohort Study in 1990. These data were linked to Danish national registers. Participants were asked whether their closest relative had ever told them that they were forgetful. Incidence rate ratios (IRR) were estimated using Poisson regression analysis. Results: At baseline, 749 (24%) study participants were categorized as forgetful, and 86 (2.7%) participants were diagnosed with dementia during a total of 31,724 person-years at risk. After adjusting for sociodemographic factors, comorbidities, and work-related factors, midlife forgetfulness was associated with a higher risk of dementia (IRR = 1.82; 95% CI: 1.12–2.97). Conclusions: This study is the first to investigate midlife forgetfulness and dementia, and the results suggest that midlife forgetfulness is an early indicator of an increased risk of dementia in old age.
Genetic Analyses of Tanzanian Local Chicken Ecotypes Challenged with Newcastle Disease Virus

Newcastle Disease (ND) is a continuing global threat to domestic poultry, especially in developing countries, where severe outbreaks of velogenic ND virus (NDV) often cause major economic losses to households. Local chickens are of great importance to rural family livelihoods through provision of high-quality protein. To investigate the genetic basis of host response to NDV, three popular Tanzanian chicken ecotypes (regional populations) were challenged with a lentogenic (vaccine) strain of NDV at 28 days of age. Various host response phenotypes, including anti-NDV antibody levels (pre-infection and 10 days post-infection, dpi), and viral load (2 and 6 dpi) were measured, in addition to growth rate. We estimated genetic parameters and conducted genome-wide association study analyses by genotyping 1399 chickens using the Affymetrix 600K chicken SNP chip. Estimates of heritability of the evaluated traits were moderate (0.18–0.35). Five quantitative trait loci (QTL) associated with growth and/or response to NDV were identified by single-SNP analyses, with some regions explaining ≥1% of genetic variance based on the Bayes-B method. Immune related genes, such as ETS1, TIRAP, and KIRREL3, were located in regions associated with viral load at 6 dpi. The moderate estimates of heritability and identified QTL indicate that NDV response traits may be improved through selective breeding of chickens to enhance increased NDV resistance and vaccine efficacy in Tanzanian local ecotypes.
Development and Validation of a Prediction Model for Organ-Specific Recurrences After Curative Resection of Colon Cancer.

BACKGROUND Early detection of postoperative recurrence is beneficial for patients with cancer; however, optimal surveillance remains an issue. To optimize the follow-up plan, the estimation of an individual patient's risk of recurrence is indispensable. OBJECTIVE This study aimed to establish a statistical model for predicting the risk of organ-specific recurrence after curative resection of colon cancer. DESIGN This was a retrospective cohort study at a tertiary referral hospital. SETTINGS This study included 1720 patients with colon cancer treated at the University of Tokyo Hospital between 1997 and 2015. Data were retrospectively retrieved from patient medical charts. The risk score was developed using a competing risk model in a derivation cohort (973 patients treated in 1997-2009) and then validated in a validation cohort (747 patients treated in 2010-2015). PATIENTS Patients who underwent curative resection for stage I to III colon cancer were included. MAIN OUTCOME MEASURES The prediction of the incidence of postoperative liver and lung metastasis of colon cancer was measured. RESULTS The factors selected for the prediction model for liver metastasis included differentiation, T category, venous invasion, N category, and preoperative CEA level. The model for lung metastasis included sex, lymphatic invasion, venous invasion, N category, preoperative CEA level, and malignant bowel obstruction. During external validation, the area under the curve at 60 months was 0.78 (95% CI, 0.71-0.84) for liver metastasis and 0.72 (95% CI, 0.64-0.81) for lung metastasis. LIMITATIONS The generalizability of the model to different healthcare settings remains to be elucidated. CONCLUSIONS We developed a prediction model to estimate the risk of recurrence in the liver and lung after curative resection of colon cancer, which demonstrated good discrimination ability in the external validation cohort. Our model can aid clinicians and patients in customizing postoperative surveillance according to an individual patient's risk of organ-specific recurrence. See Video Abstract at http://links.lww. com/DCR/A977.
Impact of Depression in Sickle Cell Disease Hospitalization-Related Outcomes: An Analysis of the National Inpatient Sample (NIS)

Background and objectives: This study aimed to analyze and discern the differences in demographics and inpatient outcomes (length of stay (LOS), total charges, disease severity, and mortality) between depressed versus non-depressed sickle cell disease (SCD) patients. Materials and Methods: A retrospective analysis was conducted using the Nationwide Inpatient Sample (2010–2014). We identified 73,225 SCD hospitalizations and comorbid depression (6317, 8.6%) as the primary and the other diagnosis, respectively, using International Classification of Diseases (ICD)-9 codes. We used linear and logistic regression model to evaluate the changes in inpatient outcomes. Results: Comorbid depression was more prevalent among middle-aged adults (11.5%), females (10.63%), and whites (12.43%). We did not find any association between income and comorbid depression among SCD patients. After adjusting for the demographic covariates, comorbid depression remained a significant risk factor for longer LOS (mean difference −1.16 days, 95% CI −1.30 to −1.03) and higher total charges (mean difference −USD5058, 95% CI −6261 to −3855) during hospitalization. SCD with comorbid depression was also significantly associated with a higher number of chronic conditions (mean difference −2.08, 95% CI −2.13 to −2.03) and 1.5 times (95% CI 1.39 to 1.63) higher odds of major severity of illness. Conclusion: Comorbid depression was significantly associated with longer LOS, more severity of illness, and higher hospital charges. Healthcare providers caring for adults with SCD should consider screening for and treating comorbid depression to improve the health-related quality of life.
Effects of Different Movement Programs on Motor Competence: A Systematic Review With Meta-Analysis.

BACKGROUND To use the meta-analytic approach to assess the effectiveness of different types of movement programs on motor competence (MC) in participants of all ages. METHODS Studies were retrieved by searching 13 databases and included when criteria were met. Studies were selected, and data were extracted by 2 authors. Random effects models using the standardized mean difference effect size (ES) were used to pool results. Risk of bias, heterogeneity, and inconsistency were examined. RESULTS Thirty-six studies met the inclusion criteria. A total of 374 ESs were calculated and partitioned into 4 groups (motor intervention, free play, physical education classes, and control group). Statistically significant improvements in MC were observed for the motor intervention (ES = 1.50; 95% confidence interval [CI], 1.18 to 1.82; n = 36), as well as for free play (ES = 0.33; 95% CI, 0.09 to 0.57; n = 5), physical education classes (ES = 0.52; 95% CI, 0.08 to 0.97; n = 15), and smaller statistically significant differences in MC were observed for the control groups (ES = 0.16; 95% CI, 0.01 to 0.31; n = 6). CONCLUSIONS All 4 groups analyzed improved MC in children, adolescents, and young adults. However, motor interventions were superior to all other groups for improving MC.
Obesity Tissue: Composition, Energy Expenditure, and Energy Content in Adult Humans

Chronic positive energy balance leads to obesity, and the “excess” weight is usually described as consisting solely of adipose tissue (AT) or its two components, fat and fat‐free mass (nonfat cell mass, extracellular fluid). This study aimed to clarify the nature of “obesity” tissue.
Overreaching Attenuates Training-induced Improvements in Muscle Oxidative Capacity.

INTRODUCTION The aim of this study was to determine if muscle oxidative capacity is influenced by alterations in training volume in middle-distance runners. METHODS Twenty-four highly-trained middle-distance runners (n=16 male; VO2peak=73.3(4.3) ml·kg·min; n=8 female, VO2peak=63.2(3.4) ml·kg·min) completed 3 weeks of normal training (NormTr), 3 weeks of high-volume training (HVTr; a 10, 20 and 30% increase in training volume during each successive week from NormTr), and a 1-week taper (TapTr; 55% exponential reduction in training volume from HVTr week 3). Before, and immediately after each training period, the rate of recovery of muscle oxygen consumption (mVO2) of the gastrocnemius medalis was measured using near-infrared spectroscopy, with the rate constant indicating muscle oxidative capacity. Time to exhaustion (TTE) and VO2peak were determined during a maximal incremental treadmill test. RESULTS Twelve subjects were classified as being functionally overreached (FOR) following HVTr (decreased running TTE and high perceived fatigue), whereas the other twelve subjects were classified as acutely fatigued (AF; no decrease in running TTE). The AF group demonstrated a significant increase in muscle oxidative capacity following HVTr (rate constant: 15.1% (SD; 9.7%) min; p=0.009), with no further improvement following TapTr, while there was no change in muscle oxidative capacity for FOR at any time point (p>0.05). Compared to the FOR group, the AF group had substantially larger improvements in TTE from pre-HVTr to post-TapTr (FOR: 8.8% (3.7%); AF: 3.2% (3.0%); p=0.04). CONCLUSION The present study was able to demonstrate that muscle oxidative capacity was increased in response to a period of HVTr, but only in runners who did not develop FOR. Furthermore, runners who did not develop FOR had substantially larger performance improvements following a taper period.
Nutritional Management and Outcomes in Malnourished Medical Inpatients: Anorexia Nervosa

Background: Anorexia Nervosa (AN) is a psychiatric disorder characterised by a physical and psychosocial deterioration due to an altered pattern on the intake and weight control. The severity of the disease is based on the degree of malnutrition. The objective of this article is to review the scientific evidence of the refeeding process of malnourished inpatients with AN; focusing on the clinical outcome. Methods: We conducted an extensive search in Medline and Cochrane; on April 22; 2019; using different search terms. After screening all abstracts; we identified 19 papers that corresponded to our inclusion criteria. Results: The article focuses on evidence on the characteristics of malnutrition and changes in body composition; energy and protein requirements; nutritional treatment; physical activity programmes; models of organisation of the nutritional treatment and nutritional support related outcomes in AN patients. Conclusion: Evidence-based standards for clinical practice with clear outcomes are needed to improve the management of these patients and standardise the healthcare process.
Once-Weekly Efpeglenatide Dose-Range Effects on Glycemic Control and Body Weight in Patients With Type 2 Diabetes on Metformin or Drug Naive, Referenced to Liraglutide

OBJECTIVE To explore the efficacy, safety, and tolerability of once-weekly efpeglenatide, a long-acting glucagon-like peptide 1 receptor agonist (GLP-1 RA), in early type 2 diabetes (T2D) (drug naive or on metformin monotherapy). RESEARCH DESIGN AND METHODS EXCEED 203 was a 12-week, randomized, placebo-controlled, double-blind, parallel-group, dose-ranging study of efpeglenatide once weekly referenced to open-label liraglutide 1.8 mg (exploratory analysis). Participants, ∼90% on metformin monotherapy, were randomized to one of five efpeglenatide doses (0.3, 1, 2, 3, or 4 mg q.w.; n = 181), placebo (n = 37), or liraglutide (≤1.8 mg daily; n = 36). The primary efficacy end point was change in HbA1c from baseline to week 13. RESULTS From a baseline HbA1c of 7.7–8.0% (61.0–63.9 mmol/mol), all efpeglenatide doses ≥1 mg significantly reduced HbA1c versus placebo (placebo-adjusted least squares [LS] mean changes 0.6–1.2%, P < 0.05 for all) to a final HbA1c of 6.3–6.8% (45.4–50.6 mmol/mol); masked efpeglenatide 4 mg was noninferior to open-label liraglutide. Greater proportions treated with efpeglenatide ≥1 mg than placebo achieved HbA1c <7% (61–72% vs. 24%, P < 0.05 for all), and greater reductions in body weight were observed with efpeglenatide 3 and 4 mg versus placebo (placebo-adjusted LS mean differences −1.4 and −2.0 kg, respectively, P < 0.05 for both). Rates of nausea and vomiting were consistent with other GLP-1 RAs and rapidly subsided after the initial 2 weeks. No neutralizing antibodies were detected with efpeglenatide. CONCLUSIONS Efpeglenatide once weekly led to significant reductions in HbA1c and weight, with a safety profile consistent with the GLP-1 RA class in patients with early T2D mostly on metformin monotherapy.
Identification of driver genes and key pathways of prolactinoma predicts the therapeutic effect of genipin

The purpose of the present study was to identify the potential targets and markers for diagnosis, therapy and prognosis in patients with prolactinoma at the molecular level and to determine the therapeutic effects of genipin in prolactinoma. The gene expression profiles of GSE2175, GSE26966 and GSE36314 were obtained from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) were identified after comparing between gene expression profiles of the prolactinoma tissues and normal tissues. Then, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and protein-protein interaction (PPI) network analysis were conducted. In addition, in vitro, scratch assay, colony-forming assay, Cell Counting Kit 8 (CCK8) assay and flow cytometry were performed to verify the functional effects of genipin. An aggregate of 12,695, 3,847 and 5,310 DEGs were identified from GSE2175, GSE26966 and GSE36314, respectively. The results of GO and KEGG analysis showed that the DEGs significant and important for prolactinoma were mostly involved with ‘spindle pole’ and ‘oocyte meiosis’. A total of 20 genes were selected as hub genes with high degrees after PPI network analysis, including mitogen-activated protein kinase 1 (MAPK1), MYC, early growth response 1 (EGR1), Bcl2 and calmodulin 1 (CALM1). CCK8 assay, colony-forming assay and scratch assay were performed to verify the anti-prolactinoma effect of genipin. The results of flow cytometry showed that apoptosis was increased by genipin. MAPK1, MYC, EGR1, Bcl2 and CALM1 were screened as main hub genes. Genipin upregulated the expression level of EGR1 and p21 (downstream mediator of EGR1) and EGR1, inhibited the proliferation and migration of prolactinoma cells. Genipin is a promising drug for treatment of patients with prolactinoma.
Safety and tolerability of iobitridol in cerebral angiography: a prospective, multicenter study

Background To date, only a few data have demonstrated the safety of iodinated contrast media for cerebral angiography. Purpose To assess contrast-related adverse events after cerebral angiography using iobitridol. Material and Methods A total of 790 patients who underwent cerebral angiography at three tertiary hospitals in the Republic of Korea between November 2017 and October 2018 were prospectively enrolled in this study. We interviewed all patients and recorded their symptoms before they left the interventional clinic after the angiography procedure and during the seven-day follow-up visit. The primary endpoints were acute (within 1 h) and delayed (1 h–7 days) adverse events associated with iobitridol injection. We also visually graded the radiographic density and image quality as secondary endpoints. Results Acute adverse events were more common than delayed adverse events. Most adverse events were either mild (96.5%) or moderate (3.45%). Among the contrast-related adverse events, feeling of warmth (59.1%) and altered taste (17.5%) were the most common acute events, whereas headache (41.9%) and allergic skin reactions (20.0%) were the most common delayed events. All cerebral angiography showed optimal density and good/excellent image quality. Conclusion The findings of this study suggest that iobitridol is a safe and effective iodinated contrast medium for use in cerebral angiography.
Case Sequence Analysis of the Robotic Colorectal Resection Learning Curve.

BACKGROUND Robotic surgery for colorectal cancer offers many potential benefits, but as with any new technology, there is a learning curve. OBJECTIVE We sought to identify trends in the uptake of robotic resection and associated complication rates. DESIGN This was a case sequence analysis of robotic surgery for colorectal cancer. SETTINGS The study was conducted using the New York Statewide Planning and Research Cooperation System database. PATIENTS Adults undergoing colorectal resection for cancer from 2008 through 2016 were identified in the New York Statewide Planning and Research Cooperative database. Case sequence analysis was used to describe surgeon experience, with cases grouped into quartiles based on the chronological order in which each surgeon performed them. MAIN OUTCOME MEASURES Outcomes included in-hospital major events (myocardial infarction, pulmonary embolism, shock, and death) and iatrogenic complications. Generalized linear mixed models were used to estimate the relationship between case sequence and operative outcomes. RESULTS A total of 2763 robotic procedures were included, with volume increasing from 76 cases in 2010 to 702 cases in 2015. The proportion of cases performed by surgeons earliest in their learning curve has increased to 18.2% in 2015. This quartile was composed of more black patients (11.4% earliest quartile vs 7.0% latest quartile; p < 0.001) and rectal resections (50.1% earliest quartile vs 38.9% latest quartile; p < 0.001). In adjusted analysis, major complications did not improve with increasing case sequence. However, with increasing cumulative surgeon case sequence iatrogenic complications were reduced, particularly in the highest volume quartile (OR = 0.29 (95% CI, 0.09-0.88); p = 0.03). Odds of prolonged length of stay (>75 percentile) were also decreased (OR = 0.50 (95% CI, 0.37-0.69); p < 0.001). LIMITATIONS Data were derived from an administrative database. CONCLUSIONS Robotic colorectal resection has been rapidly adopted. Surgeons earliest in their experience have increased iatrogenic complications and continue to make up a large proportion of cases performed. See Video Abstract at http://links.lww. com/DCR/A974.
The Applications of 3D Printing for Craniofacial Tissue Engineering

Three-dimensional (3D) printing is an emerging technology in the field of dentistry. It uses a layer-by-layer manufacturing technique to create scaffolds that can be used for dental tissue engineering applications. While several 3D printing methodologies exist, such as selective laser sintering or fused deposition modeling, this paper will review the applications of 3D printing for craniofacial tissue engineering; in particular for the periodontal complex, dental pulp, alveolar bone, and cartilage. For the periodontal complex, a 3D printed scaffold was attempted to treat a periodontal defect; for dental pulp, hydrogels were created that can support an odontoblastic cell line; for bone and cartilage, a polycaprolactone scaffold with microspheres induced the formation of multiphase fibrocartilaginous tissues. While the current research highlights the development and potential of 3D printing, more research is required to fully understand this technology and for its incorporation into the dental field.