Miracle-dz/UniFAR-FTUs huggingface dataset:
Canine Cancer: Strategies in Experimental Therapeutics

Cancer is the most common cause of death in adult dogs. Many features of spontaneously developing tumors in pet dogs contribute to their potential utility as a human disease model. These include similar environmental exposures, similar clonal evolution as it applies to important factors such as immune avoidance, a favorable body size for imaging and serial biopsy, and a relatively contracted time course of disease progression, which makes evaluation of temporal endpoints such as progression free or overall survival feasible in a comparatively short time frame. These criteria have been leveraged to evaluate novel local therapies, demonstrate proof of tumor target inhibition or tumor localization, evaluate potential antimetastatic approaches, and assess the efficacy, safety and immune effects of a variety of immune-based therapeutics. Some of these canine proof of concept studies have been instrumental in informing subsequent human clinical trials. This review will cover key aspects of clinical trials in dogs with spontaneous neoplasia, with examples of how these studies have contributed to human cancer therapeutic development.
Towards the Complete Goat Pan-Genome by Recovering Missing Genomic Segments From the Reference Genome

It is broadly expected that next generation sequencing will ultimately generate a complete genome as is the latest goat reference genome (ARS1), which is considered to be one of the most continuous assemblies in livestock. However, the rich diversity of worldwide goat breeds indicates that a genome from one individual would be insufficient to represent the whole genomic contents of goats. By comparing nine de novo assemblies from seven sibling species of domestic goat with ARS1 and using resequencing and transcriptome data from goats for verification, we identified a total of 38.3 Mb sequences that were absent in ARS1. The pan-sequences contain genic fractions with considerable expression. Using the pan-genome (ARS1 together with the pan-sequences) as a reference genome, variation calling efficacy can be appreciably improved. A total of 56,657 spurious SNPs per individual were repressed and 24,414 novel SNPs per individual on average were recovered as a result of better reads mapping quality. The transcriptomic mapping rate was also increased by ∼1.15%. Our study demonstrated that comparing de novo assemblies from closely related species is an efficient and reliable strategy for finding missing sequences from the reference genome and could be applicable to other species. Pan-genome can serve as an improved reference genome in animals for a better exploration of the underlying genomic variations and could increase the probability of finding genotype-phenotype associations assessed by a comprehensive variation database containing much more differences between individuals. We have constructed a goat pan-genome web interface for data visualization (http://animal.nwsuaf.edu.cn/panGoat).
The biophysics, ecology, and biogeochemistry of functionally diverse, vertically and horizontally heterogeneous ecosystems: the Ecosystem Demography model, version 2.2 – Part 1: Model description

Abstract. Earth system models (ESMs) have been developed to represent the role of terrestrial ecosystems on the energy, water, and carbon cycles. However, many ESMs still lack representation of within-ecosystem heterogeneity and diversity. In this paper, we present the Ecosystem Demography model version 2.2 (ED-2.2). In ED-2.2, the biophysical and physiological processes account for the horizontal and vertical heterogeneity of the ecosystem: the energy, water, and carbon cycles are solved separately for a series of vegetation cohorts (groups of individual plants of similar size and plant functional type) distributed across a series of spatially implicit patches (representing collections of micro-environments that have a similar disturbance history). We define the equations that describe the energy, water, and carbon cycles in terms of total energy, water, and carbon, which simplifies the differential equations and guarantees excellent conservation of these quantities in long-term simulation (< 0.1 % error over 50 years). We also show examples of ED-2.2 simulation results at single sites and across tropical South America. These results demonstrate the model's ability to characterize the variability of ecosystem structure, composition, and functioning both at stand and continental scales. A detailed model evaluation was conducted and is presented in a companion paper (Longo et al., 2019a). Finally, we highlight some of the ongoing model developments designed to improve the model's accuracy and performance and to include processes hitherto not represented in the model.
GTAP 4 Data Base Documentation - Chapter 9

Chapter 9 - Ancillary software: aggregation programs Robert McDougall and Betina Dimaranan 9.1 System Requirements 9.2 Annotated packing list 9.3 Installing the package 9.4 Preparing aggregations 9.5 GEMPACK version issues 9.6 Contact
Selective Retina Therapy Reduces Bruch's Membrane Thickness and Retinal Pigment Epithelium Pathology in Age-Related Macular Degeneration Mouse Models

Purpose To investigate the effect of selective retina therapy (SRT) on age-related macular degeneration (AMD)-like alterations of retinal pigment epithelium (RPE) and Bruch's membrane (BrM) in AMD mouse models as therapeutic approach for the treatment of dry AMD. Methods In B6.129P2-Apoetm1Unc/J (ApoE−/−) and B6.129X1-Nfe2I2tm1Ywk/J (NRF2−/−), one randomized eye of each mouse in groups of 15 mice was treated by SRT (532 nm, 300 ms, ∼1.4-μs pulse, 100 Hz, 50-μm spot), the fellow eye and healthy C57BL/6J mice served as controls. Clinical examinations were obtained at treatment day and 1 month later, followed by enucleation to analyze BrM thickness and ultrastructural RPE morphology. Results Nearly all ApoE−/− and NRF2−/− mice showed AMD-like retinal alterations. BrM thickness was increased in both mouse models, RPE had vacuoles within the cell body and shortened apical microvilli. SRT neither affected neuroretinal anatomy nor function. BrM thickness as well as AMD-like ultrastructural alterations of the RPE were significantly reduced in laser-treated eyes compared with fellow control and untreated control eyes. Conclusions SRT reduces BrM thickness and AMD-like RPE alterations in AMD mouse models without damage to structural or functional properties of neuroretina. It may be a prophylactic or therapeutic option for dry AMD. Translational Relevance SRT shows therapeutic effectivity in murine AMD models and might therefore become an option for the treatment of dry AMD.
Automatic Detection of Diabetic Retinopathy in Retinal Fundus Photographs Based on Deep Learning Algorithm

Purpose To achieve automatic diabetic retinopathy (DR) detection in retinal fundus photographs through the use of a deep transfer learning approach using the Inception-v3 network. Methods A total of 19,233 eye fundus color numerical images were retrospectively obtained from 5278 adult patients presenting for DR screening. The 8816 images passed image-quality review and were graded as no apparent DR (1374 images), mild nonproliferative DR (NPDR) (2152 images), moderate NPDR (2370 images), severe NPDR (1984 images), and proliferative DR (PDR) (936 images) by eight retinal experts according to the International Clinical Diabetic Retinopathy severity scale. After image preprocessing, 7935 DR images were selected from the above categories as a training dataset, while the rest of the images were used as validation dataset. We introduced a 10-fold cross-validation strategy to assess and optimize our model. We also selected the publicly independent Messidor-2 dataset to test the performance of our model. For discrimination between no referral (no apparent DR and mild NPDR) and referral (moderate NPDR, severe NPDR, and PDR), we also computed prediction accuracy, sensitivity, specificity, area under the receiver operating characteristic curve (AUC), and κ value. Results The proposed approach achieved a high classification accuracy of 93.49% (95% confidence interval [CI], 93.13%–93.85%), with a 96.93% sensitivity (95% CI, 96.35%–97.51%) and a 93.45% specificity (95% CI, 93.12%–93.79%), while the AUC was up to 0.9905 (95% CI, 0.9887–0.9923) on the independent test dataset. The κ value of our best model was 0.919, while the three experts had κ values of 0.906, 0.931, and 0.914, independently. Conclusions This approach could automatically detect DR with excellent sensitivity, accuracy, and specificity and could aid in making a referral recommendation for further evaluation and treatment with high reliability. Translational Relevance This approach has great value in early DR screening using retinal fundus photographs.
Histological tumor response assessment in colorectal liver metastases after neoadjuvant chemotherapy: impact of the variation in tumor regression grading and peritumoral lymphocytic infiltration

Background: The objective of this study was to evaluate the prognostic value of the variation in tumor regression grade (TRG) and peritumoral lymphocytic infiltration of colorectal liver metastases (CRLMs) after neoadjuvant chemotherapy (NACT). Methods: A retrospective review was performed in 98 patients with CRLMs who underwent NACT between 2010 and 2016. The TRG scores and counts of TILs at the tumor-normal interface were assessed in all 176 resected liver metastases to determine their association with prognosis. According to the variation in TRG scores, 40 patients with more than one liver metastasis were divided into a decreased TRG group and a stable TRG group. An additional independent cohort of 64 patients with 106 resected liver specimens was established to validate our main findings. Results: In the derivation cohort of 98 patients, 41.8% patients had a favourable pathological response to NACT (TRG 1-3), which were significantly associated with improved prognosis. Seventeen patients (42.5%) showed decreased TRG scores, and the remaining patients had stable scores. The multivariate analysis indicated that patients with decreased TRG scores had a better recurrence-free survival (RFS) compared with those with stable TRG scores (HR=0.42, P=0.034), and a similar trend was observed in the validation cohort (P=0.068). Dense TILs surrounding the metastases were present in 55.1% of the derivation cohort and associated with pathological response (P=0.008). Among patients with a pathological response to NACT, those with dense TILs had a superior RFS compared to those with weak TILs in both cohorts (derivation: HR=0.36, P=0.035; validation: HR=0.34, P=0.016). Conclusions: Variation in TRG scores and peritumoral lymphocytic infiltration may be proposed as secondary pathological parameters to evaluate the pathological response to NACT and predict the risk of recurrence after liver surgery.
Sex-Based Outcomes of Darunavir–Ritonavir Therapy

BACKGROUND Women account for an increasing proportion of patients with HIV-1 but remain underrepresented in antiretroviral clinical trials. OBJECTIVE To evaluate sex-based differences in efficacy and adverse events in treatment-experienced, HIV-positive women and men receiving darunavir-ritonavir therapy over 48 weeks. DESIGN Multicenter, open-label, phase 3b study designed to enroll a high proportion of women, with sample size determined on the basis of a noninferiority design with a maximum allowable difference of 15% in virologic response favoring men. (ClinicalTrials.gov registration number: NCT00381303) SETTING 65 sites in the United States, Puerto Rico, and Canada. PATIENTS 287 women and 142 men. INTERVENTION Patients received darunavir-ritonavir, 600/100 mg twice daily, plus an investigator-selected optimized background regimen. MEASUREMENTS Virologic response (HIV RNA <50 copies/mL using a time-to-loss of virologic response [TLOVR] algorithm) and adverse events were assessed over 48 weeks. RESULTS 67% of patients were women; 84% of patients were black or Hispanic. A higher proportion of women discontinued treatment than men (32.8% vs. 23.2%; P = 0.042); more women than men discontinued treatment for reasons other than virologic failure. Response rates in women and men at week 48 were 50.9% and 58.5%, respectively (intention-to-treat TLOVR), and 73.0% and 73.5%, respectively (TLOVR censored for patients who withdrew for reasons other than virologic failure). The absolute difference in response, based on logistic regression and adjusted for baseline log(10) viral load and CD4(+) cell count, was -9.6 percentage points (95% CI, -19.9 to 0.7 percentage points; P = 0.067) for intention-to-treat TLOVR and -3.9 percentage points (CI, -13.9 to 6.0 percentage points; P = 0.438) for TLOVR population that censored patients who withdrew for reasons other than virologic failure. Adverse events were similar between the sexes. The most common grade 2 to 4 adverse events that were considered at least possibly treatment related in women and men were nausea (5.2% and 2.8%, respectively), diarrhea (4.5% and 4.9%, respectively), and rash (2.1% and 2.8%, respectively). LIMITATION Baseline characteristics differed between sexes. CONCLUSION Nonsignificant, sex-based differences in response were found during the 48-week study; however, these differences were probably due to higher discontinuation rates in women, suggesting that additional efforts are needed to retain women in clinical trials.
Family Organization in the Care of Pediatric Heart Transplant Patients: The Genogram as an Investigative Tool

This study aimed to describe structure, functionality and development of pediatric heart transplant families, from the understanding of the experienced chronic condition. A descriptive, exploratory study using a qualitative approach was developed in a hospital situated in a city of Northeast Brazil, in 2012. The study was conducted with three families, using the Calgary Family Assessment Model (CFAM). In addition to the genogram, an analysis of the children’s/adolescents’ family members was conducted at the time of interview. Two families were binuclear families and one was mononuclear. From the evaluation, it was possible to determine the care and support network of children and adolescents with heart transplants, as well as some difficulties faced by the investigated families. Nurses are important in this family context since the visualization of the family genogram can generate a change in the nursing care to each family.
Comparison of Nutritional Behaviors and Physical Activities between Overweight/Obese and Normal-Weight Adults

Background: Overweight and obesity are major problems with increasing rates among adult populations. Nutritional behaviors and physical activity are the most important influencing factors. In this article, we conducted a survey on the nutritional behaviors and physical activities among normal-weight and overweight/obese adults. Materials and Methods: We conducted a survey on some of the nutritional behaviors and physical activities of 729 middle-aged adults. Data regarding desirable or undesirable use of fruits, fish, dairy products, oil, fast foods, and carbonated drinks and the intensity and duration of physical activities were collected from our data bank and analyzed using the SPSS software. Results: Our results indicated that overweight/obese people had an improper usage of fruits, oil, fast foods, and carbonated drinks and had lower physical activity. There was also a significant increase in intensity, duration per day, and weekly days of physical activity in healthy groups. Logistic regression analysis of nutritional behaviors, physical activities, and obesity also indicated that undesirable usage of oil, fast foods, and carbonated drinks and undesirable physical activity are associated with risks for overweight/obesity (odds ratio [OR] =10.70, OR = 7.45, OR = 7.48, and OR = 2.16, respectively) (P < 0.05). Conclusion: This article puts emphasis on the role of proper nutritional behaviors and higher physical activities in decreasing the risks of developing obesity, and we suggest that further interventions could be made based on the results of our study.
Midazolam as an adjuvant in supraclavicular brachial plexus block

Background&Ai Brachial plexus block is a useful alternative to general anaesthesia. Postoperative analgesia is an added advantage. Midazolam, a water soluble benzodiazepine has been used by various routes to prolong analgesia. The present study was undertaken to assess the analgesic efficacy of midazolam with bupivacaine in brachial plexus block. A prospective, randomized, double blind study was done at Karnataka Institute of Medical Sciences (KIMS), Hubli (India), from 01 March 2008 to 01 March 2009, on 50 adult patients ofASA1 and 2, aged between 18-65 years and scheduled for various upper limb surgeries. Patients were divided into two groups of 25 each. Group B received 30ml of inj. bupivacaine 0.5% +2ml normal saline and group BM received 30ml of inj. bupivacaine 0.5% + inj. midazolam (preservative free) 0.05mg/kg. Patients were observed for sedation, respiratory depression, pulse rate,SBP, DBP, duration of motor block, duration of pain relief and occurrence of any complications. Post operative analgesia was significantly longer (805.04 175.75 min) in group BM, as compared to group B (502.24 52.68 min) with p value 0.05. Hence there was no statistically significant difference. Onset of motor block in group B was 9.96 5.69 min and in group BM 7.92 5.68 min. and p value was >0.05 min. Hence there was not statistically significant difference Mild respiratory depression and sedation occurred intraoperatively in groupBMwhich required no active intervention. Addition of midazolam 50mcg/kg to 30ml of bupivacaine 0.5% for supraclavicular brachial plexus block prolonged sensory blockade and post-operative analgesia without increasing the risk of adverse effects
Long-term dynamics of urban thermal comfort in China’s four major capital cities across different climate zones

China has experienced intensive urbanization over the past decades. However, it is still unclear about the influence of urbanization on urban thermal comfort and how the effect varies with climate condition. Based on long-term daily meteorological data from 1990 to 2015 in four Chinese cities undergoing rapid urbanization, our study tried to detect the long-term dynamics of summer urban thermal comfort across different climate zones and analyze their relationships with urbanization. Our results showed that urbanization can increase urban temperature and decrease relative humidity and wind velocity. Urban thermal comfort and discomfort days also changed greatly, especially in Harbin, Northeast China from 1990 to 2015. However, such changes for different cities across different climate zones are inconsistent. Results also showed that urbanization especially for social economic activities can have a significant influence on the physiological Equivalent Temperature (PET). Compared with southern cities, the PET in northern cities such as Harbin and Changchun in this study is more sensitive to urbanization. These results reveal that the changing patterns of urban thermal comfort in Chinese cities under rapid urbanization, and help government take some effective measures to improve urban thermal environment.
A study on implementation of mother and child tracking system in Chilakaluripeta Cluster of Guntur District Andhrapradesh.

Research questions: 1) What is the status regarding availability of infrastructure and skilled personnel related to Mother and Child Tracking System (MCTS)? 2) Are there any technical errors in the design of MCTS website? 3)To study Knowledge and practices of ANMs regarding MCTS. Methods: Study was conducted in November 2012 at Chilakaluripeta Community Health & Nutritional Center of Guntur district which has 4 Primary Health Centers and 34 sub-centers. Permission was taken from District Medical and Health Officer Guntur and obtained username and password of MCTS website. MCTS website was accessed and reviewed the tracking procedure. Information from ANMs was obtained through telephone. Results: Computers and Internet connections were available in all the PHCs. Data-entry operators were available in 40% of PHCs. Regarding technical errors in website design no CAPTCHA was seen and login was not blocked even after 5 failed attempts. 47% ANMs knew about the procedure of MCTS & majority of ANMs were entering data monthly. Conclusion: There is need to increase skilled personnel availability to rectify technical errors in the design of MCTS website to provide regional language support and to increase knowledge of ANMs about tracking procedure for better implementation of MCTS.
The immunoregulatory protein B7-H3 promotes aerobic glycolysis in oral squamous carcinoma via PI3K/Akt/mTOR pathway

OSCC (oral squamous carcinoma) is one of most common malignant cancer. Although previous studies have found abnormal expression of B7-H3 in human OSCC, the exact role and molecular mechanism of B7-H3 in OSCC remain unknown. In this study, we investigated the role of B7-H3 in glucose metabolic reprogramming of OSCC cells in vitro and in vivo. We first detected the expression of B7-H3 in OSCC samples. Next, siRNAs and overexpression short-hairpin RNA of B7-H3 were transfected into SCC25 and Cal27 cells, and cell proliferation, migration and invasion were analyzed via CCK8, colony formation and transwell assays. Then glycolysis flux was determined through measuring glucose uptake and lactate production, and mRNA and protein expression levels were determined by real-time quantitative PCR and western blot respectively. The results presented here showed B7-H3 was upregulated in OSCC samples compared with normal tissues, and the expression level was associated with tumor size and nodal metastasis. B7-H3 affects OSCC cell proliferation, migration and invasion. We also found that B7-H3 promoted the Warburg effect, evidenced by increase glucose uptake and lactate production. We further demonstrated that B7-H3 enhanced OSCC glycolysis through the upregulation of HIF-1α and its downstream targets, Glut1 and PFKFB3, which are key factors in glycolysis. Mechanically, we demonstrated that B7-H3 regulates HIF-1α expression through PI3K/Akt/mTOR pathway. Metabolic imaging of human OSCC cancer xenograft in mice confirmed that B7-H3 enhanced tumor glucose uptake, glycolysis promoted genes expression and tumor growth. Taken together, our results have unveiled a mechanism that B7-H3 drives OSCC progression through enhancing of glycolytic metabolic program in OSCC.