Miracle-dz/UniFAR-FTUs huggingface dataset:
Clarifying the anatomy of common arterial trunk: a clinical study of 70 patients.

AIMS Anatomic variations in hearts with common arterial trunk are well-known, although there is no large study of living patients. Detailed knowledge of the origins of the pulmonary and coronary arteries is vital for surgical management. We sought to clarify the variations using computed tomography. METHODS AND RESULTS We prospectively studied 70 consecutive patients using echocardiography and computed tomography. In 63 (90%) patients, there was aortic dominance, while 7 (10%) had dominance of the pulmonary component. In 27 (43%) patients with aortic dominance, part of the pulmonary segment arose from a truncal valvar sinus. A long confluent pulmonary channel was more common in patients with sinusal origin compared to those with non-sinusal origin of the pulmonary segment (19 vs. 0; P = 0.0005). Close proximity between the orifices of the coronary arteries and the pulmonary component was also more frequent with sinusal origin (21 vs. 6; P < 0.001) with 5 (19%) patients having pulmonary flow obstructed by a truncal valvar leaflet. CONCLUSION Sinusal origin of the pulmonary component is common with aortic dominance, frequently in association with a long confluent pulmonary segment, which may be in close proximity to the origin of a coronary artery. One-fifth of patients with sinusal origin of pulmonary component have a truncal valvar leaflet obstructing the pulmonary orifice. These morpho-anatomic findings have important implications for management.
Association between calcitonin receptor gene polymorphisms and calcium stone urolithiasis: A meta-analysis

ABSTRACT Purpose It has been reported that calcitonin receptor (CALCR) gene polymorphisms might be associated with calcium stone urolithiasis. Owing to mixed and inconclusive results, we conducted a meta-analysis to summarize and clarify this association. Materials and Methods A systematic search of studies on the association between CALCR gene polymorphisms and calcium stone urolithiasis susceptibility was conducted in databases. Results Odds ratios and 95% confidence intervals were used to pool the effect size. Five articles were included in our meta-analysis. Conclusions CALCR rs1801197 might be associated with increased risk of calcium stone urolithiasis. There is insufficient data to fully confirm the association between CALCR rs1042138 and calcium stone urolithiasis susceptibility. Well-designed studies with larger sample size and more subgroups are required to validate the risk identified in the current meta-analysis.
Physicochemical, Sensorial and Microbiological Characterization of PoroCheese, an Artisanal Mexican Cheese Made from Raw Milk †

Poro cheese is a regional product originally from the area of Los Rios, Tabasco in Mexico. In the context of preserving the heritage of Poro cheese and protecting the specific characteristics that define its typicity through an origin designation, the present study was conducted to establish a general profile of Poro cheese by characterizing their physicochemical, textural, rheological, sensorial and microbiological characteristics. Differences in moisture, proteins, fats, NaCl, titrable acidity, pH, color texture and rheology amongst cheese factories were observed and ranges were established. Fifteen descriptors were generated to provide a descriptive analysis, eight of which were significantly different amongst the factories with no differences in the global acceptability of cheese. The favorite cheese had the highest scores for aroma attributes. Conventional and molecular methods were used to identify the main microorganisms, for which Lactobacillus plantarum, L. fermentum, L. farciminis and L. rhamnosus were the main microorganisms found in Porocheese. The obtained data constituted the parameters for characterizing Poro cheese, which will strongly help to support its origin appellation request process.
Birth outcomes in women who have taken adalimumab in pregnancy: A prospective cohort study

Background Information is needed on the safety of adalimumab when used in pregnancy for the treatment of certain autoimmune diseases. Methods and findings Between 2004 and 2016, the Organization of Teratology Information Specialists Research Center at the University of California San Diego conducted a prospective controlled observational cohort study in 602 pregnant women who had or had not taken adalimumab. Women in the adalimumab-exposed cohort had received at least one dose of the drug in the first trimester for the treatment of rheumatoid arthritis or Crohn’s Disease (N = 257). Women in the disease comparison cohort had not used adalimumab in pregnancy (N = 120). Women in the healthy comparison cohort had no rheumatic or inflammatory bowel diseases (N = 225). Women and their infants were followed to one year postpartum with maternal interviews, medical records abstraction, and physical examinations. Study outcomes were major structural birth defects, minor defects, spontaneous abortion, preterm delivery, pre and post-natal growth deficiency, serious or opportunistic infections and malignancies. 42/602 (7.0%) of pregnancies were lost-to-follow-up. 22/221 (10.0%) in the adalimumab-exposed cohort had a live born infant with a major birth defect compared to 8/106 (7.5%) in the diseased unexposed cohort (adjusted odds ratio 1.10, 95% confidence interval [CI] 0.45 to 2.73). Women in the adalimumab-exposed cohort were more likely to deliver preterm compared to the healthy cohort (adjusted hazard ratio [aHR] 2.59, 95% CI 1.22 to 5.50), but not compared to the diseased unexposed cohort (aHR 0.82, 95% CI 0.66 to 7.20). No significant increased risks were noted with adalimumab exposure for any other study outcomes. Conclusions Adalimumab exposure in pregnancy compared to diseased unexposed pregnancies was not associated with an increased risk for any of the adverse outcomes examined. Women with rheumatoid arthritis or Crohn’s Disease were at increased risk of preterm delivery, irrespective of adalimumab exposure.
Environmental Exposure to Pesticides and Breast Cancer in a Region of Intensive Agribusiness Activity in Brazil: A Case-Control Study

Background: Breast cancer is a serious public health problem and is the second most prevalent cancer type in the world. The purpose of this article is to evaluate the association between pesticide use and breast cancer in a region of intense agribusiness activity in the state of Mato Grosso, Brazil. Methods: A case-control study was conducted on women living in the city of Rondonópolis, in the south of Mato Grosso state. There were 85 cases of women with confirmed breast cancer and 266 controls who were randomly selected from primary health care users. Bivariate and stratified analyses were performed. Multiple logistic regression was then performed, keeping in the final model the factors with a significance level lower than or equal to 0.05 or considered important according to apriori biological criteria. Results: In the final model, living near cropland with pesticides (OR: 2.37; CI: 95% 1.78–3.16) and women aged over 50 years who experienced early menarche (OR: 2.08; CI: 95% 1.06–4.12) had a higher risk of developing breast cancer compared to control subjects. Conclusion: This study highlights the importance of exposure to pesticides as an environmental risk factor for the development of breast cancer among women.
Clinical profile of diabetic sensorimotor polyneuropathy in a tertiary hospital in Northwestern Nigeria

Objective: To determine the frequency, severity, and determinants of diabetic sensorimotor polyneuropathy (DSPN) in adults from a tertiary hospital in Northwestern Nigeria. Materials and Methods: A cross-sectional hospital-based study where 400 type 2 diabetes mellitus patients attending clinic in a tertiary hospital were screened for DSPN and graded for severity using the United Kingdom screening test (UKST). Logistic regression was used to identify independent predictors of DSPN after controlling for other covariates. All data were analysed using Predictive Analysis Software (PASW) version 18.0 for Windows (SPSS Inc., Chicago, IL, USA). Results: Frequency of DSPN among the study (comprising 59 males and 66 females) subjects was 125 (31.2%), of which 105 (26.3%) patients were symptomatic. Sixty-eight (17%) patients were at high risk of developing diabetic feet ulceration. Multivariate logistic regression showed that marital status (OR = 0.55; 95% CI = 0.31-0.98) was protective, while the duration of diabetes (OR 5.80; 95% CI = 3.38-9.95) was a significant independent predictor of DSPN. Conclusions: The high frequency of DSPN in patients with high risk of feet ulceration from this study prompt the need to adopt efficacious and less-expensive strategies for screening and preventing diabetic foot complications in our resource-constraint settings.
Development of flight and foraging behaviour in a juvenile seabird with extreme soaring capacities.

1) The early-life of animals is a period of high mortality, when foraging capacities are assumed to be improved progressively. In birds, this critical period involves the improvement of the flight. How do young birds gain these capacities has rarely been studied in natural conditions especially in seabirds that spend most of their life at sea. 2) We used detailed GPS and body acceleration data on 37 great frigatebirds (Fregata minor), to test the hypothesis that juveniles starting their first flights have lower flying capacities than adults, but that these capacities will improve during a long learning period, before independence from parents, specific to this seabird that can spend months on the wing at sea. 3) We found that most flight components improved over time to tend towards those of adults, especially the travel speed, range, duration and maximum altitude of trips. However, unexpectedly, juveniles had higher ascent rates, soaring and gliding capacities above the sea than adults. Moreover, energy expenditure of juveniles was similar to adults during low cost travelling movements and during active foraging, but juveniles spent more time foraging actively than adults. 4) Our results suggest that flight tactics based on long-distance effortless movements specific to this family are acquired during a long period, but soaring and gliding capacities are already inherited by juveniles and possibly favoured by morphological adaptations specific to juveniles. These adaptations might explain the extreme dispersive capacities of juveniles.
Programmed Death Ligand 1 Indicates Pre-Existing Adaptive Immune Response by Tumor-Infiltrating CD8+ T Cells in Non-Small Cell Lung Cancer

Aberrant expression of programmed death ligand 1 (PD-L1) on tumor cells impedes antitumor immunity and instigates immune evasion. The remarkable efficacy of immune checkpoint blockade has been confirmed in various solid tumors. However, the correlation between PD-L1 expression and host immunological landscape remains of considerable controversy in non-small cell lung cancer (NSCLC). In the present study, PD-L1 expression and CD8+ tumor-infiltrating lymphocyte (TIL) infiltration levels were determined by immunohistochemistry (IHC) in tumor sections of 138 NSCLC patients. The expression level of PD-L1 was positively correlated with the abundance of CD8 + TILs (p < 0.0001). Furthermore, no constitutive expression of PD-L1 was observed in the majority of six NSCLC cell lines detected by Western blot; but exposure to interferon-γ (IFN-γ), a primary cytokine secreted by activated CD8+ T cells, prominently increased PD-L1 expression. Notably, a significantly positive association was determined within PD-L1, CD8 and IFN-γ gene expression by qRT-PCR, which was corroborated by RNA-sequencing from TCGA lung cancer dataset. These findings demonstrate that PD-L1 expression indicates an adaptive immune resistance mechanism adopted by tumor cells in the aversion of immunogenic destruction by CD8+ TILs. Both higher expression of PD-L1 and infiltration of CD8+ TILs were correlated with superior prognosis (p = 0.044 for PD-L1; p = 0.002 for CD8). Moreover, Cox multivariate regression analysis showed that the combination of PD-L1 and CD8 were independent prognostic factors, which was more accurate in prediction of prognosis in NSCLC than individually. Finally, we found that IFN-γ induced the upregulation of PD-L1 in NSCLC cells, mainly through the JAK/STAT1 signaling pathway. In conclusion, PD-L1 expression is mainly induced by activated CD8+ TILs via IFN-γ in the immune milieu and indicates pre-existing adaptive immune response in NSCLC.
MicroRNA-29a Counteracts Glucocorticoid Induction of Bone Loss through Repressing TNFSF13b Modulation of Osteoclastogenesis

Glucocorticoid excess escalates osteoclastic resorption, accelerating bone mass loss and microarchitecture damage, which ramps up osteoporosis development. MicroRNA-29a (miR-29a) regulates osteoblast and chondrocyte function; however, the action of miR-29a to osteoclastic activity in the glucocorticoid-induced osteoporotic bone remains elusive. In this study, we showed that transgenic mice overexpressing an miR-29a precursor driven by phosphoglycerate kinase exhibited a minor response to glucocorticoid-mediated bone mineral density loss, cortical bone porosity and overproduction of serum resorption markers C-teleopeptide of type I collagen and tartrate-resistant acid phosphatase 5b levels. miR-29a overexpression compromised trabecular bone erosion and excessive osteoclast number histopathology in glucocorticoid-treated skeletal tissue. Ex vivo, the glucocorticoid-provoked osteoblast formation and osteoclastogenic markers (NFATc1, MMP9, V-ATPase, carbonic anhydrase II and cathepsin K) along with F-actin ring development and pit formation of primary bone-marrow macrophages were downregulated in miR-29a transgenic mice. Mechanistically, tumor necrosis factor superfamily member 13b (TNFSF13b) participated in the glucocorticoid-induced osteoclast formation. miR-29a decreased the suppressor of cytokine signaling 2 (SOCS2) enrichment in the TNFSF13b promoter and downregulated the cytokine production. In vitro, forced miR-29a expression and SOCS2 knockdown attenuated the glucocorticoid-induced TNFSF13b expression in osteoblasts. miR-29a wards off glucocorticoid-mediated excessive bone resorption by repressing the TNFSF13b modulation of osteoclastic activity. This study sheds new light onto the immune-regulatory actions of miR-29a protection against glucocorticoid-mediated osteoporosis.
Late-Night Eating-Induced Physiological Dysregulation and Circadian Misalignment are Accompanied by Microbial Dysbiosis.

SCOPE Irregular eating habits, such as late-night eating, will cause increased risk of obesity and other metabolic diseases. The aim of this study is to elucidate the impacts of late-night eating on physiological function and gut microbiota. METHODS AND RESULTS Male Wistar rats under 16 h/8 h-light/dark cycle were divided into four groups with specific dietary habits, which mimicked breakfast, lunch, dinner and late-night eating. Late-night eating, including skipping dinner for a night eating (BLN) and skipping breakfast and having a night eating (LDN), caused an increase of body weight, which is associated with decreased physical activity. Additionally, late-night eating resulted in hepatic lipid accumulation and systemic inflammation in peripheral tissues, compared to those of free feeding (FF) or breakfast, lunch and dinner (BLD) groups. The phases of key clock genes were similar in FF, BLD and BLN groups, while LDN feeding caused an overall 4-h phase delay in peripheral tissues. Moreover, late-night eating, especially LDN feeding, resulted in a significant alternation in the compositions and functions of gut microbiota, which further contributes to the development of metabolic disorder. CONCLUSION Late-night eating caused physiological dysregulation and misalignment of circadian rhythm, together with microbial dysbiosis. This article is protected by copyright. All rights reserved.
Vaccine Vectors Harnessing the Power of Cytomegaloviruses

Cytomegalovirus (CMV) species have been gaining attention as experimental vaccine vectors inducing cellular immune responses of unparalleled strength and protection. This review outline the strengths and the restrictions of CMV-based vectors, in light of the known aspects of CMV infection, pathogenicity and immunity. We discuss aspects to be considered when optimizing CMV based vaccines, including the innate immune response, the adaptive humoral immunity and the T-cell responses. We also discuss the antigenic epitopes presented by unconventional major histocompatibility complex (MHC) molecules in some CMV delivery systems and considerations about routes for delivery for the induction of systemic or mucosal immune responses. With the first clinical trials initiating, CMV-based vaccine vectors are entering a mature phase of development. This impetus needs to be maintained by scientific advances that feed the progress of this technological platform.
Mycobacterium tuberculosisβ-Carbonic Anhydrases: Novel Targets for Developing Antituberculosis Drugs

The genome of Mycobacterium tuberculosis (Mtb) encodes three β-carbonic anhydrases (CAs, EC 4.2.1.1) that are crucial for the life cycle of the bacterium. The Mtb β-CAs have been cloned and characterized, and the catalytic activities of the enzymes have been studied. The crystal structures of two of the enzymes have been resolved. In vitro inhibition studies have been conducted using different classes of carbonic anhydrase inhibitors (CAIs). In vivo inhibition studies of pathogenic bacteria containing β-CAs showed that β-CA inhibitors effectively inhibited the growth of pathogenic bacteria. The in vitro and in vivo studies clearly demonstrated that β-CAs of not only mycobacterial species, but also other pathogenic bacteria, can be targeted for developing novel antimycobacterial agents for treating tuberculosis and other microbial infections that are resistant to existing drugs. In this review, we present the molecular and structural data on three β-CAs of Mtb that will give us better insights into the roles of these enzymes in pathogenic bacterial species. We also present data from both in vitro inhibition studies using different classes of chemical compounds and in vivo inhibition studies focusing on M. marinum, a model organism and close relative of Mtb.
Effect of blood flow on platelets, leukocytes, and extracellular vesicles in thrombosis of simulated neonatal extracorporeal circulation

Extracorporeal membrane oxygenation (ECMO) has frequent and sometimes lethal thrombotic complications. The role that activated platelets, leukocytes, and small (0.3‐micron to 1‐micron) extracellular vesicles (EVs) play in ECMO thrombosis is not well understood.
RabGAPs TBC1D1 and TBC1D4 in skeletal muscle function and exercise.

The two closely related RabGAPs TBC1D1 and TBC1D4 are key signaling factors of skeletal muscle substrate utilization. In mice, deficiency in both RabGAPs leads to reduced skeletal muscle glucose transport in response to insulin and lower GLUT4 abundance. Conversely, Tbc1d1- and Tbc1d4-deficiency results in enhanced lipid use as fuel in skeletal muscle, through yet unknown mechanisms. In humans, variants in TBC1D1 and TBC1D4 are linked to obesity and insulin resistance and type 2 diabetes. While the specific function in metabolism of each of the two RabGAPs remains to be determined, TBC1D1 emerges to be controlling exercise endurance and physical capacity whereas TBC1D4 may rather be responsible for maintaining muscle insulin sensitivity, muscle contraction, and exercise. There is growing evidence that TBC1D1 also plays an important role in skeletal muscle development, since it has been found to be associated to meat production traits in several livestock species. In addition, TBC1D1 protein abundance in skeletal muscle is regulated by both, insulin receptor and insulin like growth factor-1 (IGF-1) receptor signaling. This review focusses on the specific roles of the two key signaling factors TBC1D1 and TBC1D4 in skeletal muscle metabolism, development and exercise physiology.
Intestinal Microbiota of Grass Carp Fed Faba Beans: A Comparative Study

Many reports of the intestinal microbiota of grass carp have addressed the microbial response to diet or starvation or the effect of microbes on metabolism; however, the intestinal microbiota of crisp grass carp has yet to be elucidated. Moreover, the specific bacteria that play a role in the crispiness of grass carp fed faba beans have not been elucidated. In the present study, 16S sequencing was carried out to compare the intestinal microbiota in the fore-, mid- and hind-intestine segments of grass carp following feeding with either faba beans or formula feed. Our results showed that (1) the hind-intestine presented significant differences in diversity relative to the fore- or midintestine and (2) faba beans significantly increased the diversity of intestinal microbiota, changed the intestinal microbiota structure (Fusobacteria was reduced from 64.26% to 18.24%, while Proteobacteria was significantly increased from 17.75% to 51.99%), and decreased the metabolism of energy, cofactors and vitamins in grass carp. Furthermore, at the genus and species levels, Acinetobacter accounted for 15.09% of the microbiota, and Acinetobacter johnsonii and Acinetobacter radioresistens constituted 3.41% and 2.99%, respectively, which indicated that Acinetobacter of the family Moraxellaceae contributed to changes in the intestinal microbiota structure and could be used as a potential biomarker. These results may provide clues at the intestinal microbiota level to understanding the mechanism underlying the crispiness of grass carp fed faba beans.
SENSORY NEURON INSULIN SIGNALING AND ITS ROLE IN DIABETIC NEUROPATHY

iii Dedication . iv Acknowledgements . vi List of Figures . x Chapter 1: Introduction to Dissertation . 1-29 1. Sensory Neurons of the Peripheral Nervous System . 1 2. Diabetes Mellitus . 6 3. Diabetic Neuropathy . 11 4. Insulin . 15 5. Insulin and the Nervous System . 21 6. Insulin and Diabetic Neuropathy . 24 7. Purpose and Central Hypothesis of Dissertation . 29 Chapter 2: In vivo Peripheral Nervous System Insulin Signaling . 30-51 1. Abstract . 30 2. Introduction . 31 3. Experimental Procedures . 32 4. Results and Figures . 34 5. Discussion . 49 Chapter 3: Insulin Receptor Substrate 2 Expression and Involvement in Neuronal Insulin Resistance in Diabetic Neuropathy . 52-77 1. Abstract . 52 2. Introduction . 53 3. Experimental Procedures . 54 4. Results and Figures . 58 5. Discussion . 71 Chapter 4: In vivo Peripheral Nervous System Insulin Resistance . 78-103 1. Abstract . 78 2. Introduction . 79 3. Experimental Procedures . 80 4. Results and Figures . 82 5. Discussion . 100