Miracle-dz/UniFAR-FTUs huggingface dataset:
Human Amino Acid Requirements: A Re-Evaluation

The most recent internationally stated estimates of the amino acid requirements in adult humans are those given in the 1985 report of the Joint FAO/WHO/UNU Expert Consultation on Energy and Protein Requirements. In this review we present, in brief a number of scientific concerns and problems that lead us to conclude that these current recommendations for amino acid requirements are not valid and that the appropriate values are likely to be considerably higher. Following a short review of the C-labelled amino acid tracer studies carried out at the Massachusetts of Technology (MIT) and designed to reassess the requirements for specific indispensable amino acids, we focus particular attention on the lysine requirement in adults. When various criteria and methods are used to estimate this requirement, it appears that a cohesive body of data indicates the mean requirement value for lysine in healthy adults to be about 30 mg/kg/day or 50 mg/g protein. Although this value contrasts with the FAO/WHO/UNU value of 12 mg/kg/day or 16 ma/g protein, this new, tentative requirement value is consistent with findings from studies carried out earlier at MIT on the nutritional quality of wheat proteins. We propose that it would be prudent to apply the MIT amino acid requirement pattern (see Food and Nutrition Bulletin 1990;12:298–300), rather than the 1985 FAO/WHO/UNU adult amino acid requirement pattern, in the design and implementation of sound nutrition policies and programmes that include considerations of the amount and quality of the protein component of national and regional diets.
Serum Osteoprotegerin Levels Are Associated With the Presence and Severity of Coronary Artery Disease

Background— Osteoprotegerin (OPG) is a secretory glycoprotein that belongs to the tumor necrosis factor receptor family. OPG-deficient mice develop severe osteoporosis and medial arterial calcification of the aorta and renal arteries. OPG immunoreactivity was demonstrated in the normal blood vessels and in early atherosclerotic lesions. A recent clinical study suggests that there is a significant correlation between elevated serum OPG levels and cardiovascular mortality. We examined whether serum OPG levels are associated with the progression of coronary artery disease (CAD). Methods and Results— Serum OPG levels were examined in 201 patients who underwent coronary angiography because of stable chest pain. The number of diseased vessels was used to represent the severity of CAD. Serum OPG levels were measured by ELISA and were significantly greater in patients with significant stenosis of the coronary arteries than in those without stenosis. As the severity of CAD increased, there was a significant increa.
The L-arginine-NO pathway in the pathophysiology of blood vessels from solid tumours and rats in endotoxic shock

will be published, and that a copy of the work may be made and supplied to any bona fide library or research worker. I dedicate this thesis to; To certain individuals who have inspired me over the years especially My family, in particular my mum, without whom I would not have had the determination to succeed. Marion, for being a major part of my life and providing me with continued support and an equally enduring friendship. Debra, for her love. And finally, to the many distractive friends I have made in St. Andrews, without whom I would probably have been finished an awful lot sooner.
Genetic Evaluation of Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is defined as left ventricular hypertrophy in the absence of abnormal loading conditions. In 50–60% of adolescents and adults with HCM, the disease is inherited as an autosomal dominant trait caused by mutations in cardiac sarcomere protein genes. The most cases are due to mutations in genes which determine the synthesis of myosin-binding protein C (MYBPC3) and beta-myosin heavy chain (MYH7). More rarely involved genes are those encoding myosin light chain 3 (MYL3), tropomyosin alpha-1 chain (TPM1), and cardiac troponins I and T (TNNI3, TNNT2). Mutations in genes encoding Z-disc or calcium-handling proteins account for less than 1% of cases. Multiple sarcomeric protein mutations are present in up to 5% of individuals. A further of 5% of patients have inherited metabolic or neuromuscular diseases, chromosome abnormalities, and genetic syndromes. HCM is characterized by a highly heterogeneous phenotype, highly variable intraand interfamily expressivity and incomplete penetrance, therefore by a genotype-phenotype plasticity.
Caloric Thresholds, Clinical and Health Outcomes: Optimizing Exercise Intervention Programs Based On Evidence and Health Intervention Priorities

ing modesty and clothing requirements that could limit exercise capacity and ability to exercise in a public or nongender segregated space; (9) consideration of differences in long-term commitment to a program and self-monitoring process; (10)consideration of dietary recommendations and their cultural sensitivity and relevance; (11) recognition of cultural differences with respect to the role of the communal meal time; (12) recognition of the health challenges of certain religious practices, eg, Ramadan, when the patient fasts from dawn to dusk (no food nor water); (13) identification of those individuals in the patient's social sphere in the most powerful position to provide support; and (14) understanding stressors that are particularly prevalent in a given culture, and the ways the patient believes these can be managed.
Continuous B-cell depletion in frequently relapsing, steroid-dependent and steroid-resistant nephrotic syndrome

Abstract Background Patients with frequently relapsing (FR), steroid-dependent (SD) and steroid-resistant (SR) nephrotic syndrome are a therapeutic challenge with limited treatment options. Here, we retrospectively analyze the efficacy and safety of rituximab-induced continuous B-cell depletion in these populations. Methods Patients were included if they were at least 18 years of age and had FR, SD or SR minimal change disease (MCD) or primary focal segmental glomerulosclerosis (FSGS) and were treated with a strategy of continuous B-cell depletion. Partial remission (PR) was defined as a urinary protein:creatinine ratio (UPCR) of ≤3.5 g/g and a 50% reduction in the UPCR from baseline. Complete remission (CR) was defined as a UPCR ≤0.3 g/g. Results We identified 20 patients with MCD (n = 13) or FSGS (n = 7) who fulfilled the inclusion criteria. All patients had either SD (n = 12), SR (n = 7) or FR (n = 1) disease. Patients received a median of nine rituximab doses [interquartile range (IQR) 7.5, 11] and were treated for a median time of 28 months (IQR 23, 41). Prednisone was weaned from a median of 60 mg daily (IQR 40, 60) at rituximab initiation to 4.5 mg daily (IQR 0, 5.5) by 12 months. All patients achieved PR. CR occurred in 11 of 13 patients with FR or SD disease, but only 1 of 7 patients with SR disease (logrank P = 0.01). Four relapses occurred, all in patients with SR disease. Three serious infections occurred over 70.3 patient-years. Conclusion Continuous B-cell depletion is a therapeutic option in the management of complicated nephrotic syndrome. Additional studies are needed to clarify the utility of this strategy.
Abstract LB-301: Inhibition of the co-inhibitory receptor KLRG1 reduces murine 4T1 breast cancer metastasis and MC38 colon cancer primary tumor growth and mortality

Introduction Targeting of lymphocyte co-inhibitory receptors, such as CTLA-4, PD-1, Lag-3, and Tim-3, has gained intense interest for treatment of cancer. KLRG1 is also a lymphocyte co-inhibitory receptor, expressed predominantly on effector memory CD8+ T cells and NK cells, whose ligands E- and N-cadherin are differentially expressed during epithelial-mesenchymal transition. Targeting of KLRG1 in murine cancer models has not previously been published. Methods We constructed an anti-mouse KLRG1 antibody that neutralized the interaction of KLRG1 with its ligands. Anti-KLRG1 antibody was administered as a monotherapy in a murine metastatic tumor model (4T1 murine breast cancer) and as combination therapy with anti-PD-1 (clone RMP1-14) in a murine primary tumor growth model (MC38 murine colon cancer). Results In the 4T1 murine breast cancer model, anti-KLRG1 antibody reduced lung metastases compared to control antibody as measured by mean lung weights (0.28 g vs. 0.47 g; p=0.04) and nodule count (10.7 vs. 30.1; p=0.002). In the MC38 model, primary tumor growth was inhibited by anti-KLRG1 + anti-PD-1 antibody greater than anti-KLRG1 antibody or anti-PD-1 antibody or control antibody (day 13 tumor volume 582 vs. 1259 vs. 1279 vs. 1461 mm3, respectively). Combination therapy anti-KLRG1 + anti-PD-1 produced synergistic benefit significantly greater than that of anti-PD-1 alone for tumor volume (p=0.01) and survival (p=0.02; day 18 survival 60% of mice alive treated with combination therapy compared to 0% alive treated with anti-PD-1 alone). Ex vivo KLRG1 blockade with anti-human KLRG1 antibodies resulted in human CD8+ T cell proliferation and proinflammatory cytokine secretion. Conclusions Anti-KLRG1 neutralizing antibody demonstrates efficacy in inhibiting metastases in the murine 4T1 breast cancer model and reducing primary tumor volume and improving survival as synergistic combination therapy with anti-PD-1 in the murine MC38 colon cancer model. Anti-KLRG1 blockade with anti-human KLRG1 antibodies results in activation of CD8+ T cells. These data suggest that anti-KLRG1 treatment is a promising new approach for cancer immunotherapy. Citation Format: Steven A. Greenberg, Stefano V. Gulla, Evan Thompson. Inhibition of the co-inhibitory receptor KLRG1 reduces murine 4T1 breast cancer metastasis and MC38 colon cancer primary tumor growth and mortality [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-301.
Associations between the patient-physician relationship and health-related quality of life among patients with cancer.

162 Background: Health-related quality of life (HRQOL) is an important cancer care outcome. Patient-physician communication is linked to HRQOL, yet less is known about the role of other aspects of the patient-physician relationship in explaining HRQOL outcomes in cancer patients. Using secondary data from the Accountability for Cancer Care through Undoing Racism and Equity study, we examined associations between multiple patient-physician relationship factors and HRQOL in breast and lung cancer patients. Methods: The analysis included 283 patients receiving care at two cancer centers from 2013-2017. Survey data on socio-demographics, HRQOL, and patient-physician relationship (i.e., doctors’ respectfulness, time spent with doctors, doctors’ involvement of patient in decision-making, satisfaction with quality of care) were collected at baseline and during treatment. The primary outcome was a binary measure of poor-fair (vs. good-excellent) HRQOL 90 days post-diagnosis. We employed multivariate logistic regression to assess associations between patient-physician relationship factors and HRQOL. Results: In adjusted analyses, patients reporting high levels of physician respect had 78% lower odds of reporting poor-fair HRQOL than patients reporting low levels of respect (Adjusted Odds Ratio[AOR] = 0.22; 95%CI = 0.08-0.59). Patients who were optimally involved in their care had lower odds of poor-fair HRQOL than those less involved (AOR = 0.30; 95%CI = 0.12-0.77). Finally, patients who very satisfied with the quality of their care had a 40% lower odds of poor-fair HRQOL than those less satisfied with care (AOR = 0.40; 95% CI = 0.13-0.99). There was no association between amount of time spent with doctor and HRQOL. Conclusions: Multiple aspects of the patient-physician relationship, including doctor’s respectfulness, doctors’ involvement of patient in decision-making, and patient satisfaction with quality of care are associated with HRQOL among breast and lung cancer patients. Given the important role that HRQOL plays in treatment adherence and outcomes, these findings highlight the need for systems of care that optimize the physician-patient relationship in cancer care.
A new approach for quantitative assessment of upper-extremity impairment in post-stroke patients using wearable sensors: a pilot study.

Stroke is the second leading cause of death in Europe and the leading cause of long therm disability. With the decrease in deaths rate, the number of stroke survivors is growing up and a good post-stroke rehabilitation plan is fundamental for regaining autonomy. Before starting rehabilitation, it is necessary to assess motor function impairment and this is done using clinical scales. In particular Upper-Extremity Fugl-Meyer Assessment is the most used for stroke patients in case of upper limb motor deficits. However, this scale is clinician-dependent, the evaluation is qualitative, gives only partial information and has only poor sensitivity to mild impairment. For those reasons, in this thesis a new approach for quantitative assessment of upper-extremity impairment in post stroke-patients is proposed. XSens Awinda and Myo armband systems were used for testing a total of 11 tasks from the Upper Extremity Fugl-Meyer Assessment scale. Two experiments were performed, the first one involving 9 healthy subjects and the second on one stroke patient. A complete analysis was performed on kinematic data (XSens used on all the 10 subjects) and several parameters were extracted: some of them were deriving from a single segment, while Correlation Coefficient estimation and PCA were done using data from several joints. An exploratory analysis was executed on EMG data, since recording with Myo armband was performed on only 3 healthy subjects. Also in this case, several metrics were chosen, including RMS value, Correlation Coefficient and PCA. Results obtained suggest that the selected parameters can lead to a more complete description of impairment, since they are able to capture differences between stroke and healthy subjects. Moreover the evaluation obtained is quantitative, clinician-independent and more sensitive to mild impairment. It is a method which allows to consider the contribute of the entire upper body section, in order to identify possible compensatory strategies or abnormal synergies. There are some limitations regarding the Myo armband, which only records data from forearm segment, the offline analysis and the fact that, for now, the system was tested on a single patient. However, all those limits can be easily overcome in line with the future perspectives.
Clinical Application of Modified Burns Wean Assessment Program Scores at First Spontaneous Breathing Trial in Weaning Patients from Mechanical Ventilation

Background: The purpose of this study was to evaluate the clinical application of modified Burns Wean Assessment Program (m-BWAP) scoring at first spontaneous breathing trial (SBT) as a predictor of successful liberation from mechanical ventilation (MV) in patients with endotracheal intubation. Methods: Patients requiring MV for more than 72 hours and undergoing more than one SBT in a medical intensive care unit (ICU) were prospectively enrolled over a 3-year period. The m-BWAP score at first SBT was obtained by a critical care nursing practitioner. Results: A total of 103 subjects were included in this study. Their median age was 69 years (range, 22 to 87 years) and 72 subjects (69.9%) were male. The median duration from admission to first SBT was 5 days (range, 3 to 26 days), and the rate of final successful liberation from MV was 84.5% (n=87). In the total group of patients, the successful liberation from MV group at first SBT (n=65) had significantly higher m-BWAP scores than did the unsuccessful group (median, 60; range, 43 to 80 vs. median, 53; range, 33 to 70; P<0.001). Also, the area under the m-BWAP curve for predicting successful liberation of MV was 0.748 (95% confidence interval, 0.650 to 0.847), while the cutoff value based on Youden’s index was 53 (sensitivity, 76%; specificity, 64%). Conclusions: The present data show that the m-BWAP score represents a good predictor of weaning success in patients with an endotracheal tube in place at first SBT.
DNA Sequence Variants in Human Autoimmune Diseases

BACKGROUND:The transcription factors interferon regulatory factor 5 (IRF5) and signal transducer and activator of transcription 4 (STAT4) are encoded by two of the strongest susceptibility genes for systemic lupus erythematosus (SLE). OBJECTIVE:To investigate the target genes and functional roles of IRF5 and STAT4 in human peripheral blood mononuclear cells (PBMCs). METHODS: Chromatin immunoprecipitation-sequencing (ChIP-seq) was performed in PBMCs stimulated to activate IRF5 and STAT4. The expression of the target genes of IRF5 and STAT4 was investigated in a publicly available dataset generated from PBMCs from patients with SLE and healthy controls. The genomic regions bound by the transcription complexes mediated by IRF5 and STAT4 were examined for transcription factor binding motifs and SLE-associated sequence variants.RESULTS: More than 7000 target genes for IRF5 and STAT4 were identified in stimulated PBMCs. These genes were enriched to functional pathways in the type I interferon system, and have key roles in the inflammatory response. The expression patterns of the target genes were characteristic for patients with SLE. The transcription factors high mobility group-I/Y, specificity protein 1, and paired box 4 may function cooperatively with IRF5 and STAT4 in transcriptional regulation. Eight of the target regions for IRF5 and STAT4 contain SLE-associated sequence variants.CONCLUSIONS:By participating in transcription complex with other co-factors, IRF5 and STAT4 harbour the potential of regulating a large number of target genes, which may contribute to their strong association with SLE.
Etude de la régulation de l'expression des microARN de l'herpesvirus associé au sarcome de Kaposi

La deregulation de l’expression des microARN peut induire des cancers. De plus, ils jouent un role crucial dans la pathogenese et la survie des virus. L’herpes virus humain de type 8 (HHV-8 ou KSHV) est l’agent etiologique du sarcome de Kaposi et est implique dans la generation de lymphomes agressifs de type B. De maniere interessante, le genome ce virus code 12 pre-miARN localises dans la region de latence et exprimes sur un meme pri-miARN. Les miARN du KSHV sont importants pour le maintien de la latence, l’inhibition de l’apoptose ou encore la regulation du cycle cellulaire de l’hote. Nous nous interessons a leur expression et leur regulation durant l’infection virale. Nous avons resolu la structure secondaire de l’ARN codant ces miARN afin d’identifier les criteres structuraux responsables de leur accumulation differentielle. Nous avons initie une analyse cinetique de la premiere etape de maturation et enfin nous essayons d’identifier des co-facteurs modulant leur expression.
Retinal Ganglion Cells in Strigidae Raptors: Distribution and Morphometry

The authors studied the morphometry and the topographical distribution of Retinal Ganglion Cells (RGCs) in four nocturnal raptors of the order of Strigiformes, family of Strigidae: little owl, tawny owl, scops owl, eared owl. In order to r ecognize specialized retinal vision areas (fovea and visual streak), the number of RGCs/mm 2 and the soma size in the four retinal fields (dorsal, ventral, temporal and nasal) by the histological analysis of retinal radial sections were recorded. A temporal fovea was identi fied in little owl, tawny owl and eared owl while in scops owl this visual area was localized near the fundus oculi. A radial visual streak ve ntrally directed was pointed out in the retinas of the four raptors with different shape according to its width. The Authors linked the obtained data with the predatory behavior of nocturnal raptors in their habitat.
Monitoramento do gene, que codifica a esterase, envolvido na resistência a inseticidas organofosforados em populações naturais de Aedes aegypti do Brasil

Resistance to chemical insecticides has been described to a vast order of insects and represents one of the greatest challenges for obtaining success in control programs of disease vectors. Resistance mechanisms to chemical insecticides can be divided in categories, including target-site insensitivity and metabolic mechanisms, through the expression of the organism detoxifying enzymes, such as esterases. At the moment, esterases have been identified as the main mechanism conferring resistance to organophosphates in Aedes aegypti. The main objective of this study was the analysis of the esterase genetic polymorphism and, to evaluate its role in possible mechanisms of resistance to temephos in natural populations of this mosquito. To answer these questions, we used two laboratory strains: Rockefeller (susceptibility model for all the insecticides groups) and the Recife-Resistente (kept under strong selective pressure by temephos for five generations), and nine natural populations: eight from the metropolitan area of Recife and one from Araripe (CE). These populations were collected as eggs, during the years 2004 and 2005. It was performed techniques such as biochemical assays, isozymes electrophoresis, PCR and sequencing of part of the gene, and Real-Time PCR to compare the amount of gene copies of the gene in a resistant and a susceptible strain, and in natural populations. Biochemical assays were run only in Recife-Resistente strain and, the results showed the presence of the metabolic mechanism of resistance, through high esterase activity. The esterases pattern was observed in nine populations, in 6% polyacrylamide gel stained with specific substrates to α and β-esterase enzymes. The observed heterozygosity values (Ho) varied from 0,278 to 0,533 in 2004, and in 2005, from 0,388 to 0,608. The gels also showed a region of high esterase activity, denominated locus 1. In this locus, the allele responsible for the higher esterase activity was called 3. Its frequency varied in 2004 from 0,100 in Dois Irmaos to 0,191 in Alto Jose do Pinho, and in 2005, dropped to 0,071 and 0,107 respectively. In the Recife-Resistente strain, the frequency of this allele was 0,214. The sequencing of part of exon 4 from the α-esterase gene showed that the analyzed fragment, approximately 180 pb long, is quite conserved, presenting only four polymorphic sites. The results obtained by Real-Time PCR indicated that the populations submitted to the study did not present gene amplification to the α-esterase gene, when compared to Rockefeller strain, except the populations from Engenho do Meio e Araripe. Inspite of the higher number of molecules presented by these two populations, the results still need more proofs to guarantee that the superexpression of the gene is the possible cause of the resistance. The frequency of the superexpressed allele can be monitored through time and help the management of resistance to chemical insecticides in field projects