Miracle-dz/UniFAR-FTUs huggingface dataset:
Quality of Life Among Breast Cancer Survivors 2 Years After Diagnosis: The Relationship With Adverse Childhood Events and Posttraumatic Growth

Background: Quality of life (QoL) is an important patient outcome in oncology. Many breast cancer survivors report difficulties with QoL. Adverse childhood events (ACEs) and posttraumatic growth (PTG) may influence QoL in breast cancer survivors after diagnosis. Objective: The aim of this study was to determine the association of QoL with ACEs and PTG among breast cancer survivors 2 years after diagnosis. Methods: This was a cross-sectional study, conducted on 93 Chinese breast cancer survivors diagnosed at least 2 years prior to the study. Measures included a self-reported demographic questionnaire, the Adverse Childhood Experiences questionnaires, the Posttraumatic Growth Inventory, and the Functional Assessment of Cancer Therapy–Breast Cancer QoL questionnaire. Results: Among the 93 participants, more than one-third (34.4%) experienced childhood adversity. We found a negative relationship between ACEs and QoL and a positive relationship between PTG and QoL. Conclusions: The findings suggest that childhood adversity and PTG are important predictors of QoL among breast cancer survivors at least 2 years after diagnosis. Women who had experienced ACEs had poorer health-related QoL than did those who did not. Individuals who experienced PTG following a cancer diagnosis also reported better QoL than did those who did not. Implications for Practice: A better understanding of how ACE and PTG contribute to breast cancer survivors’ QoL will help in tailoring and therefore enhancing the efficacy of interventions aimed at improving QoL.
Plant Oxidosqualene Metabolism: Cycloartenol Synthase–Dependent Sterol Biosynthesis in Nicotiana benthamiana

The plant sterol pathway exhibits a major biosynthetic difference as compared with that of metazoans. The committed sterol precursor is the pentacyclic cycloartenol (9β,19-cyclolanost-24-en-3β-ol) and not lanosterol (lanosta-8,24-dien-3β-ol), as it was shown in the late sixties. However, plant genome mining over the last years revealed the general presence of lanosterol synthases encoding sequences (LAS1) in the oxidosqualene cyclase repertoire, in addition to cycloartenol synthases (CAS1) and to non-steroidal triterpene synthases that contribute to the metabolic diversity of C30H50O compounds on earth. Furthermore, plant LAS1 proteins have been unambiguously identified by peptidic signatures and by their capacity to complement the yeast lanosterol synthase deficiency. A dual pathway for the synthesis of sterols through lanosterol and cycloartenol was reported in the model Arabidopsis thaliana, though the contribution of a lanosterol pathway to the production of 24-alkyl-Δ5-sterols was quite marginal (Ohyama et al. (2009) PNAS 106, 725). To investigate further the physiological relevance of CAS1 and LAS1 genes in plants, we have silenced their expression in Nicotiana benthamiana. We used virus induced gene silencing (VIGS) based on gene specific sequences from a Nicotiana tabacum CAS1 or derived from the solgenomics initiative (http://solgenomics.net/) to challenge the respective roles of CAS1 and LAS1. In this report, we show a CAS1-specific functional sterol pathway in engineered yeast, and a strict dependence on CAS1 of tobacco sterol biosynthesis.
Neonatal salt‐wasting and 11 β‐hydroxylase deficiency in a child carrying a homozygous deletion hybrid CYP11B2 (aldosterone synthase)–CYP11B1 (11 β‐hydroxylase)

This article reports the case of a boy diagnosed at 1.8 years of age with congenital adrenal hyperplasia due to 11 β‐hydroxylase deficiency. The patient showed salt‐wasting episodes during the neonatal period. On molecular analysis, a homozygous deletion hybrid (CYP11B2–CYP11B1) involving the CYP11B locus at 8q24.3 was found. Southern blot analysis showed the break point of the chimera gene to be located before intron 5; sequence analysis identified it at exon 4 between codons 202 and 248. This CYP11B2(5′)/B1(3′) hybrid should lack aldosterone synthase activity (due to the CYP11B1 residues at exons 5 and 6), and the enzyme it codes for should not be promoted by adrenocorticotropic hormone (ACTH) (CYP11B2 promoter sequences). The patient phenotype – neonatal salt‐wasting and 11 β‐hydroxylase deficiency – is in agreement with this hybrid structure. This is the first time a homozygous deletion hybrid generated by unequal crossover has been described in exon 4. This genetic lesion appears to be the reciprocal product from the recombination event that causes glucocorticoid‐remediable aldosteronism, a duplication dominant allele (CYP11B2–CYP11B1/B2–CYP11B1) coding for additional aldosterone synthase activity regulated by ACTH. The clinical presentation of the condition in this patient contributes to the in vivo understanding of the regulation of this complex locus in which two ‘duplicated’ genes have evolved different regulatory and enzymatic activities involved in mineralocorticoid and glucocorticoid synthesis in the adrenal glands. The fact that this allele was first predicted and has now been documented clinically and molecularly in vivo is particularly noteworthy.
Barrières à l'adoption de l'IoT : une analyse par le business model

L'internet des Objets (IoT) est aujourd'hui considere comme une approche technologique cle dans le cadre de l'innovation et de la transformation numerique des entreprises. En raison des possibilites disruptives qui lui sont pretees, notamment en termes de reconfiguration de business model (BM), les entreprises y pretent de plus en plus attention. Cependant, pour tirer pleinement partie des benefices associes a l'IoT, elles doivent surmonter les challenges et barrieres inherents. Le but de cet article est d'examiner ces challenges et barrieres a l'adoption de l'IoT. A travers une meta-analyse conduite sur un corpus empirique de 8 etudes d'instituts, cabinets conseil et ESN representant un echantillon cumule de 6237 repondants decisionnaires, nous mettons en evidence les dimensions du BM influencees par les challenges et barrieres a l'adoption de l'IoT et a l'innovation par l'IoT.
A Meta-Analysis Approach for Feature Selection in Network Traffic Research

The selection of features for network traffic analysis and anomaly detection is a challenge for experts who aim to build systems that discover traffic patterns, characterize networks, and improve security. There are no major guidelines or best practices for feature selection in the field. The literature is full of different proposals that ultimately depend on feature availability, types of known traffic, tool limitations, specific goals, and, fundamentally, the experts' knowledge and intuition. In this work we have revisited 71 principal publications in the field of network traffic analysis from 2005 to 2017. Relevant information has been curated according to formalized data structures and stored in JSON format, creating a database for the smart retrieval of network traffic analysis researches. Meta-analysis performed upon the explored publications disclosed a set of main features that are common in a considerable volume of works and could be used as a baseline for future research. Additionally, aiming for validation and generalization in network traffic research, the creation of such meta-analysis environments is highly valuable. It allows homogenizing and joining criteria for the design of experiments, thus avoiding getting lost or becoming irrelevant due to the high complexity and variability that network traffic analysis involves.
Volumetric atrophy of the amygdala in Alzheimer's disease

The present study quantitatively assessed volumes of the amygdala and its subnuclei in autopsied cases of advanced Alzheimer's disease (AD) for comparison with age-matched controls. Amygdalar nuclei showed significant atrophy in AD with the exception of the paralaminar portion of the basal nucleus. The magnocellular regions of the amygdala showed proportionately greater size reductions as a fraction of total amygdala volume than did other areas. Computerized reconstruction of the amygdala provided three-dimensional views of a variety of structural alterations accompanying the volumetric declines with AD. The apparent selective vulnerability of the magnocellular amygdalar areas coincides with the loss of large nerve cells in AD.
Cancer Risk Stratification of Indeterminate Thyroid Nodules: A Cytological Approach.

BACKGROUND Management recommendations for thyroid nodules rely primarily on the cytological diagnosis. However, 25% of biopsies render an indeterminate cytology for which management decision is more challenging due to heterogeneity of the specimens. This study aimed to stratify the cancer risk through subcategorization of indeterminate cytology. METHODS The indeterminate cytological specimens (Bethesda-III or IV) of 518 thyroid nodules consecutively evaluated at our academic cancer center between October 2008 and September 2015, blinded to the histological outcome, were retrospectively reviewed. Cytological specimens were subclassified into four groups: aspirates exhibiting nuclear atypia (n = 158; 31%); architectural atypia (n = 222; 43%); oncocytic features (n = 120; 23%); or other types of atypia (n = 18; 3%). The prevalence of malignancy and odds ratio for malignancy were calculated in 323 nodules with histological confirmation. RESULTS The prevalence of malignancy was 26% overall (20% in Bethesda-III and 29% in Bethesda-IV; p = 0.07), and 47%, 12%, 24%, and 25% for aspirates with nuclear atypia, architectural atypia, oncocytic features, or other types of atypia, respectively. The OR of nuclear atypia over architectural atypia was 6.4 (3.4-12.2; p < 0.001), and 2.7 over oncocytic features (1.4-5.1; p = 0.01), whereas the OR of architectural atypia over oncocytic features was 0.4 (0.2-0.9; p = 0.03). Results were similar for Bethesda-III and IV aspirates when analyzed independently. Furthermore, cytological subcategories improved cytology-histology correlation, as they were associated with distinct profiles of histological diagnoses (p < 0.001). CONCLUSIONS Cytological subcategories can effectively stratify the risk of malignancy of thyroid nodules with indeterminate cytology and improve cytology-histology correlation.
Caspase Activity Is Required for Stimulated B Lymphocytes to Enter the Cell Cycle1

Following activation with proliferative stimuli, including ligation of CD40, dense human tonsillar B cells (>98% cells in G0) have increased cleavage and activation of caspase-8 and -6 accompanied by decreased caspase-3 activation and apoptosis. Proliferation was blocked by either a broad specificity caspase inhibitor or inhibitors selective for caspase-6 or caspase-8. In contrast, an inhibitor selective for caspase-3 was without effect. Furthermore, induction of cyclin D and cyclin-dependent kinase 4 mRNA and protein was blocked upon inhibition of caspase-6, but not caspase-3. Thus, caspase-6-like activity is required for quiescent B cells to increase the expression of genes required for entry into G1. In support of this model, the transcriptional suppressor special AT-rich sequence-binding protein 1, a preferred caspase-6 substrate, was cleaved upon B cell stimulation. Caspase activity was not required for all signaling events, as caspase inhibitors did not affect the phosphorylation of p42/44 mitogen-activated protein kinase, the expression of the survival factor cellular inhibitor of apoptosis 2, or the production of IL-6 by stimulated G0 B cells. These findings suggest a mechanism by which caspase-6 may selectively allow entry of quiescent B cells into the cell cycle.
The Language of the Emerging Financial Market and Early Eighteenth-Century English Plays

Between the end of the seventeenth century and the beginning of the eighteenth the birth and development of a flourishing financial market provided the English stage with a variety of new characters, situations and subjects. Most of the plays were written and/or performed in 1720, when the bursting of the South Sea Bubble bit many, but a number of other works had already been composed. In spite of their different aims–some purely satirical, others more curious or documentary–they all shared the interest in the fascinating new language of the market and, in some measure, contributed to its formation and development.
TWO CD34 + STEM CELLS FROM UMBILICAL CORD BLOOD ENRICHMENT METHODS

The authors describe the relation between clamping time and blood volume collected, and two enrichment systems of CD34 + stem cells from umbilical cord blood, to determine an excellent recovery with high proliferate ability and bone marrow reconstitution. After an obstetrician-based cord blood collection, the purification of stem cells was performed either with a combination of monoclonal antibodies (negative selections) using the Stem Sep method, or with a positive cells selection thanks to their surface CD34 antigens, using the Mini Macs system. An excellent recovery of hematopoietic progenitors, burst-forming unit erythroid, colony-forming unit granulocyte and macrophage, and colony-forming unit granulocyte, erythroid, monocyte, and macrophage, inversely related to the rising of clamping time, was performed with the Mini Macs system (54% of colonies, with a 90% purity), while with Stem Sep method, hematopoietic progenitor recovery was 35% (with an 80% purity). By applying early clamping of the umbilical cord blood a greater number of CD34 + cells was obtained and their clonogenic activity increased with enrichment. This is particularly useful, considering that the number of CD34 + stem cells contained in a unit of placental blood is enough for transplanting to a child, but not for an adult engraftment. Thus, using this method, a larger number of CD34 + stem cells can be obtained, which increases the possibility to reduce graft versus host disease also in adult patients, producing survival rates similar to the ones obtained with transplantation of bone marrow from unrelated donors.
Enhancement of radiosensitivity of oral carcinoma cells by iodinated chlorin p6 copper complex in combination with synchrotron X-ray radiation.

The combination of synchrotron X-ray radiation and metal-based radiosensitizer is a novel form of photon activation therapy which offers the advantage of treating malignant tumors with greater efficacy and higher precision than conventional radiation therapy. In this study the anticancer cytotoxic efficacy of a new chlorophyll derivative, iodinated chlorin p6 copper complex (ICp6-Cu), combined with synchrotron X-ray radiation (8-10 keV) in two human oral cancer cell lines is explored. Pre-treatment of cells with 20 µM and 30 µM ICp6-Cu for 3 h was found to enhance the X-ray-induced cytotoxicity with sensitization enhancement ratios of 1.8 and 2.8, respectively. ICp6-Cu localized in cytoplasm, mainly in lysosomes and endoplasmic reticulum, and did not cause any cytotoxicity alone. The radiosensitization effect of ICp6-Cu accompanied a significant increase in the level of reactive oxygen species, damage to lysosomes, inhibition of repair of radiation-induced DNA double-strand breaks, increase in cell death and no significant effect on cell cycle progression. These results demonstrate that ICp6-Cu is a potential agent for synchrotron photon activation therapy of cancer.
Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man.

BACKGROUND AND METHODS Mutations in the estrogen-receptor gene have been thought to be lethal. A 28-year-old man whose estrogen resistance was caused by a disruptive mutation in the estrogen-receptor gene underwent studies of pituitary-gonadal function and bone density and received transdermal estrogen for six months. Estrogen-receptor DNA, extracted from lymphocytes, was evaluated by analysis of single-strand-conformation polymorphisms and by direct sequencing. RESULTS The patient was tall (204 cm [80.3 in.]) and had incomplete epiphyseal closure, with a history of continued linear growth into adulthood despite otherwise normal pubertal development. He was normally masculinized and had bilateral axillary acanthosis nigricans. Serum estradiol and estrone concentrations were elevated, and serum testosterone concentrations were normal. Serum follicle-stimulating hormone and luteinizing hormone concentrations were increased. Glucose tolerance was impaired, and hyperinsulinemia was present. The bone mineral density of the lumbar spine was 0.745 g per square centimeter, 3.1 SD below the mean for age-matched normal women; there was biochemical evidence of increased bone turnover. The patient had no detectable response to estrogen administration, despite a 10-fold increase in the serum free estradiol concentration. Conformation analysis of his estrogen-receptor gene revealed a variant banding pattern in exon 2. Direct sequencing of exon 2 revealed a cytosine-to-thymine transition at codon 157 of both alleles, resulting in a premature stop codon. The patient's parents were heterozygous carriers of this mutation, and pedigree analysis revealed consanguinity. CONCLUSIONS Disruption of the estrogen receptor in humans need not be lethal. Estrogen is important for bone maturation and mineralization in men as well as women.
Initial presentation of older injured patients to high-volume hospitals is not associated with lower 30-day mortality in Medicare data*

Objective:To evaluate whether survival of older patients with severe injuries is positively associated with initial presentation to high-volume trauma hospitals. Design:Historical cohort study. Setting:We analyzed Medicare fee-for-service records. Cases were classified by maximum Abbreviated Injury Score (AISmax); those with isolated hip fractures or AISmax <3 were excluded. The initial hospital (emergency department or inpatient) for each case was classified by its number of included inpatient cases. Patients:Patients aged ≥65 with principal injury diagnoses (ICD-9 800–959, excluding 905, 930–939, 958) admitted to hospitals or who died in emergency departments during 1999. Interventions:None. Measurements and Main Results:Thirty-day mortality was determined using Medicare denominator data and modeled as a function of hospital volume, AISmax, age, gender, and comorbidity. We found that 95,867 patients (74,894 AISmax = 3; 17,932 AISmax = 4; 3,041 AISmax = 5) were managed in 4,391 hospitals. More than 90% of the interhospital transfers were from emergency departments, mostly from low-volume to high-volume hospitals, and were more frequent with greater severity. Regression models showed no difference in 30-day survival between patients taken first to low-volume hospitals (and possibly transferred) vs. patients taken directly to high-volume hospitals. Prior studies showing a positive or negative effect of hospital volume on survival of older patients could be replicated but their findings could not be generalized. Conclusions:Existing systems of trauma care result in similar survival for older patients with serious injuries seen first at low-volume or high-volume hospitals.
Structures of N‐termini of helices in proteins

We have surveyed 393 N‐termini of α‐helices and 156 N‐termini of 310‐helices in 85 high resolution, non‐homologous protein crystal structures for N‐cap side‐chain rotamer preferences, hydrogen bonding patterns, and solvent accessibilities. We find very strong rotamer preferences that are unique to N‐cap sites. The following rules are generally observed for N‐capping in α‐helices: Thr and Ser N‐cap side chains adopt the gauche— rotamer, hydrogen bond to the N3 NH and have Ψ restricted to 164 ± 8°. Asp and Asn N‐cap side chains either adopt the gauche— rotamer and hydrogen bond to the N3 NH with Ψ = 172 ± 10°, or adopt the trans rotamer and hydrogen bond to both the N2 and N3 NH groups with Ψ = 107 ± 19°. With all other N‐caps, the side chain is found in the gauche + rotamer so that the side chain does not interact unfavorably with the N‐terminus by blocking solvation and Ψ is unrestricted. An i, i + 3 hydrogen bond from N3 NH to the N‐cap backbone C=O in more likely to form at the N‐terminus when an unfavorable N‐cap is present. In the 310‐helix Asn and Asp remain favorable N‐caps as they can hydrogen bond to the N2 NH while in the trans rotamer; in contrast, Ser and Thr are disfavored as their preferred hydrogen bonding partner (N3 NH) is inaccessible. This suggests that Ser is the optimum choice of N‐cap when α‐helix formation is to be encouraged while 310‐helix formation discouraged. The strong energetic and structural preferences found for N‐caps, which differ greatly from positions within helix interiors, suggest that N‐caps should be treated explicitly in any consideration of helical structure in peptides or proteins.
The impact of immunosuppressive therapy on an early quantitative NK cell reconstitution after allogeneic haematopoietic cell transplantation.

OBJECTIVES The goal of this study was to examine the impact of various immunosuppressive regimens on an early NK cell recovery following haematopoietic cell transplantation (alloHCT). METHODS The number of peripheral blood NK cells was analysed with the use of flow cytometry on day +30 (+/-2) after alloHCT from an HLA identical sibling (n=43) or an unrelated (n=34) donor. RESULTS Patients receiving prednisolone as a prophylaxis of acute graft-versus-host disease had lower number of NK cells compared to those not given steroids prophylactically (110(10-694) vs. 212(33-890) x 10(6)/L, p = 0.005). In contrast, administration of anti-thymocyte globulin (ATG) (7.5-15 mg/kg) as a part of preparative regimen was not found to influence the NK cell recovery. Similarly, no effect on the number of peripheral blood NK cells was observed with regard to other analysed factors: cell dose, type of myeloablative conditioning, source of stem cells, patient and donor characteristics, number of post-transplant methotrexate doses. CONCLUSIONS Immunosuppressive therapy may affect NK cell recovery following alloHCT. Since NK cells are considered a potential tool for cellular therapy of haematological malignancies, our findings should be taken into account when planning this kind of treatment in the context of allotransplantation.
Sonic Hedgehog Stimulates Mouse Embryonic Stem Cell Proliferation by Cooperation of Ca2+/Protein Kinase C and Epidermal Growth Factor Receptor As Well as Gli1 Activation

Hedgehog signaling has an essential role in the control of stem cell growth in embryonic tissues. Therefore, this study examined the effect of sonic hedgehog (Shh) on the self‐renewal of mouse embryonic stem (ES) cells and its related mechanisms. Shh increased DNA synthesis blocked by the inhibition of the smoothened receptor. Shh required Gli1 activation to induce the increases in Notch/Hes‐1 and Wnt/β‐catenin. Shh increased the intracellular calcium concentration ([Ca2+]i) and protein kinase C (PKC) activity. We show that the Shh‐induced increase in the Gli1 mRNA level requires [Ca2+]i and PKC. Shh increased the phosphorylation of epidermal growth factor receptor (EGFR), which is blocked by the matrix metalloproteinase inhibitor. Subsequently, Shh increased the nuclear factor (NF)‐κB p65 phosphorylation, which was inhibited by blocking PKC and EGFR tyrosine kinase. Shh also increased the level of the cell cycle regulatory proteins in a dose‐dependent manner. However, Shh decreased the levels of the cyclin‐dependent kinase inhibitory proteins. The effect of Shh on these proteins was inhibited by blocking PKC, EGFR, and NF‐κB as well as transfection of Gli1 small interfering RNA (siRNA). Finally, Shh‐induced progression of the G1/S‐phase was blocked by the inhibition of PKC and EGFR tyrosine kinase. In conclusion, Shh stimulates mouse ES cell proliferation through Gli1 activation as well as Ca2+/PKC and EGFR.