Miracle-dz/UniFAR-FTUs huggingface dataset:
Investigation of Adenovirus Occurrence in Pediatric Tumor Entities

ABSTRACT Adenoviruses (AdVs) contain genes coding for proteins with transforming potential, and certain AdV serotypes have been shown to induce tumors in rodents. However, data on the possible oncogenicity of AdVs in humans are scarce. We have therefore employed a real-time quantitative PCR (RQ-PCR) assay permitting highly sensitive detection of all 51 currently known human AdV serotypes to screen more than 500 tumor specimens derived from 17 different childhood cancer entities including leukemias, lymphomas, and solid tumors. Most tumor entities analyzed showed no evidence for the presence of AdV sequences, but AdV DNA was detected by RQ-PCR in different brain tumors including 25/30 glioblastomas, 22/30 oligodendrogliomas, and 20/30 ependymomas. Nonmalignant counterparts of AdV-positive brain tumors, including specimens of ependymal cells, plexus choroideus, and periventricular white matter, were screened for control purposes and revealed the presence of AdV DNA in most specimens tested. Identification of the AdV types present in positive malignant and nonmalignant brain tissue specimens revealed predominantly representatives of species B and D and, less commonly, C. To exclude contamination as a possible cause of false-positive results, specimens with AdV sequences detectable by PCR were subsequently analyzed by in situ hybridization, which confirmed the PCR findings in all instances. The central nervous system appears to represent a common site of AdV infection with virus persistence, thus providing the first evidence for the possible contribution of AdVs to the multistep process of tumor pathogenesis in brain tissue.
Dietary innovations spurred the diversification of ruminants during the Caenozoic

Global climate shifts and ecological flexibility are two major factors that may affect rates of speciation and extinction across clades. Here, we connect past climate to changes in diet and diversification dynamics of ruminant mammals. Using novel versions of Multi-State Speciation and Extinction models, we explore the most likely scenarios for evolutionary transitions among diets in this clade and ask whether ruminant lineages with different feeding styles (browsing, grazing and mixed feeding) underwent differential rates of diversification concomitant with global temperature change. The best model of trait change had transitions from browsers to grazers via mixed feeding, with appreciable rates of transition to and from grazing and mixed feeding. Diversification rates in mixed-feeder and grazer lineages tracked the palaeotemperature curve, exhibiting higher rates during the Miocene thermal maxima. The origination of facultative mixed diet and grazing states may have triggered two adaptive radiations—one during the Oligocene–Miocene transition and the other during Middle-to-Late Miocene. Our estimate of mixed diets for basal lineages of both bovids and cervids is congruent with fossil evidence, while the reconstruction of browser ancestors for some impoverished clades—Giraffidae and Tragulidae—is not. Our results offer model-based neontological support to previous palaeontological findings and fossil-based hypothesis highlighting the importance of dietary innovations—especially mixed feeding—in the success of ruminants during the Neogene.
[Trends of thyroid pathology in a referral center: steady prevalence of papillary thyroid carcinoma but goiter increase in thyroidectomies].

INTRODUCTION Changes in the prevalence of papillary thyroid carcinoma (PTC) have been reported in institutions and national cancer registries. OBJECTIVE To describe time trends in benign and malignant thyroid diseases in a national endocrine referral center. MATERIALS AND METHODS Systematic review and classification of consecutive specimens with slides/paraffin blocks in surgical pathology archives (January 1990 to December 2009). Institutional registries, size, type of surgery and number of inclusion blocks were recorded. Patients whose registries were granted before January 1990 without nodules, but treated after twelve months for a suspicious thyroid lesion, were included. These patients in a passive follow-up permitted incidence density calculations. Cases were grouped by quinquennium. RESULTS Institutional registers were conceded to 103,961 persons worthy of attention, and 1,269 were submitted to thyroidectomies (1.2%). One hundred twenty four patients none treated for thyroid diseases before 1990, developed thyroid nodules after 1991. The incidence density for goiter was 0.05 person/year and for PTC 0.04 person/year in that group. In all series woman to man relation was 9:1 with a mean age of 45 years. Total or near total thyroidectomies were performed in 60% patients and benign diseases were diagnosed in 732 (52%) cases. Thyroid surgeries increased since 2005 (p=0.03) with a rise in goiter prevalence (0.25, 0.31, 0.35, 0.38, p for trend 0.0005), without significant increase in PTC prevalence (0.41, 0.43, 0.35, 0.40, p for trend 0.71) in thyroidectomies. CONCLUSIONS Goiter as the only finding in thyroid specimens increased 52% in the last 20 years. PTC prevalence is steady with a higher number of tumors<3 cm.
Nocturnal Non-dipping Blood Pressure Profile in Black Normotensives Is Associated with Cardiac Target Organ Damage.

PURPOSE A non-dipping pattern of nocturnal blood pressure in hypertensive patients is an established predictor of cardiovascular risk, especially in Blacks. However, data on non-dipping normotensives and cardiovascular risk in this population is sparse. In this study, we aim to determine if a non-dipping profile in a cohort of Black normotensives is associated with cardiac target organ damage. METHODS We studied ambulatory blood pressure patterns in 43 normotensive Black patients of Caribbean origin and classified their profiles as dippers (DP) and non-dippers (NDP) based on their nocturnal blood pressure profiles. Cardiac target organ damage was estimated from 2-D echocardiogram. RESULTS The mean age of the cohort was 52 years. Both groups were similar with respect to baseline age, sex, weight, height, body mass index and daytime ambulatory BP. There was a statistically significant difference in nocturnal blood pressure between DP and NDP groups (112 ± 7/64 ± 2 mm Hg vs 117 ± 3/69 ± 2 mm Hg, P=.004). The NDP cohort showed evidence of cardiovascular target damage on echocardiography with a significantly increased relative wall thickness (.35 ± .07 cm vs .42 ± .05 cm, P=.001), left ventricular mass index (95 ± 14 vs 105 ± 14 g/m(2), P=. 018) and left atrial volume index (26 ± 3.5 vs. 30 ± 3.4, P=.001). Left ventricular geometry in the non-dippers also showed increased concentric remodeling, concentric and eccentric hypertrophy. CONCLUSIONS Our study demonstrates that nocturnal non-dipping of blood pressure in normotensive Blacks of Caribbean origin may be associated with cardiovascular end organ damage thereby providing new surveillance and therapeutic targets.
Regulation of Serotonin Release in the Lateral Septum and Striatum by Corticotropin-Releasing Factor

The serotonergic dorsal raphé nucleus (DRN) is innervated by corticotropin-releasing factor (CRF)-immunoreactive fibers and contains CRF receptor-binding sites, suggesting that endogenous CRF regulates this system. The present study examined the possibility that CRF in the DRN regulates the release of serotonin (5-HT) in forebrain terminal regions. Intracerebroventricular administration of CRF produced a bimodal effect on extracellular levels of 5-HT in the lateral septum. Doses of 0.3 and 1.0 μg decreased extracellular 5-HT levels, whereas both a higher (3.0 μg) and a lower (0.1 μg) dose had no effect. The reduction of extracellular 5-HT in the lateral septum by CRF (0.3 μg, i.c.v.) was blocked by pretreatment with the CRF receptor antagonistd-PheCRF12–41 (3.0 μg, i.c.v.). Direct administration of CRF (30 ng) into the DRN reduced extracellular 5-HT levels in the lateral septum and the striatum. Furthermore, injection of d-PheCRF12–41 (10 ng) into the DRN before ventricular administration of CRF (0.3 μg, i.c.v.) blocked the decrease in extracellular 5-HT in both the lateral septum and striatum. Taken together, these data support the hypothesis that CRF may modulate 5-HT release in terminal regions via its effects at the level of the DRN. This modulation supports a potential interaction between CRF and 5-HT in stress-related psychiatric disorders in which both systems have been implicated.
Longitudinal Investigation of the Relationship Among Maternal Victimization, Depressive Symptoms, Social Support, and Children’s Behavior and Development

This article is a longitudinal investigation of the relationships between maternal victimization, maternal functioning, and children’s behavior and development. Participants include 203 mother-child dyads from a low-income population recruited from pediatric primary care clinics. Data are collected when children are 4 and 8 years of age. Child outcomes are evaluated using maternal, teacher, and child self-report and objective measures of cognitive and academic functioning. Maternal victimization history is associated with maternal depressive symptoms, low levels of maternal social support, child internalizing and externalizing behavior problems, and low levels of child socialization. Child behavior problems identified at age 4 are enduring and persist to age 8. The effects of maternal victimization history on both internalizing behavior problems and socialization are mediated by maternal depressive symptoms. The effects of maternal depressive symptoms on externalizing behavior problems, socialization, and anger are mediated by maternal social support. Clinical implications of findings are discussed.
A population-level study of place of death and associated factors in Sweden

Aims: The aims of this study were to examine, on a population level, where people die in Sweden, and to investigate associations between place of death and underlying cause of death, socioeconomic and environmental characteristics, with a particular interest in people dying from life-limiting conditions typically in need of palliative care. Methods: This population-level study is based on death certificate data for all deceased individuals in Sweden in 2012, with a registered place of death (n=83,712). Multivariable logistic regression was performed to investigate associations between place of death and individual, socioeconomic and environmental characteristics. Results: The results show that, in 2012, 42.1% of all deaths occurred in hospitals, 17.8% occurred at home and 38.1% in nursing home facilities. Individuals dying of conditions indicative of potential palliative care needs were less likely to die in hospital than those dying of other conditions (OR = 0.73; 95% CI = 0.70–0.77). Living at home in urban areas was associated with higher likelihood of dying in hospital or in a nursing home (OR = 1.04 and 1.09 respectively). Educational attainment and marital status were found to be somewhat associated with the place of death. Conclusions: The majority of deaths in Sweden occur in institutional settings, with comparatively larger proportions of nursing home deaths than most countries. Associations between place of death and other variables point to inequalities in availability and/or utilization of health services at the end of life.
Quality of life in patients with traumatic brain injury-basic issues, assessment and recommendations.

INTRODUCTION Traumatic brain injuries (TBI) are one of the most common consequences of traffic accidents. Patients with mild, moderate or severe brain injuries suffer from physical, cognitive, behavioral, emotional and social problems. Most of these problems have been a long standing focus amongst practitioners and researchers. Only recently a development has started that took interest in the quality of life outcome of TBI patients. The international members of this consensus meeting reviewed the literature on Quality of Life assessment after TBI and discussed the applicability of different measurements to this specific patient group. TIME POINTS During the acute phase (T1; < 3 month after trauma) QoL it is difficult to assess due to the reduced consciousness of TBI patients. In the phase of rehabilitation (T2; < one year after trauma) and in the post-rehabilitation phase (T3) repeated assessment of QoL is recommended. INSTRUMENTS Several generic and disease-specific instruments possibly relevant to TBI patients or specifically developed for this group were assessed according to the existing evidence in the literature. Criteria for the evaluation of these instruments were: feasibility, specificity, validity, comprehensiveness, international availability, existence of norms, and psychometric quality. The cognitive impairment and the existential dimension were not sufficiently considered in most of the reviewed instruments. GROUP CONSENSUS The family's and relatives' view of the patient's QoL should not be used as a proxy but provides an additional source of information in the acute phase. At T2 and T3, assessment of the patient's quality of life should include a generic as well as a disease specific instrument. Among the generic instruments the SF-36, the EuroQol and the WHO-QoL should be considered. The literature about specific instruments for patients with TBI like the EBIC is scarce. Therefore, the group could hardly give an empirically based recommendation. The need for further investigation on QoL instruments in TBI patients is strongly emphasized.
Cortical Inhibition during Burst Suppression Induced with Isoflurane Anesthesia

Isoflurane is a widely used anesthetic which safely and reversibly induces deep coma and associated burst suppression (BS) electroencephalographic patterns. Here we investigate possible underlying causes for the state of cortical hyperexcitability which was recently shown to be one of the characteristics of BS. Our hypothesis was that cortical inhibition is diminished during isoflurane-induced BS. Experiments were performed in vivo using intracellular recordings of cortical neurons to assess their responsiveness to stimulations of connected thalamic nuclei. We demonstrate that during BS EPSPs were diminished by 44%, whereas inhibitory potentials were completely suppressed. This finding was supported by additional results indicating that a decrease in neuronal input resistance normally found during inhibitory responses under low isoflurane conditions was abolished in the BS condition. Moreover, removal of inhibition occasionally revealed excitatory components which were absent during recordings before the induction of BS. We also show that the absence of inhibition during BS is not caused by a blockage of GABA receptors, since iontophoretically applied GABA shows receptor availability. Moreover, the concentration of extracellular chloride was increased during BS, as would be expected after reduced flow of chloride through GABAA receptors. Also inhibitory responses were reinstated by selective blockage of glial glutamate transporters with dihydrokainate. These results suggest that the lack of inhibition during BS is caused by reduced excitation, probably resulting from increased glial uptake of glutamate stimulated by isoflurane, which creates a diminished activation of cortical interneurons. Thus cortical hyperexcitability during BS is favored by suppressed inhibition.
Role of somatostatin and apoptosis in breathing control in sudden perinatal and infant unexplained death.

OBJECTIVES To obtain basic information about the expression of somatostatin in the human central nervous system and, in particular, to evaluate its possible involvement in unexplained perinatal and in sudden infant death syndrome. MATERIAL Sixty-seven brainstems from subjects aged from 30 gestational weeks to 12 postnatal months, dying of both known and unknown causes, were selected for this study. The unexplained deaths included 17 sudden intrauterine deaths, 5 sudden neonatal deaths and 28 sudden infant deaths. METHOD All brainstems were fixed in 10% phosphate-buffered formalin, processed and embedded in paraffin, according to our protocol available on the web site: http://users.unimi. it/-pathol/sids/riscontro_diagnostico_e. html. The distribution of the somatostatin in the brainstem was studied by immunohistochemistry on serial sections. RESULTS We observed an intense somatostatin positivity in many brainstem nuclei prevalently involved in the respiratory activity (parabrachial/Kölliker-Fuse complex, locus coeruleus, hypoglossus nucleus, dorsal vagus motor nucleus, tractus solitarii nucleus, ambiguus nucleus, reticular formation) in stillbirths. In 10 fetuses with unexplained death the neurons of the hypoglossus nucleus were somatostatin-negative. In the postnatal deaths, we observed immunopositivity in the ventrolateral and ventral subnuclei of the tractus solitarii nucleus. Besides, in 15 sudden infant death victims and in 1 control case, somatostatin-positive neurons were also present in the hypoglossus nucleus. In 10 of these 15 cases, a high apoptotic index was also reported. CONCLUSIONS We suggest that abnormalities in the distribution of SS in the hypoglossus nucleus before and after birth may contribute to the induction of both fatal breathing in prenatal life and abnormal ventilatory control after birth leading to irreversible apnea.
The Economics of the Super‐Multiplier: A Comprehensive Treatment with Labor Markets

This paper links the super‐multiplier to Keynesian macroeconomics, showing it to be the most Keynesian of growth perspectives. Next, the paper shows that the super‐multiplier is a micro‐economically coherent theory of investment and capital accumulation. Firms’ decisions regarding capital accumulation coordinate demand and supply growth in goods markets. The paper then explores the implications of incorporating the super‐multiplier in the neo‐Kaleckian and Cambridge growth models. Lastly, it shows how labor markets and unemployment can be added into super‐multiplier models to provide a comprehensive growth model that addresses Solow's (1956, Journal of Economics, 70, 65–94) labor market knife‐edge problem. Incorporating labor markets does not change the fundamental super‐multiplier result that growth is determined by the growth of autonomous demand.
Differentiation of lung neoplasms with lepidic growth and good prognosis from those with poor prognosis using computer-aided 3D volumetric CT analysis and FDG-PET

Background Many studies have reported that transverse computed tomography (CT) imaging findings correlate with prognosis of patients with small peripheral lung neoplasm with lepidic growth. However, no studies have examined this correlation with the aid of three-dimensional (3D) CT data. Purpose To determine the most efficacious imaging factor for differentiation of lepidic growth type lung neoplasms with good prognosis from those with poor prognosis. Material and Methods We evaluated CT findings, nodule patterns, SUVmax on FDG-PET/CT, as well as nodule volume and ratios of solid parts to nodule volume that were semi-automatically measured on CT images of 64 pulmonary nodules of ≤2 cm in 60 consecutive patients (24 men and 36 women; mean age, 65 years). For logistic modeling, we used all of the significant factors observed between the neoplasms with good and with poor prognosis as independent variables to estimate the statistically significant factors for discriminating invasive adenocarcinomas with lepidic growth (lesions with poor prognosis, n = 42) from the other neoplasms, including preinvasive lesions (lesions with good prognosis, n = 22), resulting in a recommendation for the optimal criterion for predicting lesions with poor prognosis. Results The logistic regression model identified the ratio of the solid part to the whole volume of a pulmonary nodule as the only significant factor (P = 0.04) for differentiating lepidic growth type lung neoplasms with good prognosis from those with poor prognosis. A ratio of 0.238 or more showed the highest discriminatory accuracy of 84% with 91% sensitivity and 76% specificity. Conclusion Computer-aided analyses of pulmonary nodules proved most useful for establishing the optimal criterion for differentiation of lepidic growth type lung neoplasms with good prognosis from those with poor prognosis.
Altered expression of CD11/CD18 on the peripheral blood phagocytes of patients with tuberculosis

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is characterized by granulomatous lesions made up of epithelioid cells, giant cells and mononuclear leucocytes. Cell‐cell adhesion is important in granuloma formation and in the leucocyte migration which accompanies it. We have recently shown increased expression of the adhesion molecules CD11/CD18 (Leu CAMs, β2 integrins) on peripheral blood leucocytes from patients with sarcoidosis (Shakoor & Hamblin, 1992). Here we have studied the expression of CD11/CD18 and CD29 (VLA β1 integrin) on the peripheral blood leucocytes of 10 TB patients by flow cytometry. The density (expressed as mean fluorescence intensity) of CD11b on monocytes and polymorphs was increased (P < 0·005) as was CD11c (P< 0·005) and CD18 (P < 0·05) on polymorphs. CD1la expression was significantly reduced on polymorphs (P < 0·05). No differences were found in the expression of CD29, the percentages of cells expressing any molecule and, in contrast to sarcoidosis, the density of any molecule on lymphocytes. Although the cytokine tumour necrosis factor (TNF) has been implicated in the process of up‐regulation, an ELISA for TNF failed to detect significant levels in plasma. The results suggest increased peripheral phagocyte CD11/CD18 expression is a feature of TB, which may contribute to the pathological processes involved.
Novel and Unique Diagnostic Biomarkers for Bacillus anthracis Infection

ABSTRACT A search for bacterium-specific biomarkers in peripheral blood following infection with Bacillus anthracis was carried out with rabbits, using a battery of specific antibodies generated by DNA vaccination against 10 preselected highly immunogenic bacterial antigens which were identified previously by a genomic/proteomic/serologic screen of the B. anthracis secretome. Detection of infection biomarkers in the circulation of infected rabbits could be achieved only after removal of highly abundant serum proteins by chromatography using a random-ligand affinity column. Besides the toxin component protective antigen, the following three secreted proteins were detected in the circulation of infected animals: the chaperone and protease HtrA (BA3660), an NlpC/P60 endopeptidase (BA1952), and a protein of unknown function harboring two SH3 (Src homology 3) domains (BA0796). The three proteins could be detected in plasma samples from infected animals exhibiting 103 to 105 CFU/ml blood and also in standard blood cultures at 3 to 6 h post-bacterial inoculation at a bacteremic level as low as 103 CFU/ml. Furthermore, the three biomarkers appear to be present only in the secretome of B. anthracis, not in those of the related pathogens B. thuringiensis and B. cereus. To the best of our knowledge, this is the first report of direct detection of B. anthracis-specific proteins, other than the toxin components, in the circulation of infected animals.