Miracle-dz/UniFAR-FTUs huggingface dataset:
Augmentation of tumor immunity with ENHANZYN adjuvant following verteporfin PDT: photodynamic vaccination (PDV)

The immune system is implicated in the mechanism of tumor destruction following photodynamic therapy (PDT). Several investigators have shown that immune stimulation can augment PDT. In this study, a single intratumoral injection of ENHANZYNTM adjuvant was administered to tumor-bearing mice immediately following verteporfin PDT in a therapeutic modality referred to as Photodynamic Vaccination (PDV). After optimal PDT, little difference in the rate of tumor re-growth or time to tumor reappearance was seen upon addition of the adjuvant. This may be as expected as this treatment regimen results in effective long-term tumor cure in mice. The effect of adjuvant and sub-optimal PDT was less clear as both groups treated with either a high or low does of adjuvant showed tumor re-growth earlier than those animals treated with PDT alone. However, tumors of mice receiving sub-optimal PDT followed by high dose immune adjuvant did not show the rapid, uncontrolled growth seen in other groups and, in the majority of cases, tumor volume decreased steadily with time. This resulted in a superior period of survival despite the animals being tumor-bearing. Interestingly, the data obtained in this study clearly demonstrates the ability of PDT to protect against re- challenge with a second round of tumor implantation. This was seen in all groups and stresses the importance of the immune response in PDT tumor control. Addition of the high immune adjuvant does to sub-optimal PDT appeared to be the most effective treatment group in this respect, giving complete protection against tumor re-implantation.
Strategies for optimizing oxygenation in acute respiratory distress syndrome

The acute respiratory distress syndrome (ARDS) is characterized by increased permeability of the alveolocapillary barrier, leading to interstitial edema, atelectasis, and hypoxemic respiratory failure. With the advent of mechanical ventilation, the odds of survival have dramatically improved. Even so, long-term morbidity occurs in 30% to 40% of these patients, including the development of chronic lung disease, barotrauma, dependence on mechanical ventilation, and multiorgan failure. This article outlines the current modalities to improve oxygenation in ARDS. Development of novel methods to optimize oxygenation awaits better understanding of the pathogenesis of the acute respiratory distress syndrome.
RANKL: Targeting bone and cancer to treat skeletal complications of malignancy

The RANKL signaling pathway is a key mediator of osteoclastic bone resorption in response to stimuli from cancer cells. Bone resorption releases growth factors that then further stimulate cancer growth in a “vicious cycle”. RANKL inhibition effectively decreases solid tumor bone metastases, myeloma and hypercalcemia of malignancy in animal studies. In clinical trials, humanized RANKL antibody therapy is effective in all of these settings and in cancer treatment-related bone loss as well. Although there are theoretical concerns that inhibition of RANKL signaling could impact the immune system or increase the incidence of neoplasms, neither of these adverse outcomes have been realized clinically to date. Emerging research suggests that RANKL signaling plays additional roles in cancer cells independent of osteoclasts by increasing homing of cancer cells to bone and invasive potential. Osteoclast eradication caused by RANKL inhibition may also offer advantages in suppression of bone turnover compared to bisphosphonates. Thus, targeting RANKL in skeletal complications of malignancy potently suppresses bone turnover to improve skeletal mortality in those conditions, and may have direct antitumor effects as well. IBMS BoneKEy. 2009 September;6(9):323-338. 2009 International Bone & Mineral Society
Genetic approaches to study glial cells in the rodent brain

The development, function, and pathology of the brain depend on interactions of neurons and different types of glial cells, namely astrocytes, oligodendrocytes, microglia, and ependymal cells. Understanding neuron–glia interactions in vivo requires dedicated experimental approaches to manipulate each cell type independently. In this review, we first summarize techniques that allow for cell‐specific gene modification including targeted mutagenesis and viral transduction. In the second part, we describe the genetic models that allow to target the main glial cell types in the central nervous system. The existing arsenal of approaches to study glial cells in vivo and its expansion in the future are key to understand neuron–glia interactions under normal and pathologic conditions. © 2011 Wiley Periodicals, Inc.
Premature ventricular beats in the athlete: management considerations

ABSTRACT Introduction: Premature ventricular beats (PVBs) in competitive athletes are incidentally found during pre-participation ECG screening. Their clinical significance remains debatable with several studies suggesting they are a benign reflection of athlete’s heart, and others proposing they may indicate underlying structural heart disease and heightened risk for sudden cardiac death (SCD). Areas covered: Effective management of athletes with PVBs may best be accomplished using an algorithmic approach for risk stratification with a goal of differentiating benign PVBs from those reflective of underlying cardiomyopathies. Current AHA/ACC consensus recommendations provide a platform for determining optimal medical and invasive therapeutic strategies for symptom control and management of long-term complications without erroneously restricting an athlete’s ability to play. Utilizing a shared decision-making model is an optimal method for managing expectations and guiding exercise recommendations. Expert commentary: Though pre-participation ECG screening as the standard of care for competitive athletes remains controversial in the United States, a 12-lead ECG is often the first indication of underlying structural heart disease in athletes with PVBs and can therefore identify athletes at greater risk of SCD. Advancements in non-invasive imaging continue to improve in diagnostic potential and prognostication. Invasive therapies provide a curative strategy for refractory PVBs and PVB-induced cardiomyopathy.
The relationship between kinetic and thermodynamic fragilities in metallic glass-forming liquids

The correlation between the temperature dependence of the kinetic and thermodynamic properties of a series of metallic glass-forming liquids is investigated using the concept of fragility. The results indicate a correlation between the kinetic fragility and thermodynamic fragility in these liquids. The correlation depends critically on the approach used to evaluate the thermodynamic fragility. Two distinct correlation lines are found for the metal–metalloid and for the all-metallic-constituents glass-forming liquids. For the same thermodynamic fragility the metal–metalloid liquids exhibit a distinctively larger kinetic fragility than the pure-metallic liquids. From the evaluation of the Gibbs free-energy difference between the undercooled liquid and the crystalline phase mixture, a correlation between the kinetic fragility and the driving force for nucleation is found, showing that for glass formation in metallic alloys the thermodynamic and kinetic contributions act together.
Microglial activatory (immunoreceptor tyrosine‐based activation motif)‐ and inhibitory (immunoreceptor tyrosine‐based inhibition motif)‐signaling receptors for recognition of the neuronal glycocalyx

Microglia sense intact or lesioned cells of the central nervous system (CNS) and respond accordingly. To fulfill this task, microglia express a whole set of recognition receptors. Fc receptors and DAP12 (TYROBP)‐associated receptors such as microglial triggering receptor expressed on myeloid cells‐2 (TREM2) and the complement receptor‐3 (CR3, CD11b/CD18) trigger the immunoreceptor tyrosine‐based activation motif (ITAM)‐signaling cascade, resulting in microglial activation, migration, and phagocytosis. Those receptors are counter‐regulated by immunoreceptor tyrosine‐based inhibition motif (ITIM)‐signaling receptors, such as sialic acid‐binding immunoglobulin superfamily lectins (Siglecs). Siglecs recognize the sialic acid cap of healthy neurons thus leading to an ITIM signaling that turns down microglial immune responses and phagocytosis. In contrast, desialylated neuronal processes are phagocytosed by microglial CR3 signaling via an adaptor protein containing an ITAM. Thus, the aberrant terminal glycosylation of neuronal surface glycoproteins and glycolipids could serve as a flag for microglia, which display a multitude of diverse carbohydrate‐binding receptors that monitor the neuronal physical condition and respond via their ITIM‐ or ITAM‐signaling cascade accordingly. © 2012 Wiley Periodicals, Inc.
Exogenous melatonin positively influences follicular dynamics, oocyte developmental competence and blastocyst output in a goat model

Abstract: The role of melatonin in modulating mammalian reproduction is of particular interest; however, its effects on ovarian follicles and their oocytes still remain to be characterized. This study determined the influence of melatonin treatment on follicular growth patterns and on in vitro oocyte developmental competence. In a first experiment, the effects of melatonin supplementation on follicular dynamics were evaluated using daily transrectal ultrasonographies for 21 days, in 7 multiparous Sarda goats receiving a subcutaneous implant of 18 mg of melatonin and in 5 control untreated does. Melatonin caused more follicular waves (5.2 ± 0.2 versus 4 ± 0.3; P < 0.05) as the waves were shortened at around 2 days when compared with the non‐melatonin treated control goats (P < 0.001). Oocyte developmental competence was evaluated in a second experiment by applying procedures for in vitro embryo production. There were no significant differences in the total number of oocytes obtained from 6 control (n = 192) and 7 melatonin‐treated (n = 265) goats given follicle stimulating hormone to induce follicular development. Differences in oocyte developmental competence between the two groups became evident after in vitro fertilization and culture; melatonin increased the rate of cleaved oocytes in comparison with control animals (82.5 versus 63.4%; P < 0.001), advanced timing of embryo development and enhanced blastocyst output (31.5 versus 16.3%; P < 0.01). However, blastocyst quality, as evaluated by cryotolerance and gene expression analysis, was not found to be different between the groups. In conclusion, in vivo melatonin treatment is beneficial for increasing ovarian follicle turnover and improving oocyte developmental competence and kinetics of the blastocyst.
Discussion on Rational Mind and Heuristics in Medical Diagnostic Decision Making

The medical diagnostic label is the most important process in patient management. The decision process involves the thinking process of the caregiver which operates differently in emergencies and outpatient clinic. The heuristics aspect of the mind is more efficient in dealing with emergencies and the slower analyzing mind in outpatient setting. The heuristic approach is useful in rapid decisions and management of emergencies whereas the slower stepwise approach in outpatient treatment will help in reducing investigations, medical errors and cost of care. The article also gives an evidence based template for predicting the disease process based on positive and negative likelihood ratios.
Melatonin promotes neurogenesis in dentate gyrus in the pinealectomized rat

Abstract: It was previously shown that pinealectomy causes delayed loss of pyramidal neurons in rat hippocampal layers CA1/3 and that this is reversed by melatonin supplementation. Here, we used immunohistologic detection of doublecortin, a protein expressed in newborn neurons, to determine if melatonin supplementation promotes neurogenesis after pinealectomy. It was found that melatonin supplementation significantly increased the number of doublecortin immunoreactive neurons in the dentate gyrus over the postsurgical intervals of 2, 4, 6, 8, 10 and 17 months. The increase was most evident at 6 months postsurgery and thereafter, and was apparent despite a severe decline in doublecortin‐labeled cells over the 17 month postsurgical interval in all groups of rats. Doublecortin immunoreactive cells were not observed in the pyramidal layer itself. These results indicate that melatonin promotes neurogenesis in the dentate gyrus of pinealectomized rats. However, it is equivocal that these newborn neurons migrate to the pyramidal layer and account for the reappearance of neurons at this location in these rats. This study provides further evidence for a role of melatonin in promoting neurogenesis, adding another role to its already remarkably pleiotropic profile. The scope and significance of this newly discovered role remains to be determined.
Phthalate exposure and children's health

Purpose of review Phthalates are multifunctional chemicals used in personal care products, medications, and plastics. We reviewed the epidemiological literature examining the relationship between early life phthalate exposure and pediatric health outcomes. Recent findings Five studies from Asia, Europe, and the United States suggest that childhood exposure to di-2-ethylhexyl phthalate (DEHP) and butylbenzyl phthalate (BBzP) may increase the risk of allergic diseases including asthma and eczema. Six studies from four different prospective cohorts report that gestational BBzP, DEHP, di-butyl phthalate (DBP), and di-ethyl phthalate (DEP) exposures are associated with alterations in infant/toddler physical development as well as parent-reported externalizing, internalizing, and autistic-like child behavior. However, there are inconsistencies related to the specific phthalates and behavioral domains. Two small studies report shorter anogenital distance among male infants with higher gestational phthalate exposure. Summary Several epidemiological studies suggest fetal and childhood exposure to some phthalates may perturb normal development, with several studies consistently reporting increased risk of allergic diseases with DEHP and BBzP exposure. Although anticipatory guidance is not evidence-based at this time, providers can counsel concerned patients to reduce phthalate exposures in order to protect the developing fetus and child from potential adverse health outcomes.
19α-Hydroxy-3-oxo-ursa-1,12-dien-28-oic acid, an antiplasmodial triterpenoid isolated from Canthium multiflorum

A bioactivity guided fractionation of roots of Canthium multiflorum led to the isolation of the new ursenoic acid derivative 19α-hydroxy-3-oxo-ursa-1,12-dien-28-oic acid (1), which showed antiplasmodial effect without inducing change of the shape of membranes of erythrocytes.
Does a Day Make a Difference? Duration of Illness and Clinical Presentation of Group A β-Hemolytic Streptococcal Pharyngitis in Children

Our objective was to study the effect of the duration of illness on the presenting signs and symptoms of group A β-hemolytic streptococcal (GABHS) pharyngitis in children. Ten clinical signs and symptoms in children with culture-proven GABHS pharyngitis and the duration of illness were prospectively recorded. The duration of illness between onset of symptoms and the time of presentation for medical attention was classified as <24 hours or >24 hours. Signs and symptoms were compared for the two periods. Two-hundred eighteen children between the ages of 1 and 18 years with GABHS-positive throat culture who presented to a pediatric emergency department and two outpatient pediatric clinics were included in the study. Mean age (± SD) was 6.9 (± 3.4) years. Fifty-nine percent were male. There was no significant difference in age or sex among children presenting during the two time periods. Children who presented to the emergency department or one of the clinics in <24 hours were significantly younger and were likely to have fever (temperature >38°C). There was no difference in the frequency of the 10 analyzed clinical features in patients presenting in the two time periods. Thus, duration of illness does not affect the frequency of the presenting signs and symptoms of GABHS pharyngitis in children.
Molecular Analysis of a Family With Congenital Adrenal Hyperplasia - Genotype/Phenotype Discrepancy

Molecular Analysis of a Family With Congenital Adrenal Hyperplasia - Genotype/Phenotype Discrepancy Congenital adrenal hyperplasia (CAH) is a common autosomal recessive disease with a variable clinical presentation caused by a spectrum of different mutations. A significant association of genotype with phenotype has been reported. The molecular analysis of a girl with a mild form of CAH presenting with precocious pubarche, confirmed that she was heterozygous for two mutations of the CYP21 gene (exon 1, codon 30/exon 8, codon 318). Her mother was homozygous for the codon 30 mutation and her father was homozygous for the codon 318 mutation. The only anomaly in the parents was a difficulty in conceiving. The molecular analysis of this family confirmed the variability of presentation in carriers of different mutations, which caused difficulties in decisions about the timing of therapy and in genetic counseling.
Heterogeneity and phenotypic plasticity of glial cells in the mammalian enteric nervous system

Enteric glial cells are vital for the autonomic control of gastrointestinal homeostasis by the enteric nervous system. Several different functions have been assigned to enteric glial cells but whether these are performed by specialized subtypes with a distinctive phenotype and function remains elusive. We used Mosaic Analysis with Double Markers and inducible lineage tracing to characterize the morphology and dynamic molecular marker expression of enteric GLIA in the myenteric plexus. Functional analysis in individually identified enteric glia was performed by Ca2+ imaging. Our experiments have identified four morphologically distinct subpopulations of enteric glia in the gastrointestinal tract of adult mice. Marker expression analysis showed that the majority of glia in the myenteric plexus co‐express glial fibrillary acidic protein (GFAP), S100β, and Sox10. However, a considerable fraction (up to 80%) of glia outside the myenteric ganglia, did not label for these markers. Lineage tracing experiments suggest that these alternative combinations of markers reflect dynamic gene regulation rather than lineage restrictions. At the functional level, the three myenteric glia subtypes can be distinguished by their differential response to adenosine triphosphate. Together, our studies reveal extensive heterogeneity and phenotypic plasticity of enteric glial cells and set a framework for further investigations aimed at deciphering their role in digestive function and disease. GLIA 2015;63:229–241
Astrocyte‐neuron crosstalk regulates the expression and subcellular localization of carbohydrate metabolism enzymes

Astrocytes releasing glucose‐ and/or glycogen‐derived lactate and glutamine play a crucial role in shaping neuronal function and plasticity. Little is known, however, how metabolic functions of astrocytes, e.g., their ability to degrade glucosyl units, are affected by the presence of neurons. To address this issue we carried out experiments which demonstrated that co‐culturing of rat hippocampal astrocytes with neurons significantly elevates the level of mRNA and protein for crucial enzymes of glycolysis (phosphofructokinase, aldolase, and pyruvate kinase), glycogen metabolism (glycogen synthase and glycogen phosphorylase), and glutamine synthetase in astrocytes. Simultaneously, the decrease of the capability of neurons to metabolize glucose and glutamine is observed. We provide evidence that neurons alter the expression of astrocytic enzymes by secretion of as yet unknown molecule(s) into the extracellular fluid. Moreover, our data demonstrate that almost all studied enzymes may localize in astrocytic nuclei and this localization is affected by the co‐culturing with neurons which also reduces proliferative activity of astrocytes. Our results provide the first experimental evidence that the astrocyte‐neuron crosstalk substantially affects the expression of basal metabolic enzymes in the both types of cells and influences their subcellular localization in astrocytes. GLIA 2015;63:328–340
ENDOCRINE VARIETIES OF “ANDROBLASTOMA” IN OVARY AND TESTIS

IN a recent issue of the Journal Shippel (1950) described “ an unusual ovarian tumour with patterns reminiscent of arrhenoblastoma, adrenal tumour and luteoma ” and discussed the probable histogenesis of the tumour group in the ovary and testis designated by me as androblastoma. In regard to the explanation of the feminizing properties of certain identical ovarian and testicular tumours, including Dougal’s case and several other cases in the ovary, and the absence of a virilizing effect in the pure tubular “ arrhenoblastoma ”, I may refer to my paper on “ Estrogen-producing Sertoli Cell Tumours (androblastoma tubularelipoides) of the Human Testis and Ovary (Teilum, 1949) (not quoted by Shippel) and to my chapter in Meigs and Sturgis’s Progress in Gynecology (1950). In my paper on “arrhenoblastomaandroblastoma ” (Teilum, 1946), it was demonstrated that an exact histogenetical classification of these neoplasms can only be based on purely morphological considerations and irrespective of the clinical manifestations. I identified the feminizing testicular tumour as a tumour showing partially the morphological features of a virilizing arrhenoblastoma, notwithstanding the fact that clinically it was not associated with masculinization but rather with very definite evidence of a feminization. However, transitions could be demonstrated from areas of a typical arrhenoblastoma pattern to parts similar to the oestrogenic ovarian neoplasms previously misinterpreted as varieties of granulosacell tumours under the terms “ folliculome lipidique ” (Leche, Varangot, Plate) or as ‘‘ granulosa-cell tumours of tubular or of adenomatous type ” (Dougal’s and other cases). Based on these findings I concluded that, like the androgenic arrhenoblastoma ovarii, all the said oestrogenic tumour types of the ovary represent varieties of the same histogenic tumour group, duplicated in the testis in all forms of differentiation, or-in other words-the “ arrhenoblastoma ” group in the ovary had to be extended to comprise certain oestrogen-producing types of ovarian neoplasms zs well. On this morphological and histogenetic basis it was possible to explain the apparently different hormonal effects of the androblastomas in either sex (feminizing in male and virilizing in females-cf. my 1949 paper, p. 317). The fact that neoplasms belonging to the same histogenetic entity could produce feminizing properties in men and masculinizing effects in women was found to depend on a demonstrable predominance, on the one hand of lipoidal oestrogen-producing Sertoli cells and, on the other, of lipoidal androgen-producing Leydig cells. As the lipoidal feminizing varieties of the group (Sertoli cell tumour) are without any histogenetic relation to granulosa cells I found the nomenclature