Miracle-dz/UniFAR-FTUs huggingface dataset:
The Constitutive Function of Native TRPC3 Channels Modulates Vascular Cell Adhesion Molecule-1 Expression in Coronary Endothelial Cells Through Nuclear Factor &kgr;B Signaling

Rationale: Upregulation of endothelial vascular cell adhesion molecule (VCAM)-1 and the subsequent increase in monocyte recruitment constitute critical events in atherogenesis. We have recently shown that in human coronary artery endothelial cells (HCAECs) regulated expression of VCAM-1 depends, to a significant extent, on expression and function of the Ca2+-permeable channel transient receptor potential canonical (TRPC)3, regardless of the ability of the stimulatory signal to induce regulated Ca2+ influx, leading to the hypothesis that TRPC3 constitutive, rather than regulated function, contributes to the underlying signaling mechanism. Objective: The present studies addressed this important question and gathered mechanistic insight on the signaling coupling constitutive TRPC3 function to VCAM-1 expression. Methods and Results: In HCAECs, maneuvers that prevent Ca2+ influx or knockdown of TRPC3 markedly reduced tumor necrosis factor (TNF)&agr;-induced VCAM-1 and monocyte adhesion. TNF&agr; also induced TRPC3 expression and TRPC3-mediated constitutive cation influx and currents. Stable (HEK293 cells) or transient (HCAECs) overexpression of TRPC3 enhanced TNF&agr;-induced VCAM-1 compared to wild-type cells. I&kgr;B&agr; phosphorylation/degradation was reduced by TRPC3 knockdown and increased by channel overexpression. Inhibition of calmodulin completely prevented nuclear factor &kgr;B activation, whereas blocking calmodulin-dependent kinases or NADPH oxidases rendered partial inhibition. Conclusions: Our findings indicate that in HCAECs expression of VCAM-1 and monocyte adhesion depend, to a significant extent, on TRPC3 constitutive function through a signaling mechanism that requires constitutive TRPC3-mediated Ca2+ influx for proper activation of nuclear factor &kgr;B, presumably through Ca2+-dependent activation of the calmodulin/calmodulin-dependent kinase axis.
Genetic diversity, population structure and sex‐biased dispersal in three co‐evolving species

Genetic diversity and spatial structure of populations are important for antagonistic coevolution. We investigated genetic variation and population structure of three closely related European ant species: the social parasite Harpagoxenus sublaevis and its two host species Leptothorax acervorum and Leptothorax muscorum. We sampled populations in 12 countries and analysed eight microsatellite loci and an mtDNA sequence. We found high levels of genetic variation in all three species, only slightly less variation in the host L. muscorum. Using a newly introduced measure of differentiation (Jost’s Dest), we detected strong population structuring in all species and less male‐biased dispersal than previously thought. We found no phylogeographic patterns that could give information on post‐glacial colonization routes – northern populations are as variable as more southern populations. We conclude that conditions for Thompson’s geographic mosaic of coevolution are ideal in this system: all three species show ample genetic variation and strong population structure.
[Studies on the chemical constituents of Securidaca inappendiculata].

AIM To investigate the chemical constituents of Securidaca inappendiculata. METHODS Compounds were isolated by silica gel column chromatography and Medium Pressure Liquid Chromatography, respectively. Structures of the compounds were elucidated by chemical evidence and spectral (UV, IR, MS, 1HNMR and 13CNMR) analysis. RESULTS Eight compounds (1-8) were isolated and identified. Seven of them (2-7) are known compounds: oleanolic acid, p-hydroxytruxinic acid, p-coumaric acid, ethyl p-methoxycinnamate, uridine, beta-sitosterol and daucosterol. One (1) is a new hemiterpenoic acid glycoside, named securiterpenoside. CONCLUSION A new hemiterpenoic acid glycoside, named securiterpenoside, was isolated from Securidaca inappendiculata Hassk. Seven known compounds were isolated from genus Securidaca for the first time.
Digital vasomotor conditioning and body heat regulation.

Human subjects were conditioned to a tone-shock sequence during heat or cold exposure and then given 10 trials of experimental extinction in the heat. In the heat, while exhibiting a general peripheral as well as a digital vasodilatation, vasoconstriction developed as a conditioned response; the response did not extinguish. In the cold, with general peripheral and digital vasoconstriction, vasodilatation developed as the conditioned response. Since the cold-conditioned Ss did not recover completely from their cold exposure during the following heat equilibritun period, the extinction data of this group could not be accepted. A comparison was also made of the differences in thermoregulation and in conditioned responses of preselected Ss varying in latency of cold-induced digital vasodilatation. Although these Ss did differ in their thermophysiological reactions, they did not differ in regard to the nature of the conditioned response developed.
Quantitative bone scintigraphy: A methodological evaluation in prostate cancer

Purpose: To evaluate a simple method for quantification of focal activity in bone scintigraphy (BS). Material and Methods: The gamma camera was calibrated using a phantom. Quantitative bone scintigraphy (QBS) was performed on 11 men recently diagnosed with prostate cancer (PCa), for whom routine BS showed involvement of the skeleton. Following endocrine therapy for 4 to 8 months, a second QBS was performed. Changes in QBS values were then compared to changes in serum levels of prostate-specific antigen (PSA). Results: PSA response indicating regression of PCa was accompanied by a decrease in the QBS value in 8 of the 11 patients. The overall mean error of the QBS values was 15%. Conclusion: QBS according to this method is a relatively simple procedure that might contribute to objective evaluation of therapeutic effects in skeletal metastases, although its validity must be tested in a larger clinical material.
GFAP Expression in Lumbar Spinal Cord of Naive and Neuropathic Rats Treated with MK-801

The objective of the present investigation was to determine if baseline glial fibrillary acidic protein (GFAP) expression and the increases in GFAP expression induced by chronic constriction of the sciatic nerve were modified by the specific N-methyl-D-aspartate (NMDA) receptor antagonist MK-801. Changes in immunohistochemical staining densities of GFAP within the L4 spinal cord were quantified and compared in three groups of animals: (1) nonneuropathic rats, (2) nondrug-treated neuropathic rats, and (3) neuropathic rats treated for 7 days with MK-801. The results indicate that baseline GFAP staining density in naive animals is dependent on NMDA receptor activity and that an ongoing NMDA-dependent signal is, at least in part, responsible for the increase in GFAP observed following peripheral nerve injury.
Prenatal diagnosis of fragile X syndrome and the risk of expansion of a premutation

The aim of the present study was to evaluate prospectively the dynamics of the FMR1 gene. The risk of full mutation among pregnant women and the carriers, and the risk of expansion of a premutation allele to a full mutation were estimated. We identified 89 pregnant women with an expanded FMR1 gene seeking prenatal diagnosis. Amniocentesis or chorion villus sampling (CVS) was offered and a DNA test of the FMR1 gene was carried out in such pregnancies. The overall risk of full mutation among women (N=21) with a repeat size between 60 and 80 was 4.8% (one fetus with mosaicism), and the risk of expansion of the premutation allele to a full mutation was 14% in those offspring to whom the premutation allele was transmitted. The risk of full mutation among the carriers (N=13) with a repeat size between 81 and 100 was 61.5% (8/13), and the risk of expansion of a premutation allele to a full mutation was 89%. Only one case fell into the category of 101–200 repeats, and expansion to a full mutation was recorded. Fetuses of full mutation mothers inherited the larger allele in 64% (14/22) of the cases. The range of 40–59 repeats was safe: there were no fetal full mutations. The risk of full mutation was also low among the subjects with a repeat size between 60 and 80, whereas the risk increased significantly after 80 repeats. Maternal premutation size was positively correlated with the risk of having a full mutation offspring.
The cutaneous B-cell lymphoma prognostic index: a novel prognostic index derived from a population-based registry.

PURPOSE Three classification and prognostic systems exist for primary cutaneous B-cell lymphoma (PCBCL). Whereas the WHO classification defines its categories based on histology, both the European Organisation for Research and Treatment of Cancer classification and the conventional staging system consider skin site. We sought to incorporate both histology and skin site into a single prognostic index designed to predict survival in patients with PCBCL. METHODS The associations between histology, skin site, and survival were determined using adjusted proportional hazards analysis conducted on 926 patients with PCBCL identified in the Surveillance, Epidemiology, and End Results data, spanning 1973 to 2001. RESULTS Four primary CBCL prognostic index (CBCL-PI) groups were identified. Group IA included indolent histologies involving any skin site. Group IB included diffuse large B-cell histology involving favorable skin sites (head/neck, arm). Group II included diffuse large B-cell histology involving unfavorable skin sites (trunk, legs, disseminated) or immunoblastic large B-cell histology involving favorable skin sites. Group III included immunoblastic large B-cell histology involving unfavorable skin sites. The adjusted mortality hazards ratios were 1.0, 1.3 (95% CI, 0.99 to 1.7), 2.1 (95% CI, 1.6 to 2.7), and 4.5 (95% CI, 2.8 to 7.2) for groups IA/B to III, respectively. The corresponding 5-year relative survivals were 94%, 86%, 60%, and 34%. CONCLUSION The CBCL-PI identifies adverse combinations of histology and skin site, helping to reconcile differences in current classification and prognostic systems for PCBCL.
Systematics and Leaf Architecture of the Gunneraceae

Cladistic and phenetic analyses of leaf and other morphological characters ofGunnera strongly support monophyly of the genus, with the Saxifragaceae s.str. as the closest sister group. This morphologically based phylogeny provides a more coherent understanding of the evolutionary history ofGunnera than do recent phylogenetic hypotheses based on genetic data sets with Myrothamnaceae as the sister group. Simple, crenate, palinactinodromously veined leaves lacking freely ending veinlets and tricolpate, tectate-perforate pollen with a reticulate exine indicate a shared ancestry. Within the genusGunnera all six traditionally recognized subgenera are monophyletic, as supported by leaf architectural apomorphies. The monotypic subgenusOstenigunnera is the sister group to the other five subgenera, which can be divided into two principal lineages. One lineage includes the subgeneraMilligania andMisandra, characterized by a prostate stoloniferous habit with small, low-rank leaves and exclusively unisexual flowers, whereas the other lineage includes the subgeneraPerpensum, Pseudo Gunnera, andPanke, all of which possess at least some hermaphroditic flowers and larger, high-rank leaves. When the phylogeny of the subgenera is considered in light of biogeography and the fossil record, a number of cladogenetic events can be explained by continental vicariance in the Late Cretaceous. The AfricanPerpensum became distinct from the other large-leafed lineage with the separation of the African continent ca. 90 Ma. The two small-leafed lineages, the subgeneraMilligania andMisandra, split with the separation of New Zealand from Western Gondwana, about 80 Ma.Pseudo-Gunnera became isolated fromPanke prior to this time, whenPanke fossils occur in North America.Gunnera probably arose out of an early herbaceous radiation of tricolpate eudicots having close affinity to the basal Saxifragaceae, espethe genusChrysosplenium.
A Reduced Role of V/Q Scintigraphy in the Diagnosis of Acute Pulmonary Embolism

Ventilation/perfusion (V/Q) lung scintigraphy, when used for the clinical determination of the presence or absence of pulmonary embolism, has been much studied by medical imagers. Inherent to a ‘‘cold-spot’’ scan targeting the normal pulmonary tissue, the deck has always been stacked against us and our specialty frequently maligned by the referring physicians as practicing ‘‘unclear’’ and not nuclear medicine. The nonspecificity and, at times reputed, nonsensitivity of the V/Q scan for embolism as imaging protocols evolved led to a probability scheme (1) of reporting positive or negative findings in shades of gray rather than as
A phase 2 study of bevacizumab with cisplatin plus intensity‐modulated radiation therapy for stage III/IVB head and neck squamous cell cancer

For patients with stage III through IVB head and neck squamous cell carcinoma (HNSCC), concurrent high‐dose cisplatin plus radiation therapy is a widely accepted standard of care. HNSCC tumors that express high levels of vascular endothelial growth factor have been associated with a worse prognosis, and bevacizumab may sensitize tumors to cisplatin and radiation.
An Analysis of Safety and Adverse Events Following Cochlear Implantation in Children Under 12 Months of Age.

OBJECTIVE To determine perioperative morbidity of children ≤12 months undergoing cochlear implantation (CI). STUDY DESIGN Retrospective analysis using the American College of Surgeons National Surgical Quality Improvement Program Pediatric Database (ACS-NSQIP-P). SETTING General acute care children's hospitals, children's hospitals within larger hospitals, specialty children's hospitals, and general acute care hospitals with a pediatric wing. PATIENTS Children who underwent CI were queried using the ACS-NSQIP-P from 2012 to 2015. INTERVENTION Cochlear implantation. MAIN OUTCOME MEASURES Risk factors analyzed include age, prematurity, and presence of congenital disorders. Outcomes analyzed include operative time, length of stay, general surgical complications, readmissions, and related reoperations. RESULTS Over the database accrual period, the percentage of children ≤12 months at the time of surgery increased from 2012 to 2015 (6.08-7.78%, p = 0.0752). Total operative time, length of stay (≥1 d), and readmissions for those ≤12 months were significantly greater compared with those >12 months at the time of surgery (p < 0.001, p = 0.0037, and p < 0.0001, respectively). There were no statistically significant differences in general surgical complications (i.e., superficial incisional surgical site infections, organ/space surgical site infections, and/or unplanned reoperations) in cases ≤12 months. Complications specific to CI such as facial nerve paralysis, cerebrospinal fluid leak, and mastoiditis were not recorded in the ACS-NSQIP-P. CONCLUSION Infants had no more general surgical complications in the immediate postoperative period compared with older children, although total operative time, length of stay, and readmissions were found to be significantly greater in frequency.
Frequency and Molecular Characteristics of Calreticulin Gene (CALR) Mutations in Patients with JAK2-Negative Myeloproliferative Neoplasms

In 2013, Nangalia et al. and Klampfl et al. found a recurrent and abundant mutation in the calreticulin gene (CALR), mutually exclusive with JAK2 and MPL alterations. At present, the data concerning the new mutation, i.e. its prevalence, allele burden and clinical significance, are scarce. We report the incidence and molecular characteristics of CALR mutations in a group of 184 Polish patients with myeloproliferative neoplasms (MPNs). Clinical data analysis revealed significant differences between JAK2 V617F-mutated and CALR-mutated groups. In essential thrombocythemia patients, hemoglobin levels and leukocyte counts were significantly higher in JAK2-positive than in CALR-positive patients (p = 0.023 and p = 0.017, respectively), but the CALR-positive patients had significantly higher platelet counts (p = 0.022). Patients harboring CALR mutations were also younger at the time of diagnosis (p = 0.039). In primary myelofibrosis patients, the degree of anemia was less severe in those who were CALR exon 9 mutation-positive than in those who were JAK2 V617F-positive (p = 0.048). © 2014 S. Karger AG, Basel
Bright light treatment for high‐anxious young adults: a randomized controlled pilot study

Background: Available treatments for anxiety have limitations and/or side effects. The aim of this study was to examine the influence of bright light exposure as a treatment in high‐anxious young adults. Methods: In an acute exposure study, participants (n = 33) were randomly assigned to 45 min of (1) bright light or (2) placebo. Participants then performed a 5‐week study (n = 29). Following a 1‐week baseline, participants were randomly assigned to 4 weeks of daily exposure to either (1) bright light (45 min/day) or (2) placebo treatment, initiated ≤1 hr after awakening. Before and after the experiment, clinical ratings were conducted with the Hamilton Anxiety Scale (HAM‐A), Hamilton Depression Scale, and Clinical Global Impressions scale. Following each week, blood pressure, anxiety (Spielberger State–Trait Anxiety Inventory Y1), depression, mood, sleep, and side effects were assessed. Results: No significant treatment effect was found in the acute exposure study. Likewise, in the 5‐week study, no significant treatment effect was found. However, bright light elicited marginally greater reductions in psychic symptoms of the HAM‐A (P = .06) and other measures. Conclusions: This pilot study provides little compelling evidence for an anxiolytic effect of bright light in high‐anxious young adults. Depression and Anxiety, 2011. © 2011 Wiley‐Liss, Inc.
Microsatellite instability and epigenetic inactivation of MLH1 and outcome of patients with endometrial carcinomas of the endometrioid type.

PURPOSE Most studies of microsatellite instability (MSI) and outcomes in endometrial cancer patients have included varied histologic subtypes. Nonetheless, MSI occurs almost exclusively in endometrioid tumors. The impact of MSI on outcomes in patients with endometrial cancer is controversial. We sought to determine whether MSI and MLH1 methylation are associated with clinicopathologic variables and survival outcomes in a large series of patients with endometrial carcinomas of the endometrioid type. PATIENTS AND METHODS Tumor samples, blood, and clinicopathologic data were prospectively collected and analyzed for 446 patients with endometrioid carcinomas. MSI was determined using five National Cancer Institute (NCI) consensus panel markers, and the methylation status of the MLH1 promoter was determined by combined bisulfite restriction analysis (COBRA). Associations with clinicopathologic variables and survival outcomes were evaluated. RESULTS MSI was identified in 147 cases (33%). MSI was associated with higher International Federation of Gynecology and Obstetrics (FIGO) grade (P < .0001). MSI+ tumors without MLH1 methylation were associated with younger age (P < .001). MSI was not associated with overall survival (OS; hazard ratio [HR], 1.011; 95% CI, 0.688 to 1.484; P = .96) or disease-free survival (DFS; HR 0.951; 95% CI, 0.554 to 1.635; P = .86). The combined MSI/MLH1 methylation status (treating MSI- as the reference) did not predict OS (MSI+/MLH1-U: HR, 0.62; 95% CI, 0.27 to 1.44; P = .26; MSI+/MLH1-M: HR, 0.95; 95% CI, 0.62 to 1.46; P = .82) or DFS (MSI+/MLH1-U: HR, 0.51; 95% CI, 0.22 to 1.19; P = .12; MSI+/MLH1-M: HR, 0.93; 95% CI, 0.62 to 1.40; P = .72). CONCLUSION MSI is not associated with survival in patients with endometrioid endometrial cancer.
The Addition of Morphine Prolongs Fentanyl-Bupivacaine Spinal Analgesia for the Relief of Labor Pain

The combination intrathecal fentanyl (25 &mgr;g) and bupivacaine (2.5 mg) provides effective labor analgesia for approximately 90 minutes. The purpose of this prospective, randomized, double-blinded investigation was to determine if the addition of morphine (150 &mgr;g) to the intrathecal combination of fentanyl (25 &mgr;g) and bupivacaine (2.5 mg) would prolong labor analgesia. By using the combined spinal epidural technique, 95 healthy primiparous laboring women in early labor received 2 mL of one of the two intrathecal study solutions, either FB (n = 48): fentanyl (25 &mgr;g) and bupivacaine (2.5 mg); or FBM (n = 47): fentanyl (25 &mgr;g) and bupivacaine (2.5 mg) plus morphine (150 &mgr;g). The mean duration of labor analgesia was significantly longer in the FBM group than in the FB group (252 ± 63 min vs 148 ± 44 min, P < 0.01). There were no significant differences between the two groups regarding the sensory levels, the incidence of nausea, vomiting, pruritus, hypotension, or operative delivery. In conclusion, the addition of 150 &mgr;g of morphine to the intrathecal combination of fentanyl plus bupivacaine prolonged the duration of labor analgesia duration without increasing adverse effects.
Cutaneous lymphoid hyperplasia presenting as a solitary facial nodule: clinical, histopathological, immunophenotypical, and molecular studies.

OBJECTIVE To elucidate the clinicopathological, immunophenotypical, and molecular characteristics of cutaneous lymphoid hyperplasia presenting as a solitary facial nodule. DESIGN Retrospective study. SETTING University dermatology department. PATIENTS Three patients with a solitary facial nodule were studied clinically, histologically, immunophenotypically, and molecularly for T-cell receptor and immunoglobulin heavy chain gene rearrangements. MAIN OUTCOME MEASURES Histological, immunophenotypical, and molecular characteristics in relation to the clinical outcome. RESULTS Histologically, dense diffuse lymphocytic infiltrates were present throughout the dermis, occasionally extending into the subcutaneous fat and the epidermis and hair follicles. Small lymphocytes predominated, but in 2 cases there were also medium to large atypical lymphocytes, with some blastlike lymphocytes. The lymphocytic population was mixed with more CD3(+) T cells than CD20(+) B cells, without germinal centers. There were more CD4(+) than CD8(+) cells, and some of the T cells stained for the memory T-cell marker CD45RO. Numerous CD68(+) histiocytes were scattered or formed small aggregates, and in 1 case small granulomas and many scattered S100 protein-positive and CD1a(+)dendritic cells were present. In addition, several polytypic plasma cells, eosinophils, and extravasated erythrocytes were found. Immunostaining for CD10, CD21, CD30, CD56, and BCL6 was negative. The Ki-67 proliferation index was relatively low (5%-10%). Results of the T-cell receptor gene rearrangement studies were positive in 2 cases, 1 of which also harbored clonal B cells. Serologic test results for Borrelia burgdorferi, Borrelia afzelii, and Borrelia garinii were negative in all 3 cases. Two lesions regressed spontaneously after an incisional biopsy, and none of the cases showed recurrence or extracutaneous spread during a follow-up period of 5.0 to 5.5 years. CONCLUSIONS Cutaneous lymphoid hyperplasia that presents as a solitary facial nodule may share clinical, cytological, immunophenotypical, and molecular features with both benign reactive lymphocytic infiltrates and cutaneous lymphomas, and therefore a careful clinical and therapeutic approach is warranted.