Miracle-dz/UniFAR-FTUs huggingface dataset:
The Role of the Ets2 Transcription Factor in the Proliferation, Maturation, and Survival of Mouse Thymocytes1

In this study, we investigated the effects of Ets2 expression on the proliferation, maturation, and survival of thymocytes by establishing transgenic mice that specifically express Ets2 or a dominant negative form of Ets2, Δets2, in the thymus. We show that, in young animals, there are fewer T cells in Δets2 transgenic thymi and that the maturation of these T cells is affected at the CD4−CD8− double-negative to CD4+CD8+ double-positive transition compared with wild-type littermate mice. Partial recovery in the number of thymocytes and full T cell maturation are restored with increasing age of Δets2 transgenic animals. However, thymocytes from adult Δets2 transgenic mice cultured ex vivo are more sensitive to cell death and to glucocorticoid-induced apoptosis than are T cells from control littermate mice. We also show that T cells from adult ets2 transgenic mice proliferate faster than their wild-type littermates. The proliferation and survival of these T cells are clearly affected upon apoptotic signals: glucocorticoid-induced apoptosis induces T cells from ets2 transgenic mice to continue to proliferate in vivo and to survive better ex vivo than T cells from control littermates. It has been shown that c-Myc expression is required for thymic proliferation and improves thymocyte survival of dexamethasone-treated animals. We show that the expression of c-Myc, an Ets2 target, is elevated in T cells freshly isolated from thymi of ets2 transgenic mice pretreated with dexamethasone. Together, these results show that Ets2 plays a role in the proliferation and survival of thymocytes, implicating a Myc-dependent pathway.
Multiple A waves in Guillain–Barré syndrome

In 13 of 14 patients with Guillain–Barré syndrome (GBS), we observed multiple A waves in at least one limb nerve on routine electroneurographic studies within 7 days after onset of symptoms. The patient without A waves had a severe axonal type of GBS with tetraplegia and almost complete loss of M responses following electrical stimulation of limb nerves. In the remaining 13 patients, on average 8 ± 2 (mean ± SD) A waves were present in each tibial nerve (n = 24) and 4 ± 1 A waves in each peroneal nerve (n = 26). About half of the A waves were below 50 μV in amplitude, whereas amplitudes were higher than 120 μV in only 22 of 299 A waves. Of these A waves, 68 were not constantly elicitable. There was a significant correlation between the number of A waves up to 50 ms poststimulus and the reduction in amplitude of the compound muscle action potential when elicited with proximal compared to distal stimulation in the peroneal (n = 26, P < 0.0005; Kendall's τ) and tibial nerves (n = 24, P < 0.002). Therefore, in GBS both conduction block and A waves are presumably signs of inflammatory nerve lesions. The existence of multiple A waves soon after onset of symptoms seems to be a sensitive sign of GBS. © 1999 John Wiley & Sons, Inc. Muscle Nerve 22: 394–399, 1999
A New Stereo Pair Disparity Index (SPDI) for Detecting Built-Up Areas from High-Resolution Stereo Imagery

Within-class spectral variation and between-class spectral confusion in remotely sensed imagery degrades the performance of built-up area detection when using planar texture, shape, and spectral features. Terrain slopes and building heights extracted from auxiliary data, such as Digital Surface Models (DSMs) however, can improve the results. Stereo imagery incorporates height information unlike single remotely sensed images. In this study, a new Stereo Pair Disparity Index (SPDI) for indicating built-up areas is calculated from stereo-extracted disparity information. Further, a new method of detecting built-up areas from stereo pairs is proposed based on the SPDI, using disparity information to establish the relationship between two images of a stereo pair. As shown in the experimental results for two stereo pairs covering different scenes with diverse urban settings, the SPDI effectively differentiates between built-up and non-built-up areas. Our proposed method achieves higher accuracy built-up area results from stereo images than the traditional method for single images, and two other widely-applied DSM-based methods for stereo images. Our approach is suitable for spaceborne and airborne stereo pairs and triplets. Our research introduces a new effective height feature (SPDI) for detecting built-up areas from stereo imagery with no need for DSMs.
Tricyclic Antidepressant Amitriptyline-induced Glial Cell Line-derived Neurotrophic Factor Production Involves Pertussis Toxin-sensitive Gαi/o Activation in Astroglial Cells*

Background: A significant non-neural, monoamine-independent mechanism underlies the antidepressant effect of amitriptyline. Results: Amitriptyline-evoked GDNF production is mediated by pertussis toxin (PTX)-sensitive Gαi/o. Conclusion: PTX-sensitive Gαi/o activation is critical for the cascade that underpins the biological effect of amitriptyline. Significance: Further elaboration of the intracellular mechanism of amitriptyline could lead to greater understanding of depression and novel antidepressant treatments. Further elaborating the mechanism of antidepressants, beyond modulation of monoaminergic neurotransmission, this study sought to elucidate the mechanism of amitriptyline-induced production of glial cell line-derived neurotrophic factor (GDNF) in astroglial cells. Previous studies demonstrated that an amitriptyline-evoked matrix metalloproteinase (MMP)/FGF receptor (FGFR)/FGFR substrate 2α (FRS2α)/ERK cascade is crucial for GDNF production, but how amitriptyline triggers this cascade remains unknown. MMP is activated by intracellular mediators such as G proteins, and this study sought to clarify the involvement of G protein signaling in amitriptyline-evoked GDNF production in rat C6 astroglial cells (C6 cells), primary cultured rat astrocytes, and normal human astrocytes. Amitriptyline-evoked GDNF mRNA expression and release were inhibited by pertussis toxin (PTX), a Gαi/o inhibitor, but not by NF449, a Gαs inhibitor, or YM-254890, a Gαq inhibitor. The activation of the GDNF production cascade (FGFR/FRS2α/ERK) was also inhibited by PTX. Deletion of Gαο1 and Gαi3 by RNAi demonstrated that these G proteins play important roles in amitriptyline signaling. G protein activation was directly analyzed by electrical impedance-based biosensors (CellKeyTM assay), using a label-free (without use of fluorescent proteins/probes or radioisotopes) and real time approach. Amitriptyline increased impedance, indicating Gαi/o activation that was suppressed by PTX treatment. The impedance evoked by amitriptyline was not affected by inhibitors of the GDNF production cascade. Furthermore, FGF2 treatment did not elicit any effect on impedance, indicating that amitriptyline targets PTX-sensitive Gαi/o upstream of the MMP/FGFR/FRS2α/ERK cascade. These results suggest novel targeting for the development of antidepressants.
Angioendotheliomatosis associated with Castleman's lymphoma and POEMS syndrome

Castleman's lymphoma, a benign localized lymphoid hyperplasia, has been reported in association with POEMS syndrome, a multisystem reactive disorder that includes several skin manifestations. Benign reactive angioendotheliomatosis is a rare skin disorder that is associated with various systemic disorders. A patient with long‐standing Castleman's lymphoma and POEMS syndrome also developed benign reactive angioendotheliomatosis.
Comparative structural and functional characterization of putative protein effectors belonging to the PcF toxin family from Phytophthora spp

The PcF Toxin Family (Pfam 09461) includes the characterized phytotoxic protein PcF from Phytophthora cactorum, as well as several predicted protein effectors from other Phytophthora species recently identified by comparative genomics. Here we provide first evidence that such ‘putatives’, recombinantly expressed in bacteria and purified to homogeneity, similarly to PcF, can trigger defense‐related responses on tomato, that is leaf withering and phenylalanine ammonia lyase induction, although with various degrees of effectiveness. In addition, structural prediction by computer‐aided homology modeling and subsequent structural/functional comparison after rational engineering of the disulfide‐structured protein fold by site‐directed mutagenesis, highlighted the surface‐exposed conserved amino acid stretch SK(E/C)C as a possible structural determinant responsible for the differential phytotoxicity within this family of cognate protein effectors.
Cortical Lewy body disease

Cortical Lewy body disease reflects the presence of cortical Lewy bodies but without a clear clinical correlation Cortical Lewy body disease is a pathological observation rather than a distinct clinicopathological entity. Cortical Lewy bodies (CLB) are typically found in Parkinson’s disease and dementia with Lewy bodies (DLB), although they may also occur in other neurological disorders. Unlike their brain stem counterparts, CLB are less distinctive and are poorly visualised using conventional histochemical methods. The protein α-synuclein is the main component of Lewy bodies and the related dystrophic Lewy neurites1; immunohistochemistry using antibodies raised against this protein has greater sensitivity in demonstrating Lewy pathology within the cerebral cortex than histochemical methods and anti-ubiquitin immunohistochemistry. Dementia is a common occurrence in Parkinson’s disease, with a prevalence of 20–40% in cross sectional studies,2,3 but a cumulative incidence approaching 80%. 4 The clinical phenotype of this dementia shares many features with DLB. In neither condition, however, has the relation between the presence of CLB and the dementing process been clearly defined. The situation is complex in that there are several possible pathophysiological mechanisms that may underpin cognitive impairment in both Parkinson’s disease and DLB (table 1). View this table: Table 1 Possible pathophysiological mechanisms for dementia in Parkinson’s disease and dementia with Lewy bodies This therefore leads to various fundamental questions regarding the role of the CLB and the contribution of this inclusion to dementia in DLB and Parkinson’s disease. Given the heterogeneous processes involved, the degree of interaction or synergism occurring between α-synuclein pathology and, for example, Alzheimer-type pathology that results in dementia also needs to be established. Clinically, Parkinson’s disease with dementia (PDD) and DLB share many phenotypic similarities. Familial forms of Parkinson’s disease and DLB have been described.5,6 Cognitive impairment in both conditions has significant dysexecutive and visuospatial-visuoconstructional components, often …
Effect of folic acid supplements on homocysteine concentration in plasma of gestating sows

An experiment comprising 19 German Landrace sows was established to evaluate the effect of folic acid supplements (10 mg/kg concentrate) on homocysteine and folic acid concentration in plasma and serum, respectively, of highly pregnant sows as compared to an unsupplemented control (basal diet contained 0.62 mg folic acid/kg concentrate). Blood samples were taken between day 75 and 110 of gestation for homocysteine analysis and on day 100 of gestation for folic acid determination. Due to the folic acid supplements serum folic acid concentration increased significantly (104 nmol/1 in controls and 140 nmol/1 in supplemented sows). In contrast, homocysteine concentration in the plasma was not significantly influenced by folic acid supplements (16.6 μmol/1 in controls and 15.2 μmol/1 in supplemented sows). Further investigations seem to be necessary to clarify the physiology of homocysteine metabolism in swine.
Utilization of Human Cadaveric Acellular Dermis for Abdominal Hernia Reconstruction

Background:Incisional hernias with history of recurrence or infection remain a challenge, with high postoperative morbidity and recurrence rates. The purpose of this study is to evaluate outcomes of patients treated with human cadaveric acellular dermis as an adjunct to abdominal wall reconstruction. Methods:We retrospectively reviewed 39 abdominal wall reconstructions with human cadaveric acellular dermis performed in 37 patients and compared them with 39 randomly selected cases. Results:There is a significant decrease in recurrence rates when human cadaveric acellular dermis is added as an overlay to primary closure plus rectus muscle advancement and imbrication in patients with medium-sized hernias. No differences were observed when adding human cadaveric acellular dermis as an overlay to patients with large-size hernias treated with underlay mesh. The use of human cadaveric acellular dermis did not increase postoperative morbidity rates. Conclusions:Improved results with human cadaveric acellular dermis are obtained by achieving tension-free repairs.
Statistical Methods for Cost-Effectiveness Analyses That Use Data from Cluster Randomized Trials

Introduction. The best data for cost-effectiveness analyses (CEAs) of group-level interventions often come from cluster randomized trials (CRTs), where randomization is by cluster (e.g., the hospital attended), not by individual. Methods for these CEAs need to recognize both the correlation between costs and outcomes and that these data may be dependent on the cluster. General checklists and methodological guidance for critically appraising CEA ignore these issues. This article develops a new checklist and applies it in a systematic review of CEAs that use CRTs. Methods. The authors developed a checklist for CEAs that use CRTs, informed by a conceptual review of statistical methods. This checklist included criteria such as whether the analysis allowed for both clustering and the correlation between individuals’ costs and outcomes. The authors undertook a systematic literature review of full economic evaluations that used CRTs. The quality of studies was assessed with the new checklist and by the “Drummond checklist. ” Results. The authors identified 62 papers that met the inclusion criteria. On average, studies satisfied 9 of the 10 criteria for the checklist but only 20% of criteria for the new checklist. More than 40% of studies adopted statistical methods that completely ignored clustering, and 75% disregarded any correlation between costs and outcomes. Only 4 studies employed appropriate statistical methods that allowed for both clustering and correlation. Conclusions. Most economic evaluations that use data from CRTs ignored clustering or correlation. Statistical methods that address these issues are available, and their use should be encouraged. The new checklist can supplement generic CEA guidelines and highlight where research practice can be improved.
Treatment of Attention Deficit Hyperactivity Disorder with Neurotherapy

Significant public health concerns exist regarding our current level of success in treating ADHD. Medication management is very helpful in 60-70% of patients. Side effects, lack of compliance and the fact that stimulant medications cannot be given late in the day limit the benefits largely to school hours. While stimulants improve behavior and attention, less of an effect has been noted on academic and social performance. Continuing concerns exist about long-term safety, and studies on long-term cardiovascular and neurophysiological effects have not been carried out. Neurotherapy for ADHD offers an effective alternate for patients whose treatment is limited by side effects, poor medication response and in cases in which the patients and/or their parents refuse to consider medications. Studies indicate clinical improvement is largely related to measurable improvements in the EEG signature, evidenced by declining theta/beta ratios over frontal/central cortex and/or reduced theta/alpha band amplitudes.
Invasive Left Ventricular Energetics During Enhanced External Counterpulsation

Enhanced external counterpulsation (EECP) is a noninvasive technique that provides beneficial effects for patients with chronic, symptomatic angina pectoris. However, the direct left ventricular effects of EECP have not been studied invasively. We examined invasive right atrial pressure and left ventricular hemodynamics during EECP. Ten patients referred for diagnostic evaluation underwent left heart catheterization from the radial artery. At baseline and during EECP, left ventricular pressure and volume were measured using a micromanometer pressure-conductance catheter, along with recording of right atrial and central aortic pressures. Hemodynamics were recorded at different lower extremity cuff configuration and cuff inflation pressures. As cuff inflation pressure increased, EECP resulted in a dose-dependent increase in right atrial and aortic diastolic pressure (P < 0.0001). The increase in ventricular preload resulted in increased left ventricular volume. Maximum positive (P = 0.0003) and negative left ventricular dP/dt (P < 0.0001) increased. Left ventricular diastolic pressure decreased. There was a neutral effect on myocardial mechanical efficiency. In conclusion, EECP acutely increased right atrial and central aortic diastolic pressure. The increase in preload attenuated the reduction in left ventricular diastolic pressure resulting from systolic unloading. The increased preload counterbalanced the afterload reduction, resulting in a neutral effect on myocardial efficiency.
[Effects of phytoestrogen alpha-zearalanol on normal human breast].

OBJECTIVE To study the effects of phytoestrogen alpha-zearalanol (alpha-ZAL) on normal human breast. METHODS Ten specimens of normal human breast tissues were subcutaneously implanted into 30 athymic nude mice aged 9-10 weeks, one for 3 mice. These mice were then randomly divided into three groups: control group (without hormone treatment, n = 10), 1 mg/kg alpha-ZAL group (n = 10), and 5 mg/kg alpha-ZAL group (n = 10). All breast tissues were taken out 6 weeks later. Immunohistochemistry was used to determine the protein expressions of proliferating cell nuclear antigen (PCNA), inhibiting apoptosis gene Bcl-2, estrogen receptor (ER), and progesterone receptor (PR). Reverse transcription polymerase chain reaction (RT-PCR) was used to measure the expression levels of estrogen sulfotransferase (EST) mRNA and bridging integrator protein-1 (BIN1) mRNA. Morphological features of grafts before and after treatment were also observed. RESULTS Alpha-ZAL had no significant effects on Bcl-2, PCNA, ER, and PR expression of mammary epithelial cells in graft specimens. Alpha-ZAL upregulated BIN1 mRNA expression in grafts, but had no significant effect on ESTmRNA expression. CONCLUSIONS Alpha-ZAL does not affect the morphology, proliferating, and apoptosis of epithelial cells in normal human breast tissues implanted into nude mice, but it may increase the gene expression of tumor-inhibiting BIN1, suggesting that alpha-ZAL may have potential proteotive effect on normal human breast.
Indication and survival bias: Threats to resuscitative endovascular balloon occlusion of the aorta outcomes research.

To the Editor: W e read with interest the study by Aso et al. Their objective was to compare earlymortality between resuscitative endovascular balloon occlusion of the aorta (REBOA) and resuscitative thoracotomy (RT) in trauma patients with hemorrhagic shock. They found that although lower in REBOA-treated patients,mortality did not significantly differ between compared groups. However, this results could be flawed by the presence of indication and survival bias, a fact that is consistent in comparative effectiveness REBOA published literature. REBOA is thought to emulate resuscitative thoracotomy with the advantage of being a less invasive procedure, and thus it has been advocated to improve survival among noncompressible torso hemorrhage (NCTH) patients. To date, two studies have reported the effect of REBOA on mortality, compared it with RT. These studies showed that REBOA is a safe and effective option to be used in NCTH patients. However, similar to the study by Aso et al, results from these studies could be comprised by the presence of indication and survival bias. Indication bias occurs in observational studies of interventions when patients are classified by the nonrandomized intervention they received during their medical treatment ignoring the factors that influenced the need for intervention. Survival bias arises when comparing patient groups in which patients may die before treatment is initiated. Both are selection biases that, if present, can comprise validity of results. In the reports by Aso et al, DuBose et al., and Abe et al, patients in the RT group were more like to present with significantly lower values of blood pressure. Furthermore, a significantly higher proportion of RT patients arrived in cardiac arrests or required closed cardiopulmonary resuscitation. Moreover, in the study by Abe et al., REBOAtreated patients presented to the emergency department with a significantly higher probability of survival, compared with those patients that underwent RT. The fact that across studies, RT patients were more likely to present with worse levels of hemodynamic instability and lower probability of survival indicates a consistent and systematic risk of indication
Expression of tumor-specific transplantation antigen in cell lines transformed by wild-type of tsA mutant simian virus 40

The simian virus 40-induced tumor-specific surface antigen(s) (TSSA) and tumor-specific transplantation antigen(s) (TSTA)were detected in cells transformed by wild-type or temperature-sensitive mutant simian virus 40 by an antibody-mediated cytolytic assay for TSSA and an immunization test for TSTA. Cells transformed by tsA mutants, which lose their transformed phenotype when grown at nonpermissive temperatures, nonetheless do express TSSA and TSTA as well as T-antigen at both temperatures.
Insulin resistance and hyperinsulinemia in homozygous beta-thalassemia.

Insulin resistance and hyperinsulinemia have been reported in homozygous beta-thalassemia before the development of diabetes. However, insulin sensitivity (SI) has never been studied in normoinsulinemic patients. Furthermore, whether hyperinsulinemia is due to increased beta-cell secretion or to decreased hepatic insulin extraction is poorly understood. We estimated SI, beta-cell secretion, and hepatic insulin extraction using the minimal model analysis of a frequently sampled intravenous glucose tolerance test (2.8 g/m2) in two groups of nondiabetic pubertal patients with homozygous beta-thalassemia (seven hyperinsulinemic and seven normoinsulinemic patients) and seven control subjects matched for age, body mass index, and pubertal stage. In both thalassemic groups, SI was reduced by approximately 40% (3.52 +/- 0.57 and 3.74 +/- 0.66 v 6.89 +/- 1.02 10(-4). min-1 [microU/mL], P = . 011) and was inversely correlated with iron overload (r = -.707, P = .006). All parameters of beta-cell secretion were not significantly different in patients and controls. On the other hand, basal posthepatic insulin delivery (BDR) was more than doubled in hyperinsulinemic patients with respect to normoinsulinemic patients or controls (15.1 +/- 2.4 v 6.1 +/- 1.1 and 7.5 +/- 2.3 pmol/L.min-1, P = .012), and the same was true for total posthepatic insulin delivery ([TID] 6.3 +/- 1.0 v 2.9 +/- 0.5 and 2.9 +/- 0.7 pmol/L.240 min-1, P = .015). Hepatic insulin extraction was significantly lower in hyperinsulinemic patients than in normoinsulinemic patients or controls (49.3% +/- 9.4% v 73.0% +/- 3.7% and 77.4% +/- 3.9%, P = .011), and in patients it was inversely correlated with iron overload (r = -.829, P = .0001). In conclusion, insulin resistance is present even in normoinsulinemic patients, beta-cell responsiveness to glucose is normal, and hyperinsulinemia is mainly due to decreased hepatic insulin extraction. In nondiabetic thalassemic patients, these defects are possibly related to iron overload.