Miracle-dz/UniFAR-FTUs huggingface dataset:
Chronic Immune Therapy Induces a Progressive Increase in Intratumoral T Suppressor Activity and a Concurrent Loss of Tumor-Specific CD8+ T Effectors in her-2/neu Transgenic Mice Bearing Advanced Spontaneous Tumors1

A single intratumoral injection of IL-12 and GM-CSF-encapsulated microspheres induces the complete regression of advanced spontaneous tumors in her-2/neu transgenic mice. However, tumor regression in this model is transient and long-term cure is not achieved due to recurrence. Posttherapy molecular analysis of immune activation/suppression markers within the tumor microenvironment demonstrated a dramatic up-regulation of IFN-γ and a concomitant down-regulation of Forkhead/winged-helix protein 3 (Foxp3), TGFβ, and IL-10 expression. Therapy-induced reversion of immune suppression was transient since all three markers of suppression recovered rapidly and surpassed pretherapy levels by day 7 after treatment, resulting in tumor resurgence. Repeated treatment enhanced short-term tumor regression, but did not augment long-term survival. Serial long-term analysis demonstrated that although chronic stimulation enhanced the IFN-γ response, this was countered by a parallel increase in Foxp3, TGFβ, and IL-10 expression. Analysis of tumor-infiltrating T lymphocyte populations showed that the expression of Foxp3 and IL-10 was associated with CD4+CD25+ T cells. Repeated treatment resulted in a progressive increase in tumor-infiltrating CD4+CD25+Foxp3+ T suppressor cells establishing their role in long-term neutralization of antitumor activity. Analysis of tumor-infiltrating CD8+ T cells demonstrated that although treatment enhanced IFN-γ production, antitumor cytotoxicity was diminished. Monitoring of CD8+ T cells that specifically recognized a dominant MHC class I her-2/neu peptide showed a dramatic increase in tetramer-specific CD8+ T cells after the first treatment; however, continuous therapy resulted in the loss of this population. These results demonstrate that both enhanced suppressor activity and deletion of tumor-specific T cells are responsible for the progressive loss of efficacy that is associated with chronic immune therapy.
Reverse shoulder arthroplasty for type 1 sequelae of a fracture of the proximal humerus

Aims The aim of this study was to analyze the results of reverse shoulder arthroplasty (RSA) in patients with type 1 sequelae of a fracture of the proximal humerus in association with rotator cuff deficiency or severe stiffness of the shoulder. Patients and Methods A total of 38 patients were included: 28 women and ten men. Their mean age at the time of arthroplasty was 73 years (54 to 91). Before the RSA, 18 patients had been treated with open reduction and internal fixation following a fracture. A total of 22 patients had a rotator cuff tear and 11 had severe stiffness of the shoulder with < 0° of external rotation. The mean follow‐up was 4.3 years (1.5 to 10). The Constant score and the range of movement of the shoulder were recorded preoperatively and at final follow‐up. Preoperatively, radiographs in two planes were performed, as well as CT or arthro‐CT scans; radiographs were also performed at final follow‐up. Results The mean Constant score improved from 25 points (5 to 47) preoperatively to 57 points (15 to 81) postoperatively. The mean forward elevation of the shoulder increased from 73° (10° to 130°) preoperatively to 117° (15° to 170°) postoperatively. Previous surgery did not influence the outcome. Patients with rotator cuff tears had lower Constant scores than patients without (p = 0.037). Those with preoperative stiffness of the shoulder had lower postoperative external rotation compared with patients without stiffness (p = 0.046). There was no radiographic evidence of loosening. Three complications occurred, leading to revision surgery in two patients. In all, 17 patients rated their result as very good (45%), another 17 as good (45%), two as satisfactory (5%), and two as unsatisfactory (5%). Discussion RSA is an effective form of treatment for patients with type 1 sequelae of a fracture of the proximal humerus associated with rotator cuff deficiency or stiffness of the shoulder, with high rates of satisfaction. Rotator cuff tears and stiffness of the shoulder had an adverse effect on the clinical outcome.
Functional redundancy of R7 RGS proteins in ON-bipolar cell dendrites.

PURPOSE In the Gbeta5(-/-) mouse, the electroretinogram (ERG) b-wave is absent, and the R7 subfamily of regulators of G protein signaling (RGS), which includes RGS6, -7, -9, and -11, is downregulated. Mutant mouse strains deficient in RGS7 or -11 were characterized, and the SG711 strain which is deficient in both proteins was examined, to learn whether the loss of some of these RGS proteins causes the absence of the ERG b-wave. METHODS Antibodies to RGS7 and -11 were generated to determine their expression levels and localizations in retinas with various genetic backgrounds by Western blot analysis and immunohistochemistry, respectively. The implicit times and amplitudes of ERG a- and b-waves were analyzed to examine photoreceptor and bipolar cell functions. RESULTS RGS7 and -11 co-localized to the dendritic tips of the ON-bipolar cells. In the RGS11(-/-) mouse, the level of RGS7 protein increased. However, the level of RGS11 protein remained unchanged in the RGS7 mutant mouse, where a truncated RGS7 protein was expressed due to the deletion of exon 10. In the SG711 mouse retina, the Gbeta5-S protein level was reduced. The ERG b-wave of SG711 mice was markedly delayed. In contrast, RGS11(-/-) mice showed a moderately delayed b-wave, whereas the RGS7 mutant mice showed normal ERG responses. CONCLUSIONS The data demonstrate the presence of a delayed ERG b-wave in SG711 mice and a functionally redundant role for RGS11 and -7 at the tips of ON-bipolar cell dendrites. These results suggest that RGS11 or -7 works as the major physiological GAP (GTPase acceleration protein) for Galphao1 in ON-bipolar cells.
Engineering biomaterials to integrate and heal: The biocompatibility paradigm shifts

This article focuses on one of the major failure routes of implanted medical devices, the foreign body reaction (FBR)—that is, the phagocytic attack and encapsulation by the body of the so‐called “biocompatible” biomaterials comprising the devices. We then review strategies currently under development that might lead to biomaterial constructs that will harmoniously heal and integrate into the body. We discuss in detail emerging strategies to inhibit the FBR by engineering biomaterials that elicit more biologically pertinent responses. Biotechnol. Bioeng. 2012; 109:1898–1911. © 2012 Wiley Periodicals, Inc.
Computed tomography of the upper cheek teeth in horses with infundibular changes and apical infection.

REASONS FOR PERFORMING STUDY Infundibular changes are frequently encountered computed tomographic studies of the equine maxillary cheek teeth but the possible importance of this finding is not known. Infundibular caries is a possible cause for pulpitis and apical infection in some horses. OBJECTIVES To study the relationship between the 2 pathologies and the frequency of changes. METHODS The maxillary cheek teeth 108-208, 109-209 and 110-210 of 25 horses were evaluated using computed tomography and both the prevalence of infundibular and apical infection changes as the possible link with apical infection evaluated statistically. RESULTS The prevalence of infundibular changes was high in both normal and diseased teeth. Both apical infection and the occurrence of infundibular changes were more prevalent in 109-209 and 110-210. In spite of this, the 2 processes could not be linked to one another. No differences were noted between the left and right sides. CONCLUSIONS A direct relationship between the 2 processes was not established statistically and other underlying causes for the high occurrence of both apical infection and infundibular changes in diseased and normal 108-208, 109-209 and 110-210 are considered.
Kisspeptin (kiss 1) network signaling of hypothalamic gonadotropin-releasing hormone (GnRH) neurons.

To regulate reproduction in mammals, internal and external status is communicated to the hypothalamic-pituitary-gonadal axis via a coordinated balance of stimulatory and inhibitory neurochemical systems. This review describes the neuroanatomical organization of the kisspeptin system in the hypothalamus, and summarizes its role in signaling hypothalamic GnRH neurons, namely: multimodal actions of kisspeptin in the control of GnRH secretion during different physiological states of animals; involvement of kisspeptin in relaying metabolic information to hypothalamic GnRH neurons; neurobiological mechanisms underlying kisspeptin activation of GnRH neurons during puberty onset; effect of gonadal steroids in the early postnatal period in rodents on kisspeptin expression in the hypothalamus and gonadotropin secretion in adults; effect of photoperiod and metabolic cues on the activation/inhibition of hypothalamic-pituitary-gonadal axis in seasonally breeding species by kisspeptin.
Adolescents' perception of career choice of nursing among selected secondary schools in Jos, Nigeria

The main purpose of this study was to examine the adolescents’ perception and choice of nursing as a career in senior secondary schools, and to determine factors that may influence their choice and perception. The study was conducted in four selected schools in Jos metropolis. Each of these schools is unique in features. They include: two government secondary schools (urban and rural) and two private secondary schools (urban and rural). A total of 240 respondents were used for the study. A self-administered questionnaire was used for data collection. Data collected were analyzed and presented in frequency tables, percentages, bar chart and chi-square. Findings indicate that 7.5% (n=18) of respondents chose nursing as a career, out of which 83.33% (n=15) were females, while 16.67% (n=3) were males. Interestingly, out of 46.25% of total respondents who would consider nursing as a career, 56.76% were females while 43.26% were males. There is no significant relationship between gender in considering nursing as a career choice (X²=3.76, critical value=3.841, df=1, p value=0.05); the ownership type of schools, and consideration of nursing as a career choice shows no significance (t=-2.098, critical value=1.658, df=118, p value=0.05.). There is equally no significant relationship between location (X²=25.5, critical value=3.841, df=1, p value=0.05), and consideration of nursing as a career choice. Key words: Adolescent, perception, career, choice, secondary, schools.
Spectrum Effect and Spectrum Bias in the Screening Test Performance for Amnestic Mild Cognitive Impairment: What are the Clinical Implications?

BACKGROUND A single cutoff is widely used to screen amnestic mild cognitive impairment (aMCI). However, results of screening test performance are never adjusted for spectrum effect and spectrum bias. OBJECTIVES To assess the potential impact of spectrum effect and spectrum bias on screening test performance and clinical decision. METHODS The ability of the combination of Memory Impairment Screen (MIS), the Isaacs Set Test (IST), and the Mini-Mental State Examination (MMSE) to distinguish aMCI (n = 3,330) from patients with subjective cognitive complaints (SCC) (n = 1,522) was investigated across a wide range of age and educational backgrounds. The spectrum effect was defined as the variation of the sensitivity and/or the specificity across different subgroups. A spectrum bias was highlighted if the likelihood ratio (LR) observed in a subgroup of subjects statistically differed from the LR observed in the overall sample. RESULTS For the MIS-IST pairing, the overall sensitivity and specificity were equal to 72.5% and 75.2% , the positive LR (LR+) and the negative LR (LR-) were equal to 2.91 and 0.37, respectively. Across the different age-education subgroups, the sensitivities ranged from 43.7% to 92.5% and specificities from 39.3% to 95.2%. LR+ and LR- ranged from 1.51 to 9.10 and 0.13 to 0.59, respectively. A statistically significant spectrum bias was found in some subgroups and may result in differences between the post-test probabilities. Similar results were also found for the MMSE. CONCLUSION These findings could potentially affect the clinician's decision with a possible greater impact in elderly patients with a lower educational level.
Clinical Research in Interventional Pain Management Techniques: The Clinician's Point of View

Abstract: Interventional pain management techniques are considered for patients whose pain proves refractory to conventional treatment. According to the evidence‐based medicine (EBM) guidelines, the highest level of evidence for efficacy and safety of a treatment is generated in high‐quality randomized controlled trials and systematic reviews. A randomized controlled trial is defined as an experiment that determines the influence of an intervention on the natural history of the disease, which means that the comparative group should receive placebo, which is a sham intervention in case of the interventional pain management techniques. The systematic review summarizes in a structured way the results of the available information. When randomized controlled trials are available, observational studies will often be discarded. As new information on a treatment becomes available the perceived value may change, thus determining the survival time of clinical evidence. This survival time is not different when based on randomized or nonrandomized studies.
Obesity, insulin resistance and diabetes: sex differences and role of oestrogen receptors

Obesity increases the risk of coronary artery disease through insulin resistance, diabetes, arterial hypertension and dyslipidemia. The prevalence of obesity has increased worldwide and is particularly high among middle‐aged women and men. After menopause, women are at an increased risk to develop visceral obesity due to the loss of endogenous ovarian hormone production. Effects of oestrogens are classically mediated by the two nuclear oestrogen receptors (ERs) α and β. In addition, more recent research has shown that the intracellular transmembrane G‐protein‐coupled oestrogen receptor (GPER) originally designated as GPR30 also mediates some of the actions attributed to oestrogens. Oestrogen and its receptors are important regulators of body weight and insulin sensitivity not only in women but also in men as demonstrated by ER mutations in rodents and humans. This article reviews the role of sex hormones and ERs in the context of obesity, insulin sensitivity and diabetes as well as the related clinical issues in women and men.
CX3CL1–CX3CR1 Interaction Increases the Population of Ly6C−CX3CR1hi Macrophages Contributing to Unilateral Ureteral Obstruction–Induced Fibrosis

Chemokines modulate inflammatory responses that are prerequisites for kidney injury. The specific role of monocyte-associated CX3CR1 and its cognate ligand CX3CL1 in unilateral ureteral obstruction (UUO)–induced kidney injury remains unclear. In this study, we found that UUO caused a CCR2-dependent increase in numbers of Ly6Chi monocytes both in the blood and kidneys and of Ly6C−CX3CR1+ macrophages in the obstructed kidneys of mice. Using CX3CR1gfp/+ knockin mice, we observed a rapid conversion of infiltrating proinflammatory Ly6C+CX3CR11o monocytes/macrophages to anti-inflammatory Ly6C−CX3CR1hi macrophages. CX3CR1 deficiency affected neither monocyte trafficking nor macrophage differentiation in vivo upon renal obstruction, but CX3CR1 expression in monocytes and macrophages was required for increases in fibrosis in the obstructed kidneys. Mechanistically, CX3CL1–CX3CR1 interaction increases Ly6C−CX3CR1hi macrophage survival within the obstructed kidneys. Therefore, CX3CL1 and CX3CR1 may represent attractive therapeutic targets in obstructive nephropathy.
Calibration Issues of Dual-Polarization Radar Measurements

Abstract Techniques for the absolute calibration of radar reflectivity Z and differential reflectivity ZDR measured with dual-polarization weather radars are examined herein. Calibration of Z is based on the idea of self-consistency among Z, ZDR, and the specific differential phase KDP in rain. Extensive spatial and temporal averaging is used to derive the average values of ZDR and KDP for each 1 dB step in Z. Such averaging substantially reduces the standard error of the KDP estimate so the technique can be used for a wide range of rain intensities, including light rain. In this paper, the performance of different consistency relations is analyzed and a new self-consistency methodology is suggested. The proposed scheme substantially reduces the impact of variability in the drop size distribution and raindrop shape on the quality of the Z calibration. The new calibration technique was tested on a large polarimetric dataset obtained during the Joint Polarization Experiment in Oklahoma and yielded an accura.
Epidemiology and prevention of childhood injuries

Traumatic injury is the leading cause of death in children after infancy. The leading causes of childhood injury deaths are motor vehicle crashes, submersion injury, homicide, suicide, and fires. Injuries are not random events. Factors associated with injuries allow identification of high-risk populations and targeted interventions. Injury research includes development of conceptual models to include preinjury, event, and postevent features that can be modified to prevent or limit injuries. Successful prevention strategies often include multifaceted approaches such as education, incentives for safe human behavior, legislation/enforcement, and environmental changes. Preventive programs must weigh both societal and economic values and costs. Careful evaluation for effectiveness of injury prevention programs to decrease or limit injury continues to be a challenge. Generally, passive measure such as improved engineering are more effective than measures that require modification of human behaviors. Childhood injury prevention programs have reduced deaths from some causes such as motor vehicle crashes, but deaths from gun-related homicide and suicide remain high. Critical care providers can actively engage in both prevention efforts and improved acute care of the severely injured child.
Exploring determinants of adoption intentions towards Enterprise 2.0 applications: an empirical study

Enterprise 2.0 is identified as one of the most promising technological innovations in the business domain, with immense potential for enriching communication, enabling collaboration and facilitating learning. Although organisations are increasingly implementing Enterprise 2.0 as a useful means of knowledge sharing and collaboration, no empirical research has been performed to identify individuals’ motivations to participate in Enterprise 2.0 activities. The high practical relevance and dearth of research indicate the importance of the present study. This study aims to apply the Unified Theory of Acceptance and Use of Technology to propose a research model that incorporates context-specific variables as enhancing constructs to predict individuals’ adoption intentions towards Enterprise 2.0 applications. We also categorise Enterprise 2.0 users into silent and social users and conduct a comparative analysis to examine whether differences exist in factors predicting users’ adoption intentions towards Enterprise 2.0 applications. To test the model, structural equation modelling is employed to analyse data collected from respondents working in seven Chinese companies conducting trial operations of an Enterprise 2.0 platform. The findings of this research provide managers with effective methods to promote individuals’ participation in Enterprise 2.0 activities. This research also provides a theoretical foundation for academics and practical implications for the development of Enterprise 2.0.
Effects of stereotactic radiosurgery on an animal model of hippocampal epilepsy.

OBJECTIVE Stereotactic radiosurgery has been shown in small clinical series to reduce or abolish seizures in patients with lesion-related or idiopathic epilepsy. The radiation dose necessary to eliminate epileptogenesis is unknown, and the histological and metabolic effects of radiosurgery remain undefined. We hypothesized that in a rat model of kainic acid-induced hippocampal epilepsy, radiosurgery could provide a significant reduction in seizure frequency while limiting biochemical and structural histological damage to the brain. METHODS Kainic acid (8 g) was injected into the rat hippocampus using stereotactic targeting. Focal seizures so generated were identified with scalp and depth electroencephalography (EEG). Epileptic rats were randomized to a control group (n = 20) and to radiosurgery groups in which maximum doses of 20, 40, 60, or 100 Gy (8-9 animals per group) were administered. Over a 42-day period, seizure frequency was determined by direct observation for 8 hours per week. Scalp EEG was performed weekly in all animals. Magnetic resonance imaging (MRI) studies (T1- and T2-weighted water-proton and quantitative sodium images) were obtained on Days 7, 21, and 42. RESULTS As compared with the control group, treated animals showed significant reductions in the number of seizures during each successive week after 20-Gy radiosurgery (P = 0.01-0.002). When we combined the number of seizures observed in the latter half of the study (Weeks 4-6), we found a significant reduction in seizures after 20-Gy (P = 0.007), 40-Gy (P = 0.03), 60-Gy (P = 0.03), and 100-Gy (P = 0.03) radiosurgery as compared with control animals. Increasing doses of radiosurgery correlated with higher percentages of rats that became seizure-free by EEG criteria. MRI-determined total sodium concentration in the injected hippocampus was 49.8+/-3 mmol/L, compared with 42.8 mmol/L on the contralateral side (within normal limits). This significant increase in sodium concentration was present in control rats (because of the kainic acid) and did not change with increasing radiosurgery dose. No parenchymal effects from radiosurgery were identified after 20, 40, and 60 Gy, and only two rats had necrosis at 100 Gy. All animals showed hippocampal injury from kainic acid by proton MRI and histological examination. CONCLUSION In this rat hippocampal epilepsy model, stereotactic radiosurgery was followed by a significant dose-dependent reduction in the frequency of observed and EEG-defined seizures. These effects were not accompanied by increased radiation-induced structural or metabolic brain injury as assessed by proton and sodium MRI or histological examination. The role of radiosurgery as a new, nondestructive surgical therapy for idiopathic epilepsy warrants further investigation.
Fine structural changes in idiopathic pulmonary haemosiderosis

Lung biopsies from four children and two adults with idiopathic pulmonary haemosiderosis have been examined by transmission electron microscopy. No qualitative differences were identified between the children and the adults but the changes were more severe in the children. In each case the major damage involved the capillary endothelium and its basement membrane. Capillary endothelial swelling was very noticeable and in one case the endothelium was attenuated but gaps between endothelial cells were very difficult to find. Capillary narrowing and platelet aggregation were common. The capillary endothelial basement membrane showed focal thickening, particularly on the thick side of the air/blood barrier, but no electron dense deposits were identified. Degenerative changes in the alveolar epithelium were not so marked as those in the capillary endothelium and the epithelial basement membrane was normal except for haemosiderin deposition. Haemosiderin was also noted on elastin and within intra‐alveolar macrophages. Other secondary changes included mild interstitial oedema and fibrosis. These findings indicate that the major site of damage is the alveolar capillary, but provide no evidence of the cause of the disease.