Miracle-dz/UniFAR-FTUs huggingface dataset:
Restoration of MHC-I on Tumor Cells by Fhit Transfection Promotes Immune Rejection and Acts as an Individualized Immunotherapeutic Vaccine

The capacity of cytotoxic-T lymphocytes to recognize and destroy tumor cells depends on the surface expression by tumor cells of MHC class I molecules loaded with tumor antigen peptides. Loss of MHC-I expression is the most frequent mechanism by which tumor cells evade the immune response. The restoration of MHC-I expression in cancer cells is crucial to enhance their immune destruction, especially in response to cancer immunotherapy. Using mouse models, we recovered MHC-I expression in the MHC-I negative tumor cell lines and analyzed their oncological and immunological profile. Fhit gene transfection induces the restoration of MHC-I expression in highly oncogenic MHC-I-negative murine tumor cell lines and genes of the IFN-γ transduction signal pathway are involved. Fhit-transfected tumor cells proved highly immunogenic, being rejected by a T lymphocyte-mediated immune response. Strikingly, this immune rejection was more frequent in females than in males. The immune response generated protected hosts against the tumor growth of non-transfected cells and against other tumor cells in our murine tumor model. Finally, we also observed a direct correlation between FHIT expression and HLA-I surface expression in human breast tumors. Recovery of Fhit expression on MHC class I negative tumor cells may be a useful immunotherapeutic strategy and may even act as an individualized immunotherapeutic vaccine.
Histological Alterations of Gill, Liver and Kidney of Black-Chinned Tilapia Sarotherodon melanotheron Contaminated by Heavy Metals from Bietri Bay in Ebrie Lagoon, Cote d’Ivoire

Histological changes in gills, liver and kidney were used to evaluate the health of Black-Chinned Tilapia Sarotherodon melanotheron obtained from Bietri Bay in Ebrie Lagoon during February 2008 and January 2009. Several histological alterations were observed in the gills, including proliferation in the epithelium of gill filaments and secondary lamellae, proliferation of mucous cells, cyst at the top of secondary lamellae, dilation and congestion in gill filaments blood vessel, atrophy of secondary lamellae, lamellar disorganization with focal fusion and hyperplasia of the epithelial cells and between secondary lamellae. The liver showed dilation in cells hepatic, focal areas of necrosis, cells hepatic degeneration, vacuolar degeneration with infiltration of lipid, blood vessels degeneration, hemorrhage and severe dilation in liver cells. In the kidney, the pathological alterations included vacuolization, dilation in renal cells, severe dilation with renal cells degeneration, hemorrhage, parasitic cyst, vacuolar degeneration in the epithelium of renal tubules, parasites, dilation in renal blood vessels and cyst. It was concluded that the environmental contamination of Bietri Bay induced several histopathological alterations in the tissues of Sarotherodon melanotheron.
Role of Oxidative Stress in the Genesis of Ventricular Arrhythmias

Ventricular arrhythmias, mainly lethal arrhythmias, such as ventricular tachycardia and fibrillation, may lead to sudden cardiac death. These are triggered as a result of cardiac injury due to chronic ischemia, acute myocardial infarction and various stressful conditions associated with increased levels of circulating catecholamines and angiotensin II. Several mechanisms have been proposed to underlie electrical instability of the heart promoting ventricular arrhythmias; however, oxidative stress which adversely affects ion homeostasis due to changes in the ion channel structure and function, seems to play a critical role in eliciting different types of ventricular arrhythmias. Prevention or mitigation of the severity of ventricular arrhythmias due to antioxidants has been indicated as the fundamental contribution in the field of preventive cardiology; however, novel interventions have to be developed for greater effectiveness and specificity in attenuating the adverse effects of oxidative stress. In this review, we have attempted to discuss proarrhythmic effects of oxidative stress differing in time and concentration dependence and highlight a molecular and cellular concept how it alters cardiac cell automaticity and conduction velocity sensitizing the probability of ventricular arrhythmias with resultant sudden cardiac death due to ischemic heart disease and other stressful situations. It is concluded that pharmacological approaches targeting multiple mechanisms besides oxidative stress might be more effective in the treatment of ventricular arrhythmias than current antiarrhythmic therapy.
Neutrophil Extracellular Traps (NETs) Promote Pro-Metastatic Phenotype in Human Breast Cancer Cells through Epithelial–Mesenchymal Transition

Neutrophil extracellular traps (NETs) have been associated with several steps of tumor progression, including primary growth and metastasis. One of the key features for the acquisition of the metastatic ability is the epithelial–mesenchymal transition (EMT), a complex cellular program. In this study, we evaluated the ability of isolated NETs in modulating the pro-metastatic phenotype of human breast cancer cells. Tumor cells were treated with isolated NETs and then samples were generated for cell migration, quantitative RT-PCR, western blotting, immunofluorescence, and flow cytometry assays. RNA-seq data from The Cancer Genome Atlas (TCGA) database were assessed. NETs changed the typical epithelial morphology of MCF7 cells into a mesenchymal phenotype, a process that was accompanied by enhanced migratory properties. Additional EMT traits were observed: increased expression of N-cadherin and fibronectin, while the E-cadherin expression was repressed. Notably, NETs positively regulated the gene expression of several factors linked to the pro-inflammatory and pro-metastatic properties. Analyses of TCGA data showed that samples from breast cancer patients exhibit a significant correlation between pro-tumoral and neutrophil signature gene expression, including several EMT and pro-metastatic factors. Therefore, NETs drive pro-metastatic phenotype in human breast cancer cells through the activation of the EMT program.
Transcranial magnetic stimulation of small animals: A modeling study of the influence of coil geometry, size and orientation

Several recent studies have investigated the mechanisms of repetitive transcranial magnetic stimulation (rTMS) using small animals. However, there is still limited knowledge about the distribution of the induced electric field, and its dependence on coil size, geometry and orientation. In this work we calculate the electric field induced in a realistically shaped homogeneous mouse model by commercially available coils in several different orientations. The results show that the secondary field, resulting from charge accumulation at the skin - air interface, drastically changes the magnitude, decay and focality of the primary field induced by the coil. Accurate knowledge about the distribution of the field is invaluable in designing experimental protocols and new coils for small animal stimulation.
Results of transcatheter Fontan fenestration to treat protein losing enteropathy

Transcatheter fenestration to create an interatrial communication has been used to treat patients with protein losing enteropathy (PLE) after Fontan operation. No systematic data have been reported assessing the results of this procedure. Our institutional database was queried to identify patients after Fontan operation who had transcatheter fenestration to treat PLE. Clinical notes, laboratory data, echocardiograms, and cardiac catheterization data were reviewed. From 1995 to 2005, 16 transcatheter fenestration procedures were performed in seven patients. Median age at fenestration was 18 years (range 13–41 years). Median duration of follow‐up was 3.6 years (range 0.2–10.4 years). Techniques for fenestration included blade/balloon septostomy, stent placement, Amplatzer‐fenestrated ASD device, and balloon dilation of previous stent. Size of the fenestration created was 5.2 ± 1.1 mm. Systemic venous pressure remained unchanged after fenestration. Cardiac index increased significantly. Reduction of ascites and edema was noted after 9 of the 16 procedures. Ten of 16 (63%) of fenestrations spontaneously occluded. Three patients are free of ascites although recurrence of PLE occurred in all. One patient with a patent fenestration continues to have ascites. Two patients had Fontan takedown. One patient had conversion to a fenestrated extracardiac conduit Fontan and died postoperatively. The results of transcatheter Fontan fenestration are often disappointing. Maintaining fenestration patency is difficult. Even after “successful” fenestration, resolution of PLE may be incomplete and recurrences have occurred in all. Early consideration should be given to Fontan takedown or cardiac transplant in severely symptomatic patients with PLE who do not respond to fenestration. Transcatheter fenestration may be a bridge to a definitive procedure. © 2007 Wiley‐Liss, Inc.
Phenotypic Profiles of Enterotoxigenic Escherichia coli Associated with Early Childhood Diarrhea in Rural Egypt

ABSTRACT Enterotoxigenic Escherichia coli (ETEC) causes substantial diarrheal morbidity and mortality in young children in countries with limited resources. We determined the phenotypic profiles of 915 ETEC diarrheal isolates derived from Egyptian children under 3 years of age who participated in a 3-year population-based study. For each strain, we ascertained enterotoxin and colonization factor (CF) expression, the O:H serotype, and antimicrobial susceptibility. Sixty-one percent of the strains expressed heat-stable enterotoxin (ST) only, 26% expressed heat-labile enterotoxin (LT) alone, and 12% expressed both toxins. The most common CF phenotypes were colonization factor antigen I (CFA/I) (10%), coli surface antigen 6 (CS6) (9%), CS14 (6%), and CS1 plus CS3 (4%). Fifty-nine percent of the strains did not express any of the 12 CFs included in our test panel. Resistance of ETEC strains to ampicillin (63%), trimethoprim-sulfamethoxazole (52%), and tetracycline (43%) was common, while resistance to quinolone antibiotics was rarely detected. As for the distribution of observed serotypes, there was an unusually wide diversity of O antigens and H types represented among the 915 ETEC strains. The most commonly recognized composite ETEC phenotypes were ST CS14 O78:H18 (4%), ST (or LTST) CFA/I O128:H12 (3%), ST CS1+CS3 O6:H16 (2%), and ST CFA/I O153:H45 (1.5%). Temporal plots of diarrheal episodes associated with ETEC strains bearing common composite phenotypes were consistent with discrete community outbreaks either within a single or over successive warm seasons. These data suggest that a proportion of the disease that is endemic to young children in rural Egypt represents the confluence of small epidemics by clonally related ETEC strains that are transiently introduced or that persist in a community reservoir.
The neurocognitive profiles of children adopted from care and their emotional and behavioral problems at home and school

ABSTRACT Adoptees’ mental health problems in childhood and later life are well described, but little attention has been paid to domestically adopted children’s emotional and behavioral problems and neurocognitive profiles. The aim of this study was to describe the neurocognitive profiles of domestically adopted children in the UK and their parent- and teacher-rated emotional and behavioral problems. Forty-five children (M age = 75.96 months, SD = 12.98; 51.1% female) who were placed for adoption from public care at a M age of 22.14 months (SD = 14.21) completed a battery of age standardized neurocognitive tests, and adoptive parents and school teachers rated their emotional and behavioral problems. Children had more emotional and behavioral problems than the general population and over a fifth scored low (> 1 SD below the expected range for their age) in 5/6 neurocognitive tasks. Children who scored low on the non-verbal reasoning task were more likely to have more parent- and teacher-rated behavioral problems, and children’s performance on the inhibitory control and cognitive flexibility tasks were associated with parent-rated behavioral problems. Children’s verbal reasoning scores were positively associated with both parent- and teacher-rated emotional problems. Children who were adopted later in childhood scored significantly lower in non-verbal reasoning. Although longitudinal studies are needed to clarify the nature of neurocognitive functioning as a marker for later mental health problems, our findings underscore the importance of using comprehensive assessments to better recognize adopted children’s difficulties and inform appropriate intervention initiatives.
Novel Chlamydiales strains isolated from a water treatment plant.

Chlamydiae are obligate intracellular bacteria infecting free-living amoebae, vertebrates and some invertebrates. Novel members are regularly discovered, and there is accumulating evidence supporting a very important diversity of chlamydiae in the environment. In this study, we investigated the presence of chlamydiae in a drinking water treatment plant. Samples were used to inoculate Acanthamoeba monolayers (Acanthamoeba co-culture), and to recover autochthonous amoebae onto non-nutritive agar. Chlamydiae were searched for by a pan-chlamydia 16S rRNA gene PCR from both Acanthamoeba co-cultures and autochthonous amoebae, and phylotypes determined by 16S rRNA gene sequencing. Autochthonous amoebae also were identified by 18S rRNA gene amplification and sequencing. From a total of 79 samples, we recovered eight chlamydial strains by Acanthamoeba co-culture, but only one of 28 amoebae harboured a chlamydia. Sequencing results and phylogenetic analysis showed our strains belonging to four distinct chlamydial lineages. Four strains, including the strain recovered within its natural host, belonged to the Parachlamydiaceae; two closely related strains belonged to the Criblamydiaceae; two distinct strains clustered with Rhabdochlamydia spp. ; one strain clustered only with uncultured environmental clones. Our results confirmed the usefulness of amoeba co-culture to recover novel chlamydial strains from complex samples and demonstrated the huge diversity of chlamydiae in the environment, by identifying several new species including one representing the first strain of a new family.
103. Bispectral index-guided intraoperative sedation with dexmedetomidine and midazolam infusion in outpatient cataract surgery

BACKGROUND This study aimed to evaluate the role of alfa-2 agonist infusion, with dexmedetomidine or midazolam, on hemodynamic and respiratory parameters while titrating the sedation level with the bispectral index (BIS) during cataract surgery. METHODS Ninety consenting ASA class I-III patients who were electively undergoing cataract surgery were enrolled in the double blind study. A random infusion of 0.25 microg kg(-1) hr(-1) Dexmedetomidine (Group D), 25 microg kg(-1) hr(-1) midazolam (Group M), or saline for controls (Group C) was administered after mounting a BIS monitor and routine anesthetic care. The target BIS level was >85. An additional bolus dose in 1 mL increments of the study drug or cessation of the infusion was adjusted according to the BIS level. Changes in respiratory and vital parameters were noted and, in case of mild pain, 25 microg fentanyl was administered as a bolus. Pain and sedation were evaluated in the early postoperative period using visual analogue and four rating sedation scales. RESULTS In Group D, heart rate decreased in the later periods of surgery (35-50 min) and in the early postoperative period (5(th) and 15(th) min). Dose adjustments were required in six and ten patients in Groups D and M, respectively. Pain scores were lower with dexmedetomidine infusion. CONCLUSIONS Dexmedetomidine infusion mildly decreased heart rate in the later periods of surgery with better pain scores in the postoperative period. Dexmedetomidine should be an alternative for intraoperative sedation in outpatient cataract surgery.
A Developmental Study of the Feedback-Related Negativity From 10–17 Years: Age and Sex Effects for Reward Versus Non-Reward

We employed event-related potentials to examine the feedback-related negativity (FRN), during a non-learning reward versus non-reward task. We compared 10–12-year-old, 13–14-year-old, and 15–17-year-old youth (n = 91). Age effects included a larger FRN for younger age groups, regardless of feedback type, and a decrease in peak latency for feedback, across age groups as a linear trend. Males showed larger responses irrespective of feedback type and longer latency for rewarded feedback. Source modeling revealed reward/non-reward differences in the anterior cingulate cortex (ACC) and orbitofrontal cortex, most strongly in the subgenual ACC. Males showed more subgenual ACC activity for feedback overall.
Diet, Tuberculosis, and the Paleopathological Record

Osseous manifestation of infectious disease is of paramount importance to paleopathologists seeking to interpret ancient health, but the relationships among infectious agent exposure, development of disease, and skeletal involvement are complex. The outcome of an exposure strongly depends on multiple factors, including ecology, diet, nutrition, immune function, and the genetics of pathogen and host. Mycobacterial diseases are often studied in ancient remains but also are especially influenced by these factors; individual and population differences in severity and course are apparent following onset of active disease. The osteological record for these diseases represents the complex interplay of host and pathogen characteristics influencing within‐ and among‐individual skeletal lesion prevalence and distribution. However, many of these characteristics may be assessed independently through the archaeological record. Here, we explore the contributions of dietary protein and iron to immune function, particularly the course and outcome of infection with Mycobacterium tuberculosis. We emphasize how nutrition may influence the dissemination of bacilli to the skeleton and subsequent formation of diagnostic lesions. We then generate models and hypotheses informed by this interplay and apply them to four prehistoric New World areas. Finally, discrepancies between our expectations and the observed record are explored as a basis for new hypotheses.
Are Selective Endothelin A Receptor Antagonists Better than Mixed Antagonists?

Summary: Pharmacological antagonism of the endothelin system presents a novel target for the treatment of a range of cardiovascular diseases. The antagonists developed so far differ in their endothelin receptor subtype specificity. Indeed, at present there is no consensus opinion as to what level of receptor selectivity defines a particular antagonist as 'selective' or 'mixed'. Antagonists that are highly selective for the endothelin A receptor (ETA) receptor subtype have a number of hypothetical advantages over non‐selective antagonists. This theory is based on the analysis of the function of the endothelin B (ETB) receptor. Current evidence suggests that activation of the ETB receptor results in vasodilatation, diuresis and natriuresis, each of which are properties that might be advantageous to maintain in conditions such as cardiac failure and hypertension. However, definitive evidence to suggest a therapeutic advantage of selective ETA receptor antagonists requires long‐term, head‐to‐head studies to be performed.
Microbiological and Biochemical Effectiveness of an Antiseptic Gel on the Bacterial Contamination of the Inner Space of Dental Implants: A 3-Month Human Longitudinal Study

Microbial penetration inside the implant's internal cavity produces a bacterial reservoir that is associated with an area of inflamed connective tissue facing the fixture-abutment junction. The aim of this clinical trial is to evaluate the effectiveness of a 1% chlorhexidine gel on the internal bacterial contamination of implants with screw-retained abutments and on the level of AST secreted in peri-implant crevicular fluid. Twenty-five patients (aged 29 to 58 years) each received one implant. Three months after the end of the restorative treatment, and immediately after a clinical and radiographic examination and the abutment removal, microbiological samples were obtained from the internal part of each fixture and biochemical samples were collected by peri-implant sulci. The patients were then divided into two groups: the control (CG; n=10) and test (TG; n=15) groups. The CG had the abutment screwed into place and the crown cemented without any further intervention. In contrast, before the abutment placement and screw tightening, the TG had the internal part of the fixture filled with a 1% chlorhexidine gel. Three months later, the same clinical, microbiological and biochemical procedures were repeated in both groups. Total bacterial count, specific pathogens and AST activity were detected. The clinical parameters remained stable throughout the study. From baseline to the 3-month examination, the total bacterial counts underwent a significant reduction only in the TG. In contrast, the AST activity showed a significant increase in the CG. The administration of a 1% chlorhexidine gel appears to be an effective method for the reduction of bacterial colonization of the implant cavity and for safeguarding the health status of peri-implant tissue over a 3-month administration period.
Stability of the factor structure of the Neuropsychiatric Inventory in a 31-month follow-up study of a large sample of nursing-home patients with dementia

ABSTRACT Background: Neuropsychiatric symptoms (NPS) are highly prevalent among nursing home patients with dementia. Several studies have investigated subsyndromes of NPS but the stability of these subsyndromes over time has rarely been examined. We have examined the stability over time of the factor structure of the Neuropsychiatric Inventory-Nursing Home version (NPI-NH) in a large sample of nursing-home patients with dementia. Methods: Nursing-home patients with dementia were assessed with the NPI-NH at baseline (n = 895), and at 12-month (n = 592) and 31-month (n = 278) follow-up assessments, giving three partly overlapping samples. Exploratory factor analysis was done to investigate neuropsychiatric subsyndromes of the NPI-NH at each assessment in these samples. Results: Three- or four-factor solutions were found, termed agitation, psychosis, apathy, and affective symptoms. Depression and anxiety (affective), delusion and hallucination (psychosis), and agitation and irritability (agitation) were the symptoms that most often co-occurred in the same factor. Apathy did not load together with affective symptoms at any of the assessments. Conclusions: Subsyndromes of the NPI-NH are relatively stable over 31-month follow-up assessments in nursing-home patients with dementia, indicating that these subsyndromes may be useful for following the natural course of symptoms as well as observing the effect of interventions. Our findings lend support to the distinction between apathy and affective symptoms, which may have important clinical implications.