Miracle-dz/UniFAR-FTUs huggingface dataset:
Current state of diagnostic technologies in the autoimmunology laboratory

Abstract The methods for detecting and measuring autoantibodies have evolved markedly in recent years, encompassing three generations of analytical technologies. Many different immunoassay methods have been developed and used for research and laboratory practice purposes, from the early conventional (or monoplex) analytical methods able to detect single autoantibodies to the more recent multiplex platforms that can quantify tens of molecules. Although it has been in use for over 50 years, indirect immunofluorescence remains the standard method for research on many types of autoantibodies, due to its characteristics of diagnostic sensitivity and also to recent technological innovations which permit it a greater level of automation and standardization. The recent multiplex immunometric methods, with varying levels of automation, present characteristics of higher diagnostic accuracy, but are not yet widely diffused in autoimmunology laboratories due to the limited number of autoantibodies that are detectable, and due to the high cost of reagents and systems. Technological advancement in autoimmunology continues to evolve rapidly, and in the coming years new proteomic techniques will be able to radically change the approach to diagnostics and possibly also clinical treatment of autoimmune diseases. The scope of this review is to update the state of the art of technologies and methods for the measurement of autoantibodies, with special reference to innovations in indirect immunofluorescence and in multiple proteomic methods.
Trends in dental caries in Latin American and Caribbean 5-6- and 11-13-year-old children: a systematic review.

OBJECTIVES To determine trends in dental caries prevalence and severity in Latin America and Caribbean. METHODS A systematic review was done of studies published between 1970 and 2000 among 5-6- and 11-13-year-old children that used WHO caries diagnostic criteria. RESULTS Over the last 30 years, there has been a significant decrease in caries severity for children 5-6 years old and also a significant decrease in caries prevalence and severity for children 11-13 years old. The same broad trends were observed when caries prevalence and severity was analyzed for the last 20 and 10 years but these were not statistically significant. CONCLUSIONS Evidence of a decrease in dental caries in Latin American and Caribbean children has been shown, although the decrease was less prominent in the past few years.
Layer‐ and cell‐type‐specific suprathreshold stimulus representation in rat primary somatosensory cortex

Sensory stimuli are encoded differently across cortical layers and it is unknown how response characteristics relate to the morphological identity of responding cells. We therefore juxtasomally recorded action potential (AP) patterns from excitatory cells in layer (L) 2/3, L4, L5 and L6 of rat barrel cortex in response to a standard stimulus (e.g. repeated deflection of single whiskers in the caudal direction). Subsequent single‐cell filling with biocytin allowed for post hoc identification of recorded cells. We report three major conclusions. First, sensory‐evoked responses were layer‐ and cell‐type‐specific but always < 1 AP per stimulus, indicating low AP rates for the entire cortical column. Second, response latencies from L4, L5B and L6 were comparable and thus a whisker deflection is initially represented simultaneously in these layers. Finally, L5 thick‐tufted cells dominated the cortical AP output following sensory stimulation, suggesting that these cells could direct sensory guided behaviours.
CC16 gene A38G polymorphism and susceptibility to asthma: an updated meta-analysis.

OBJECTIVE To comprehensively evaluate the association between the CC16 gene A38G polymorphism and the risk of asthma. METHODS Studies were retrieved from databases including PubMed, EMBASE, Web of Science and the Chinese Biomedical Literature Database according to the inclusive and exclusive criteria. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the associations. MATERIALS Fifteen case-control studies with 1,623 cases and 3,294 controls were recruited for the analysis of the association between the CC16 gene A38G polymorphism and the risk of asthma. RESULTS The overall ORs showed no significant associations between the CC16 gene A38G polymorphism and the risk of asthma (AA vs. GG: OR=1.04, 95%CI=0.86-1.25; AG vs. GG: OR=1.08, 95%CI=0.94-1.24; AA + AG vs. GG: OR=1.07, 95%CI=0.94-1.22; AA vs. AG + GG: OR=1.01, 95%CI=0.85-1.19; A vs. G: OR=1.04, 95%CI=0.95-1.14). Moreover, similar results were obtained in the subgroup analysis stratified by ethnicity (Asian: AG vs. GG: OR=1.02, 95%CI=0.87-1.21; Caucasian: AG vs. GG: OR=1.22, 95%CI=0.94-1.57) and age (Child: AG vs. GG: OR=1.21, 95%CI=0.84-1.74; Adult: AG vs. GG: OR=1.06, 95%CI=0.91-1.23). CONCLUSION CC16 gene A38G polymorphism is not associated with the risk of asthma.
Preferential Localization of the Epstein-Barr Virus (EBV) Oncoprotein LMP-1 to Nuclei in Human T Cells: Implications for Its Role in the Development of EBV Genome-Positive T-Cell Lymphomas

ABSTRACT The Epstein-Barr virus (EBV)-encoded latent membrane protein-1 (LMP-1) is thought to play a role in the EBV-induced B-cell transformation and immortalization. EBV has also been implicated in certain human T-cell lymphomas; however, the phenotypic effects of the expression of this oncoprotein in T cells are not known. To learn whether LMP-1 also induces phenotypic changes in T cells, we stably expressed it in human cell lines of T and B lineages and 25 LMP-1-expressing T-cell clones and 7 B-cell clones were examined. Our results show for the first time that, in sharp contrast to B cells, LMP-1 preferentially localizes to nuclei in T cells and does not induce the phenotypic changes in these cells that it induces in B cells, does not associate with TRAF proteins, and does not arrest the cell cycle in the G2/M phase. A computer-assisted analysis revealed that LMP-1 lacks the canonical nuclear localization signal. Our results suggest that this oncoprotein may not play the same role in the lymphomagenesis of T cells as it does in B cells.
Is the ischemic blood–brain barrier insufficiency responsible for full-blown Alzheimer's disease?

Abstract The goal of this paper is to provide scientists with a comprehensive review of the state-of-the-art influence the ischemic blood–brain barrier (BBB) has on the final development of Alzheimer's disease and to provide detailed food-for-thought which will hopefully stimulate more researchers in this area of neuroscience. Understanding new and fundamental concepts about the behavior of the BBB during long-term reperfusion after ischemia with a variety of new neuropathogenic factors can hopefully provide some interesting clues related to the pathologic processes issues that have been receiving considerable attention in the human clinic. We present the recent data to understand the role of the BBB in maturation of both diseases and try to differentiate between primary and secondary pathologic mechanisms. In conclusion, the neuropathogenesis of Alzheimer's disease involves an initial ischemic neuronal alterations leading to enhanced neuronal vulnerability to β-amyloid peptide and the ischemic breakdown of the BBB with leakage of serum borne β-amyloid peptide into brain parenchyma, activation of β-amyloid peptide-dependent toxicity culminating in the formation of amyloid plaques and finally end in full-blown Alzheimer's disease. In summary, probably we have combined mechanism(s) of ischemia processes, ischemic and chronic BBB dysfunction and β-amyloid peptide-dependent injury in pathology of neurodegeneration that is observed in Alzheimer's disease. We speculate that Alzheimer's disease may be caused by silent and sublethal ischemic episodes that attack and slowly steal the minds of its victims. Finally, our review proposes the ischemic BBB-dependent mechanism(s) that probably are responsible for full-blown Alzheimer's disease.
Impact of vertebrate probiotics on honeybee yeast microbiota and on the course of nosemosis

Vital pollinators whose role in ecosystems can hardly be overestimated, honeybees suffer from numerous illnesses, among which varroatosis and nosemosis seem most dangerous. Unfortunately, there is no cure that could resolve these grave honeybee health problems. Therefore, a great number of various kinds of diet supplements to help combat these illnesses are recommended for honeybee feeding. These include commercial probiotics whose primarily composition is based on the bacteria from the Lactobacillus genus. Symbiotic microbiota prevent the growth of pathogenic species by competing for nutrition and attachment sites to the epithelium of the intestine. The microorganisms associated with the honeybee come from pollen consumption or through contact with older workers (e.g. trophallaxis). Bacteria from the Lactobacillus (LAB) genus are some of the most important intestinal symbionts, and the LAB members most frequently isolated from honeybees are: Lactobacillus kunkeei, L. plantarum, L. pentosus, L. fermentum, L. floricola, L. acidophilus and L. johnsonii (4, 12, 27, 41, 42, 44). Honeybee Lactobacillus bacteria, as all members of this genus, produce a short chain fatty acids which can be absorbed through the rectal wall and provide additional nutrition. Furthermore, bacteria from the Lactobacillus and Bifidobacterium genera which inhabit honeybees’ crop play a very important role in the production of honey and beebread (8-11, 13, 24, 25, 43, 44). Impact of vertebrate probiotics on honeybee yeast microbiota and on the course of nosemosis1)
[Clinical and epidemiological data of patients with malignomas of the head and neck].

BACKGROUND The present study describes clinical and epidemiological data of patients with malignomas of the head and neck documented in the Munich Cancer Register. PATIENTS AND METHODS Data of head and neck cancer patients treated at four departments of head and neck surgery and one of oral-maxillo-facial surgery in the area of Munich from 1978 up to now are reported. RESULTS Incidence and mortality as a function of age, sex, and tumor localization are described in comparison to clinical and epidemiological data as specified in tumor registers of the Saarland and the USA. Moreover, TNM stages, survival, recurrence, and metastasis rates are presented. CONCLUSION Based on the documentation of the Munich Cancer Register our study is the first to present a detailed description of clinical and epidemiological data of patients suffering from head and neck malignomas.
ASL Perfusion MRI Predicts Cognitive Decline and Conversion From MCI to Dementia

We compared the predictive value of cerebral perfusion as measured by arterial-spin labeling magnetic resonance imaging (ASL-MRI) with MRI-derived hippocampal volume for determining future cognitive and functional decline and subsequent conversion from mild cognitive impairment to dementia. Forty-eight mild cognitive impairment subjects received structural and ASL-MRI scans at baseline and clinical and neuropsychologic assessments annually. Thirteen subjects became demented during the period of longitudinal observation (2.7±1.0 y). Cox regression analyses suggest that baseline hippocampal volume [relative risk (RR)=0.99, P=0.004], baseline right inferior parietal (RR=0.64, P=0.01) and right middle frontal (RR=0.73, P=0.01) perfusion were associated with conversion to dementia. Results from linear mixed effects modeling suggest that baseline perfusion from the right precuneus predicted subsequent declines in Clinical Dementia Rating Sum of Boxes (P=0.002), Functional Activates Questionnaire (P=0.01), and selective attention (ie, Stroop switching, P=0.009) whereas baseline perfusion from the right middle frontal cortex predicted subsequent episodic memory decline (ie, total recognition discriminability score from the California Verbal Learning Test, P=0.03). These results suggest that hypoperfusion as detected by ASL-MRI can predict subsequent clinical, functional, and cognitive decline and may be useful for identifying candidates for future Alzheimer disease treatment trials.
Human MI-ER1 Alpha and Beta Function as Transcriptional Repressors by Recruitment of Histone Deacetylase 1 to Their Conserved ELM2 Domain

ABSTRACT mi-er1 (previously called er1) was first isolated from Xenopus laevis embryonic cells as a novel fibroblast growth factor-regulated immediate-early gene. Xmi-er1 was shown to encode a nuclear protein with an N-terminal acidic transcription activation domain. The human orthologue of mi-er1 (hmi-er1) displays 91% similarity to the Xenopus sequence at the amino acid level and was shown to be upregulated in breast carcinoma cell lines and tumors. Alternative splicing at the 3′ end of hmi-er1 produces two major isoforms, hMI-ER1α and hMI-ER1β, which contain distinct C-terminal domains. In this study, we investigated the role of hMI-ER1α and hMI-ER1β in the regulation of transcription. Using fusion proteins of hMI-ER1α or hMI-ER1β tethered to the GAL4 DNA binding domain, we show that both isoforms, when recruited to the G5tkCAT minimal promoter, function to repress transcription. We demonstrate that this repressor activity is due to interaction and recruitment of a trichostatin A-sensitive histone deacetylase 1 (HDAC1). Furthermore, deletion analysis revealed that recruitment of HDAC1 to hMI-ER1α and hMI-ER1β occurs through their common ELM2 domain. The ELM2 domain was first described in the Caenorhabditis elegans Egl-27 protein and is present in a number of SANT domain-containing transcription factors. This is the first report of a function for the ELM2 domain, highlighting its role in the regulation of transcription.
1-Hydroxypyrene as a Biomarker of Occupational Exposure to Polycyclic Aromatic Hydrocarbons (PAH) in Boilermakers

A repeated measures short-term prospective study was performed in boilermakers to determine occupational polycyclic aromatic hydrocarbon (PAH) exposure using the biomarker, 1-hydroxypyrene (1-OHP). Two work sites were studied; an apprentice school (metal fume exposure) and a boiler overhaul (residual oil fly ash [ROFA] and metal fume exposure). Pre- and postshift urine samples (n = 241; 41 male subjects) were analyzed for cotinine and 1-OHP. Descriptive statistics and generalized estimating equations were calculated. At the apprentice school cross-shift 1-OHP levels did not significantly differ. At the overhaul 1-OHP levels increased during the week in smokers and nonsmokers; in nonsmokers the 1-OHP level increased significantly postshift compared to preshift. In conclusion this study suggests that boilermakers exposed to occupational particulates are exposed to PAH. The urinary 1-OHP level may be a useful biomarker of PAH exposure in boilermakers exposed to ROFA, particularly in nonsmokers.
Bombesin and Neurotensin Reduce Endotoxemia, Intestinal Oxidative Stress, and Apoptosis in Experimental Obstructive Jaundice

Objective:To evaluate the effect of bombesin (BBS) and neurotensin (NT) on intestinal histopathology, intestinal oxidative stress, and endotoxemia in experimental obstructive jaundice. Summary Background Data:Obstructive jaundice compromises gut barrier function, resulting in endotoxemia. BBS and NT, exerting various biologic actions on gastrointestinal tissues, preserve gut mucosal integrity in cases of injury or atrophy. Methods:Seventy male Wistar rats were randomly divided into 5 groups: I = controls, II = sham operated, III = bile duct ligation (BDL), IV = BDL + BBS (30 μg/kg/d), V = BDL + NT (300 μg/kg/d). By the end of the experiment, on day 10, endotoxin was measured in portal and aortic blood. Tissue sections of the terminal ileum were examined histologically, and villus density, mucosal thickness, mitotic activity and apoptosis in crypts were assessed. In addition, ileal mucosa was analyzed for DNA and protein content. To estimate intestinal oxidant/antioxidant equilibrium, lipid peroxidation, protein oxidation, and thiol redox state (reduced glutathione [GSH], oxidized glutathione [GSSG], total nonprotein mixed disulfides [NPSSR], protein thiols [PSH], and protein disulfides [PSSP]) were determined on tissue homogenates from the terminal ileum. Results:BBS or NT administration significantly reduced portal and systemic endotoxemia observed in obstructive jaundice. Both factors reversed obstructive jaundice-induced morphologic features of intestinal atrophy, increasing villus density and mucosal thickness. This effect was accompanied by induction of mitoses and reduction of apoptosis in intestinal crypts. Mucosal DNA and protein content were reduced, although not to significant levels, in BDL animals and restored to control levels after BBS or NT treatment. Moreover, BBS or NT administration protected the intestine in jaundiced rats against oxidative stress, as demonstrated by reduction of intestinal lipid peroxidation, increase of the antioxidant GSH, and decrease of the oxidized forms GSSG and NPSSR, while BBS additionally reduced protein oxidation as well. Conclusions:Administration of BBS or NT in bile duct–ligated rats exerts beneficial effects on intestinal oxidative stress, cell proliferation, apoptosis, and endotoxemia. This observation might be of potential value in patients with extrahepatic cholestasis.
Clinical Usefulness of Human Epididymis Protein 4 in Lung Cancer

Human epididymis protein 4 (HE4) has been suggested as a useful new biomarker of lung cancer; however, few relevant large-scale studies have been published. In this study, we evaluated the utility of serum HE4 for lung cancer detection. HE4 levels were measured in serum samples from 100 lung cancer patients, 57 patients with benign lung diseases, and 274 healthy controls by using a chemiluminescent immunoassay, and variations in HE4 levels were analyzed by clinical status such as lung cancer, benign lung disease, and healthy condition, Tumor, Lymph Nodes, Metastasis (TNM) stage, tumor score, and histological cancer type. Lung cancer patients had significantly higher serum HE4 levels than patients with benign lung diseases and healthy controls (P<0.0001). The area under the ROC curve for HE4 was 0.84 (95% confidence interval, 0.78–0.89; P<0.0001) between lung cancer patients and healthy controls. Serum HE4 levels were significantly higher in patients with advanced disease (according to TNM stage) than in healthy controls (P<0.0001). HE4 levels were significantly elevated in patients with tumors of all types, those of different histological subgroups, and those with the smallest tumors (P=0.002). This report supports the potential of serum HE4 as an ancillary diagnostic marker for lung cancer detection.
Analysis of a patch-PCB-antenna for mobile phones

In this paper an alternative analysis of a patch-PCB-combination (called ‘antenna’ in this paper) for handheld devices is presented. In many publications like [2, 3] this antenna is interpreted as consisting of two resonators (PCB and patch) which are coupled through an electrical field. In the respective equivalent circuit the E-field-coupling is described by using a transformer. The aim of the work presented in this paper is to determine an equivalent circuit for the antenna only by analytical analyzing its simulated impedance-behaviour. The attributes of this equivalent circuit are compared to those of the equivalent circuit found in [2, 3]. Additionally, on the basis of the derived equivalent circuit some further investigations on the function of the antenna are presented.
Macromolecular crowding perturbs protein refolding kinetics: implications for folding inside the cell

We have studied the effects of macromolecular crowding on protein folding kinetics by studying the oxidative refolding of hen lysozyme in the absence and presence of high concentrations of bovine serum albumin and Ficoll 70. The heterogeneity characteristic of the lysozyme refolding process is preserved under crowded conditions. This, together with the observation that the refolding intermediates that accumulate to significant levels are very similar in the absence and presence of Ficoll, suggests that crowding does not alter substantially the energetics of the protein folding reaction. However, the presence of high concentrations of macromolecules results in the acceleration of the fast track of the refolding process whereas the slow track is substantially retarded. The results can be explained by preferential excluded volume stabilization of compact states relative to more unfolded states, and suggest that, relative to dilute solutions, the rates of many protein folding processes are likely to be altered under conditions that more closely resemble the intracellular environment.
Brain delivery of olanzapine by intranasal administration of transfersomal vesicles

The aim of this study was to investigate the presence of a possible direct correlation between vesicle elasticity and the amount of drug reaching the brain intranasally. Therefore, transfersomes were developed using phosphatidylcholine (PC) as the lipid matrix and sodium deoxycholate (SDC), Span® 60, Cremophor® EL, Brij® 58, and Brij® 72 as surfactants. The influence of the type of surfactant and PC-to-surfactant ratio on vesicle morphology, size, membrane elasticity, drug entrapment, and in vitro drug release was studied. The prepared transfersomes were mainly spherical in shape, with diameters ranging from 310 to 885 nm. Transfersomes containing SDC and Span 60 with optimum lipid-to-surfactant molar ratio showed suitable diameters (410 and 380 nm, respectively) and deformability indices (17.68 and 20.76 mL/sec, respectively). Values for absolute drug bioavailability in rat plasma for transfersomes containing SDC and those containing Span 60 were 24.75 and 51.35%, whereas AUC0–360min values in rat brain were 22,334.6 and 36,486.3 ng/mL/min, respectively. The present study revealed that the deformability index is a parameter having a direct relation with the amount of the drug delivered to the brain by the nasal route.
Inactivation of p16 in Human Mammary Epithelial Cells by CpG Island Methylation

ABSTRACT Proliferation of human mammary epithelial cells (HMEC) is limited to a few passages in culture due to an arrest in G1 termed selection or mortality stage 0, M0. A small number of cells spontaneously escape M0, continue to proliferate in culture, and then enter a second mortality stage, M1, at which they senesce. Evidence that M0 involves the Rb pathway comes from the observation that expression of human papillomavirus type 16 E7 alleviates the M0 proliferation block, and we further show that the Rb-binding region of E7 is required to allow cells to bypass M0. In contrast, E6 does not prevent HMEC from entering M0 but, rather, is involved in M1 bypass. Here we show that inactivation of the D-type cyclin-dependent kinase inhibitor p16INK4A is associated with escape from the M0 proliferation block. Early-passage HMEC express readily detectable amounts of p16 protein, whereas normal or E6-expressing HMEC that escaped M0 expressed markedly reduced amounts of p16 mRNA and protein. This initial reduction of p16 expression was associated with limited methylation of the p16 promoter region CpG island. At later passages, a further reduction in p16 expression occurred, accompanied by increased CpG island methylation. In contrast, reduction of p16 expression did not occur in E7-expressing HMEC that bypassed M0, due to inactivation of Rb. These observations in the E6-expressing HMEC correlate well with the finding that CpG island methylation is a mechanism of p16 inactivation in the development of human tumors, including breast cancer.