Miracle-dz/UniFAR-FTUs huggingface dataset:
Weaknesses of histological analysis in celiac disease diagnosis: new possible scenarios

Abstract Introduction. Celiac disease (CD) is an autoimmune disorder triggered by the ingestion of gluten. Serology and organ culture system can support CD diagnosis, despite histology being the gold standard. Aim. We wanted to test the uniformity of application of Marsh–Oberhuber criteria by five different histologists. We also compared histological and serological data with cultural results to consider new possible strategies in CD diagnosis. Methods. We studied 114 patients, who were divided in two groups. Group A was composed of 66 patients on a gluten-containing diet, with gluten-related signs and symptoms, showing positive serological anti-endomysial antibodies (EMA) and anti-tissue transglutaminase (anti- tTG). Group B was composed of 48 disease-control patients, presenting serological EMA and anti-tTG negative results. All patients studied underwent esophagogastroduodenoscopy with duodenal biopsy and duodenal mucosa organ culture. All histological samples were evaluated by five different histologists according to an appropriate questionnaire following Marsh–Oberhuber classification. Cohen κ inter-test was used for evaluating the agreement between histologists regarding group A. Results. Strength of agreement was fair/moderate for villous:crypt ratio, moderate/good for villous height and crypt depth, and poor for intraepithelial lymphocytosis. Patients belonging to group A presented positive serological as well as cultural results in 100% of cases. None of the patients belonging to group B presented serological or cultural positive results. Discussion. Our study stresses the limits of histological interpretation due to the lack of uniformity in the use of Marsh–Oberhuber classification. These findings could cast doubt on the role of histology as CD gold standard and could open a debate on the most appropriate CD diagnostic procedure.
Implementation of Pastry-based P2P system to share sensor data

With research effort of ubiquitous computing development, wireless sensor networks have also been studied and deployed in many places. Recently, various works for sharing the existing sensor data have been tried. In this paper, we propose a P2P-based system for sharing sensor data. It uses a structured P2P – Pastry to provide DHT-based routing without server and has been deployed in KOREN. We classify the sensor data into real-time data and past data, and Scribe in Pastry is applied to multicast the real-time data and PAST in Pastry is used to store and provide the past data. Also, as Pastry itself does not provide the search function, we propose to use PAST for providing search function using keywords.
The effect of body position on postprandial perceptions, gastric emptying, and intragastric meal distribution: An ultrasonographic study in reclining healthy subjects

Abstract Objective. Postprandial dyspepsia is common and may be associated with abnormal intragastric distribution of food. We aimed to determine the effect of body position on gastric emptying, meal distribution, and postprandial perceptions in healthy subjects. Material and methods. Eight adolescents (4 females and 4 males aged 14 years) were investigated using three-dimensional ultrasonography. The subjects were studied twice in a random order: once in the right lateral recumbent (RLR) position and once in the left lateral recumbent (LLR) position. Postprandial perceptions, gastric volumes, and antral areas were recorded immediately after the ingestion of 500 ml of a low-caloric meat soup over 4 min, and at 10 and 20 min following the meal. Results. Postprandial perceptions (epigastric pain, nausea, and fullness) were more pronounced in the RLR position compared to the LLR position, particularly at the end of the meal ingestion (p < 0.01). Gastric volumes were significantly smaller in the RLR position compared to the LLR position at 10 min (p < 0.01) and 20 min (p < 0.05). Antral areas were significantly wider in the RLR position compared to the LLR position at 10 min (p < 0.05) and 20 min (p < 0.01). Conclusion. Postprandial perceptions are more pronounced, gastric emptying is faster, and antral area is wider in the RLR position compared to the LLR position. The results suggest that lying on the left side after a meal may be a measure to reduce postprandial dyspeptic sensations.
Nuts for diabetes prevention and management

Type 2 diabetes mellitus is an important preventable disease and a growing public health problem. Epidemiologic and clinical studies suggest that healthy eating, physical activity, and BW control are the main driving forces to reduce diabetes risk. Owing to their low available carbohydrate content, favorable fat and protein profile as well as phytonutrient content, nut consumption has been associated with a reduced risk of development and management of diabetes. Nuts, by virtue of its cardioprotective actions, have also been shown to reduce biomarkers of risk factors for diabetic complications. Although more studies are warranted, the emerging picture is that nut consumption beneficially influences diabetes risk and management beyond blood glucose control.
The IFN-γ–Dependent Suppressor of Cytokine Signaling 1 Promoter Activity Is Positively Regulated by IFN Regulatory Factor-1 and Sp1 but Repressed by Growth Factor Independence-1b and Krüppel-Like Factor-4, and It Is Dysregulated in Psoriatic Keratinocytes

Epidermal keratinocytes can counteract the detrimental effects of IFN-γ by inducing the expression of suppressor of cytokine signaling (SOCS)1, which plays an important anti-inflammatory and self-protective role. To date, limited information exists on its expression and regulation in human diseased keratinocytes. In this study, we compared the expression levels of SOCS1 in keratinocytes isolated from skin affected by psoriasis with cells obtained from healthy donors, unveiling that keratinocytes are more prone than healthy cells to upregulate SOCS1 mRNA expression in response to IFN-γ. We explored the regulatory mechanisms involved in socs1 gene transcription, and found that Sp1 and IFN regulatory factor-1 transcription factors are, respectively, responsible for the basal and IFN-γ–induced activity of human socs1 promoter. In parallel, we demonstrated that socs1 promoter is negatively regulated by two transcriptional repressors, namely, growth factor independence-1b and Krüppel-like factor 4, which tightly control SOCS1 transcription on IFN-γ stimulation. Interestingly, although the expression of Sp1 and IFN regulatory factor-1 activators of socs1 promoter is unaltered, growth factor independence-1b and Krüppel-like factor 4 are significantly reduced in psoriatic compared with healthy keratinocytes. This reduction and the consequent unbalanced binding of transcriptional activators and repressors to socs1 promoter after IFN-γ stimulation might be responsible for the enhanced expression of SOCS1 in psoriatic cells. We suggest that SOCS1 exaggerated upregulation in psoriatic keratinocytes could represent a mechanism through which these cells attempt to protect themselves from IFN-γ effects. However, the SOCS1 increased levels in psoriatic keratinocytes are not sufficient to completely inhibit the expression of proinflammatory genes.
Heterologous T Cells Can Help Restore Function in Dysfunctional Hepatitis C Virus Nonstructural 3/4A-Specific T Cells during Therapeutic Vaccination

The hepatitis C virus (HCV)-specific T cell response in patients with chronic HCV is dysfunctional. In this study, we aimed at restoring immunological function through therapeutic vaccination in a transgenic mouse model with impaired HCV-specific T cell responses due to a persistent presence of hepatic HCV nonstructural (NS)3/4A Ags. The HCV-specific T cells have an actively maintained dysfunction reflected in reduced frequency, impaired cytokine production, and impaired effector function in vivo, which can be partially restored by blocking regulatory T cells or programmed cell death ligand 1. We hypothesized that the impairment could be corrected by including sequences that created a normal priming environment by recruiting “healthy” heterologous T cells and by activating innate signaling. Endogenously expressed hepatitis B core Ag (HBcAg) can recruit heterologous T cells and activate TLR (TLR7) signaling. Hence, by combining HCV NS3/4A with different forms of HBcAg we found that heterologous sequences somewhat improved activation and expansion of NS3/4A-specific T cells in a wild-type host. Importantly, the signals provided by HBcAg effectively restored the activation of HCV-specific T cells in a tolerant NS3/4A-transgenic mouse model. The adjuvant effect could also be transferred to the priming of dysfunctional HLA-A2–restricted NS3-specific T cells in vivo. Thus, recruiting healthy heterologous T cells to the site of priming may also help restore HCV-specific responses present in a chronically infected host.
The Role of the Transcription Factor CREB in Immune Function

CREB is a transcription factor that regulates diverse cellular responses, including proliferation, survival, and differentiation. CREB is induced by a variety of growth factors and inflammatory signals and subsequently mediates the transcription of genes containing a cAMP-responsive element. Several immune-related genes possess this cAMP-responsive element, including IL-2, IL-6, IL-10, and TNF-α. In addition, phosphorylated CREB has been proposed to directly inhibit NF-κB activation by blocking the binding of CREB binding protein to the NF-κB complex, thereby limiting proinflammatory responses. CREB also induces an antiapoptotic survival signal in monocytes and macrophages. In T and B cells, CREB activation promotes proliferation and survival and differentially regulates Th1, Th2, and Th17 responses. Finally, CREB activation is required for the generation and maintenance of regulatory T cells. This review summarizes current advances involving CREB in immune function—a role that is continually being defined.
Autophagy Negatively Regulates Keratinocyte Inflammatory Responses via Scaffolding Protein p62/SQSTM1

The scaffolding adaptor protein p62/SQSTM1 (p62) has been shown to be an autophagy receptor that acts as a link between the ubiquitination and autophagy machineries. However, the roles of autophagy and p62 in human keratinocytes are not well understood. In this study, we show that keratinocyte autophagy negatively regulates p62 expression, which is essential for the prevention of excessive inflammation and the induction of cathelicidin in human keratinocytes. Stimulation of TLR2/6 or TLR4 in primary human keratinocytes robustly activated autophagy pathways and up-regulated p62 expression through induction of NADPH oxidases 2 and 4 and the generation of reactive oxygen species. MyD88 and TNFR-associated factor 6, key signaling molecules that mediate TLR activation, played an essential role in the induction of autophagy and p62 expression. Additionally, blockade of autophagy significantly increased the generation of inflammatory cytokines and expression of p62 in primary human keratinocytes. Notably, silencing hp62 through RNA interference resulted in a significant decrease in NF-κB activation, inflammatory cytokine production, cathelicidin expression, and cell proliferation (as well as cyclin D1 expression) in keratinocytes. Epidermal expression of p62 was further found to be significantly higher in psoriatic skin than in skin affected by atopic dermatitis or from healthy controls. Collectively, our data provide new insights into the roles of autophagy and p62 in controlling cutaneous inflammation.
Synergistic Interactions of TLR2/6 and TLR9 Induce a High Level of Resistance to Lung Infection in Mice

Infectious pneumonias exact an unacceptable mortality burden worldwide. Efforts to protect populations from pneumonia have focused historically on antibiotic development and vaccine-enhanced adaptive immunity. However, we have reported recently that the lungs’ innate defenses can be induced therapeutically by inhalation of a bacterial lysate that protects mice against otherwise lethal pneumonia. In this study, we tested in mice the hypothesis that TLRs are required for this antimicrobial phenomenon and found that resistance could not be induced in the absence of the TLR signaling adaptor protein MyD88. We then attempted to recapitulate the protection afforded by the bacterial lysate by stimulating the lung epithelium with aerosolized synthetic TLR ligands. Although most single or combination treatments yielded no protection, simultaneous treatment with ligands for TLR2/6 and TLR9 conferred robust, synergistic protection against virulent Gram-positive and Gram-negative pathogens. Protection was associated with rapid pathogen killing in the lungs, and pathogen killing could be induced from lung epithelial cells in isolation. Taken together, these data demonstrate the requirement for TLRs in inducible resistance against pneumonia, reveal a remarkable, unanticipated synergistic interaction of TLR2/6 and TLR9, reinforce the emerging evidence supporting the antimicrobial capacity of the lung epithelium, and may provide the basis for a novel clinical therapeutic that can protect patients against pneumonia during periods of peak vulnerability.
Mediators of Diabetic Renal Disease: The Case for TGF-β as the Major Mediator

The critical role of hyperglycemia in the genesis of diabetic nephropathy has been established by cell culture stud- ies, experimental animal models, and clinical trials. Certain cytokines and growth factors have been identified as likely mediators of the effects of high ambient glucose on the kidney, but prominent among these is TGF-, a prototypical hypertro- phic and fibrogenic cytokine. Overexpression of TGF- has been demonstrated in the glomerular and tubulointerstitial compartments of experimental diabetic animals. The TGF- receptor signaling system is also triggered, as evidenced by upregulation of the TGF- type II receptor and activation of the downstream Smad signaling pathway. Treatment of dia- betic mice with neutralizing anti-TGF- antibodies prevents the development of renal hypertrophy, mesangial matrix ex- pansion, and the decline in renal function. Antibody therapy also reverses the established lesions of diabetic glomerulopa- thy. These studies argue strongly in support of the hypothesis that overactivity of the TGF- system in the kidney is a crucial mediator of diabetic renal hypertrophy and mesangial matrix expansion. The structural renal changes in diabetes consist of glomer- ular and tubuloepithelial hypertrophy, followed by thickening of glomerular and tubular basement membranes and progres- sive accumulation of extracellular matrix proteins in the mes- angium and the interstitium. Identifying mediators of increased synthesis or decreased degradation of matrix molecules in diabetic renal disease may help design novel, effective thera- pies to avert glomerulosclerosis and tubulointerstitial fibrosis and the development of proteinuria and progressive renal insufficiency. TGF- is one effector molecule that has been studied ex-
A Role for IL-15 in the Migration of Effector CD8 T Cells to the Lung Airways following Influenza Infection

The cytokines generated locally in response to infection play an important role in CD8 T cell trafficking, survival, and effector function, rendering these signals prime candidates for immune intervention. In this paper, we show that localized increases in the homeostatic cytokine IL-15 induced by influenza infection is responsible for the migration of CD8 effector T cells to the site of infection. Moreover, intranasal delivery of IL-15–IL-15Rα soluble complexes (IL-15c) specifically restores the frequency of effector T cells lost in the lung airways of IL-15–deficient animals after influenza infection. Exogenous IL-15c quantitatively augments the respiratory CD8 T cell response, and continued administration of IL-15c throughout the contraction phase of the anti-influenza CD8 T cell response magnifies the resultant CD8 T cell memory generated in situ. This treatment extends the ability of these cells to protect against heterologous infection, immunity that typically depreciates over time. Overall, our studies describe what to our knowledge is a new function for IL-15 in attracting effector CD8 T cells to the lung airways and suggest that adjuvanting IL-15 could be used to prolong anti-influenza CD8 T cell responses at mucosal surfaces to facilitate pathogen elimination.
Analysis of demand-supply interaction and inventory build-up strategies for products with short life cycles

Revenues and profits from short life cycle products will depend upon careful formulation and execution of production plans in response to demands in the marketplace. This research contributes to the development of the production and inventory build-up strategies for short life cycle products under different demand-supply scenarios. A modified Bass diffusion model is used to characterise the product demand pattern with consideration of demand-sales interaction. We develop cost models based on production costs, inventory carrying costs, backlog costs, and cost of lost sales for a number of different production scenarios. The optimal production rate is obtained by minimising the total cost. We also investigate the benefit of an initial build-up of inventory before the product’s sales period starts.
Falls in a Proportional Region Population in Korean Elderly: Incidence, Consequences, and Risk Factors

Methods: The study participants were community-dwelling elderly people aged 65 years or old as a population based sample of one large city. A total of 828 people 65 years or older participated in this study. They were interviewed over the telephone by a trained interviewer using a structured questionnaire to obtain a fall history and details of their most recent fall including date, time, place, circumstances, and associated injury. As for risk factors for falls, we asked about living arran- gement (with family or alone), alcohol intake, exercise, visual and hearing impairments, memory and sensory problems, lower limb weakness, and arthritis symptoms. Fear of falling and fear-related activity restriction were also evaluated. Results: The incidence of falls during the last one year was 13.0%. Women experienced falls more frequently. Falls occurred mainly in spring and summer and from 10 AM to 3 PM. Common causes of falls were slipping and tripping. 14.9% of those who fell suffered consequent fractures. Being female was a significant risk factor for falls; and females tended to get injured more severely following a fall. During the recent one year, decreased proprioception in the lower extremity was a significant risk factor for falls. Those with histories of falls, and especially women, tended to limit their activities due to the fear of falling. Conclusion: Overall, it appears that elderly women are more greatly affected by falls at several levels. Female partici- pants fell more frequently and suffered more severe consequences. Fall-related injuries and risk factors for falls dis- proportionately affected women. And, being female and any amount of decreased sensation in the feet were significant risk factors for falls.
Udder health in dairy goats

In this thesis, monitoring and control of udder health in dairy goats was studied. The diagnostic properties of somatic cell count as a monitoring tool for udder health of a goat herd and of individual goats was evaluated. Furthermore, the diagnostic value of bacteriological culture of bulk milk and of individual milk samples was assessed. The importance of various udder health pathogens was studied. Staphylococcus aureus seems to be the most important udder health pathogen in goats. Somatic cell count served reasonably well in detecting this agent, but bacteriological culture was an insensitive test. Risk factors for infection with this pathogen were studied. In an economic frame-work, the costs associated with udder health problems were estimated.
CD5 Promotes IL-10 Production in Chronic Lymphocytic Leukemia B Cells through STAT3 and NFAT2 Activation

B lymphocytes from chronic lymphocytic leukemia (CLL) display some CD5 transcripts for CD5 containing the known exon 1 (E1A) and other CD5 transcripts containing the new exon 1 (E1B). These malignant B cells, as well as B cell lines transfected with cDNA for E1A-cd5 or with cDNA for E1B-cd5 produce IL-10, raising the possibility that CD5 participates in the secretion of IL-10. We identified transcription factors involved in this production in CD5+ B lymphocytes from CLL patients and in E1A-cd5–transfected or E1B-cd5–transfected Jok cells. STAT3 is activated via phosphorylation of serine 727 but also NFAT2 through its translocation into the nucleus. Chromatin immunoprecipitation experiments confirmed the role of STAT3 and allowed the discovery of a role for NFAT2 in IL-10 production. Both transcription factors bind not only to the enhancer of the Il-10 gene but also to the promoter of the Il-5 and Il-13 genes. Furthermore, transfection of B cell lines with E1A-cd5 or E1B-cd5 established that activation of STAT3 and NFAT2 is regulated by CD5. The same holds true for the production of IL-10, IL-5, and IL-13 and the expression of the receptors for these cytokines. This interpretation was confirmed by two experiments. In the first, downregulation of CD5 by small interfering RNAs lowered the production of IL-10. In the second experiment, transfection of the GFP-NFAT2 gene into B lymphocytes induced nuclear translocation of NFAT2 in CD5+ but not in CD5− B cells. Thus, CD5 expression is associated with NFAT2 activity (and mildly STAT3 activity), indicating that CD5 controls IL-10 secretion.
Contributions of Antinucleoprotein IgG to Heterosubtypic Immunity against Influenza Virus

Influenza A virus causes recurring seasonal epidemics and occasional influenza pandemics. Because of changes in envelope glycoprotein Ags, neutralizing Abs induced by inactivated vaccines provide limited cross-protection against new viral serotypes. However, prior influenza infection induces heterosubtypic immunity that accelerates viral clearance of a second strain, even if the external proteins are distinct. In mice, cross-protection can also be elicited by systemic immunization with the highly conserved internal nucleoprotein (NP). Both T lymphocytes and Ab contribute to such cross-protection. In this paper, we demonstrate that anti-NP IgG specifically promoted influenza virus clearance in mice by using a mechanism involving both FcRs and CD8+ cells. Furthermore, anti-NP IgG rescued poor heterosubtypic immunity in B cell-deficient mice, correlating with enhanced NP-specific CD8 T cell responses. Thus, Ab against this conserved Ag has potent antiviral activity both in naive and in influenza-immune subjects. Such antiviral activity was not seen when mice were vaccinated with another internal influenza protein, nonstructural 1. The high conservation of NP Ag and the known longevity of Ab responses suggest that anti-NP IgG may provide a critically needed component of a universal influenza vaccine.