Miracle-dz/UniFAR-FTUs huggingface dataset:
Ultrathin Ceramic Membranes as Scaffolds for Functional Cell Coculture Models on a Biomimetic Scale

Abstract Epithelial tissue serves as an interface between biological compartments. Many in vitro epithelial cell models have been developed as an alternative to animal experiments to answer a range of research questions. These in vitro models are grown on permeable two-chamber systems; however, commercially available, polymer-based cell culture inserts are around 10 μm thick. Since the basement membrane found in biological systems is usually less than 1 μm thick, the 10-fold thickness of cell culture inserts is a major limitation in the establishment of realistic models. In this work, an alternative insert, accommodating an ultrathin ceramic membrane with a thickness of only 500 nm (i.e., the Silicon nitride Microporous Permeable Insert [SIMPLI]-well), was produced and used to refine an established human alveolar barrier coculture model by both replacing the conventional inserts with the SIMPLI-well and completing it with endothelial cells. The structural–functional relationship of the model was evaluated, including the translocation of gold nanoparticles across the barrier, revealing a higher translocation if compared to corresponding polyethylene terephthalate (PET) membranes. This study demonstrates the power of the SIMPLI-well system as a scaffold for epithelial tissue cell models on a truly biomimetic scale, allowing construction of more functionally accurate models of human biological barriers.
HIV-1 Nef Binds a Subpopulation of MHC-I throughout Its Trafficking Itinerary and Down-regulates MHC-I by Perturbing Both Anterograde and Retrograde Trafficking*

The HIV protein Nef is thought to mediate immune evasion and promote viral persistence in part by down-regulating major histocompatibility complex class I protein (MHC-I or HLA-I) from the cell surface. Two different models have been proposed to explain this phenomenon as follows: 1) stimulation of MHC-I retrograde trafficking from and aberrant recycling to the plasma membrane, and 2) inhibition of anterograde trafficking of newly synthesized HLA-I from the endoplasmic reticulum to the plasma membrane. We show here that Nef simultaneously uses both mechanisms to down-regulate HLA-I in peripheral blood mononuclear cells or HeLa cells. Consistent with this, we found by using fluorescence correlation spectroscopy that a third of diffusing HLA-I at the endoplasmic reticulum, Golgi/trans-Golgi network, and the plasma membrane (PM) was associated with Nef. The binding of Nef was similarly avid for native HLA-I and recombinant HLA-I A2 at the PM. Nef binding to HLA-I at the PM was sensitive to specific inhibition of endocytosis. It was also attenuated by cyclodextrin disruption of PM lipid micro-domain architecture, a change that also retarded lateral diffusion and induced large clusters of HLA-I. In all, our data support a model for Nef down-regulation of HLA-I that involves both major trafficking itineraries and persistent protein-protein interactions throughout the cell.
NOD2/CARD15 Gene Variants Are Linked to Failure of Antibiotic Treatment in Perianal Fistulating Crohn's Disease

OBJECTIVES:The Crohn's disease (CD) susceptibility gene, nucleotide-binding oligomerizetion domain 2 (NOD2)/caspase recruitment domain 15 (CARD15), is linked to the innate immune response associated with altered epithelial bacterial defense. Its relevance in antibiotic therapy of perianal fistulating CD remains elusive. The aim of the study was to explore systematically the association between NOD2/CARD15 variants and clinical response of perianal fistulas in patients using antibiotic therapy.METHODS:Fifty-two patients (median age 36 yr) with draining perianal fistulas were treated with ciprofloxacin (N = 49) or metronidazole (N = 3) for a median duration of 7 wk. Complete response was defined as the absence of any draining fistula despite gentle finger compression. Genotyping for NOD2/CARD15 variants and human beta (β)-defensin 2 (HBD-2) copies was performed by 5′ nuclease assays (Applied Biosystems, Foster City, CA). The examiners and laboratory investigators were blinded. The Fisher exact test and Wilcoxon signed rank test were used for statistical analysis.RESULTS:Ciprofloxacin was discontinued in one patient due to diarrhea after 2 wk. Complete fistula response was observed in 13 of 39 patients with NOD2/CARD15 wild-type (33.3%) compared with none in patients carrying NOD2/CARD15 variants (0%, P = 0.02). The median number of HBD-2 gene copies between responders and partial/nonresponders was similar.CONCLUSIONS:The study result suggests a substantial contribution of NOD2/CARD15 to the antibiotic treatment outcome of perianal fistulating CD. NOD2/CARD15 variants may predispose to an altered intestinal microflora in perianal fistulas that is less responsive to antibiotic treatment.
Plasma Homocysteine, Cobalamin/Folate Status, and Vascular Disease in a Large Population of Psychogeriatric Patients

Background: Cobalamin/folate deficiency and vascular disease are prevalent in elderly subjects and may lead to mental symptoms, but may even more often influence the severity of other organic and non-organic mental diseases. In the present study, we have evaluated cobalamin–folate status and the presence of vascular disease in 1,982 psychogeriatric patients investigated and diagnosed in a psychogeriatric clinic. The objective of the present study is to obtain information on the role of cobalamin/folate status and vascular disease in different diagnoses of psychogeriatric patients and their association with plasma homocysteine (tHcy). Methods: We have measured serum cobalamin, blood/serum folate, serum creatinine, plasma tHcy and evaluated the presence of vascular disease in 1,982 well-defined psychogeriatric patients. Results and Conclusions: The present study indicates that cobalamin/folate deficiencies do not play an important role in cognitive dysfunction in psychogeriatric patients, since only about 7% of the study population had metabolic cobalamin/folate deficiencies. Furthermore, cobalamin/folate deficiencies were rare in younger patients (below 70 years of age). We were also able to confirm our previous finding that there was no association between dementia of Alzheimer type (AD) and plasma tHcy level or metabolic cobalamin/folate deficiencies. Furthermore, we observed a low proportion of vascular disease in patients with AD, which does not give support for an association between well-defined AD and the presence of vascular disease. The presence of vascular disease was higher and of similar degree in patients with mild cognitive impairment and depression, which indicates an association between these diagnoses and the presence of vascular disease. The present study also shows that at plasma tHcy levels below 14 µmol/l, the likelihood of cobalamin/folate deficiency is small and further investigation of cobalamin/folate status could be omitted.
The Prevalence of CDKN2A Germ-Line Mutations and Relative Risk for Cutaneous Malignant Melanoma: An International Population-Based Study

Germ-line mutations of CDKN2A have been identified as strong risk factors for melanoma in studies of multiple-case families. However, an assessment of their relative risk for melanoma in the general population has been difficult because they occur infrequently. We addressed this issue using a novel population-based case-control study design in which “cases” have incident second- or higher-order melanomas [multiple primary melanoma (MPM)] and “controls” have incident first primary melanoma [single primary melanoma (SPM)]. Participants were ascertained from nine geographic regions in Australia, Canada, Italy, and United States. In the 1,189 MPM cases and 2,424 SPM controls who were eligible and available for analysis, the relative risk of a subsequent melanoma among patients with functional mutations who have an existing diagnosis of melanoma, after adjustments for age, sex, center, and known phenotypic risk factors, is estimated to be 4.3 (95% confidence interval, 2.3-7.7). The odds ratio varied significantly depending on the type of mutation involved. The results suggest that the relative risk of mutation carriers in the population may be lower than currently believed and that different mutations on the CDKN2A gene may confer substantially different risks of melanoma. (Cancer Epidemiol Biomarkers Prev 2006;15(8)1520–5)
Dietary carbohydrate, fiber and sugar and risk of breast cancer according to menopausal status in Malaysia.

BACKGROUND Dietary carbohydrate, fiber and sugar intake has been shown to play a role in the etiology of breast cancer, but the findings have been inconsistent and limited to developed countries with higher cancer incidence. OBJECTIVE To examine the association of premenopausal and postmenopausal breast cancer risk with dietary carbohydrate, fiber and sugar intake. MATERIALS AND METHODS This population based case-control study was conducted in Malaysia with 382 breast cancer patients and 382 controls. Food intake pattern was assessed via an interviewer-administered food frequency questionnaire. Logistic regression was used to compute odds ratios (OR) with 95% confidence intervals (CI) and a broad range of potential confounders were included in analysis. RESULTS A significant two fold increased risk of breast cancer among premenopausal (OR Q4 to Q1=1.93, 95%CI: 1.53-2.61, p-trend=0.001) and postmenopausal (OR Q4 to Q1=1.87, 95%CI: 1.03-2.61, p-trend=0.045) women was observed in the highest quartile of sugar. A higher intake of dietary fiber was associated with a significantly lower breast cancer risk among both premenopausal (OR Q4 to Q1=0.31, 95%CI: 0.12-0.79, p-trend=0.009) and postmenopausal (OR Q4 to Q1=0.23, 95%CI: 0.07-0.76, p-trend=0.031) women. CONCLUSIONS Sugar and dietary fiber intake were independently related to pre- and postmenopausal breast cancer risk. However, no association was observed for dietary carbohydrate intake.
Role of Endoplasmic Reticulum Stress in Brain Damage After Cardiopulmonary Resuscitation in Rats

ABSTRACT Postcardiac arrest syndrome yields poor neurological outcomes, but the mechanisms underlying this condition remain poorly understood. This study investigated whether endoplasmic reticulum (ER) stress-mediated apoptosis is induced in injured brain after resuscitation. Sprague-Dawley rats were subjected to 6 min of cardiac arrest (CA) and then resuscitated successfully. In the first experiment, animals were sacrificed 1, 3, 6, 12, or 24 h (n = 3 per group) after successful cardiopulmonary resuscitation. Brain tissues were analyzed by real-time polymerase chain reaction and Western blotting. In the second experiment, either dimethyl sulfoxide or salubrinal (Sal; 1 mg/kg), an ER stress inhibitor, was injected 30 min before the induction of CA (n = 10 per group). Neurological deficits were evaluated 24 h after CA. Brain specimens were analyzed using electron microscopy, terminal deoxynucleotidyl transferase dUTP nick end labeling assays and immunohistochemistry. We found that the messenger RNA and protein levels of glucose-regulated protein 78, X-box binding protein 1, C/EBP homologous protein, and caspase 12 were significantly elevated after resuscitation. We also observed that rats treated with Sal exhibited an improved neurological deficit score (32.3 ± 15.5 in the Sal group vs. 49.8 ± 20.9 in controls, P < 0.05). In addition, morphological improvements in the hippocampal ER were observed in the Sal group compared with the dimethyl sulfoxide group 24 h after reperfusion. Furthermore, in situ immunostaining revealed that markers of ER stress were significantly inhibited by Sal pretreatment. Our findings suggested that ER stress and the associated apoptotic pathways were activated in the hippocampus after resuscitation. Administration of Sal 30 min before cardiopulmonary resuscitation ameliorated neurological dysfunction 24 h after CA, possibly through the inhibition of ER stress after postresuscitation brain injury.
Hepatocellular Carcinomas Show Abnormal Expression of Fibronectin Protein

Fibronectin plays an important role in cell-to-cell adhesion, cell migration, and cell signaling. In the liver, fibronectin expression has been studied primarily as a component of the extracellular matrix, but little information is available on the expression of fibronectin protein in the neoplastic cells of hepatocellular carcinomas (HCCs). Twenty-four surgically resected HCCs were immunostained with fibronectin. Tumor and normal liver tissues were concurrently analyzed in all cases, and expression in the tumor was evaluated in comparison to the nonneoplastic liver. The average age at resection was 54 ± 18 years for the 18 men and 6 women. Twenty-one of the cases were classic HCCs including 6 cases that were well differentiated, 12 cases moderately differentiated, and 3 cases poorly differentiated. The remaining 3 cases were moderately differentiated fibrolamellar carcinomas. In the normal liver, fibronectin labeled the sinusoids and weakly to moderately stained the cytoplasm of hepatocytes. In HCCs, 15/24 showed overexpression of fibronectin in the cytoplasm, 8/24 showed no change from the nonneoplastic liver, and one case showed decreased cytoplasmic staining. In addition, an abnormal membranous staining pattern was noted in 16/24 HCCs. In contrast to the HCCs, none of the three fibrolamellar carcinomas showed increased cytoplasmic or membranous staining. Excluding fibrolamellar carcinoma, increased cytoplasmic staining and/or an abnormal membranous staining was noted in 19/21 (90%) of HCCs. Fibronectin shows abnormal cytoplasmic and/or membranous staining in the majority of HCCs. The implications of fibronectin overexpression are uncertain but may reflect a critical step in tumor genesis.
Inferring User Consumption Preferences from Social Media

SUMMARY Social Media has already become a new arena of our lives and involved di ﬀ erent aspects of our social presence. Users’ personal information and activities on social media presumably reveal their personal interests, which o ﬀ er great opportunities for many e-commerce applica-tions. In this paper, we propose a principled latent variable model to in- fer user consumption preferences at the category level (e.g. inferring what categories of products a user would like to buy). Our model naturally links users’ published content and following relations on microblogs with their consumption behaviors on e-commerce websites. Experimental re- sults show our model outperforms the state-of-the-art methods signiﬁcantly in inferring a new user’s consumption preference. Our model can also learn meaningful consumption-speciﬁc topics automatically.
Comparison of Perirectal versus Rectal Swabs for Detection of Asymptomatic Carriers of Toxigenic Clostridium difficile

ABSTRACT For long-term care and spinal cord injury patients, the sensitivity, specificity, and positive and negative predictive values of perirectal versus rectal cultures for detection of asymptomatic carriers of Clostridium difficile were 95%, 100%, 100%, and 97%, respectively. Perirectal cultures provide an accurate method to detect asymptomatic carriers of C. difficile.
Various sulfated carbohydrate tumor marker candidates identified by focused glycomic analyses

Glycomic analysis focused on sulfated O-glycans was performed to identify novel serum carbohydrate tumor markers. Sulfated glycans were enriched by α-neuraminidase digestion of pyridylaminated glycans prepared from sera, followed by anion exchange chromatography. Sulfated O-glycan profiles were constructed by two types of high performance liquid chromatography separation. Comparison of the profiles from 20 healthy controls with those of 11 gastric and 9 pancreatic cancer patients identified 14 marker candidates. The structures of these candidates were precisely analyzed using various methods including enzymatic digestion and mass spectrometry. The candidates comprised 9 core1 and 5 core2 glycans. All these candidates were monosulfated, and 11 were also mono- or difucosylated, and included various determinants such as 6-sulfo type2 lactosamine, 6-sulfo Lewis X, 6-sulfo Lewis Y, 3'-sulfo type1 lactosamine and 3'-sulfo Lewis A. Furthermore, among the core1 glycans, five candidates displayed a type1 and type2 lactosamine hybrid backbone. The levels of these candidate glycans in the sera from all 40 subjects were quantified using a selected reaction monitoring assay. These analyses revealed: (i) the levels of all candidates were elevated in sera of at least one or more patients; (ii) core1 candidates having type1-type2 hybrid backbones with 6-sulfo Lewis X, 6-sulfo type2 lactosamine or 3'-sulfo Lewis A were elevated in sera of variety of patients; and (iii) levels of the candidates varied widely among patients, suggesting analysis of multiple candidates will be an effective means of screening various cancers. To fully evaluate the clinical utility of these candidates, a further verification study is required.
Coparenting profiles in the context of Mexican-origin teen pregnancy: links to mother-daughter relationship quality and adjustment.

The current study explored the multifaceted nature of the mother-adolescent coparental relationship with data from 167 Mexican-origin adolescent mothers and their own mothers at 10 months post childbirth. Profiles of mother-adolescent coparenting were created with latent profile analysis using adolescents' reports of three dimensions of coparenting (communication, involvement, and conflict). Four profiles were identified: (a) Harmonious Coparents (equal involvement, high communication, low conflict); (b) Harmonious-Adolescent Primary (adolescent is more involved than mother, high communication, low conflict); (c) Conflictual Coparents (equal involvement, high communication, high conflict); and (d) Conflictual-Adolescent Primary (adolescent is more involved than mother, moderate communication, high conflict). Families characterized by high mother-daughter conflict and psychological control prior to childbirth were more likely to belong in the Conflictual Coparents profile. In addition, adolescents' and mothers' depressive symptoms and parenting efficacy after childbirth were linked to profile membership, such that the Harmonious-Adolescent Primary profile reported the most positive adjustment patterns, whereas profiles with high coparental conflict (i.e., Conflictual Coparenting and Conflictual-Adolescent Primary profiles) showed the least positive adjustment patterns. Discussion considers the applied implications of identifying precursors to healthy and problematic mother-daughter coparenting for families of adolescent mothers in the early years of parenting.
Estimating demand function parameters of mobile applications

ABSTRACT The vibrant market for mobile applications has raised awareness of several professional and also voluntary software developers. The key question especially for professional developers is how to improve the profit gained with a developed app. Recent research provided evidence on the factors that determine the demand of a mobile app. This paper presents a procedure to estimate demand function parameters that are required for developing pricing, advertising and also product update strategies. More specifically, the procedure estimates an app’s maximal willingness to pay, demand elasticity on price and network value. The procedure is based on the Fulfilled Expectations Cournot Model and requires knowledge about the apps being considered as substitutes to each other. It is applied to a data set consisting of download rank data of Apple iPhone apps.
Acute mechanical bowel obstruction: clinical presentation, etiology, management and outcome.

AIM To identify and analyze the clinical presentation, management and outcome of patients with acute mechanical bowel obstruction along with the etiology of obstruction and the incidence and causes of bowel ischemia, necrosis, and perforation. METHODS This is a prospective observational study of all adult patients admitted with acute mechanical bowel obstruction between 2001 and 2002. RESULTS Of the 150 consecutive patients included in the study, 114 (76%) presented with small bowel and 36 (24%) with large bowel obstruction. Absence of passage of flatus (90%) and/or feces (80.6%) and abdominal distension (65.3%) were the most common symptoms and physical finding, respectively. Adhesions (64.8%), incarcerated hernias (14.8%), and large bowel cancer (13.4%) were the most frequent causes of obstruction. Eighty-eight patients (58.7%) were treated conservatively and 62 (41.3%) were operated (29 on the first day). Bowel ischemia was found in 21 cases (14%), necrosis in 14 (9.3%), and perforation in 8 (5.3%). Hernias, large bowel cancer, and adhesions were the most frequent causes of bowel ischemia (57.2%, 19.1%, 14.3%), necrosis (42.8%, 21.4%, 21.4%), and perforation (50%, 25%, 25%). A significantly higher risk of strangulation was noticed in incarcerated hernias than all the other obstruction causes. CONCLUSION Absence of passage of flatus and/or feces and abdominal distension are the most common symptoms and physical finding of patients with acute mechanical bowel obstruction, respectively. Adhesions, hernias, and large bowel cancer are the most common causes of obstruction, as well as of bowel ischemia, necrosis, and perforation. Although an important proportion of these patients can be nonoperatively treated, a substantial portion requires immediate operation. Great caution should be taken for the treatment of these patients since the incidence of bowel ischemia, necrosis, and perforation is significantly high.
All-digital self-adaptive PVTA variation aware clock generation system for DFS

An all-digital self-adaptive clock generation system capable of adapt the clock frequency to compensate the effects of PVTA variations on the IC propagation delay and satisfy an externally set propagation length condition is presented. The design uses time-to-digital converters (TDCs) to measure the propagation length and a variable length ring oscillator (VLRO) to synthesize the clock signal. The VLRO naturally adapts its frequency to the PVTA variations suffered by its logic gates while the TDCs are used to track these variations across the chip and modify the VLRO length in order to adapt the clock frequency to them. The system measurements, for a 45nm FPGA, show that it adapts the VLRO length, and therefore the clock frequency, to satisfy the propagation length condition. Measurements also prove the system capabilities to act as a dynamic frequency scaling clock source since the propagation length condition value act as a frequency selection input and a strong linear relation between the input value and the resultant clock period is present.
Oncolytic Specificity of Newcastle Disease Virus Is Mediated by Selectivity for Apoptosis-Resistant Cells

ABSTRACT Newcastle disease virus (NDV) is a negative-sense RNA virus that has been shown to possess oncolytic activity. NDV's selective replication in tumor cells has been previously suggested to be due to the lack of a proper antiviral response in these cells. Here we demonstrate that NDV possesses oncolytic activity in tumor cells capable of a robust type I interferon (IFN) response, suggesting that another mechanism underlies NDV's tumor specificity. We show that the oncolytic selectivity of NDV for tumor cells is dependent upon tumor cell resistance to apoptosis. Utilizing the human non-small-cell lung cancer cell line A549 overexpressing the antiapoptotic protein Bcl-xL, we show significant enhancement of oncolytic activity and NDV replication. Interestingly, while the Bcl-xL-overexpressing cells were resistant to apoptotic stimuli induced by chemotherapeutic agents and early viral replication, during the subsequent viral cycles, we observed a paradoxical increase in apoptosis in response to NDV. The increased oncolytic activity seen was secondary to enhanced viral replication and syncytium formation. The induction of a type I IFN response was enhanced in Bcl-xL cells. Overall, these findings propose a new mechanism for cancer cell specificity for NDV, making it an attractive anticancer agent for chemoresistant tumors with enhanced antiapoptotic activity.