Miracle-dz/UniFAR-FTUs huggingface dataset:
Inflammation, oxidative stress and altered heat shock response in type 2 diabetes: the basis for new pharmacological and non-pharmacological interventions

Abstract Type 2 diabetes mellitus (DM2) is a chronic disease characterised by variable degrees of insulin resistance and impaired insulin secretion. Besides, several pieces of evidence have shown that chronic inflammation, oxidative stress, and 70 kDa heat shock proteins (HSP70) are strongly involved in DM2 and its complications, and various pharmacological and non-pharmacological treatment alternatives act in these processes/molecules to modulate them and ameliorate the disease. Besides, uncontrolled hyperglycaemia is related to several complications as diabetic retinopathy, neuropathy and hepatic, renal and cardiac complications. In this review, we address discuss the involvement of different inflammatory and pro-oxidant pathways related to DM2, and we described molecular targets modulated by therapeutics currently available to treat DM2.
Association between previous high-dose antipsychotic therapy and brexpiprazole discontinuation after the initiation of brexpiprazole in patients with schizophrenia or schizoaffective disorder

The objective of this study was to identify the factors associated with brexpiprazole discontinuation after initiating brexpiprazole in patients with schizophrenia or schizoaffective disorder. All patients with schizophrenia or schizoaffective disorder who were started on brexpiprazole in our institution between May 2018 and April 2019 were retrospectively screened. The continuation rate of brexpiprazole during a follow-up period of 16 weeks was examined. Multivariate Cox regression analysis was conducted to identify predictors of brexpiprazole discontinuation. During the follow-up period, 52 out of 120 patients (43.4%) discontinued brexpiprazole. Thirty-three subjects discontinued due to a lack of efficacy, eight more due to intolerability and a further 11 for other reasons. The continuation rate of brexpiprazole among patients who were previously on high-dose antipsychotics (chlorpromazine-equivalent doses > 800 mg) was significantly lower than that in those who were previously on low-dose antipsychotics (chlorpromazine-equivalent doses ≤ 800 mg). The Cox regression analysis showed that only having been subject to a high dose of their previous antipsychotics was independently associated with an increased risk of brexpiprazole discontinuation (P < 0.001). Patients who were previously on high-dose antipsychotics discontinued brexpiprazole mainly due to inefficacy. Previous high-dose antipsychotic therapy is an independent risk factor for brexpiprazole discontinuation in patients with schizophrenia or schizoaffective disorder.
Autophagic Survival Precedes Programmed Cell Death in Wheat Seedlings Exposed to Drought Stress

Although studies have shown the concomitant occurrence of autophagic and programmed cell death (PCD) in plants, the relationship between autophagy and PCD and the factors determining this relationship remain unclear. In this study, seedlings of the wheat cultivar Jimai 22 were used to examine the occurrence of autophagy and PCD during polyethylene glycol (PEG)-8000-induced drought stress. Autophagy and PCD occurred sequentially, with autophagy at a relatively early stage and PCD at a much later stage. These findings suggest that the duration of drought stress determines the occurrence of PCD following autophagy. Furthermore, the addition of 3-methyladenine (3-MA, an autophagy inhibitor) and the knockdown of autophagy-related gene 6 (ATG6) accelerated PEG-8000-induced PCD, respectively, suggesting that inhibition of autophagy also results in PCD under drought stress. Overall, these findings confirm that wheat seedlings undergo autophagic survival under mild drought stress, with subsequent PCD only under severe drought.
HPV-related Sinonasal Carcinoma

Supplemental Digital Content is available in the text. The prevalence and prognostic value of human papillomavirus (HPV) infection and epidermal growth factor receptor (EGFR) alteration in sinonasal squamous cell carcinoma (SNSCC) are not known. The reliability of p16 overexpression as a surrogate for HPV infection in SNSCC is also unclear. We investigated the prognostic and diagnostic significances of HPV infection, EGFR alteration, and p16 expression in SNSCC. We analyzed high-risk HPV infection by HPV-RNA in situ hybridization and EGFR gene copy number gain (CNG) by chromogenic in situ hybridization and by determining the protein expressions of p16, Rb, and EGFR by immunohistochemistry in 101 SNSCC cases. HPV infection (n=9, 8.9%) and p16 overexpression (n=15, 14.9%) were associated with better overall survival (P=0.0042 and 0.005, respectively). The HPV+ cases were located predominantly at the nasal cavity with nonkeratinizing histology and partial loss of Rb. Notably, 40% (6/15) of p16+ SNSCCs were HPV−. Two of these cases showed complete loss of Rb expression by immunohistochemistry, suggesting a reason for the above discrepancy. EGFR CNG, detected in 30.5% of the SNSCCs, was correlated with EGFR protein overexpression (P=0.0001). HPV infection and EGFR CNG were mutually exclusive. The HPV+/EGFR CNG− group had significantly better overall survival than the HPV−/EGFR CNG− and HPV−/EGFR CNG+ groups (P=0.0471 and 0.0343, respectively). Our results suggest that HPV infection is a favorable prognostic marker in SNSCC, but p16 is not a perfect surrogate marker; the Rb expression pattern may improve the diagnostic accuracy. The molecular subclassification of SNSCCs based on HPV infection and EGFR copy number status might provide important information for therapeutic strategies.
Late implant placement following ridge preservation versus early implant placement: A pilot randomized clinical trial for periodontally compromised non-molar extraction sites.

AIM To compare late implant placement following alveolar ridge preservation (LP/ARP) and early implantation (EP) in periodontally compromised non-molar extraction sites with respect to soft tissue levels, esthetics, and patient-reported outcomes. MATERIALS AND METHODS Sixteen patients were randomly allocated to groups LP/ARP (n = 9) or EP (n = 7). Group LP/ARP received ARP using deproteinized bovine bone mineral containing 10% collagen and a native bilayer collagen membrane, and group EP received only extraction. Implant placement was performed 4-8 weeks post-extraction in group EP and 4 months post-alveolar ridge preservation in group LP/ARP. The soft tissue levels, pink/white esthetic scores, and periodontal parameters were evaluated 1-year post-loading. Patient's discomfort level was evaluated at the time of extraction/ARP and implant placement. RESULTS No implant failure or biologic complications occurred. There was no statistically significant difference in the median change of the midfacial mucosal margin (0.03 for group LP/ARP, -0.19 mm for group EP) and the mesial/distal papilla (0.62/0.25 mm for group LP/ARP, 0.29/-0.5 mm for group EP), pink/white esthetic scores, periodontal parameters, and patient's discomfort between the two groups. CONCLUSION Both implant placement protocols led to comparable outcomes in soft tissue levels, periodontal parameters, and patient's discomfort level.
An unbiased immunoaffinity-based strategy for profiling covalent drug targets in vivo.

Activity-based chemical proteomics approaches used for identifying cellular targets of drugs are mainly dependent on the availability of probes derived from drugs. However, all chemical probes are structurally different from the drugs themselves, and cannot fully mimic the real actions of drugs in cells. Here we present a concise and unbiased immunoaffinity-based strategy for identifying covalent drug targets in vivo. By using the specific antibody, we not only confirm the well-known ibrutinib-binding target BTK, but also identify some previously undescribed strongly binding proteins, such as CKAP4 in human cell lines, and TAP1 in mouse organs. The observed target profiles between species may partially explain why certain drug candidates are very effective in mice but not in human. This approach avoids the chemical modification of drugs, eliminates the non-specific bindings of chemical probes, and allows to unbiasedly decode the underlying mechanisms of action of covalent drugs.
Over-expression of CmSOS1 confers waterlogging tolerance in Chrysanthemum.

Manipulating the level of expression of SOS1, a protein which regulates the movement and distribution of sodium ions, has been shown to enhance the salinity tolerance of a number of plant species, but its involvement in the response to hypoxia is less well established. Here, the contribution of the chrysanthemum homolog CmSOS1 on the expression of waterlogging tolerance has been explored. The over-expression of CmSOS1 improved the survival rate of plants exposed to waterlogging, while the performance of CmSOS1 knock-down plants was inferior to that of wild type ones. The leaf's relative electrical conductivity, malondialdehyde (MDA), peroxide (H2 O2 ) and superoxide contents were all lowered in stressed over-expressors, whereas their soluble protein content and superoxide dismutase and catalase activity levels were all heightened. To further explore the mechanism, an oxidative stress regulator CmRCD1 was found to interact with CmSOS1, while CmRCD1 knock-down plants also appeared sensitive to waterlogging in chrysanthemum. The sensitivity to waterlogging of the Arabidopsis thaliana sos1 and rcd1 mutants was confirmed. The conclusion was that CmSOS1, via its interaction with CmRCD1, enhances the plants' waterlogging tolerance, presumably by maintaining the integrity of the plants' membranes and strengthening their capacity to neutralize reactive oxygen species. This article is protected by copyright. All rights reserved.
The potential application of human PIG‐A assay on azathioprine‐treated inflammatory bowel disease patients

The rodent Pig‐a assay has been used extensively as a potential regulatory assay for evaluating the in vivo mutagenicity of test substances. Although the assay can be conducted in different mammalian species, there have been only a few reports describing its use in humans, and rarely in genotoxicant‐exposed human populations. In this study, PIG‐A mutation frequencies (MFs) were evaluated in 36 azathioprine (AZA; human carcinogen)‐treated inflammatory bowel disease (IBD) patients and 36 healthy volunteers. IBD patients exhibited a slight but statistically higher MF (6.10 ± 4.44 × 10−6) than healthy volunteers (4.97 ± 2.74 × 10−6) (P = 0.0489). The estimated relative risk for the exposed patients was 1.22 which indicated that AZA is a risk factor for inducing PIG‐A mutation. However, the PIG‐A MF showed no associations with AZA treatment duration or total AZA exposure. In addition, we performed the cytokinesis‐block micronucleus test on the same samples. The frequencies of micronuclei (MN) and nuclear buds (NBUD) in IBD patients (MN: 4.70 ± 2.86‰; NBUD: 1.89 ± 0.95‰) were significantly higher than in healthy volunteers (MN: 1.47 ± 0.77‰, P < 0.001; NBUD: 0.90 ± 0.58‰, P = 0.004). MN frequency also had significant correlations with AZA treatment duration (P = 0.011) and total AZA exposure (P = 0.018). Our findings indicate that AZA‐treated IBD patients have only a marginally significant increase in PIG‐A MF; in contrast, a much stronger AZA‐associated increase in genotoxicity was detected with the lymphocyte MN assay. Environ. Mol. Mutagen. 2019. © 2019 Wiley Periodicals, Inc.
Estado menopáusico e síndrome metabólica em mulheres no climatério atendidas em um ambulatório no sul do Brasil

09 Parte I: Artigo de revisao 11 Prevalencia de sindrome metabolica e seus componentes na transicao menopausica Parte II: Artigo original I 37 Menopausal status and metabolic syndrome in women in climacteric period treated at a clinic in southern Brazil Parte II: Artigo original II 58 Lipid Accumulation Product (LAP) and its relation with cardiometabolic risk, socioeconomic and reproductive characteristics in women in climacteric period
Antigenic fingerprinting of RSV-A infected hematopoietic cell transplant recipients reveals importance of mucosal anti-RSV-G antibodies in control of RSV infection in humans.

BACKGROUND Respiratory syncytial virus (RSV) infection causes significant morbidity in hematopoietic cell transplants (HCT) patients. However, antibody response that correlate with recovery from RSV disease are not fully understood. METHODS In this study, antibody repertoire in paired serum and nasal wash samples from acutely RSV-A infected HCT patients who recovered early (<14 days RSV shedding) were compared with late-recovered patients (>14 days shedding) using gene fragment phage display libraries (GFPDL) and surface plasmon resonance (SPR). RESULTS Anti-F serum response were similar between these two groups for antibody repertoires, neutralization titers, anti-F binding antibodies (pre-fusion and post-fusion proteins), antibody avidity and binding to specific antigenic sites. In contrast, nasal washes from early-recovered individuals demonstrated higher binding to F peptide containing p27. While the serum RSV-G antibody repertoires in the two groups were similar, the strongest difference between early-recovered and late-recovered patients was observed in the titers of nasal wash antibodies, especially binding to the central conserved domain (CCD). Most importantly, a significantly higher antibody affinity to RSV-G was observed in nasal washes from early-recovered individuals compared with late-recovered HCT patients. CONCLUSIONS These findings highlight the importance of mucosal antibodies in resolution of RSV-A infection in the upper respiratory tract.
Protein docking model evaluation by 3D deep convolutional neural networks

MOTIVATION Many important cellular processes involve physical interactions of proteins. Therefore, determining protein quaternary structures provides critical insights for understanding molecular mechanisms of functions of the complexes. To complement experimental methods, many computational methods have been developed to predict structures of protein complexes. One of the challenges in computational protein complex structure prediction is to identify near-native models from a large pool of generated models. RESULTS We developed a convolutional deep neural network-based approach named DOVE (DOcking decoy selection with Voxel-based deep neural nEtwork) for evaluating protein docking models. To evaluate a protein docking model, DOVE scans the protein-protein interface of the model with a 3D voxel and considers atomic interaction types and their energetic contributions as input features applied to the neural network. The deep learning models were trained and validated on docking models available in the ZDock and DockGround databases. Among the different combinations of features tested, almost all outperformed existing scoring functions. AVAILABILITY Codes available at http://github.com/kiharalab/DOVEhttp://kiharalab.org/dove/. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Exploring the Interface between Inflammatory and Therapeutic Glucocorticoid Induced Bone and Muscle Loss

Due to their potent immunomodulatory anti-inflammatory properties, synthetic glucocorticoids (GCs) are widely utilized in the treatment of chronic inflammatory disease. In this review, we examine our current understanding of how chronic inflammation and commonly used therapeutic GCs interact to regulate bone and muscle metabolism. Whilst both inflammation and therapeutic GCs directly promote systemic osteoporosis and muscle wasting, the mechanisms whereby they achieve this are distinct. Importantly, their interactions in vivo are greatly complicated secondary to the directly opposing actions of GCs on a wide array of pro-inflammatory signalling pathways that underpin catabolic and anti-anabolic metabolism. Several clinical studies have attempted to address the net effects of therapeutic glucocorticoids on inflammatory bone loss and muscle wasting using a range of approaches. These have yielded a wide array of results further complicated by the nature of inflammatory disease, underlying the disease management and regimen of GC therapy. Here, we report the latest findings related to these pathway interactions and explore the latest insights from murine models of disease aimed at modelling these processes and delineating the contribution of pre-receptor steroid metabolism. Understanding these processes remains paramount in the effective management of patients with chronic inflammatory disease.
Controlling Actuation Performance in Physically Cross-linked Polylactone Blends Using Polylactide Stereocomplexation.

Within the field of shape-changing materials, synthetic chemical modification has been widely used to introduce key structural units and subsequently expand the mechanical functionality of actuator devices. The introduction of architectural elements which facilitate in-situ control over mechanical properties and complete geometric reconfiguration of a device, are highly desirable to increase the morphological diversity of polymeric actuator materials. The subject of the present study is a multiblock copolymer with semicrystalline poly(L lactide) and poly(ε caprolactone) (PLLA-PCL) segments. By harnessing the stereocomplexation of this copolymer chains with a poly(D lactide) oligomer (PDLA), we provide anchoring points for physical network formation, and demonstrate how a blending process can be used to efficiently vary the mechanical properties of a shape-memory actuator. We investigate the effect of molecular structure on the actuation performance of the material in cyclic thermomechanical tests, with a maximum reversible shape change ε`rev = 13.4 ± 1.5% measured at 3.1 wt. % of polylactide stereocomplex content in the multiblock copolymer matrix. The thermophysical properties, crystalline structure and phase morphology were analyzed by DSC, WAXS and AFM respectively, elucidating the structure-to-function relationship in physically cross-linked blended materials. The work demonstrates a one-step technique for manufacturing a polymeric actuator and tuning its performance in-situ. This approach should greatly improve the efficiency of physically cross-linked actuator fabrication, allowing composition and physical behavior to be precisely and easily controlled.
A critical look: Challenges in differentiating human pluripotent stem cells into desired cell types and organoids

Too many choices can be problematic. This is certainly the case for human pluripotent stem cells (hPSCs): they harbor the potential to differentiate into hundreds of cell types; yet it is highly challenging to exclusively differentiate hPSCs into a single desired cell type. This review focuses on unresolved and fundamental questions regarding hPSC differentiation and critiquing the identity and purity of the resultant cell populations. These are timely issues in view of the fact that hPSC‐derived cell populations have or are being transplanted into patients in over 30 ongoing clinical trials. While many in vitro differentiation protocols purport to “mimic development,” the exact number and identity of intermediate steps that a pluripotent cell takes to differentiate into a given cell type in vivo remains largely unknown. Consequently, most differentiation efforts inevitably generate a heterogeneous cellular population, as revealed by single‐cell RNA‐sequencing and other analyses. The presence of unwanted cell types in differentiated hPSC populations does not portend well for transplantation therapies. This provides an impetus to precisely control differentiation to desired ends—for instance, by logically blocking the formation of unwanted cell types or by overexpressing lineage‐specifying transcription factors—or by harnessing technologies to selectively purify desired cell types. Conversely, approaches to differentiate three‐dimensional “organoids” from hPSCs intentionally generate heterogeneous cell populations. While this is intended to mimic the rich cellular diversity of developing tissues, whether all such organoids are spatially organized in a manner akin to native organs (and thus, whether they fully qualify as organoids) remains to be fully resolved.
Different ways to assess overweight and obesity related to metabolic syndrome

INTRODUCTION: Obesity is a health problem related to diabetes mellitus and atherosclerosis events. Metabolic syndrome includes some of atherosclerosis risk factors and has a fat accumulation as one of its main physiopathologic mechanisms but its assessment changes among criteria used for its diagnosis. OBJECTIVE: Aim of this study was to define the contribution of different variations of overweight/obesity on diagnosis of metabolic syndrome and endothelial dysfunction. METHODS: We designed an observational and cross-sectional study to study a group of patients presenting with metabolic syndrome according to the Adult Treatment Panel III (ATP) criteria, and were compared considering three different assessment examinations of overweight/obesity. Moreover, results of flow vasodilatation test were correlated. RESULTS: Abdominal circumference criterion was fulfilled in 85,7 % of cases, that of the waist/hip rate in 100 %, and body mass rate in 69 %. There is a strong correlation (r: 0, 86) between abdominal circumference and the body mass rate. Endothelial dysfunction was more closely correlated with abdominal circumference and in a lesser level with the body mass rate. CONCLUSIONS: Measurement of abdominal circumference is a useful variable to assess metabolic syndrome and its relation with endothelial dysfunction.
Hotel restaurant brand attributes : Exploratory Factor Analysis

No doubt attracting and retaining customers in any restaurant operation including the hotel restaurant is essential for it performance and operational survival. That is the reason why creating a strong brand is one of strategies used by many restaurant operations in achieving the purpose. Nevertheless, despite the increasing interest in the concept of brand loyalty, brand awareness, brand image, brand competitiveness in the restaurant setting and its operational aspects, there has been still very little research looking at the association of the brands with the hotel restaurant setting in particular. With that, this paper reviewing the hotel restaurant brand attributes dealing with food quality, service quality and physical environment. The items in each construct is empirically tested and run through the exploratory factor analysis to see the underlying relationships and the grouping of them is consistent with the way the questionnaire is developed and subsequently used the construct as predictor for customer dining experience, satisfaction and post purchase behavior.
Analysis of the Emergence and Decline of Waterfront Markets in the Nakhonchaisri Basin : Based on Spatial Con fi guration

his article has as its objective to explain the emergence and decline of waterfront markets in the Nakornchaisri basin, Nakornpathom Province, Thailand, with a focus on spatial confi guration characteristics and spatial centrality using spatial confi guration analysis and principles. The analysis incorporates the theories of natural movement, movement economy process, and spatial centrality. The space syntax program was used in the analysis to produce a spatial model map representing transportation route networks of the past and the present for comparison to determine how and why the changes occurred.