Miracle-dz/UniFAR-FTUs huggingface dataset:
A competition between hydrophobic and electrostatic interactions in protein–ligand systems. Binding of heterogeneously halogenated benzotriazoles by the catalytic subunit of human protein kinase CK2

A series of chlorine‐substituted benzotriazole derivatives, representing all possible substitution patterns of halogen atoms attached to the benzotriazole benzene ring, were synthetized as potential inhibitors of human protein kinase CK2. Basic ADME parameters for the free solutes (hydrophobicity, electronic properties) together with their binding affinity to the catalytic subunit of protein kinase CK2 were determined with reverse‐phase HPLC, spectrophotometric titration, and Thermal Shift Assay Method, respectively. The analysis of position‐dependent thermodynamic contribution of a chlorine atom attached to the benzotriazole ring confirmed the previous observation for brominated benzotriazoles, in which substitution at positions 5 and 6 with bromine was found crucial for ligand binding. In all tested halogenated benzotriazoles the replacement of Br with Cl decreases the hydrophobicity, while the electronic properties remain virtually unaffected. Supramolecular architecture identified in the just resolved crystal structures of three of the four possible dichloro‐benzotriazoles shows how substitution distant from the triazole ring affects the pattern of intermolecular interactions. Summarizing, the benzotriazole benzene ring substitution pattern has been identified as the main driver of ligand binding, predominating the non‐specific hydrophobic effect.
Sociocognitive factors associated with lifestyle intervention attrition after successful weight loss among participants with prediabetes-The PREVIEW study.

INTRODUCTION Major risk factors for type 2 diabetes are lifestyle choices such as lack of physical activity (PA) and poor diet. Many individuals either do not take part or struggle to complete interventions supporting lifestyle changes. Demographic and theory-based sociocognitive factors associated with PREVIEW intervention attrition after successful weight loss were examined. METHODS Participants (1,856) who started the weight maintenance phase after completion of low-energy diet were retrospectively divided into three clusters depending on the point they left the trial. Discriminant analysis examined which demographic and theory-based sociocognitive variables were associated with cluster membership. RESULTS Most of the participants were women and well-educated. Two discriminant functions were calculated (χ2 (24) = 247.0, p ≥ . 05, d = 0.78). The demographic variables, such as age and ethnicity, and the social cognitive variable outcome expectancies on the other side were associated with cluster membership. Older age, Caucasian ethnicity, and fewer expected disadvantages of PA were associated with high success. DISCUSSION The discriminant model gave insight into some factors associated with early attrition. For practitioners planning interventions it underlines the necessity to take extra attention to younger participants and to those being afraid that being physically active causes unpleasant ramifications.
Streptococcus caledonicus sp. nov., isolated from sheep.

Five strains of an unidentified Gram-positive, catalase-negative, chain-forming coccus-shaped organism recovered from sheep in Scotland were characterized using phenotypic and molecular taxonomic methods. Based on morphological and biochemical criteria, the strains were tentatively identified as streptococci but they did not appear to correspond to any recognised species of the genus. Comparative 16S rRNA gene sequencing showed the strains were highly related to each other and confirmed their placement in the genus Streptococcus, with a maximum nucleotide identity of around 97 % to extant species. Best matches were with Streptococcus hillyeri followed by Streptococcus porci. Average nucleotide identity and in silico DNA-DNA hybridization values determined from whole-genome sequence were also consistent with the group representing a novel species. Best matches, again seen to S. hillyeri, followed by S. porci and S. plurextorum, were below accepted cut-off values for species delineation. Based on biochemical criteria and molecular genetic evidence, it is proposed that the unknown isolates from sheep be assigned to a new species of the genus Streptococcus as Streptococcus caledonicus sp. nov. The type strain of Streptococcus caledonicus is S784/96/1T=CCUG 73951T=NCTC 14363T.
Molecular, epidemiological and haematological evaluation in Theileria orientalis infected cattle from an endemic region in India

Abstract The objective of the present study was to investigate the epidemiological and haematological parameters with simultaneous molecular detection of Theileria orientalis infection of crossbred jersey (CBJ) cattle. Haematological values like mean hemoglobin (Hb) (7.31 ± 2.3 g/dl), packed cell volume (PCV) (21.69 ± 6.11%), red blood cells count (RBCs) (4.40 ± 1.6 M/μl), white blood cells count (WBCs) (6.93 ± 3.06 103/µl) and mean corpuscular hemoglobin concentration (MCHC) (33.56 ± 3.51 g/dl) were decreased significantly (p < 0.05), whereas mean corpuscular volume (MCV) (51.06 ± 6.14fl) and eosinophil count (0.39 ± 0.44 103/µl) were significantly (p < 0.05) increased in cattle infected with T. orientalis. Analysis of major piroplasm surface protein (MPSP) of 110 blood samples randomly collected from cattle from seven districts by PCR indicated that an average of 70% of cattle was positive for T. orientalis infection. In particular, Puri and Khorda districts were identified as relatively high-risk areas for T. orientalis infection, with infection rates of 76.66% and 72.4%, respectively. The phylogenetic analysis of isolated T. orientalis MPSP gene (MN334767) classified it into type 5. Earlier Indian isolates were classified into three types viz.type 1, type 3 and type 7 and this is the first time to detect type 5 in Odisha, India.
Profiles of immune‐related genes and immune cell infiltration in the tumor microenvironment of diffuse lower‐grade gliomas

The tumor microenvironment is highly correlated with tumor occurrence, progress, and prognosis. We aimed to investigate the immune‐related gene (IRG) expression and immune infiltration pattern in the tumor microenvironment of lower‐grade glioma (LGG). We employed the Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm to calculate immune and stromal scores and identify prognostic IRG based on The Cancer Genome Atlas data set. The potential molecular functions of these genes were explored with the help of functional enrichment analysis and the protein–protein interaction network. Remarkably, three cohorts that were downloaded from the Chinese Glioma Genome Atlas database were analyzed to further verify the prognostic values of these genes. Moreover, the Tumor IMmune Estimation Resource (TIMER) algorithm was used to estimate the abundance of infiltrating immune cells and explore the immune infiltration pattern in LGG. And unsupervised cluster analysis determined three clusters of the immune infiltration pattern and indicated that CD8+ T cells and macrophages were significantly associated with LGG outcomes. Altogether, our study identified a list of prognostic IRGs and provided a perspective to explore the immune infiltration pattern in LGG.
Lowering the increased intracellular pH of human‐induced pluripotent stem cell‐derived endothelial cells induces formation of mature Weibel‐Palade bodies

Differentiation of human‐induced pluripotent stem cells (hiPSCs) into vascular endothelium is of great importance to tissue engineering, disease modeling, and use in regenerative medicine. Although differentiation of hiPSCs into endothelial‐like cells (hiPSC‐derived endothelial cells [hiPSC‐ECs]) has been demonstrated before, controversy exists as to what extent these cells faithfully reflect mature endothelium. To address this issue, we investigate hiPSC‐ECs maturation by their ability to express von Willebrand factor (VWF) and formation of Weibel‐Palade bodies (WPBs). Using multiple hiPSCs lines, hiPSC‐ECs failed to form proper VWF and WPBs, essential for angiogenesis, primary and secondary homeostasis. Lowering the increased intracellular pH (pHi) of hiPSC‐ECs with acetic acid did result in the formation of elongated WPBs. Nuclear magnetic resonance data showed that the higher pHi in hiPSC‐ECs occurred in association with decreased intracellular lactate concentrations. This was explained by decreased glycolytic flux toward pyruvate and lactate in hiPSC‐ECs. In addition, decreased expression of monocarboxylate transporter member 1, a member of the solute carrier family (SLC16A1), which regulates lactate and H+ uptake, contributed to the high pHi of hiPSC‐EC. Mechanistically, pro‐VWF dimers require the lower pH environment of the trans‐Golgi network for maturation and tubulation. These data show that while hiPSC‐ECs may share many features with mature EC, they are characterized by metabolic immaturity hampering proper EC function.
Synergistic Treatment of Tumor by Targeted Biotherapy and Chemotherapy via Site-Specific Anchoring of Aptamers on DNA Nanotubes

Background Aptamers have been widely used as targeted therapeutic agents due to its relatively small physical size, flexible structure, high specificity, and selectivity. Aptamers functionalized nanomaterials, not only enhance the targeting of nanomaterials, but can also improve the stability of the aptamers. We developed aptamer C2NP (Apt) conjugated straight DNA nanotubes (S-DNT-Apt) and twisted DNA nanotubes (T-DNT-Apt) as nanocarriers for doxorubicin (DOX). Methods The twisted DNA nanotubes (T-DNT) and straight DNA nanotubes (S-DNT) were assembled with a scaffold and hundreds of staples. Apt was site-specifically anchored on DNA nanotubes with either different spatial distribution (3 or 6 nm) or varied stoichiometry (15Apt or 30Apt). The developed nanocarriers were characterized with agarose gel electrophoresis and transmission electron microscopy. The drug loading and release in vitro were evaluated by measuring the fluorescence intensity of DOX using a microplate reader. The stability of DNT in cell culture medium plus 10% of FBS was evaluated by agarose gel electrophoresis. The cytotoxicity of DNA nanostructures against K299 cells was tested with a standard CCK8 method. Cellular uptake, cell apoptosis, cell cycle and reactive oxygen species level were investigated by flow cytometry. The expression of p53 was examined by Western Blot. Results T-DNT-30Apt-6 exhibited the highest cytotoxicity when the concentration of Apt was 120 nM. After intercalation of DOX, the cytotoxicity of DOX@T-DNT-30Apt-6 was further enhanced due to the combination of chemotherapy of DOX and biotherapy of Apt. The enhanced cytotoxicity of DOX@T-DNT-30Apt-6 can be explained by the increase in the cellular uptake, cell apoptosis and intracellular ROS levels. Additionally, the interaction between Apt and its receptor CD30 could upregulate the expression of p53. Conclusion These results demonstrate that both stoichiometry and spatial arrangement of Apt on T-DNT-Apt influence the anticancer activity. The developed twisted DNA nanotubes may be a solution for the synergistic treatment of cancer.
Imported Malaria in Countries where Malaria Is Not Endemic: a Comparison of Semi-immune and Nonimmune Travelers

The continuous increase in long-distance travel and recent large migratory movements have changed the epidemiological characteristics of imported malaria in countries where malaria is not endemic (here termed non-malaria-endemic countries). While malaria was primarily imported to nonendemic countries by returning travelers, the proportion of immigrants from malaria-endemic regions and travelers visiting friends and relatives (VFRs) in malaria-endemic countries has continued to increase. VFRs and immigrants from malaria-endemic countries now make up the majority of malaria patients in many nonendemic countries. SUMMARY The continuous increase in long-distance travel and recent large migratory movements have changed the epidemiological characteristics of imported malaria in countries where malaria is not endemic (here termed non-malaria-endemic countries). While malaria was primarily imported to nonendemic countries by returning travelers, the proportion of immigrants from malaria-endemic regions and travelers visiting friends and relatives (VFRs) in malaria-endemic countries has continued to increase. VFRs and immigrants from malaria-endemic countries now make up the majority of malaria patients in many nonendemic countries. Importantly, this group is characterized by various degrees of semi-immunity to malaria, resulting from repeated exposure to infection and a gradual decline of protection as a result of prolonged residence in non-malaria-endemic regions. Most studies indicate an effect of naturally acquired immunity in VFRs, leading to differences in the parasitological features, clinical manifestation, and odds for severe malaria and clinical complications between immune VFRs and nonimmune returning travelers. There are no valid data indicating evidence for differing algorithms for chemoprophylaxis or antimalarial treatment in semi-immune versus nonimmune malaria patients. So far, no robust biomarkers exist that properly reflect anti-parasite or clinical immunity. Until they are found, researchers should rigorously stratify their study results using surrogate markers, such as duration of time spent outside a malaria-endemic country.
ANTI MICROBIAL EVALUATION OF POLYHERBAL EXTRACT IN THE TREATMENT OF PERIODONTITIS

To formulate and evaluate polyherbal extract, prepared by combined extracts of Psidium guajava, Emblica officinalis, Terminalia bellerica L and Syzygium aromaticum for treatment of Periodontitis. The formulation containing herbs viz., the leaves of Psidium guajava (Myrtaecae), fruits of Emblica officinalis L. (Euphorbiaceae), leaves of Terminalia bellerica L. (Combretaceae), dried flower buds of Syzygium aromaticum (Myrtaceae),The Antimicrobial efficacy of the formulated Polyherbal extract was tested on Streptococcus mutans, Escherichia coli, Staphylococcus aureus and Proteus vulgaris by Dip well technique. Dip well method showed that the polyherbal extract has good antimicrobial activity when compared with the standard Antibiotic. The present study revealed that the polyherbal extract exhibited comparatively better activity than standard.
Effects of guanotrophication and warming on the abundance of green algae, cyanobacteria and microcystins in Lake Lesser Prespa, Greece

Lake Lesser Prespa in Greece is a vital breeding habitat for the Dalmatian and Great White Pelican and a shelter for numerous rare and endemic species. However, eutrophication processes are distressing the lake system and the outbreaks of cyanobacterial blooms during the warm months may pose a threat to aquatic organisms due to the presence of microcystins (MCs). In this study we hypothesize that nutrients (eutrophication), nutrient-rich pelican droppings (guanotrophication) and warming (climate change) can affect the algal growth and MCs production in the water layer of Lake Lesser Prespa. Seston collected from three lake sites was incubated at ambient (20°C) and high (30°C) temperature with or without the addition of nutrients (nitrogen (N), phosphorus (P)), or pelican droppings. Results showed increased chlorophyll-a at higher temperature (30°C). N addition yielded higher chlorophyll-a levels than the non-treated water or when only P was added. The addition of both N and P as well as the addition of pelican dropping resulted in the highest chlorophyll-a at both temperatures. Notably, in the dropping-treatments, cyanobacteria and MCs were promoted while changes were evoked in the relative contribution of toxic MC-variants. Guanotrophication may thus influence the cyanobacterial dynamics and most likely their toxicity profile at Lesser Prespa.
The ‘exotic other’ in medical curricula: Rethinking cultural diversity in course manuals

Abstract Introduction: Implementation of cultural diversity training in medical education faces challenges, including ambiguity about the interpretation of ‘cultural diversity’. This is worrisome as research has demonstrated that the interpretation employed matters greatly to practices and people concerned. This study therefore explored the construction of cultural diversity in medical curricula. Methods: Using a constructivist approach we performed a content analysis of course materials of three purposefully selected undergraduate curricula in the Netherlands. Via open coding we looked for text references that identified differences labelled in terms of culture. Iteratively, we developed themes from the text fragments. Results: We identified four mechanisms, showing together that culture is unconsciously constructed as something or someone exotic, deviant from the standard Dutch or Western patient or disease, and therefore problematic. Conclusions: We complemented earlier identified mechanisms of othering and stereotyping by showing how these mechanisms are embedded in educational materials themselves and reinforce each other. We argue that the embedded notion of ‘problematic stranger’ can lead to a lack of tools for taking appropriate medical action and to insecurity among doctors. This study suggests that integrating more attention to biological and contextual differences in the entire medical curriculum and leaving out static references such as ethnicity and nationality, can enhance quality of medical training and care.
Mobilizing individual social capital resources for HIV care support: results of a pilot intervention in St. Petersburg, Russia

ABSTRACT Half of HIV-positive persons in Russia are on antiretroviral therapy (ART), and only 27% are virally suppressed. A feasibility pilot intervention to mobilize social capital resources for HIV care support was conducted in St. Petersburg. Out-of-care or ART-nonadherent HIV-positive persons (n = 24) attended a five-session intervention to increase access social capital resources (i.e., family, friends, or providers) to mobilize supports for entering care, initiating care, and adhering to ART. HIV care indicators were assessed at baseline, an immediate followup (FU-1), and 6-month followup (FU-2) points. At FU-1, participants more frequently discussed their care experiences with others, verifying the intervention’s mechanism of action. Participants increased in scales of medication taking adherence (p = 0.002, FU-1; p = 0.011, FU-2), self-efficacy (p = 0.042; FU-1), and outcome expectancies (p = 0.016, FU-2). Among persons not on ART, HIV Medication Readiness scale scores increased at FU-1 (p = 0.032) but became attenuated at FU-2. Participants tended to more frequently keep care appointments (79%, baseline to 90%, FU-1, p = 0.077); to have undetectable viral load (54%, baseline to 74%, FU-2; p = 0.063); and to have fewer past-month days with delayed or incomplete medication doses (7.8, baseline to 4.2, FU-1; p = 0.084). This novel social capital intervention is promising for improving HIV care-related outcomes and warrants a full-scale evaluation.
Reactive oxygen species and nitric oxide imbalances lead to in vivo and in vitro arrhythmogenic phenotype in acute phase of experimental Chagas disease

Chagas Disease (CD) is one of the leading causes of heart failure and sudden death in Latin America. Treatments with antioxidants have provided promising alternatives to ameliorate CD. However, the specific roles of major reactive oxygen species (ROS) sources, including NADPH-oxidase 2 (NOX2), mitochondrial-derived ROS and nitric oxide (NO) in the progression or resolution of CD are yet to be elucidated. We used C57BL/6 (WT) and a gp91PHOX knockout mice (PHOX-/-), lacking functional NOX2, to investigate the effects of ablation of NOX2-derived ROS production on the outcome of acute chagasic cardiomyopathy. Infected PHOX-/- cardiomyocytes displayed an overall pro-arrhythmic phenotype, notably with higher arrhythmia incidence on ECG that was followed by higher number of early afterdepolarizations (EAD) and 2.5-fold increase in action potential (AP) duration alternans, compared to AP from infected WT mice. Furthermore, infected PHOX-/- cardiomyocytes display increased diastolic [Ca2+], aberrant Ca2+ transient and reduced Ca2+ transient amplitude. Cardiomyocyte contraction is reduced in infected WT and PHOX-/- mice, to a similar extent. Nevertheless, only infected PHOX-/- isolated cardiomyocytes displayed significant increase in non-triggered extra contractions (appearing in ~75% of cells). Electro-mechanical remodeling of infected PHOX-/—cardiomyocytes is associated with increase in NO and mitochondria-derived ROS production. Notably, EADs, AP duration alternans and in vivo arrhythmias were reverted by pre-incubation with nitric oxide synthase inhibitor L-NAME. Overall our data show for the first time that lack of NOX2-derived ROS promoted a pro-arrhythmic phenotype in the heart, in which the crosstalk between ROS and NO could play an important role in regulating cardiomyocyte electro-mechanical function during acute CD. Future studies designed to evaluate the potential role of NOX2-derived ROS in the chronic phase of CD could open new and more specific therapeutic strategies to treat CD and prevent deaths due to heart complications.
Association between chronic pancreatitis and pancreatic cancer: A 10‐year retrospective study of endoscopically treated and surgical patients

Pancreatic cancer (PC) has a poor prognosis. Chronic pancreatitis (CP) associates with high morbidity and mortality, and serves as a risk factor for PC. Our study aimed to assess the association between endoscopically treated CP patients and PC, and to establish the rate of CP among patients undergoing surgery for pancreatic ductal adenocarcinoma (PDAC). We retrospectively analyzed 458 CP patients undergoing endoscopic treatment (ET) between 2000 and 2010 and 349 PDAC patients undergoing pancreatic resection between 2000 and 2014 at the Helsinki University Hospital. The likelihood of diagnosing PC was highest within 2 years of a CP diagnosis: 21 of 30 PC diagnoses occurred during this time. After 2 years follow‐up: 9 of 30 PC diagnoses occurred 2–12 years from CP diagnosis. Two patients were diagnosed with CP before PDAC. Multivariate analysis showed two prognostic factors indicative of PC development: biliary stricture (HR 9.21; 95% CI 3.76–22.08) and a higher age (per 5‐year increases) at CP onset (HR 1.55; 95% CI 1.30–1.85). Among 458 CP patients, the median overall survival without PC was 14.7 years (95% CI 12.0–17.3), falling to 1.6 years (95% CI 1.2–2.0) with PC. The high incidence of PC among CP patients at the beginning of follow‐up likely reflected an initially missed PC diagnoses. In long‐term follow‐up, an increasing PC incidence might reflect the PC‐predisposing impact of CP. Thus, we recommend careful follow‐up for patients presenting with a recently diagnosed CP and risk factors for PC.