Miracle-dz/UniFAR-FTUs huggingface dataset:
Tyrosine Threonine Kinase Inhibition Eliminates Lung Cancers by Augmenting Apoptosis and Polyploidy

The spindle assembly checkpoint maintains genomic integrity. A key component is tyrosine threonine kinase (TTK, also known as Mps1). TTK antagonism is hypothesized to cause genomic instability and cell death. Interrogating The Cancer Genome Atlas revealed high TTK expression in lung adenocarcinomas and squamous cell cancers versus the normal lung (P < 0.001). This correlated with an unfavorable prognosis in examined lung adenocarcinoma cases (P = 0.007). TTK expression profiles in lung tumors were independently assessed by RNA in situ hybridization. CFI-402257 is a highly selective TTK inhibitor. Its potent antineoplastic effects are reported here against a panel of well-characterized murine and human lung cancer cell lines. Significant antitumorigenic activity followed independent treatments of athymic mice bearing human lung cancer xenografts (6.5 mg/kg, P < 0.05; 8.5 mg/kg, P < 0.01) and immunocompetent mice with syngeneic lung cancers (P < 0.001). CFI-402257 antineoplastic mechanisms were explored. CFI-402257 triggered aneuploidy and apoptotic death of lung cancer cells without changing centrosome number. Reverse phase protein arrays (RPPA) of vehicle versus CFI-402257–treated lung cancers were examined using more than 300 critical growth-regulatory proteins. RPPA bioinformatic analyses discovered CFI-402257 enhanced MAPK signaling, implicating MAPK antagonism in augmenting TTK inhibitory effects. This was independently confirmed using genetic and pharmacologic repression of MAPK that promoted CFI-402257 anticancer actions. TTK antagonism exerted marked antineoplastic effects against lung cancers and MAPK inhibition cooperated. Future work should determine whether CFI-402257 treatment alone or with a MAPK inhibitor is active in the lung cancer clinic.
Low sleep time is associated with higher levels of blood pressure and fat mass in Amerindian schoolchildren

While altered sleep patterns (ie, low sleep time) have been studied and reported in adults as a new cardiometabolic risk factor, less information is available on how sleep patterns impact children of different ethnicities. The aim of this study was to compare the levels of blood pressure and other cardiometabolic risk factors in relation to different levels of sleep time in schoolchildren of Amerindian Mapuche or European‐ancestry of Southern Chile.
Tits Buildings and K-Stability

Abstract A polarized variety is K-stable if, for any test configuration, the Donaldson–Futaki invariant is positive. In this paper, inspired by classical geometric invariant theory, we describe the space of test configurations as a limit of a direct system of Tits buildings. We show that the Donaldson–Futaki invariant, conveniently normalized, is a continuous function on this space. We also introduce a pseudo-metric on the space of test configurations. Recall that K-stability can be enhanced by requiring that the Donaldson–Futaki invariant is positive on any admissible filtration of the co-ordinate ring. We show that admissible filtrations give rise to Cauchy sequences of test configurations with respect to the above mentioned pseudo-metric.
Rice Homeobox Protein KNAT7 Integrates the Pathways Regulating Cell Expansion and Wall Stiffness1[OPEN]

Rice KNAT7 interacts with a growth master regulator, GRF4, and a secondary wall regulator, NAC31, to coordinate cell expansion and wall thickening in fiber cells. During growth, plant cells must coordinate cell expansion and cell wall reinforcement by integrating distinct regulatory pathways in concert with intrinsic and external cues. However, the mechanism underpinning this integration is unclear, as few of the regulators that orchestrate cell expansion and wall strengthening have been identified. Here, we report a rice (Oryza sativa) Class II KNOX-like homeobox protein, KNOTTED ARABIDOPSIS THALIANA7 (KNAT7), that interacts with different partners to govern cell expansion and wall thickening. A loss-of-function mutation in KNAT7 enhanced wall mechanical strength and cell expansion, resulting in improved lodging resistance and grain size. Overexpression of KNAT7 gave rise to the opposite phenotypes, with plants having weaker cell walls and smaller grains. Biochemical and gene expression analyses revealed that rice KNAT7 interacts with a secondary wall key regulator, NAC31, and a cell growth master regulator, Growth-Regulating Factor 4 (GRF4). The KNAT7-NAC31 and KNAT7-GRF4 modules suppressed regulatory pathways of cell expansion and wall reinforcement, as we show in internode and panicle development. These modules function in sclerenchyma fiber cells and modulate fiber cell length and wall thickness. Hence, our study uncovers a mechanism for the combined control of cell size and wall strengthening, providing a tool to improve lodging resistance and yield in rice production.
Classification of Clinically Diagnosed Alzheimer's Disease Associated with Diabetes Based on Amyloid and Tau PET Results.

BACKGROUND/OBJECTIVE Although type 2 diabetes mellitus (DM) is a risk factor for the development of dementia, the underlying brain pathologies and mechanisms vary among patients. In this study, we classified patients with clinically diagnosed Alzheimer's disease (AD) associated with DM into subgroups based on their amyloid and tau accumulation patterns on positron emission tomography (PET), and analyzed the differences in clinical features and brain imaging findings between the subgroups. METHODS Sixty-four patients with probable or possible AD associated with DM were classified using PiB (detects amyloid, A) and PBB3 (detects tau, T) PET studies. Patients were classified into the A+/T+ group (n = 35, AD pathology), the A- /T+ group (n = 19, tauopathy), and the A- /T- group (n = 10, non-amyloid/non-tau neuronal damage). RESULTS Compared with the A+/T+ group, the A- /T+ group showed less-well controlled glycemia, longer duration of diabetes, more glucose variability, higher frequency of insulin therapy and biochemical hypoglycemia, and greater impairment of frontal lobe function, slower progression of cognitive decline, fewer APOE4 carriers, less severe medial temporal lobe atrophy, and lower frequency of posterior cerebral hypoperfusion. This subgroup showed different clinical and radiological features from AD. CONCLUSION Among patients with clinically diagnosed AD with DM, there are subgroups with neuronal damage independent of AD pathology. A subgroup of dementia patients suspected of having tauopathy is strongly associated with DM-related metabolic abnormalities. This study highlights the identification of a novel dementia subgroup (diabetes-related dementia), which is important for considering appropriate therapies and care in clinical practice.
Acute kidney injury prediction models: current concepts and future strategies.

PURPOSE OF REVIEW Acute kidney injury (AKI) is a critical condition associated with poor patient outcomes. We aimed to review the current concepts and future strategies regarding AKI risk prediction models. RECENT FINDINGS Recent studies have shown that AKI occurs frequently in patients with common risk factors and certain medical conditions. Prediction models for AKI risk have been reported in medical fields such as critical care medicine, surgery, nephrotoxic agent exposure, and others. However, practical, generalizable, externally validated, and robust AKI prediction models remain relatively rare. Further efforts to develop AKI prediction models based on comprehensive clinical data, artificial intelligence, improved delivery of care, and novel biomarkers may help improve patient outcomes through precise AKI risk prediction. SUMMARY This brief review provides insights for current concepts for AKI prediction model development. In addition, by overviewing the recent AKI prediction models in various medical fields, future strategies to construct advanced AKI prediction models are suggested.
Molecular characterization of durum wheat backcross inbred lines derived from Triticum turgidum var. dicoccoides

Wild species of Triticeae, as a result of their adaptability to a wide range of environments in the course of their evolution, include populations with a large variability for many characters such as morphological traits, drought and cold tolerance, resistance to insects and fungal diseases, quality and quantity of grain storage protein. The mapping populations currently used are derived from interspecific crosses between cultivated and wild species accessions because of the low polymorphism at the DNA level among wheat cultivars. In order to investigate the genetic basis of important qualitative and quantitative traits and to introduce new, useful alleles into durum wheat, a set of backcross inbred lines (BILs) was developed from the cross of durum wheat cv Latino and one accession of Triticum turgidum var. dicoccoides (MG29896) with agronomically important traits. The BILs were tested in replicated field experiments for grain protein content and grain yield components and a subset of 28 BILs was selected for molecular marker characterization. The introgression of several segments of Triticum turgidum var. dicoccoides donor genome located on the durum wheat chromosomes was detected.
AH2 encodes a MYB domain protein that determines hull fate and affects grain yield and quality in rice.

The palea and lemma (hull) are grass-specific organs, and determine grain size and quality. In the study, AH2 encodes a MYB domain protein, and functions in the development of hull and grain. Mutation of AH2 produces smaller grains and alters grain quality including decreased amylose content and gel consistency, and increased protein content. Meantime, part of the hull lost the outer silicified cells, and induces a transformation of the outer rough epidermis to inner smooth epidermis cells, and the body of the palea was reduced in the ah2 muant. We confirmed the function of AH2 by complementation, CRISPR-Cas9, and cytological and molecular tests. Additionally, AH2, as a repressor, repress transcription of the downstream genes. Our results revealed that AH2 plays an important role in the determination of hull epidermis development, palea identity, and grain size. This article is protected by copyright. All rights reserved.
Isolation of Strong Antioxidants from Paeonia Officinalis Roots and Leaves and Evaluation of Their Bioactivities

Paeonia officinalis extracts from leaves and roots were tested for their antioxidant potential using in vitro chemical (Folin-Ciocalteu, 2,2-diphenyl-1-picrylhydrazyl radical (DPPH), 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS), oxygen radical absorbance capacity (ORAC), hydroxyl radical antioxidant capacity (HORAC), hydroxyl radical scavenging capacity HOSC)) and cellular antioxidant activity (CAA) assays. Leaf extracts were stronger antioxidants than root extracts, while methanol was a more effective solvent than water in chemical assays. However, the selected water extract of leaves was a stronger antioxidant in CAA than the methanol extract (0.106 vs. 0.046 µmol quercetin equivalents/mg). Twenty compounds were identified by ultra performance liquid chromatography-quadrupole-time-of-flight (UPLC-Q-TOF) mass spectrometer, while on-line screening of their antioxidant capacity by high performance liquid chromatography (HPLC) with a DPPH•-scavenging detector revealed that gallic acid derivatives are the major peony antioxidants. Root water and leaf methanol extracts inhibited α-amylase in a dose dependent manner. The IC50 value for the strongest inhibitor, the methanol extract of leaves, was 1.67 mg/mL. In addition, the cytotoxicity assessment of extracts using human Caco-2 cells demonstrated that none of them possessed cytotoxic effects.
A Surgical Endovascular Trauma Service Increases Case Volume and Decreases Time to Hemostasis.

OBJECTIVES The aim of this study was to evaluate the effect of a recently active endovascular trauma service (ETS) on case volume and time to hemostasis, as a complement to an existing interventional radiology (IR) service. SUMMARY BACKGROUND DATA Endovascular techniques are vital for trauma care, but timely access can be a challenge. There is a paucity of data on the effect of a multispecialty team for delivery of endovascular hemorrhage control. METHODS The electronic medical record of trauma patients undergoing endovascular procedures between 2013 and 2018 was queried for provider type (IR or ETS). Case volume and rates were expressed per 100 monthly admissions, normalizing for seasonal variation. Interrupted time series analysis was used to model the case rate pre- and post-introduction of the ETS. Admission-to-procedure-time data were collected for pelvic angioembolization as a marker of patients requiring emergency hemostasis. RESULTS During 6 years, 1274 admission episodes required endovascular interventions. Overall case volume increased from 2.7 to 3.6 at a rate of 0.006 (P = 0.734) after introduction of the ETS. IR case volume decreased from 3.3 to 2.6 at a rate of 0.03 (P = 0.063). ETS case volume increased at a rate of 0.048 (P < 0.001), which was significantly different from the IR trend (P < 0.001). Median (interquartile range) time-to-procedure (hours) was significantly shorter for pelvic angioembolization [3.0 (4.4) vs 4.3 (3.6); P < 0.001] when ETS was compared to IR. CONCLUSION A surgical ETS increases case volume and decreases time to hemostasis for trauma patients requiring time sensitive interventions. Further work is required to assess patient outcome following this change.
Surgical site infections in Eastern Mediterranean region: a systematic review and meta-analysis

Abstract Background: Surgical site infections (SSIs) are the most common and costly type of hospital-acquired infections (HAIs) worldwide. Despite individual studies, there is also no clear statistics on the SSI prevalence rate in the East Mediterranean region. The aim of this study was to investigate the prevalence of SSI in the Eastern Mediterranean region. Methods: This systematic review and meta-analysis were performed by searching three international databases (Web of Science, PubMed and Scopus) from 1 January 2001 to 31 December 2018. The keywords used included ‘Prevalence’ OR ‘incidence’ OR ‘surgical site infection’ OR ‘wound infection’ OR ‘Postoperative Wound Infections’ and ‘Middle east’. The Hoy et al.’s tool was used to evaluate the quality of the articles. Result: Out of 889 initial studies, 40 studies from 12 countries of the Eastern Mediterranean region were included in the final stage of the study. Based on the results of random effect method, the overall prevalence of SSI in 137,452 patients was 7.9% (95% Confidence Interval (CI): 7.1, 8.8; I2=96.7%). The prevalence of SSI in cardiac surgery and general surgery wards was 10 and 9.2%, respectively. The prevalence of SSI was lower in women than in males, although this difference was related to caesarean section. Conclusions: Considering the high prevalence of SSI in the Eastern Mediterranean region, timely diagnosis, proper prevention and postoperative control are necessary in the region using the same international guides in all countries.
Apratoxin S4 Inspired by a Marine Natural Product, a New Treatment Option for Ocular Angiogenic Diseases.

Purpose Abnormal blood vessel formation is a defining feature of many blinding eye diseases. Targeting abnormal angiogenesis by inhibiting VEGF has revolutionized the treatment of many ocular angiogenic diseases over the last decade. However, a substantial number of patients are refractory to anti-VEGF treatment or may develop resistance over time. The objective of this study was to determine the efficacy and the mechanism of action of Apratoxin S4 in ocular angiogenesis. Methods Retinal vascular cell proliferation, migration, and the ability to form tube-like structure were studied in vitro. Ex vivo aortic ring, choroid, and metatarsal assays were used to study Apratoxin S4's impact on vessel outgrowth in a multicellular environment. Apratoxin S4 was also tested in mouse models of oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV), and in a rabbit model of persistent retinal neovascularization (PRNV). Western blot and ELISA were used to determine the expression of key angiogenic regulators after Apratoxin S4 treatment. Results Apratoxin S4 strongly inhibits retinal vascular cell activation by suppressing multiple angiogenic pathways. VEGF-activated vascular cells and angiogenic vessels are more susceptible to Apratoxin S4 treatment than quiescent vascular cells and vessels. Both intraperitoneal and intravitreal delivery of Apratoxin S4 are able to impede ocular neovascularization in vivo. Apratoxin S4 specifically attenuates pathological ocular angiogenesis and exhibits a combinatorial inhibitory effect with standard-of-care VEGF inhibitor drug (aflibercept). Conclusions Apratoxin S4 is a potent antiangiogenic drug that inhibits the activation of retinal endothelial cells and pericytes through mediating multiple angiogenic pathways.
First Clinical Case of In Vivo Acquisition of DHA-1 Plasmid-Mediated AmpC in a Salmonella enterica subsp. enterica Isolate

A pan-susceptible Salmonella enterica serovar Worthington isolate was detected in the stool of a man returning from Sri Lanka. Under ceftriaxone treatment, a third-generation cephalosporin (3GC)-resistant Salmonella Worthington was isolated after 8 days. Molecular analyses indicated that the two isolates were identical. However, the latter strain acquired a blaDHA-1-carrying IncFII plasmid probably from a Citrobacter amalonaticus isolate colonizing the gut. ABSTRACT A pan-susceptible Salmonella enterica serovar Worthington isolate was detected in the stool of a man returning from Sri Lanka. Under ceftriaxone treatment, a third-generation cephalosporin (3GC)-resistant Salmonella Worthington was isolated after 8 days. Molecular analyses indicated that the two isolates were identical. However, the latter strain acquired a blaDHA-1-carrying IncFII plasmid probably from a Citrobacter amalonaticus isolate colonizing the gut. This is the first report of in vivo acquisition of plasmid-mediated resistance to 3GCs in S. enterica.
Different Roles of Heat Shock Proteins (70 kDa) During Abiotic Stresses in Barley (Hordeum vulgare) Genotypes

In this work, the involvement of heat shock proteins (HSP70) in barley (Hordeum vulgare) has been studied in response to drought and salinity. Thus, 3 barley genotypes usually cultivated and/or selected in Italy, 3 Middle East/North Africa landraces and genotypes and 1 improved genotype from ICARDA have been studied to identify those varieties showing the best stress response. Preliminarily, a bioinformatic characterization of the HSP70s protein family in barley has been made by using annotated Arabidopsis protein sequences. This study identified 20 putative HSP70s orthologs in the barley genome. The construction of un-rooted phylogenetic trees showed the partition into four main branches, and multiple subcellular localizations. The enhanced HSP70s presence upon salt and drought stress was investigated by both immunoblotting and expression analyses. It is worth noting the Northern Africa landraces showed peculiar tolerance behavior versus drought and salt stresses. The drought and salinity conditions indicated the involvement of specific HSP70s to counteract abiotic stress. Particularly, the expression of cytosolic MLOC_67581, mitochondrial MLOC_50972, and encoding for HSP70 isoforms showed different expressions and occurrence upon stress. Therefore, genotypes originated in the semi-arid area of the Mediterranean area can represent an important genetic source for the improvement of commonly cultivated high-yielding varieties.
Benthic Diatom Communities in Korean Estuaries: Species Appearances in Relation to Environmental Variables

In the Korean Peninsula’s southern estuaries, the distributive characteristics of epilithic diatoms and the important environmental factors predicting species occurrence were examined. The collection of diatoms and measurements of water quality and land-use were performed every May between 2009 and 2016, with no influence from the Asian monsoon and snow. Throughout the study, 564 diatoms were classified with first and second dominant species of Nitzschia inconspicua and N. perminuta. Based on diatom appearance and standing crops, the 512 sampling stations were divided into four groups by cluster analysis, and two regions, namely the West and East Sea. Geographically, G1, G2, G3, and G4 were located in the East Sea, Southeast Sea, West Sea, and Southwest Sea, respectively. Canonical correspondence analysis (CCA) results indicated that environmental factors, such as turbidity, electric conductivity (EC), and total phosphorus (TP), significantly influenced the distribution of epilithic diatoms. A random forest model showed that major environmental factors influencing the diatom species appearance included EC, salinity, turbidity, and total nitrogen. This study demonstrated that the spatial distribution of epilithic diatoms in the southern estuaries of the Korean Peninsula was determined by several factors, including a geographically higher tidal current-driven turbidity increase and higher industrial or anthropogenic nutrient-loading.
Quantification and confirmation of four aflatoxins using a LC–MS/MS QTRAP system in multiple reaction monitoring, enhanced product ion scan, and MS3 modes

A simple, rapid, and efficient liquid chromatography tandem mass spectrometry (LC–MS/MS) method, operated in electrospray ionization and quadrupole linear ion trap modes, has been developed for the identification and structural characterization of aflatoxins in peanuts and its derivative products or bean sauce. Samples (5 g) were extracted with acetonitrile/water/formic acid (79:20:1, v/v). After centrifugation and dilution, the extracts were separated on a C18 analytical column by gradient elution (acetonitrile/0.2% formic acid) and analyzed by UPLC–MS/MS. External calibration was used for qualification. The developed multiple reaction monitoring–information-dependent acquisition–enhanced product ion method enabled quantification and confirmation of the analytes in a single run. Enhanced product ion mode was used for qualitative analysis, while multiple reaction monitoring mode was used for quantitative analysis. An in-house library was constructed for identification. Calibration curves showed good linearity with correlation coefficients (r) higher than 0.994. Limits of detection were determined to be below 0.26 µg kg−1 for most analytes. The recoveries for those substances were in the acceptable range of 80.2%–119.1%. A new LC–MS3 method was established for further confirmation. One pickled pepper peanut was found to contain aflatoxins B1, B2, and G1 with contents of 90.93, 26.64, and 1.92 µg kg−1, respectively.