Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of Thalassaemia Screening Tests in the Antenatal and Non-Antenatal Populations in Singapore.

INTRODUCTION Haemoglobinopathy testing is performed for carrier screening and evaluation of microcytic anaemia. We evaluated the effectiveness of thalassaemia screening tests at our institution and suggest ways of improving the testing algorithm. MATERIALS AND METHODS A total of 10,084 non-antenatal and 11,364 antenatal samples with alkaline gel electrophoresis (AGE), capillary electrophoresis (CE), haemoglobin H (HbH) inclusion test, mean corpuscular haemoglobin (MCH) and mean corpuscular volume (MCV) were retrospectively reviewed. A subgroup of 187 samples with genetic testing was correlated with HbH inclusions and MCH/ MCV. The effect of iron deficiency on percentage hemoglobin A2 (HbA2) was studied. RESULTS HbH inclusion test showed low sensitivity of 21.43% for α-thalassaemia mutations but higher sensitivity of 78.95% for --SEA deletion. By receiver operating characteristic (ROC) analysis, MCH ≤28 pg or MCV ≤80 fl for non-antenatal samples and MCH ≤27 pg or MCV ≤81 fl for antenatal samples had >98% sensitivity for HbH inclusions. Above these thresholds, the probability that HbH inclusions would be absent was <99% (negative predictive value [NPV] >99%). MCH ≥28 pg had 100% sensitivity (95% CI 95.63%-100%) for α-thalassaemia mutations and 97.68% calculated NPV in the antenatal population. Detection of haemoglobin variants by CE correlated highly with AGE (99.89% sensitivity, 100% specificity). Severe iron deficiency reduced HbA2 in hemoglobin (P <0.001) and α-thalassaemia (P = 0.0035), but not in β-thalassaemia. CONCLUSION MCH/MCV thresholds have adequate sensitivity for α-thalassaemia in the antenatal population, and genotyping plays an important role as HbH inclusion test shows low sensitivity. CE without AGE, may be used as initial screening for haemoglobin variants. Our study provides contemporary data to guide thalassaemia screening algorithms in Singapore.
MicroRNA‐3191 promotes migration and invasion by downregulating TGFBR2 in colorectal cancer

Mutations in transforming growth factor beta receptor II (TGFBR2) are detected in up to 30% of overall colorectal cancer (CRC). Dysregulation of some microRNAs participated in the CRC pathogenesis. In this study, we used the gene ontology analyses, the Kyoto Encyclopedia of Genes and Genomes pathway analyses and gene set enrichment analysis to indicate that miR‐3191 was involved in the regulation of transforming growth factor beta (TGF‐BETA) signal pathway in CRC. These bioinformatics results were supported by data obtained from CRC samples and experiments in vitro. The luciferase reporter assay was used to confirm that miR‐3191 modulates TGF‐BETA signal pathway by targeting TGFBR2. By transwell migration and invasion assays, we showed that miR‐3191 promoted CRC cell migration and invasion by downregulating TGFBR2. And it may serve as a novel therapeutic strategy for treating CRC patients.
Nocardia infections in solid organ transplantation: Guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of Nocardia infections after solid organ transplantation (SOT). Nocardia infections have increased in the last two decades, likely due to improved detection and identification methods and an expanding immunocompromised population. The risk of developing nocardiosis after transplantation varies with the type of organ transplanted and the immunosuppression regimen used. Nocardia infection most commonly involves the lung. Disseminated infection can occur, with spread to the bloodstream, skin, or central nervous system. Early recognition of the infection and initial appropriate treatment is important to achieve good outcomes. Species identification and antimicrobial susceptibility testing are strongly recommended, as inter‐ and intraspecies susceptibility patterns can vary. Sulfonamide is the first‐line treatment of Nocardia infections, and combination therapy with at least two antimicrobial agents should be used initially for disseminated or severe nocardiosis. Trimethoprim‐sulfamethoxazole (TMP‐SMX) prophylaxis may be helpful in preventing Nocardia infection after SOT.
Two stochastic processes shape diverse senescence patterns in a single-cell organism

Despite advances in aging research, a multitude of aging models, and empirical evidence for diverse senescence patterns, understanding is lacking of the biological processes that shape senescence, both for simple and complex organisms. We show that for a isogenic Escherichia coli bacterial population senescence results from two stochastic processes. A primary random deterioration process within the cell, such as generated by random accumulation of damage, leads to an exponential increase in mortality early in life followed by a late age mortality plateau; a secondary process of stochastic asymmetric transmission of an unknown factor at cell fission influences mortality. This second process is required to explain the difference between the classical mortality plateaus detected for young mothers’ offspring and the near non-senescence of old mothers’ offspring as well as the lack of a mother offspring correlation in age at death. We observed that life span is predominantly determined by underlying stochastic stage dynamics. Our findings support models based on stage-specific actions of alleles for the evolution of senescence. This support might be surprising since these models that have not specifically been developed in the context of simple, single cell organisms. We call for exploration of similar stochastic influences beyond simple organisms.
Position-Selective Synthesis and Biological Evaluation of Four Isomeric A-Ring Amino Derivatives of the Alkaloid Luotonin A

Following two orthogonal synthetic routes, a series of all four possible A-ring amino derivatives of the natural product Luotonin A (a known Topoisomerase I inhibitor) was synthesized. In both strategies, intramolecular cycloaddition reactions are the key step. The target compounds were obtained in good yields by mild catalytic transfer hydrogenation of the corresponding nitro precursors. In-vitro evaluation of the antiproliferative activity towards human tumor cell lines revealed the 4-amino compound (5b) to be the most effective agent, showing an interesting profile of cytotoxic activity. Among other effects, a significant G2/M cell cycle arrest was observed for this compound, suggesting that either Topoisomerase I is not the only biological target, or that some atypical mechanism is responsible for inhibition of this enzyme.
Extensive Reliability Evaluation of Docking-Based Target-Fishing Strategies

The development of target-fishing approaches, aimed at identifying the possible protein targets of a small molecule, represents a hot topic in medicinal chemistry. A successful target-fishing approach would allow for the elucidation of the mechanism of action of all therapeutically interesting compounds for which the actual target is still unknown. Moreover, target-fishing would be essential for preventing adverse effects of drug candidates, by predicting their potential off-targets, and it would speed up drug repurposing campaigns. However, due to the huge number of possible protein targets that a small-molecule might interact with, experimental target-fishing approaches are out of reach. In silico target-fishing represents a valuable alternative, and examples of receptor-based approaches, exploiting the large number of crystallographic protein structures determined to date, have been reported in the literature. To the best of our knowledge, no proper evaluation of such approaches is, however, reported yet. In the present work, we extensively assessed the reliability of docking-based target-fishing strategies. For this purpose, a set of X-ray structures belonging to different targets was selected, and a dataset of compounds, including 10 experimentally active ligands for each target, was created. A target-fishing benchmark database was then obtained, and used to assess the performance of 13 different docking procedures, in identifying the correct target of the dataset ligands. Moreover, a consensus docking-based target-fishing strategy was developed and evaluated. The analysis highlighted that specific features of the target proteins could affect the reliability of the protocol, which however, proved to represent a valuable tool in the proper applicability domain. Our study represents the first extensive performance assessment of docking-based target-fishing approaches, paving the way for the development of novel efficient receptor-based target fishing strategies.
Serum-based inhibition of pitviper venom by eastern indigo snakes (Drymarchon couperi)

ABSTRACT When organisms possess chemical defenses, their predators may eventually evolve resistance to their toxins. Eastern indigo snakes (Drymarchon couperi; EIS) prey on pitvipers and are suspected to possess physiological resistance to their venom. In this study, we formally investigated this hypothesis using microassays that measured the ability of EIS blood sera to inhibit (A) hemolytic and (B) snake venom metalloproteinase (SVMP) activity of copperhead (Agkistrodon contortrix) venom. To serve as controls, we also tested the inhibitory ability of sera from house mice (Mus musculus) and checkered gartersnakes (Thamnophis marcianus), a snake that does not feed on pitvipers. Sera from both EIS and gartersnakes inhibited over 60% of SVMP activity, while only EIS sera also inhibited venom hemolytic activity (78%). Our results demonstrate that EIS serum is indeed capable of inhibiting two of the primary classes of toxins found in copperhead venom, providing the first empirical evidence suggesting that EIS possess physiological resistance to venom upon injection. Because we documented resistance to hemolytic components of pitviper venom within EIS but not gartersnakes, we speculate this resistance may be driven by selection from feeding on pitvipers while resistance to SVMP may be relatively widespread among snakes. Summary: We confirm eastern indigo snakes possess a physiological resistance to pitviper venom and speculate that venom resistance in snakes may be a product of antagonistic interactions and phylogenetically conserved traits.
ScDREB10, an A-5c type of DREB Gene of the Desert Moss Syntrichia caninervis, Confers Osmotic and Salt Tolerances to Arabidopsis

Drought and salinity are major factors limiting crop productivity worldwide. DREB (dehydration-responsive element-binding) transcription factors play important roles in plant stress response and have been identified in a wide variety of plants. Studies on DREB are focused on the A-1 (DREB1) and A-2 (DREB2) groups. Studies on A-5 group DREBs, which represent a large proportion of the DREB subfamily, is limited. In this study, we characterized and analyzed the stress tolerance function of ScDREB10, an A-5c type DREB gene from the desert moss Syntrichia caninervis. Transactivation assay in yeast showed that ScDREB10 had transactivation activity. Transient expression assay revealed that ScDREB10 was distributed both in the nucleus and cytosol of tobacco leaf epidermal cells. Overexpression of ScDREB10 significantly increased the germination percentage of Arabidopsis seeds under osmotic and salt stresses, and improved the osmotic and salt stress tolerances of Arabidopsis at the seedling stage and is associated with the expression of downstream stress-related genes and improved reactive oxygen species (ROS) scavenging ability. Our study provides insight into the molecular mechanism of stress tolerance of A-5 type DREB proteins, as well as providing a promising candidate gene for crop salt and drought stress breeding.
Oral magnetite nanoparticles disturb the development of Drosophila melanogaster from oogenesis to adult emergence

Abstract The potential impacts of nanomaterials (NMs) on fetal development have attracted great concerns because of the increased potential exposure to NMs during pregnancy. Drosophila melanogaster oogenesis and developmental transitions may provide an attractive system to study the biological and environmental effects of NMs on the embryonic development. In this study, the effects of three types of magnetite (Fe3O4) nanoparticles (MNPs): UN-MNPs (pristine), CA-MNPs (citric acid modified) and APTS-MNPs (3-aminopropyltriethoxylsilane coated) on the development of Drosophila at 300 and 600 μg/g dosage were studied. The uptake of MNPs by female and male flies caused obvious reduction in the female fecundity, and the developmental delay at the egg–pupae and pupae–adult transitions, especially in those treated by the positive APTS-MNPs. Further investigation demonstrates that the parental uptake of MNPs disturbs the oogenesis period, induces ovarian defect, reduces the length of eggs, decreases the number of nurse cells and delays egg chamber development, which may contribute to the decrease of fecundity of female Drosophila and the development delay of their offspring. Using the synchrotron radiation-based micro-X-ray fluorescence (SR-μXRF), the dyshomeostasis of trace elements such as Fe, Ca and Cu along the anterior–posterior axis of the fertilized eggs was found, which may be an important reason for the development delay of Drosophila.
Synthesis of Phthalides and α,β-butenolides by Transition Metal-Catalyzed Activation of C—H Bonds

Phthalides and α,β-butenolides are two related classes of oxygenated heterocycles with a wide range of biological activities. An innovative strategy to prepare these compounds is based on C—H bond functionalization reactions, in which two simple, unfunctionalized molecules are coupled together with cleavage of a C—H bond and formation of a C—X bond (X=C or heteroatom). This paper reviews the methods for the synthesis of phthalides and α,β-butenolides by C—H bond functionalization from non-halogenated starting materials. Over 30 methods are reported, mostly developed during the past ten years.
Comparison of ELISA and PCR of the 18S rRNA gene for detection of human strongyloidiasis using serum sample

Abstract Background: Strongyloides stercoralis infection is a neglected tropical disease with global distribution which is fatal in immunosuppressed patients. This study aimed to determine the prevalence of strongyloidiasis in immunocompromised individuals and cases with infectious diseases, as well as comparing ELISA and conventional PCR with coprological examination, in the central parts of Mazandaran province, northern Iran. Methods: A single serum and a fresh stool samples were obtained from 272 and 220 patients, respectively. Serum was tested by ELISA and PCR of the 18S rRNA gene, and stool samples were examined with various parasitological methods. The optimum point for ELISA reaction and cut-off points were recognized by receiver operating characteristic curves (ROC). Results: Out of 220 stool specimens, 14(6.3%) cases were positive for S. stercoralis larvae. The overall seroprevalence rate was 27.9% (76/272). The seroprevalence rate was 25.2% and 30.1% in immunocompromised group and patients with infection, respectively. Based on the ROC curve of ELISA compared with microscopy, the optimum cut-off point was 12.74 with 79% sensitivity and 76% specificity. The optimum cut-off point was 10.42 with 69% sensitivity and specificity using ROC curve of ELISA compared with PCR. Conclusions: This study seroprevalence rate for Strongyloides infection in the studied group. It also observed that the ELISA technique and the PCR used here have 100 demonstrated a high % sensitivity and acceptable specificity compared with coprological examination. It seems that the ELISA technique is a good screening assay in ruling out strongyloidiasis in such patients.
Yb-Doped BaCeO3 and Its Composite Electrolyte for Intermediate-Temperature Solid Oxide Fuel Cells

BaCe0.9Yb0. 1O3−α was prepared via the sol-gel method using zirconium nitrate, ytterbium trioxide, cerium nitrate and barium acetate as raw materials. Subsequently, it reacted with the binary NaCl~KCl salt to obtain BaCe0.9Yb0. 1O3−α-NaCl~KCl composite electrolyte. The structure, morphology, conductivity and fuel cell performance of the obtained samples were investigated. Scanning electron microscope (SEM) images showed that BaCe0.9Yb0. 1O3−α and NaCl~KCl combined with each other to form a homogeneous 3-D reticulated structure. The highest power density and conductivity of BaCe0.9Yb0. 1O3−α-NaCl~KCl was 393 mW·cm−2 and 3.0 × 10−1 S·cm−1 at 700 °C, respectively.
Targeted Assessment of G0S2 Methylation Identifies a Rapidly Recurrent, Routinely Fatal Molecular Subtype of Adrenocortical Carcinoma

Purpose: Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy with few therapies; however, patients with locoregional disease have variable outcomes. The Cancer Genome Atlas project on ACC (ACC-TCGA) identified that cancers of patients with homogeneously rapidly recurrent or fatal disease bear a unique CpG island hypermethylation phenotype, “CIMP-high. ” We sought to identify a biomarker that faithfully captures this subgroup. Experimental Design: We analyzed ACC-TCGA data to characterize differentially regulated biological processes, and identify a biomarker that is methylated and silenced exclusively in CIMP-high ACC. In an independent cohort of 114 adrenocortical tumors (80 treatment-naive primary ACC, 22 adrenocortical adenomas, and 12 non-naive/nonprimary ACC), we evaluated biomarker methylation by a restriction digest/qPCR-based approach, validated by targeted bisulfite sequencing. We evaluated expression of this biomarker and additional prognostic markers by qPCR. Results: We show that CIMP-high ACC is characterized by upregulation of cell cycle and DNA damage response programs, and identify that hypermethylation and silencing of G0S2 distinguishes this subgroup. We confirmed G0S2 hypermethylation and silencing is exclusive to 40% of ACC, and independently predicts shorter disease-free and overall survival (median 14 and 17 months, respectively). Finally, G0S2 methylation combined with validated molecular markers (BUB1B-PINK1) stratifies ACC into three groups, with uniformly favorable, intermediate, and uniformly dismal outcomes. Conclusions: G0S2 hypermethylation is a hallmark of rapidly recurrent or fatal ACC, amenable to targeted assessment using routine molecular diagnostics. Assessing G0S2 methylation is straightforward, feasible for clinical decision-making, and will enable the direction of efficacious adjuvant therapies for patients with aggressive ACC.
The Possible Involvement of miR-371a-5p Regulating XIAP in the Pathogenesis of Recurrent Pregnancy Loss

Apoptosis is an interactive and dynamic biological process involved in all phases of embryogenesis. If apoptosis dominates the trophoblast cell growth process, it will result in adverse pregnancy outcomes. X-linked inhibitor of apoptosis protein (XIAP) is a potent caspase inhibitor and an important barrier to apoptotic cell death. MicroRNAs involve in posttranscriptional gene expression regulation and apoptosis. Online sequence alignment analysis showed that there was a putative binding site of miR-371a-5p on the 3′-untranslated region (UTR) of XIAP. Thirty chorionic villi samples were collected to examine the expression of miR-371a-5p and XIAP. The dual-luciferase reporter assay was applied to determine the relationship between miR-371a-5p and XIAP by human placental choriocarcinoma cells (JEG-3) cells in vitro. After 48-hour transfection of mimics and inhibitor by JEG-3 cells in vitro, Western blotting was used to, respectively, detect the protein expression levels of XIAP and caspase-3. Flow cytometry was used to validate the apoptosis ratio of transfection. The expression of miR-371a-5p and XIAP in recurrent pregnancy loss was greatly decreased. The results from the luciferase reporter assay strongly suggested binding of the XIAP 3′-UTR by miR-371a-5p. Apoptosis percentage of miR-371a-5p mimic was significantly greater than that of normal control. However, apoptosis percentage of miR-371a-5p inhibitor was significantly lower than that of normal control. A significant decrease in luciferase activity was observed in miR-371a-5p mimics-transfected JEG-3 cells compared with controls. These findings provide the evidence that miR-371a-5p is one of the regulating factors according to apoptosis pathway of XIAP-caspase-3 and may be involved in the pathogenesis of recurrent pregnancy loss.
A Current Review of Dose-escalated Radiotherapy in Locally Advanced Non-small Cell Lung Cancer

Abstract Background The mainstay therapy for locally advanced non-small cell lung cancer is concurrent chemoradiotherapy. Loco-regional recurrence constitutes the predominant failure patterns. Previous studies confirmed the relationship between increased biological equivalent doses and improved overall survival. However, the large randomized phase III study, RTOG 0617, failed to demonstrate the benefit of dose-escalation to 74 Gy compared with 60 Gy by simply increasing fraction numbers. Conclusions Though effective dose-escalation methods have been explored, including altered fractionation, adapting individualized increments for different patients, and adopting new technologies and new equipment such as new radiation therapy, no consensus has been achieved yet.
Cold‐evoked potentials versus contact heat‐evoked potentials—Methodological considerations and clinical application

Previous studies investigated cold‐evoked potentials (CEPs) for the assessment of the integrity of cold‐mediating A‐delta fibres and the spinothalamic tract. Nevertheless, several methodological questions remained unanswered to proceed to clinical application. How do latencies and amplitudes vary between CEPs and contact heat‐evoked potentials (CHEPs)? Are there differences between variable and fixed thermode positions or between glabrous and hairy skin? Are CEPs recordable in patients with abnormal cold processing?
IMI – Defining and Classifying Myopia: A Proposed Set of Standards for Clinical and Epidemiologic Studies

Purpose We provide a standardized set of terminology, definitions, and thresholds of myopia and its main ocular complications. Methods Critical review of current terminology and choice of myopia thresholds was done to ensure that the proposed standards are appropriate for clinical research purposes, relevant to the underlying biology of myopia, acceptable to researchers in the field, and useful for developing health policy. Results We recommend that the many descriptive terms of myopia be consolidated into the following descriptive categories: myopia, secondary myopia, axial myopia, and refractive myopia. To provide a framework for research into myopia prevention, the condition of “pre-myopia” is defined. As a quantitative trait, we recommend that myopia be divided into myopia (i.e., all myopia), low myopia, and high myopia. The current consensus threshold value for myopia is a spherical equivalent refractive error ≤ −0.50 diopters (D), but this carries significant risks of classification bias. The current consensus threshold value for high myopia is a spherical equivalent refractive error ≤ −6.00 D. “Pathologic myopia” is proposed as the categorical term for the adverse, structural complications of myopia. A clinical classification is proposed to encompass the scope of such structural complications. Conclusions Standardized definitions and consistent choice of thresholds are essential elements of evidence-based medicine. It is hoped that these proposals, or derivations from them, will facilitate rigorous, evidence-based approaches to the study and management of myopia.