Miracle-dz/UniFAR-FTUs huggingface dataset:
Emodin Induces Death in Human Cervical Cancer Cells Through Mitotic Catastrophe

Background: Anthraquinones, including emodin, are compounds with numerous pharmacological properties, including anticancer properties. The aim of this study experiment was to examine the effect of emodin, a natural compound present in the roots and rhizomes of Rheum palmatum, on the induction of mitotic catastrophe in cervical cancer cells. Material and Methods: HeLa celIs were treated with different emodin concentrations for 48 h, and cell growth was measured with 3-(4-,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolyl. The cell-cycle distribution and the level of apoptosis were determined by means of flow cytometry, using annexin V-fluorescein isothiocyanate staining and propidium iodide. Morphological changes in the mitotic apparatus were evaluated using optical and confocal microscopy techniques. Results: Emodin induced an increase in the number of polymorphonuclear cells, giant cells, cells with micronuclei, cells with abnormal mitosis and damaged spindle. The reorganization of F-actin depended on the concentration of emodin. With the increase in emodin concentration, inhibition of mitotic activity was demonstrated, which was manifested by a decrease in the mitotic index, mainly in metaphase of the mitotic process and an increase in the number of cells inhibited in the G2/M phase. At the same time, an increase in the number of apoptotic cells was found. Conclusion: Emodin leads to death of cervical cancer cells by induction of a mitotic catastrophe.
Long‐term dietary shift and population decline of a pelagic seabird—A health check on the tropical Atlantic?

In the face of accelerating ecological change to the world's oceans, seabirds are some of the best bio‐indicators of marine ecosystem function. However, unravelling ecological changes that pre‐date modern monitoring programmes remains challenging. Using stable isotope analysis of feathers and regurgitants collected from sooty terns (Onychoprion fuscatus) nesting at a major Atlantic colony, we reconstructed a long‐term dietary time series from 1890 to the present day and show that a significant dietary shift occurred during the second half of the twentieth century coinciding with an apparent population collapse of approximately 84%. After correcting for the “Suess Effect,” δ13C in feathers declined by ~1.5‰ and δ15N by ~2‰ between the 1890s and the present day, indicating that birds changed their diets markedly over the period of population decline. Isotopic niches were equally wide before and after the population collapse but isotopic mixing models suggest that birds have grown ever more reliant on nutrient‐poor squid and invertebrates as teleost fish have declined in availability. Given that sooty terns rely heavily on associations with sub‐surface predators such as tuna to catch fish prey, the rapid expansion of industrialized fisheries for these species over the same period seems a plausible mechanism. Our results suggest that changes to marine ecosystems over the past 60 years have had a dramatic impact on the ecology of the most abundant seabird of tropical oceans, and highlight the potentially pervasive consequences of large predatory fish depletion on marine ecosystem function.
NR2F2 loss‑of‑function mutation is responsible for congenital bicuspid aortic valve.

Congenital bicuspid aortic valve (BAV) represents the most common type of cardiac birth defect affecting 0.4‑2% of the general population, and accounts for a markedly increased incidence of life‑threatening complications, including valvulopathy and aortopathy. Accumulating evidence has demonstrated the genetic basis of BAV. However, the genetic basis for BAV in the majority of cases remains to be elucidated. In the present study, the coding regions and splicing donors/acceptors of the nuclear receptor subfamily 2 group F member 2 (NR2F2) gene, which encodes a transcription factor essential for proper cardiovascular development, were sequenced in 176 unrelated cases of congenital BAV. The available family members of the proband carrying an identified NR2F2 mutation and 280 unrelated, sex‑ and ethnicity‑matched healthy individuals as controls were additionally genotyped for NR2F2. The functional effect of the mutation was characterized using a dual‑luciferase reporter assay system. As a result, a novel heterozygous NR2F2 mutation, NM_021005. 3: c.288C>A; p.(Cys96*), was identified in a family with BAV, which was transmitted in an autosomal dominant mode with complete penetrance. The nonsense mutation was absent from the 560 control chromosomes. Functional analysis identified that the mutant NR2F2 protein had no transcriptional activity. Furthermore, the mutation disrupted the synergistic transcriptional activation between NR2F2 and transcription factor GATA‑4, another transcription factor that is associated with BAV. These findings suggested NR2F2 as a novel susceptibility gene of human BAV, which reveals a novel molecular pathogenesis underpinning BAV.
"It's All about Breaking down Those Barriers…": Exploring Survivors' Perspectives on Services and Treatment Needs following Commercial Sexual Exploitation during Childhood.

PURPOSE In recent years, there has been an increase in funds and services available to address the needs of commercially sexually exploited children (CSEC). While previous studies have explored the mental, behavioral, and physical needs of CSEC victims and survivors, few studies have focused on the service needs CSEC victims and survivors themselves deem most important. The current study seeks to bridge this gap by garnering American CSEC victims' and survivors' perspectives regarding CSEC service strengths, weaknesses, and gaps. METHOD Semi-structured, in-depth interviews were conducted with 13 adult survivors of CSEC to examine their perceptions of current CSEC services in the United States. All interviews were recorded, transcribed verbatim, and imported into a qualitative data analysis program. Using an inductive approach, two major themes emerged: short-term needs and long-term needs. RESULTS Short-term needs included victim identification, housing, and emergency medical care. Long-term needs included life-skills, community building, legal assistance, and medical care. The results point to the complex needs of CSEC victims/survivors. DISCUSSION While CSEC services continue to develop, there remain many gaps in care in the services available. Study findings provide valuable insight to practitioners and researchers alike and identify the most critical needs of CSEC victims and survivors. Implications for practice and research are discussed.
Laboratory test based assessment of WHO alcohol risk drinking levels

Abstract Low-risk thresholds for alcohol use differ across various national guidelines. To assess the novel WHO risk drinking levels in light of alcohol-sensitive common laboratory tests, we analysed biomarkers of liver status, inflammation and lipid profiles from a population-based survey of individuals classified to abstainers and different WHO risk drinking levels defined in terms of mean alcohol consumption per day. The study included 22,327 participants aged 25–74 years from the National FINRISK Study. Data on alcohol use, health status, diet, body weight and lifestyle (smoking, coffee consumption and physical activity) were recorded from structured interviews. Alcohol data from self-reports covering the past 12 months were used to categorize the participants into subgroups of abstainers and WHO risk drinking categories representing low, moderate, high and very high risk drinkers. Serum liver enzymes (GGT, ALT), C-reactive protein (CRP) and lipid profiles were measured using standard laboratory techniques. Alcohol risk category was roughly linearly related with the occurrence of elevated values for GGT, ALT and CRP. Alcohol drinking also significantly influenced the incidence of abnormalities in serum lipids. Significantly higher odds for abnormal GGT, ALT and altered lipid profiles remained in alcohol drinkers even after adjustment for age, waist circumference, physical inactivity, smoking and coffee consumption. A more systematic use of laboratory tests during treatment of individuals classified to WHO risk drinking categories may improve the assessment of alcohol-related health risks. Follow-ups of biomarker responses may also prove to be useful in health interventions aimed at reducing alcohol consumption.
Is echocardiographic evaluation of diastolic function useful in determining clinical care? Doppler echocardiography yields dubious estimates of left ventricular diastolic pressures.

Quantification of left ventricular (LV) diastolic function is necessary to diagnose heart failure (HF) when LV systolic function is normal.1–4 Furthermore, repetitive assessment of LV filling pressures is an important guide for titration of diuretic treatment and can predict survival of HF patients.5 Because of patient discomfort and the risks involved in invasive procedures, a noninvasive estimate of diastolic LV function and pressures is highly desirable. In current cardiological practice, noninvasive evaluation of diastolic LV function is based on Doppler echocardiographic visualization of LV inflow and/or LV tissue reextension. LV inflow and LV tissue reextension, however, are only indirectly related to LV filling pressures through laws of physics such as the Bernoulli principle and Laplace law. Noninvasive estimates of LV filling pressures can therefore be offset not only by limitations of the imaging technique but also by shortcomings inherent to derivation of pressures from inflow or reextension signals. As a result of these problems with noninvasive estimates of LV diastolic function and pressures, the cardiological community has witnessed over the past 20 years repetitive cycles in which a Doppler echocardiographic index was first proposed as robust and shortly thereafter discredited by contradictory evidence. The latest of such cycles involved the ratio of early transmitral velocity to tissue Doppler mitral annular early diastolic velocity (E/E ). The value of the E/E ratio as a reliable estimate of LV filling pressures was demonstrated in a variety of cardiac diseases6–10 and endorsed by European and American consensus statements on diastolic HF4 and diastolic LV dysfunction11 before being seriously questioned both in hypertrophic12 and dilated cardiomyopathy.13 This continuing uncertainty14 surrounding the value of noninvasive estimates of LV filling pressures and diastolic LV dysfunction asks for a reappraisal of physiological assumptions linking LV filling pressures to myocardial reextension kinetics, of pitfalls of diastolic LV dysfunction indices, and of limitations of current Doppler echocardiographic imaging techniques.
Cocaine'omics: Genome‐wide and transcriptome‐wide analyses provide biological insight into cocaine use and dependence

We investigated the genetic and molecular architecture of cocaine dependence (CD) and cocaine use by integrating genome‐/transcriptome‐wide analyses. To prioritize candidates for follow‐up investigation, we also sought to translate gene expression findings across species. Using data from the largest genome‐wide association study (GWAS) of CD to date (n = 3176, 74% with CD), we assessed genomic heritability, gene‐based associations, and tissue enrichment. We detected a significant single‐nucleotide polymorphism heritability of 28% for CD and identified three genes (two loci) underlying this predisposition: the C1qL2 (complement component C1 q like 2), KCTD20 (potassium channel tetramerization domain containing 20), and STK38 (serine/threonine kinase 38) genes. Tissue enrichment analyses indicated robust enrichment in numerous brain regions, including the hippocampus. We used postmortem human hippocampal RNA‐sequencing data from previous study (n = 15, seven chronic cocaine users) to follow up genome‐wide results and to identify differentially expressed genes/transcripts and gene networks underlying cocaine use. Cross‐species analyses utilized hippocampal gene expression from a mouse model of cocaine use. Differentially expressed genes/transcripts in humans were enriched for the genes nominally associated with CD via GWAS (P < 0.05) and for differentially expressed genes in the hippocampus of cocaine‐exposed mice. We identified KCTD20 as a central component of a hippocampal gene network strongly associated with human cocaine use, and this gene network was conserved in the mouse hippocampus. We outline a framework to map and translate genome‐wide findings onto tissue‐specific gene expression, which provided biological insight into cocaine use/dependence.
Gerontechnological factors affecting successful aging of elderly

Abstract In this article, the gerontological factors affecting the successful aging of the elderly have been uncovered, the quality of life and successful aging issues have been related to gerontology and investigated on a different dimension. It has been emphasized that the importance of gerontechnology on the successful aging, creation of awareness through formal and non-formal education, qualitative and quantitative researches should be increased. Qualitative and quantitative researches on the subject were evaluated together, gerontology and gerontechnology were considered together with successful aging, and gerontology functions and ergonomics should be taken into consideration in increasing quality of life. In addition, the concept of geronsafety, a new concept in gerontology, has been put forward, emphasizing the effects of safety on gerontology and successful aging.
The complete mitochondrial genome of Phrynocephalus helioscopus (Reptilia, Squamata, Agamidae)

Abstract The toad-headed lizards of genus Phrynocephalus are one of the most prevalent animals in the central Asian desert. A few studies have investigated molecular phylogenesis of Phrynocephalus, yet yield inconsistent results. Moreover, these studies were only based on a few specific DNA fragments of mitochondrial genome. To facilitate the clarification of molecular phylogenesis of Phrynocephalus, we conducted this study to sequence the entire mitochondrial genome of the Phrynocephalus helioscopus collected from Northwest China. The length of complete mitochondrial DNA is 16,249 nucleotides, consisting of 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and 2 control regions (CR). The gene arrangement and composition of P. helioscopus resemble those of other Phrynocephalus sand lizard, except for P. przewalskii and P. versicolor. The overall A, T, C, G base composition of the heavy-strand was 35.9%, 26.4%, 25.2%, 12.5%, respectively, which is biased toward AT (about 62.3%). The AT-biased base composition was similar to what observed in most vertebrates. The complete mitochondrial genome of P. helioscopus may help to clarify the phylogenetic relationships related to Phrynocephalus oviparity.
Tumoral EHF predicts the efficacy of anti-PD1 therapy in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a highly immune-suppressive tumor with a low response rate to single checkpoint blockade therapy. ETS homologous factor (EHF) is a tumor suppressor in PDAC. Here, we report a novel function of EHF in pancreatic cancer immune microenvironment editing and efficacy prediction for anti-PD1 therapy. Our findings support that the deficiency of tumoral EHF induced the accumulation of regulatory T (T reg) cells and myeloid-derived suppressor cells (MDSCs) and a decrease in the number of tumor-infiltrating CD8+ T cells. Mechanistically, EHF deficiency induced the conversion and expansion of T reg cells and MDSCs through inhibiting tumor TGF&bgr;1 and GM-CSF secretion. EHF suppressed the transcription of TGFB1 and CSF2 by directly binding to their promoters. Mice bearing EHF overexpression tumors exhibited significantly better response to anti-PD1 therapy than those with control tumors. Our findings delineate the immunosuppressive mechanism of EHF deficiency in PDAC and highlight that EHF overexpression may improve PDAC checkpoint immunotherapy.
Abrogation of Triazole Resistance upon Deletion of CDR1 in a Clinical Isolate of Candida auris

Candida auris has rapidly emerged as a health care-associated and multidrug-resistant pathogen of global concern. In this work, we examined the relative expression of the four C. auris genes with the highest degree of homology to Candida albicans CDR1 and MDR1 among three triazole-resistant clinical isolates as compared to the triazole-susceptible genome reference clinical isolate. ABSTRACT Candida auris has rapidly emerged as a health care-associated and multidrug-resistant pathogen of global concern. In this work, we examined the relative expression of the four C. auris genes with the highest degree of homology to Candida albicans CDR1 and MDR1 among three triazole-resistant clinical isolates as compared to the triazole-susceptible genome reference clinical isolate. We subsequently utilized a novel Cas9-mediated system for genetic manipulations to delete C. auris CDR1 and MDR1 in both a triazole-resistant clinical isolate and a susceptible reference strain and observed that MICs for all clinically available triazoles decreased as much as 128-fold in the CDR1 deletion strains. The findings of this work reveal for the first time that C. auris CDR1 and MDR1 are more highly expressed among triazole-resistant clinical isolates of C. auris and that the overexpression of CDR1 is a significant contributor to clinical triazole resistance.
Competition, competitive repulsion, and coexistence.

Abstract This manuscript is concerned with concepts rather than abstruse details or mathematics. Discussed are: competition; extended competition, proposed for competition in the strict sense, extended and modified by all related interactions including predation, parasitism, disease, and even cooperation, all of which can be “weapons of competition”; competitive repulsion, proposed for the sum of forces that determine spacings, including ecologic spacings, of individuals and populations; Darwin (biotic) equilibriums; competitive extinction, Gause's principle, limited and limiting resources, and single-resource competition; de facto coexistence of competing species, exemplified by green plants competing for sunlight; niche competition; the two concepts of competitive exclusion; devision of resources and of their utilizers; cause and effect in real situations; and niches, niche overlap, and coexistence. Stressed is the complexity of the real world, and the confusion that can and does arise from modeling it too simply.
Dynamics of DNA replication in a eukaryotic cell

Significance All eukaryotic cells initiate DNA replication at multiple genomic sites. For most cell types these sites lack a well-defined sequence signature, so it is not understood how they are selected. To analyze the factors that influence initiation site selection and determine the dynamics of replication throughout the genome, we developed an integrative computational model of DNA replication in the model organism Schizosaccharomyces pombe. This analysis showed that the locations of initiation sites are determined not only by the sequence preferences of the S. pombe origin recognition complex (ORC), but also by the interference of transcription with the formation of prereplication complexes. Our findings suggest that transcription has influenced evolution of the binding properties of ORC and replication dynamics in eukaryotes. Each genomic locus in a eukaryotic cell has a distinct average time of replication during S phase that depends on the spatial and temporal pattern of replication initiation events. Replication timing can affect genomic integrity because late replication is associated with an increased mutation rate. For most eukaryotes, the features of the genome that specify the location and timing of initiation events are unknown. To investigate these features for the fission yeast, Schizosaccharomyces pombe, we developed an integrative model to analyze large single-molecule and global genomic datasets. The model provides an accurate description of the complex dynamics of S. pombe DNA replication at high resolution. We present evidence that there are many more potential initiation sites in the S. pombe genome than previously identified and that the distribution of these sites is primarily determined by two factors: the sequence preferences of the origin recognition complex (ORC), and the interference of transcription with the assembly or stability of prereplication complexes (pre-RCs). We suggest that in addition to directly interfering with initiation, transcription has driven the evolution of the binding properties of ORC in S. pombe and other eukaryotic species to target pre-RC assembly to regions of the genome that are less likely to be transcribed.
A novel unstructured performance-based task of executive function in children with attention-deficit/hyperactivity disorder

ABSTRACT Objective: Executive functions (EFs) have been assessed with performance-based measures and rating scales. Research has shown a lack of association between these two methods. One factor that might contribute to this difference is the structure provided on performance-based measures that is not provided on rating scales. This study examined the role of structure on self-directed task completion, an aspect of EF, using a novel unstructured performance-based task (UPT). Method: Children aged 8–12 years (38 attention-deficit/hyperactivity disorder, ADHD; 42 typically developing) and their caregivers participated. We compared performance on the UPT, performance-based measures of EF (Stroop test and Trail-Making Test), and a rating scale to assess EF (Barkley Deficits in Executive Functioning Scale–Children and Adolescents, BDEFS–CA). Results: Group differences were found across all measures. Significant associations emerged between the UPT and Stroop test, Trail-Making Test, and BDEFS–CA, but no significant associations were found between the Stroop test or Trail-Making Test and the BDEFS–CA. In regression analyses, performance-based tasks and the rating scale both uniquely predicted UPT performance. The UPT was a significant predictor of group status when entered with performance-based tasks, but the UPT did not enter as a significant predictor when entered with the rating scale. Conclusion: The UPT is a promising measure to assess self-directed task completion in children with ADHD.
A Pilot Prospective, Multicenter Observational Study of Dopamine Agonist Withdrawal Syndrome in Parkinson's Disease

Dopamine agonist withdrawal syndrome (DAWS) has been reported in patients with Parkinson's disease (PD) who rapidly decrease or stop their dopamine agonist (DA) treatment. Retrospective studies suggest a high prevalence of DAWS (14%–18%) in PD, but there are no prospective studies. We report data from the first pilot European multicenter prospective study addressing the frequency of probable DAWS (Rabinak‐Nirenberg criteria) in PD patients. The self‐completed Nonmotor Symptoms Questionnaire (which addresses the core features of DAWS) was administered at clinical follow‐up at 1 month in 51 patients (33 male; mean age: 73.0 ± 9.9 years; PD duration: 12.2 ± 6.3 years) who had discontinued dopamine agonists. Twelve out of fifty‐one patients (24%) met clinical criteria for DAWS, the most common symptoms of which were anxiety (91.7%), pain (50%), sweating (41.7%), and anhedonia (16.7%), after the withdrawal of a DA (ropinirole, pramipexole, or cabergoline). In this first prospective evaluation of DAWS in the clinic, preliminary data indicate a high rate after discontinuation of a range of DAs, particularly in the context of impulse control disorders. Larger, controlled studies are required to establish a definitive management pathway.