Miracle-dz/UniFAR-FTUs huggingface dataset:
Prognostic significance of nucleolar assessment in invasive breast cancer

Nucleolar morphometric features have a potential role in the assessment of the aggressiveness of many cancers. However, the role of nucleoli in invasive breast cancer (BC) is still unclear. The aims of this study were to investigate the optimal method for scoring nucleoli in IBC and their prognostic significance, and to refine the grading of breast cancer (BC) by incorporating nucleolar score.
The neck–shaft angle: an update on reference values and associated factors

Background and purpose — The neck–shaft angle (NSA) is valuable for diagnostics and therapy of the hip, but current reference values derive mostly from studies on anatomic specimens, small cohorts, or are hospital-based. Moreover, associated factors such as age, sex, or anthropometric data have rarely been considered. Therefore, we determined associated factors for NSA and reassessed the historical reference values in a general adult population. Methods — NSAs on both sides of 3,226 volunteers from the population-based Study of Health in Pomerania (SHIP) were measured with MRI. SHIP drew a representative sample of the population of Pomerania (northeastern Germany). NSAs were compared with sex, age, and anthropometric data by bivariable linear regression models. Reference values were assessed by quantile regressions for 2.5th and 97.5th percentiles. Results — The mean NSA was 127° (SD 7), while men had a lower NSA than women (95% confidence interval [CI] 0.4°–1.4°). The reference range was 114°–140°. Age was inversely associated with NSA (CI –0.2 to –0.1). Body height was positively associated with the NSA, while BMI and waist circumference showed a negative association. There was no association between body weight and NSA. Interpretation — The historical lower limit of 120° might be too high, so the radiological prevalence of hip pathology might have been overestimated. The previously reported influence of age, sex, and body height on the NSA has been confirmed.
Síndromes de inestabilidad cromosómica asociados con inmunodeficiencia: Aspectos citogenéticos de importancia en el diagnóstico

Chromosomal instability syndromes are caused by alterations in DNA repair and damage response. These diseases belong to the group of well-defi ned syndrome associated primary immunodefi ciencies because they have immune system failure. Additionally, they present abnormalities in the chromosome structure and behavior, which have to be evidenced by cytogenetic methods. The diagnosis of these disorders is a challenge, since it involves the participation of specialists in Immunology and Genetics. In this paper Ataxia Telangiectasia, Nijmegen, Bloom and ICF Syndromes are reviewed, focusing on the cytogenetic basis of the diagnosis.
Cadmium transcriptionally regulates Scd1 expression in silver pomfret

Cadmium (Cd) is one of the major contaminants in aquatic ecosystem. Stearoyl‐coenzyme A desaturase 1 (Scd1) has been implicated in adaptive responses to environmental stressors. The objectives of this study are (a) to characterize scd1 mRNA from silver pomfret (Pampus argenteus); (b) to investigate the expression and activity of Scd1 in silver pomfret exposed to Cd; and (c) to investigate how Cd modifies scd1 gene transcription in silver pomfret. Results indicated that Scd1 was generally conserved across fish species and scd1 mRNA level was higher by far in the brain and liver, followed by the kidney and intestine. Exposure to Cd led to significant changes of the expression and activity of Scd1 in in the liver and intestine. The liver mRNA abundance of scd1 was significantly lower in the Cd‐treated groups than in the control group. The 10 days treatment with 1 mg/L Cd significantly upregulated the intestinal scd1 mRNA level, an approximately 9‐fold higher in the 1 mg/L Cd‐treated group as compared with the control group. Accordingly, Scd1 activity indices (18:1n‐9/18:0) in the liver were significantly decreased in the 0.5 mg/L group compared with the control group, while Scd1 activity indices in the intestine were significantly increased in the 1 mg/L group compared with the control group. Moreover, overexpression of sterol regulatory element binding transcription factor 1 (Srebp1) and peroxisome proliferator–activated receptor γ (Pparγ )in HEK 293T cells produced a 2‐fold increment in the activity of the scd1 promoter. Furthermore, srebp1 had a similar expression pattern to scd1 in the liver and intestine of silver pomfret exposed to Cd. These results indicated that Cd could regulate scd1 expression, possibly through the transcriptional factor Srebp1.
Persistent epigenetic memory impedes rescue of the telomeric phenotype in human ICF iPSCs following DNMT3B correction

DNA methyltransferase 3B (DNMT3B) is the major DNMT that methylates mammalian genomes during early development. Mutations in human DNMT3B disrupt genome-wide DNA methylation patterns and result in ICF syndrome type 1 (ICF1). To study whether normal DNA methylation patterns may be restored in ICF1 cells, we corrected DNMT3B mutations in induced pluripotent stem cells from ICF1 patients. Focusing on repetitive regions, we show that in contrast to pericentromeric repeats, which reacquire normal methylation, the majority of subtelomeres acquire only partial DNA methylation and, accordingly, the ICF1 telomeric phenotype persists. Subtelomeres resistant to de novo methylation were characterized by abnormally high H3K4 trimethylation (H3K4me3), and short-term reduction of H3K4me3 by pharmacological intervention partially restored subtelomeric DNA methylation. These findings demonstrate that the abnormal epigenetic landscape established in ICF1 cells restricts the recruitment of DNMT3B, and suggest that rescue of epigenetic diseases with genome-wide disruptions will demand further manipulation beyond mutation correction.
Association between suicide rates and lithium levels in drinking water: A literature review

Suicide is a serious public health problem worldwide, and many countries are committed to developing prevention programs to reduce the incidence of suicide. To date, several strategies have been proposed for suicide prevention, both at the population and at the individual level, some of which may be pharmacological. A substantial amount of data shows that lithium significantly reduces mortality in patients with mood disorders and reduction in rates of suicidality. Initiating from this evidence, some recent studies have investigated whether a relationship might exist between levels of lithium in drinking water and mortality rates for suicide in the general population. There is growing evidence that even very low lithium levels induced by routine consumption of lithium from tap water may have anti-suicidal effects both in patients with mood disorders, and in the general population. The objective of this paper is to review the evidence investigating the association between suicide rates and lithium levels in drinking water. Methods. Studies were identified through systematic search in PubMed. Studies were included if they investigating the relationship between the level of lithium in drinking water and suicides rates in the general population. The search in PubMed provided 35 results. After removal of 14 duplicates, of 10 reviews, of 2 opinions of the remaining 9 records were screened for eligibility. Results. Seven out of nine studies found an association between trace-dose lithium and suicide rates. Studies report that lithium levels in drinking water may play a role in reducing suicide risk the general population. Conclusion. The available literature indicates that higher lithium levels in drinking water may be associated with lower suicide rates.
Forecasting Banking Volatility in Amman Stock Exchange by Using ARIMA Model

Different techniques of forecasting can be employed in financial markets. This paper introduces one of these techniques which is known as Box-Jenkins model, in which it can be employed for analyzing a financial time series data. The major target of this study is to predict the banking sector volatility in Amman Stock Exchange as an emerging market. This can be achieved by finding the tentative ARIMA model that has the ability to forecast the volatility behavior of the banking sector . The data are obtained from the website of “Amman Stock Exchange” (ASE) on a weekly basis using the historical indices in the period from1/1/2010-1/4/2015 . We tested the stationary by using the unit root test which indicates that there is stationary at the level, then used a minimum mean square error, t-statistics value and p-statistics value for selecting most appropriate ARIMA model at 95% confidence interval. On the other hand the capability of ARIMA model in modelling and forecasting ASE evaluated by using “Akaike's Information Criterion” (AIC). The resulted model for banking sector volatility is ARIMA (2, 0, 2). Finally, the best ARIMA model was formed and tabulated in the entire paper.
Exosomes derived from adipose tissue, bone marrow, and umbilical cord blood for cardioprotection after myocardial infarction

Human mesenchymal stem cells (MSCs) have the potential for improving cardiac function following myocardial infarction (MI). This study was performed to explore the cardioprotection of bone marrow mesenchymal stem cells (BMMSCs), adipose tissue‐derived mesenchymal stem cells (ADMSCs), and umbilical cord blood‐derived mesenchymal stem cells (UCBMSCs) for myocardium in rats after MI. MI models were established in rats, which were injected with PBS, BMMSCs, ADMSCs, and UCMSCs. Cardiac function was detected by ultrasonic cardiogram. TTC staining, TUNEL staining, and immunohistochemistry were adopted to determine infarction area, cardiomyocyte apoptosis, and microvascular density (MVD), respectively. Exosomes were derived from BMMSCs, ADMSCs, and UCBMSCs, and identified by morphological observation and CD63 expression detection. Neonatal rat cardiomyocytes (NRCMs) were isolated and cultured with hypoxia, subjected to PBS and exosomes derived from BMMSCs, ADMSCs, and UCMSCs. Flow cytometry and enzyme‐linked immunosorbent assay were used to determine NRCM apoptosis and the levels of angiogenesis‐related markers (VEGF, bFGF, and HGF). According to ultrasonic cardiogram, BMMSCs, ADMSCs, and UCMSCs facilitated the cardiac function of MI rats. Furthermore, three kinds of MSCs inhibited cardiomyocyte apoptosis, infarction area, and increased MVD. NRCMs treated with exosomes derived from BMMSCs, ADMSCs, and UCMSCs reduced the NRCM apoptosis and promoted angiogenesis by increasing levels of VEGF, bFGF, and HGF. Notably, exosomes from ADMSCs had the most significant effect. On the basis of the results obtained from this study, exosomes derived from BMMSCs, ADMSCs, and UCBMSCs inhibited the cardiomyocyte apoptosis and promoted angiogenesis, thereby improving cardiac function and protecting myocardium. Notably, exosomes from ADMSCs stimulated most of the cardioprotection factors.
The fire ant social supergene is characterized by extensive gene and transposable element copy number variation

In the fire ant Solenopsis invicta, a supergene composed of ~600 genes and having two variants, SB and Sb, regulates colony social form. In single queen colonies, all individuals carry only the SB allele, while in multiple queen colonies, some individuals carry the Sb allele. In this study, we characterized genes with copy number variation between SB and Sb‐carrying individuals. We showed extensive acquisition of gene duplicates in the Sb genome, with some likely involved in polygyne‐related phenotypes. We found 260 genes with copy number differences between SB and Sb, of which 239 have greater copy number in Sb. We observed transposable element (TE) accumulation on Sb, likely due to the accumulation of repetitive elements on the nonrecombining chromosome. We found a weak correlation between TE copy number and differential expression, suggesting some TEs may still be proliferating in Sb while many of the duplicated TEs have presumably been silenced. Among the 115 non‐TE genes with higher copy in Sb, enzymes responsible for cuticular hydrocarbon synthesis were highly represented. These include a desaturase and an elongase, both potentially responsible for differential queen odour and likely beneficial for polygyne ants. These genes seem to have translocated into the supergene from other chromosomes and proliferated by multiple duplication events. While the presence of TEs in supergenes is well documented, little is known about duplication of non‐TE genes and their possible adaptive role. Overall, our results suggest that gene duplications may be an important factor leading to monogyne and polygyne ant societies.
The impact of previous therapy strategy on the efficiency of anlotinib hydrochloride as a third-line treatment on patients with advanced non-small cell lung cancer (NSCLC): a subgroup analysis of ALTER0303 trial.

Background Lung cancer remains one of the deadliest cancers worldwide. The ALTER0303 trial revealed that anlotinib might be used as a third-line or further treatment in non-small cell lung cancer (NSCLC) patients. Meanwhile, the impact of previous therapy strategies on the efficiency of anlotinib still remains unknown. Methods The subgroup of patients in ALTER0303 were analyzed by using Kaplan-Meier estimates, Pearson χ2, or Fisher's exact test. Results There was no statistical significance on progression-free survival (PFS) and overall survival (OS) among patients in different previous antiangiogenic treatments groups. Patients in the chest radiotherapy (CRT) group had longer median PFS than the non-CRT group (5.93 vs. 4.63 m, P=0.027). Regardless of what kind of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKI) and chemotherapy regimens were used previously, all patients gained longer PFS in the anlotinib group, while only patients treated with vinorelbine/platinum in the EGFR wild type group, pemetrexed/platinum, vinorelbine/platinum, and gefitinib in the EGFR mutation group, and EGFR TKI used as the first line group could benefit from anlotinib on OS. When the OS was calculated from the time of diagnosis to the death, anlotinib could have increased median OS about 6 months (33.8 vs. 27.8 m, P<0.001) compared to the placebo with a hazard ratio (HR) (95% CI): 0.77 (0.60, 1.00). Conclusions This study indicated that previous bevacizumab or endostatin treatments had no impact on the efficiency of anlotinib. Patients with CRT history benefited more from anlotinib on PFS. EGFR TKI and chemotherapy treatment history had more impact on OS than PFS in patients treated with anlotinib compared to placebo.
The association between birthweight and grandparental type 2 diabetes and cardiovascular disease in a multiethnic population

Abstract Intergenerational links of chronic disease have been suggested, as birthweight (BW) is associated with cardiovascular disease (CVD) and type 2 diabetes (T2D) in both parents and grandparents. However, most studies investigating these relationships have used relatively homogenous, white, majority populations. This study aimed to investigate the association between BW and CVD and T2D in a multiethnic population, that is, where the parents and grandparents often developed in a different environment from that where the child was born. Participants were women from a population-based cohort study of pregnant women (STORK Groruddalen), attending Child Health Clinics for antenatal care in three administrative city districts in Oslo, Norway, 2008–2010. Information about socioeconomic and lifestyle factors were collected among mothers and fathers. Parents reported history of CVD or T2D among grandparents. In logistic regressions, higher BW z-scores were associated with lower odds of T2D among maternal (OR 0.71 (95% CI 0.53, 0.97) and paternal (0.68 (0.49, 0.94) grandmothers after adjustments for parental and grandmothers’ characteristics. BW was not associated with CVD, but the association in maternal grandfathers was borderline significant. Our results indicate intergenerational transmission of chronic diseases like T2D in a multiethnic population.
Antisense oligonucleotide therapeutics in neurodegenerative diseases: the case of polyglutamine disorders.

Polyglutamine (polyQ) disorders are a group of nine neurodegenerative diseases that share a common genetic cause, which is an expansion of CAG repeats in the coding region of the causative genes that are otherwise unrelated. The trinucleotide expansion encodes for an expanded polyQ tract in the respective proteins, resulting in toxic gain-of-function and eventually in neurodegeneration. Currently, no disease-modifying therapies are available for this group of disorders. Nevertheless, given their monogenic nature, polyQ disorders are ideal candidates for therapies that target specifically the gene transcripts. Antisense oligonucleotides (ASOs) have been under intense investigation over recent years as gene silencing tools. ASOs are small synthetic single-stranded chains of nucleic acids that target specific RNA transcripts through several mechanisms. ASOs can reduce the levels of mutant proteins by breaking down the targeted transcript, inhibit mRNA translation or alter the maturation of the pre-mRNA via splicing correction. Over the years, chemical optimization of ASO molecules has allowed significant improvement of their pharmacological properties, which has in turn made this class of therapeutics a very promising strategy to treat a variety of neurodegenerative diseases. Indeed, preclinical and clinical strategies have been developed in recent years for some polyQ disorders using ASO therapeutics. The success of ASOs in several animal models, as well as encouraging results in the clinic for Huntington's disease, points toward a promising future regarding the application of ASO-based therapies for polyQ disorders in humans, offering new opportunities to address unmet medical needs for this class of disorders. This review aims to present a brief overview of key chemical modifications, mechanisms of action and routes of administration that have been described for ASO-based therapies. Moreover, it presents a review of the most recent and relevant preclinical and clinical trials that have tested ASO therapeutics in polyQ disorders.
"THERE IS NO OTHER WAY OUT": EDUCATIONAL DECISION-MAKING IN AN ERA OF AIDS: HOW DO HIV-POSITIVE MOTHERS VALUE EDUCATION?

This paper examines the logic behind some of the hypotheses found in influential studies and literature on the potential impact of HIV/AIDS on affected people’s values in life, and more specifically, on the value they attach to education. It has been suggested that caregivers or children, faced with illness, death and a decreased life expectancy as a consequence of AIDS, might no longer be interested in investing in education. However, there does not appear to be any detailed empirical research on how AIDS does make an impact on people’s values in life, their views on the future or the value attached to education. This paper begins to investigate how affected caregivers value education for both themselves and their children. The sample comprised ten HIV-positive mothers, nine of whom have at least one child of school-going age. One group discussion and five in-depth interviews were conducted, using semi-structured questionnaires. This research suggests that HIV-positive mothers are, in fact, strongly inclined to invest in their own education and especially their children’s education. As caregivers, they have an increased sense of the importance of independence for both themselves and their children, and they regard education as the means to achieve that independence. Hence, providing schooling for their children is an intrinsic part of their caregiving. Background and introduction Various studies have indicated the already visible, devastating effects of HIV/AIDS for the children in heavily affected regions. One of the ways in which the AIDS pandemic already does and will almost certainly continue to
Isoquinoline-based biaryls as a robust scaffold for microtubule inhibitors.

We here report the discovery of isoquinoline-based biaryls as a new scaffold for colchicine domain tubulin inhibitors. Colchicinoid inhibitors offer highly desirable cytotoxic and vascular disrupting bioactivities, but their further development requires improving in vivo robustness and tolerability: properties that both depend on the scaffold structure employed. We have developed isoquinoline-based biaryls as a novel scaffold for high-potency tubulin inhibitors, with excellent robustness, druglikeness, and facile late-stage structural diversification, accessible through a tolerant synthetic route. We confirmed their bioactivity mechanism in vitro, developed soluble prodrugs, and established safe in vivo dosing in mice. By addressing several problems facing the current families of inhibitors, we expect that this new scaffold will find a range of in vivo applications towards translational use in cancer therapy.
Robust Binary Network

Modern deep neural networks are the state-of-the-art techniques for many applications such as computer vision and natural language processing, but they are vulnerable to adversarial attacks [3, 5, 7]. As Figure 1 shows, small but welldesigned noise makes the state-of-the-art model predict wrong label with very high confidence. The existence of adversarial examples reveals some unsatisfying properties of modern deep learning model and poses a threat to safety-critic applications.
Deep Representation Learning with Genetic Programming

A representation can be seen as a set of variables, known as features, that describe a phenomenon. Machine learning (ML) algorithms make use of these representations to achieve the task they are designed for, such as classification, clustering or sequential decision making. ML algorithms require compact, yet expressive, representations; otherwise they might take too much time to return an output, or not have enough information to correctly discriminate the phenomena being presented with. Representation learning is the subfield of computer science that deals with the automatic generation of representations (as opposed to human engineered representations). Representation learning has achieved notoriously good results in the recent years thanks to the emergence of massive layered structures comprised of non-linear operations, known as deep architectures, such as Deep Neural Networks (DNN). DNN, and other deep architectures alike, work by gradually reducing and abstracting the input representation in each successive layer. In this technical report, we describe a research proposal to develop a new type of deep architecture for representation learning, based on Genetic Programming (GP). GP is a machine learning framework that belongs to evolutionary computation. GP has already been used in the past for representation learning; however, many of those approaches required of human experts knowledge from the representations’ domain. In this proposal, we explore the pitfalls of developing representation learning systems with GP that do not require experts’ knowledge, and propose a solution based on layered GP structures, similar to those found in DNN.