Miracle-dz/UniFAR-FTUs huggingface dataset:
CONTRIBUTIONS OF CYTOGENETICS TO CANCER RESEARCH

The two conflicting visions of tumorigenesis that are widely discussed are the gene-mutation hypothesis and the aneuploidy hypothesis. In this review we will summarize the contributions of cytogenetics in the study of cancer cells and propose a hypothetical model to explain the influence of cytogenetic events in carcinogenesis, emphasizing the role of aneuploidy. The gene mutation hypothesis states that gene-specific mutations occur and that they maintain the altered phenotype of the tumor cells, and the aneuploidy hypothesis states that aneuploidy is necessary and sufficient for the initiation and progression of malignant transformation. Aneuploidy is a hallmark of cancer and plays an important role in tumorigenesis and tumor progression. Aneuploid cells might be derived from polyploid cells, which can arise spontaneously or are induced by environmental agents or chemical compounds, and the genetic instability observed in polyploid cells leads to chromosomal losses or rearrangements, resulting in variable aberrant karyotypes. Because of the large amount of evidence indicating that the correct chromosomal balance is crucial to cancer development, cytogenetic techniques are important tools for both basic research, such as elucidating carcinogenesis, and applied research, such as diagnosis, prognosis and selection of treatment. The combination of classic cytogenetics, molecular cytogenetics and molecular genetics is essential and can generate a vast amount of data, enhancing our knowledge of cancer biology and improving treatment of this disease.
Advancing physiological maturation in human induced pluripotent stem cell‐derived cardiac muscle by gene editing an inducible adult troponin isoform switch

Advancing maturation of stem cell‐derived cardiac muscle represents a major barrier to progress in cardiac regenerative medicine. Cardiac muscle maturation involves a myriad of gene, protein, and cell‐based transitions, spanning across all aspects of cardiac muscle form and function. We focused here on a key developmentally controlled transition in the cardiac sarcomere, the functional unit of the heart. Using a gene‐editing platform, human induced pluripotent stem cell (hiPSCs) were engineered with a drug‐inducible expression cassette driving the adult cardiac troponin I (cTnI) regulatory isoform, a transition shown to be a rate‐limiting step in advancing sarcomeric maturation of hiPSC cardiac muscle (hiPSC‐CM) toward the adult state. Findings show that induction of the adult cTnI isoform resulted in the physiological acquisition of adult‐like cardiac contractile function in hiPSC‐CMs in vitro. Specifically, cTnI induction accelerated relaxation kinetics at baseline conditions, a result independent of alterations in the kinetics of the intracellular Ca2+ transient. In comparison, isogenic unedited hiPSC‐CMs had no cTnI induction and no change in relaxation function. Temporal control of adult cTnI isoform induction did not alter other developmentally regulated sarcomere transitions, including myosin heavy chain isoform expression, nor did it affect expression of SERCA2a or phospholamban. Taken together, precision genetic targeting of sarcomere maturation via inducible TnI isoform switching enables physiologically relevant adult myocardium‐like contractile adaptations that are essential for beat‐to‐beat modulation of adult human heart performance. These findings have relevance to hiPSC‐CM structure‐function and drug‐discovery studies in vitro, as well as for potential future clinical applications of physiologically optimized hiPSC‐CM in cardiac regeneration/repair.
NANDA‐I, NOC, and NIC Linkages to SARS‐Cov‐2 (Covid‐19): Part 1. Community Response

PURPOSE We developed linkages using interoperable standardized nursing terminologies, NANDA International (NANDA‐I) nursing diagnoses, Nursing Interventions Classification (NIC), and Nursing Outcomes Classification (NOC), to present initial guidance for the development of care plans focused on COVID‐19 for nurses practicing in community or public health roles. METHODS Seven nurse experts identified the linkages of NANDA‐I, NOC and NIC for our work related to the COVID‐19 pandemic. A model was developed to guide the project. The first step in creating linkages focused on the identification of nursing diagnoses. Then, for each nursing diagnosis, outcomes aligned with all components of the diagnosis were categorized and a list of nursing interventions was selected. The experts used their clinical judgment to make final decisions on the linkages selected in this study. FINDINGS Two community level nursing diagnoses were identified as key problems appropriate for a pandemic related to COVID‐19: Deficient Community Health and Ineffective Community Coping. For the nursing diagnosis Deficient Community Health, eight nursing outcomes and 12 nursing interventions were selected. In comparison for the nursing diagnosis, Ineffective Community Coping, nine nursing outcomes and 18 nursing interventions were identified. A total of40 concepts were identified for future development across the three classifications. CONCLUSIONS The nursing diagnoses, outcomes and interventions selected during this linkage process provide knowledge to support the community challenged with responding to the COVID‐19 pandemic, provide the opportunity to quantify the impact of nursing care, and enhance nursing practice by promoting the use of three standardized terminologies. IMPLICATIONS FOR NURSING PRACTICE NANDA‐I, NOC and NIC linkages identified in this manuscript provide resources to support clinical decisions and care plan development for nurses practicing in the community.
Characterizing the microbiome of ectoparasitic louse flies feeding on migratory raptors

Louse flies (Diptera: Hippoboscidae) are obligate ectoparasites that often cause behavioral, pathogenic, and evolutionary effects on their hosts. Interactions between ectoparasites and avian hosts, especially migrating taxa, may influence avian pathogen spread in tropical and temperate ecosystems and affect long-term survival, fitness and reproductive success. The purpose of this study was to characterize the vector-associated microbiome of ectoparasitic louse flies feeding on migrating raptors over the fall migration period. Surveys for louse flies occurred during fall migration (2015–2016) at a banding station in Pennsylvania, United States; flies were collected from seven species of migrating raptors, and we sequenced their microbial (bacteria and archaea) composition using high-throughput targeted amplicon sequencing of the 16S rRNA gene (V4 region). All louse flies collected belonged to the same species, Icosta americana. Our analysis revealed no difference in bacterial communities of louse flies retrieved from different avian host species. The louse fly microbiome was dominated by a primary endosymbiont, suggesting that louse flies maintain a core microbial structure despite receiving blood meals from different host species. Thus, our findings highlight the importance of characterizing both beneficial and potentially pathogenic endosymbionts when interpreting how vector-associated microbiomes may impact insect vectors and their avian hosts.
Smartphone and Paper-Based Fluorescence Reader: A Do It Yourself Approach

Given their photoluminescent character, portable quantum dot readers are often sophisticated and relatively expensive. In response, we engineered a “do it yourself” fluorescence reader employing paper materials and a mid-range smartphone camera. Black paperboard facilitated a versatile, lightweight and foldable case; whereas cellophane paper was observed to behave as a simple, yet effective, optical bandpass filter leading to an advantageous device for the quantitative interrogation of quantum dot nanocrystals concentrations (from 2.5 to 20 nM), which are suitable for optical point-of-care biosensing. The streptavidin-coated nanocrystals employed are commercially available and the developed reader was benchmarked with a standard portable quantum dot reader, thereby demonstrating advantages in terms of cost and linear analytical range.
On Territoriality in Ungulates and an Evolutionary Model

The behavioral characteristics of territorial ungulates are reviewed and compared with non-territorial species in terms of social distribution, spatial dispersion, and interaction patterns. Territoriality is related proximally to dominance and ultimately to mating exhancement. Alternative male mating strategies are categorized. Selective gains are estimated by the potential mating enhancement factor (PMEF) and costs by reduced chances of survival. The likely lifetime mating enhancement (LLME) resulting from territorial versus roving/rank dominance strategies are calculated for model populations. Ecological conditions favoring territoriality are discussed, and a comparison is made with territorial systems in other animal groups. There is a need for more empirical data.
I Feel Better Naked: Communal Naked Activity Increases Body Appreciation by Reducing Social Physique Anxiety

ABSTRACT Positive body image predicts several measures of happiness, well-being, and sexual functioning. Prior research has suggested a link between communal naked activity and positive body image, but has thus far not clarified either the direction or mechanisms of this relationship. This was the first randomized controlled trial of the effects of nakedness on body image. Two potential explanatory mediators of this effect were also investigated. Fifty-one participants were randomly assigned to one of two groups in which they interacted with other people either naked (naked condition) or clothed (control condition). All participants completed measures of body appreciation before and after the intervention, as well as measures of the relative perceived attractiveness of others and social physique anxiety immediately after the intervention. Perceived attractiveness of others was neither affected by the manipulation nor correlated with body appreciation. However, as expected, participants in the naked condition reported more body appreciation, an effect that was mediated by reductions in social physique anxiety. This research provides initial evidence that naked activity can lead to improvements in body image and evidence of a specific explanatory mechanism. Theoretical and practical implications are discussed.
SEAPORT: Assessing the Portability of Serverless Applications

: The term serverless is often used to describe cloud applications that comprise components managed by third parties. Like any other cloud application, serverless applications are often tightly-coupled with providers, their features, models, and APIs. As a result, when their portability to another provider has to be assessed, application owners must deal with identiﬁcation of heterogeneous lock-in issues and provider-speciﬁc technical details. Unfortunately, this process is tedious, error-prone, and requires signiﬁcant technical expertise in the domains of serverless and cloud computing. In this work, we introduce SEAPORT, a method for automatically assessing the portability of serverless applications with respect to a chosen target provider or platform. The method introduces (i) a canonical serverless application model, and (ii) the concepts for portability assessment involving classiﬁcation and components similarity calculation together with the static code analysis. The method aims to be compatible with existing migration concepts to allow using it as a complementary part for serverless use cases. We present an architecture of a decision support system supporting automated assessment of the given application model with respect to the target provider. To validate the technical feasibility of the method, we implement the system prototypically.
Performance of Cluster-based High Availability Database in Cloud Containers

: Database is an important component in any software application, which enables efﬁcient data management. High availability of databases is critical for an uninterruptible service offered by the application. Virtualization has been a dominant technology behind providing highly available solutions in the cloud including database, where database servers are provisioned and dynamically scaled based on demands. However, containerization technology has gained popularity in recent years because of light-weight and portability, and the technology has seen increased number of enterprises embracing containers as an alternative to heavier and resource-consuming virtual machines for deploying applications and services. A relatively new cluster-based synchronous multi-master database solution has gained popularity recently and has seen increased adoption against the traditional master-slave replication for better data consistency and high availability. This article evaluates the performance of a cluster-based high availability database deployed in containers and compares it to the one deployed in virtual machines. A popular cloud software platform, OpenStack, is used for virtual machines. Docker is used for containers as it is the most popular container technology at the moment. Results show better performance by HA Galera cluster database setup using Docker containers in most of the Sysbench benchmark tests compared to a similar setup using OpenStack virtual machines.
Preconception Health and Lifestyle Behaviours of Women Planning a Pregnancy: A Cross-Sectional Study

Preconception care and lifestyle behaviours significantly influence health outcomes of women and future generations. A cross-sectional survey of Australian women in preconception, stratified by pregnancy planning stage (active planners (currently trying to conceive) vs. non-active planners (pregnancy planned within 1–5 years)), assessed health behaviours and their alignment to preconception care guidelines. Overall, 294 women with a mean (SD) age of 30.7 (4.3) years were recruited and 38.9% were overweight or obese. Approximately half of women (54.4%) reported weight gain within the previous 12 months, of which 69.5% gained ≥ 3kg. The vast majority of women (90.2%) were unaware of reproductive life plans, and 16.8% over the age of 25 had not undertaken cervical screening. Of active planners (n = 121), 47.1% had sought medical/health advice in preparation for pregnancy and 81.0% had commenced supplementation with folic acid, iodine or a preconception multivitamin. High-risk lifestyle behaviours including cigarette smoking (7.3%), consumption of alcohol (85.3%) and excessive alcohol consumption within three months (56.3%), were frequently reported in women who were actively trying to conceive. Results indicate that women who are actively planning a pregnancy require support to optimise health and lifestyle in preparation for pregnancy to improve alignment with current preconception care recommendations.
Long-Term Adherence to Renin–Angiotensin System Inhibitors and β-Blockers After Heart Failure Hospitalization in Senior Patients

Aims: We investigated long-term adherence to renin–angiotensin system inhibitors (RASIs) and β-blockers, and associated predictors, in senior patients after hospitalization for heart failure (HF). Methods: A population-based data set identified 4488 patients who survived 60 days following their index hospitalization for HF in Western Australia from 2003 to 2008 with a 3-year follow-up. Their person-linked Pharmaceutical Benefits Scheme records identified medications dispensed during follow-up. Drug discontinuation was defined as the first break ≥90 days following the previous supply. Medication adherence was calculated using the proportion of days covered (PDC), with PDC ≥ 80% defined as being adherent. Multivariable logistic regression models were used to identify predictors of PDC < 80%. Results: In the cohort (57% male, mean age: 76.6 years), 77.4% were dispensed a RASI and 52.7% a β-blocker within 60 days postdischarge. Over the 3-year follow-up, 28% and 42% of patients discontinued RASI and β-blockers, respectively. Only 64.6% and 47.5% of RASI and β-blocker users, respectively, were adherent to their treatment over 3 years, with adherence decreasing over time (trend P < .0001 for RASI and trend P = .02 for β-blockers). Older age, increasing Charlson comorbidity score, chronic kidney disease, and chronic obstructive pulmonary disease were independent predictors of PDC < 80% for both drug groups. Conclusion: Among seniors hospitalized for HF, discontinuation gaps were common for RASI and β-blockers postdischarge, and long-term adherence to these medications was suboptimal. Where appropriate, strategies to improve long-term medication adherence are indicated in HF patients, particularly in elderly patients with comorbidities.
Comparison of clinical characteristics and outcomes of patients with coronavirus disease 2019 at different ages

Background: Information about the clinical characteristics and mortality of patients with coronavirus disease 2019 at different ages is limited. Results: The older group had more patients with dyspnea and fewer patients with fever and muscle pain. Older patients had more underlying diseases, secondary infection, myocardial injury, renal dysfunction, coagulation dysfunction, and immune dysfunction on admission. More older patients received immunoglobulin therapy and mechanical ventilation. The proportions of patients with multiple organ injuries, critically ill patients and death increased significantly with age. The older groups had higher cumulative death risk than the younger group. Hypertension, cerebrovascular disease, comorbidities, acute cardiac injury, shock and complications are independent predictors of death. Conclusions: The symptoms of the elderly patients were more atypical, with more comorbidities, secondary infection, organ injuries, immune dysfunction and a higher risk of critical illness. Older age was an important risk factor for mortality. Methods: 1000 patients diagnosed with coronavirus disease 2019 from January 1, 2020 to February 14, 2020 were enrolled. According to age, patients were divided into group 1 (<60 years old), group 2 (60-74 years old) and group 3 (≥75 years old). The clinical symptoms, first laboratory results, CT findings, organ injuries, disease severity and mortality were analyzed.
What place does molecular topology have in today’s drug discovery?

ABSTRACT Introduction Most methods in molecular and drug design are currently based on physicochemical descriptors. However, molecular topology, which relies on topological descriptors, has also shown value for molecular design even if it does not take into account the physical or chemical properties of ligands and receptors, including the ligand-receptor interaction itself. Areas covered Herein, the authors provide new insights into the importance of molecular topology according to some of the latest discoveries in physics and chemistry. Furthermore, the authors report on the most significant achievements in drug design using molecular topology over the last 5 years and give their expert perspectives on the subject as a whole. Expert opinion Molecular topology is a new paradigm which is independent of physicochemical molecular descriptors. This fact explains the viability of both the discovery of new lead compounds with a minimum of information derived from mathematical-topological patterns and the interpretation results in structural and physicochemical terms.
A cost-effective approach to DNA methylation detection by Methyl Sensitive DArT sequencing

Several studies suggest the relation of DNA methylation to diseases in humans and important phenotypes in plants drawing attention to this epigenetic mark as an important source of variability. In the last decades, several methodologies were developed to assess the methylation state of a genome. However, there is still a lack of affordable and precise methods for genome wide analysis in large sample size studies. Methyl sensitive double digestion MS-DArT sequencing method emerges as a promising alternative for methylation profiling. We developed a computational pipeline for the identification of DNA methylation using MS-DArT-seq data and carried out a pilot study using the Eucalyptus grandis tree sequenced for the species reference genome. Using a statistic framework as in differential expression analysis, 72,515 genomic sites were investigated and 5,846 methylated sites identified, several tissue specific, distributed along the species 11 chromosomes. We highlight a bias towards identification of DNA methylation in genic regions and the identification of 2,783 genes and 842 transposons containing methylated sites. Comparison with WGBS, DNA sequencing after treatment with bisulfite, data demonstrated a precision rate higher than 95% for our approach. The availability of a reference genome is useful for determining the genomic context of methylated sites but not imperative, making this approach suitable for any species. Our approach provides a cost effective, broad and reliable examination of DNA methylation profile on MspI/HpaII restriction sites, is fully reproducible and the source code is available on GitHub (https://github.com/wendelljpereira/ms-dart-seq).
Early Life Famine Exposure, Ideal Cardiovascular Health Metrics, and Risk of Incident Diabetes: Findings From the 4C Study

OBJECTIVE We aim to investigate the impact of ideal cardiovascular health metrics (ICVHMs) on the association between famine exposure and adulthood diabetes risk. RESEARCH DESIGN AND METHODS This study included 77,925 participants from the China Cardiometabolic Disease and Cancer Cohort (4C) Study who were born around the time of the Chinese Great Famine and free of diabetes at baseline. They were divided into three famine exposure groups according to the birth year, including nonexposed (1963–1974), fetal exposed (1959–1962), and childhood exposed (1949–1958). Relative risk regression was used to examine the associations between famine exposure and ICVHMs on diabetes. RESULTS During a mean follow-up of 3.6 years, the cumulative incidence of diabetes was 4.2%, 6.0%, and 7.5% in nonexposed, fetal-exposed, and childhood-exposed participants, respectively. Compared with nonexposed participants, fetal-exposed but not childhood-exposed participants had increased risks of diabetes, with multivariable-adjusted risk ratios (RRs) (95% CIs) of 1.17 (1.05–1.31) and 1.12 (0.96–1.30), respectively. Increased diabetes risks were observed in fetal-exposed individuals with nonideal dietary habits, nonideal physical activity, BMI ≥24.0 kg/m2, or blood pressure ≥120/80 mmHg, whereas significant interaction was detected only in BMI strata (P for interaction = 0.0018). Significant interactions have been detected between number of ICVHMs and famine exposure on the risk of diabetes (P for interaction = 0.0005). The increased risk was observed in fetal-exposed participants with one or fewer ICVHMs (RR 1.59 [95% CI 1.24–2.04]), but not in those with two or more ICVHMs. CONCLUSIONS The increased risk of diabetes associated with famine exposure appears to be modified by the presence of ICVHMs.