Miracle-dz/UniFAR-FTUs huggingface dataset:
Construction of a Selectable Marker Recycling System and the Use in Epitope Tagging of Multiple Nuclear Genes in the Unicellular Red Alga Cyanidioschyzon merolae

The nuclear genome of the unicellular red alga Cyanidioschyzon merolae can be modified by homologous recombination with exogenously introduced DNA. However, it is presently difficult to modify multiple chromosome loci because of the limited number of available positive selectable markers. In this study, we constructed a modified URA5.3 gene (URA5.3T), which can be repeatedly used for nuclear genome transformation, as well as two plasmid vectors for 3× FLAG- or 3× Myc-epitope tagging of nuclear-encoded proteins using URA5.3T. In the URA5.3T marker, the promoter region and open reading frame were located between directly repeated URA5.3 terminator sequences, and the URA5.3 gene can be eliminated by 5-fluoroorotic acid selection through homologous recombination. To demonstrate the utility of the constructed system, a 3× FLAG-tag and 3× Myc-tag were introduced at the C-termini of two of the six Rab proteins in C. merolae, CmRab18 and CmRab7, respectively, and the differential expression levels were successfully monitored by immunoblot analysis using these epitope tags. The URA5.3T marker's introduction and elimination cycle can be repeated. Thus, we have constructed a marker recycling system for C. merolae nuclear transformation. A novel procedure to obtain a high plating efficiency of C. merolae cells on solid gellan gum plates is also presented.
Reducing Effect of Saikosaponin A, an Active Ingredient of Bupleurum falcatum, on Intake of Highly Palatable Food in a Rat Model of Overeating

Recent lines of experimental evidence have indicated that saikosaponin A (SSA)—a bioactive ingredient of the medicinal plant, Bupleurum falcatum L. —potently and effectively reduced operant self-administration of chocolate and reinstatement of chocolate-seeking behavior in rats. The present study was designed to assess whether the protective properties of SSA on addictive-like, food-related behaviors generalize to a rat model of overeating of palatable food. To this end, rats were habituated to feed on a standard rat chow for 3 h/day; every 4 days, the 3-h chow-feeding session was followed by a 1-h availability of highly palatable, calorie-rich Danish butter cookies or Oreo chocolate cookies. Even though fed, rats consumed large amounts of cookies; intake of calories from cookies (consumed in 1 h) was even larger than that of calories from chow (consumed in 3 h). SSA (0, 0.25, 0.5, and 1 mg/kg, i.p.) was administered 10 min before cookie presentation. Treatment with SSA resulted in a dose-related decrease in intake of both butter and chocolate cookies. Administration of the cannabinoid CB1 receptor antagonist/inverse agonist, rimonabant (0, 0.3, 1, and 3 mg/kg, i.p.; tested as reference compound), produced a similar reduction in intake of butter cookies. These results (a) contribute to the set-up and validation of a rat model of overeating, characterized by the intake of large amounts of unnecessary calories and (b) provide an additional piece of evidence to the anorectic profile of SSA in rats.
Review and comparative assessment of similarity-based methods for prediction of drug-protein interactions in the druggable human proteome

Drug-protein interactions (DPIs) underlie the desired therapeutic actions and the adverse side effects of a significant majority of drugs. Computational prediction of DPIs facilitates research in drug discovery, characterization and repurposing. Similarity-based methods that do not require knowledge of protein structures are particularly suitable for druggable genome-wide predictions of DPIs. We review 35 high-impact similarity-based predictors that were published in the past decade. We group them based on three types of similarities and their combinations that they use. We discuss and compare key aspects of these methods including source databases, internal databases and their predictive models. Using our novel benchmark database, we perform comparative empirical analysis of predictive performance of seven types of representative predictors that utilize each type of similarity individually and all possible combinations of similarities. We assess predictive quality at the database-wide DPI level and we are the first to also include evaluation over individual drugs. Our comprehensive analysis shows that predictors that use more similarity types outperform methods that employ fewer similarities, and that the model combining all three types of similarities secures area under the receiver operating characteristic curve of 0.93. We offer a comprehensive analysis of sensitivity of predictive performance to intrinsic and extrinsic characteristics of the considered predictors. We find that predictive performance is sensitive to low levels of similarities between sequences of the drug targets and several extrinsic properties of the input drug structures, drug profiles and drug targets. The benchmark database and a webserver for the seven predictors are freely available at http://biomine.cs. vcu.edu/servers/CONNECTOR/.
“Engaging in my rural community”: perceptions of people aged 85 years and over

ABSTRACT Purpose: Globally, numbers of people aged 85 years and over are increasing. Many older people, including those 85 years and over, are ageing in rural areas. For successful ageing in place, physical and social environments must be appropriate. The aim of this study is to understand the influence the physical and social environments have on enabling those aged 85 years and over to remain engaged in a rural community. Method: Utilizing an environmental gerontological approach, semi-structured interviews were undertaken with 15 people who lived independently in a rural community. Following transcription data were analyzed and themes identified. Results: Two themes were identified; “Negotiating the physical environment: ‘Getting there and back’” and “Maintaining social networks: ‘Places to go, people to see’”. The findings provide insight into the importance of driving, parking close to amenities and negotiating the local environment to this group of older people and their ability to engage with their community. All participants agreed social engagement with friends, family or neighbors was important to them. Conclusion: These findings highlight the interconnection between physical and social environments. An enabling physical environment is essential to support social participation of people aged 85 years and over.
COPD affects worker productivity and health care costs

Purpose This study aimed to measure the true burden of COPD by calculating incremental direct and indirect costs. Direct medical resource use, productivity metrics, and COPD-specific resource use and costs were also evaluated. Patients and methods This was a retrospective, observational, matched cohort study using administrative claims data from the Truven Health MarketScan® Commercial Claims and Encounters and the Health and Productivity Management databases (2007–2010). Working-age (18–65 years) patients with COPD were identified as having at least one hospitalization or one emergency department visit or two outpatient visits. Patients in the non-COPD cohort did not have a diagnosis of COPD during the study period. Outcomes were evaluated in the first full calendar year after the year of identification (index). Results Of the 5,701 patients with COPD identified, 3.6% patients were frequent exacerbators (≥2), 10.4% patients were infrequent exacerbators (1), and 86% patients were non-exacerbators (0). When compared with the 17,103 patients without COPD, the incremental direct cost of COPD was estimated at $6,246/patient/year (95% confidence interval: $4,620, $8,623; P<0.001). Loss in productivity was significantly greater in patients with COPD, with an average of 5 more days/year of absence from work and incremental indirect costs from short-term disability of $641 (P<0.001). Direct costs for frequent exacerbators ($17,651/year) and infrequent exacerbators ($14,501/year) were significantly higher than those for non-exacerbators ($11,395, P<0.001). Conclusion Working-age patients with COPD incur statistically significantly higher direct and indirect costs and use more resources compared with those who do not have COPD.
The shift in seasonality of legionellosis in the USA

Abstract According to the Centers for Disease Control and Prevention (CDC), from 2000 to 2014, reported cases of legionellosis per 100 000 population increased by 300% in the USA, although reports on disease seasonality are inconsistent. Using two national databases, we assessed seasonal patterns of legionellosis in the USA. We created a monthly time series from 1993 to 2015 of reported cases of legionellosis from the CDC, and from 1997 to 2006 of medical claims of legionellosis-related hospitalisation in older adults from the Centers for Medicaid and Medicare Services (CMS). We split the study time interval into two segments (before and after 2003), and applied a Poisson harmonic regression model to each dataset and each segment. The time series of monthly counts exhibited a significant shift of seasonal peaks from mid-September (9.676 ± 0.164 months) before 2003 to mid-August (8.452 ± 0.042 months) after 2003, along with an alarming increase in the amplitude of seasonal peaks in both CDC and CMS data. The lowest monthly reported cases of legionellosis in 2015 (281) exceed the maximum value reported before 2003 (206). We also observed a discrepancy between CDC and CMS data, suggesting that not all cases of legionellosis diagnosed by hospital-based laboratories were reported to the CDC. Improved reporting of legionellosis is required to better inform the public and organise disease prevention.
Vitamin D status and risk of infections after liver transplantation in the Swiss Transplant Cohort Study

Increasing evidence indicates a role of vitamin D in the immune system affecting response to infections. We aimed to characterize the role of vitamin D status, i.e. deficiency [25‐OH vitamin D (25‐OHD) <50 nmol/l] and no deficiency (25‐OHD ≥50 nmol/l) in incident infections after liver transplantation. In 135 liver transplant recipients, blood samples drawn at time of liver transplantation and 6 months afterwards were used to determine 25‐OHD levels. Incident infections episodes were prospectively collected within the Swiss Transplant Cohort Study database. Poisson regression was applied to address associations between vitamin D status and incident infections. Vitamin D deficiency was common at time of transplantation and 6 months afterwards without a significant change in median 25‐OHD levels. In univariable analyses, vitamin D deficiency was a risk factor for incident infections in the first 6 months post‐transplant incidence rate ratio (IRR 1.52, 95% CI 1.08–2.15, P = 0.018) and for bacterial infections occurring after 6 up to 30 months post‐transplant (IRR 2.29, 95% CI 1.06–4.94, P = 0.034). These associations were not detectable in multivariable analysis with adjustment for multiple confounders. Efforts to optimize vitamin D supplementation in liver transplant recipients are needed. Our data question the role of vitamin D deficiency in incident infections.
The Role of Histamine and Histamine Receptors in Mast Cell-Mediated Allergy and Inflammation: The Hunt for New Therapeutic Targets

Histamine and its receptors (H1R–H4R) play a crucial and significant role in the development of various allergic diseases. Mast cells are multifunctional bone marrow-derived tissue-dwelling cells that are the major producer of histamine in the body. H1R are expressed in many cells, including mast cells, and are involved in Type 1 hypersensitivity reactions. H2R are involved in Th1 lymphocyte cytokine production. H3R are mainly involved in blood–brain barrier function. H4R are highly expressed on mast cells where their stimulation exacerbates histamine and cytokine generation. Both H1R and H4R have important roles in the progression and modulation of histamine-mediated allergic diseases. Antihistamines that target H1R alone are not entirely effective in the treatment of acute pruritus, atopic dermatitis, allergic asthma, and other allergic diseases. However, antagonists that target H4R have shown promising effects in preclinical and clinical studies in the treatment of several allergic diseases. In the present review, we examine the accumulating evidence suggesting novel therapeutic approaches that explore both H1R and H4R as therapeutic targets for histamine-mediated allergic diseases.
Understanding and Comprehending

Schools should be instructing students in formal thought and expression—what we call “comprehending”—rather than in everyday or “home” thought and language—what we call “understanding. ” In this essay we suggest general changes in the standard reading and writing curricula. Finally, we examine the language of writing instruction, in college-level individual writing conferences, to take a close look at issues involved in implementing the curricula for higher and lower achieving students.
Automatic measurement of fall risk indicators in timed up and go test

ABSTRACT Fall risk assessment is usually conducted in specialized centers using clinical tests. Most of the time, these tests are performed only after the occurrence of health problems potentially affecting gait and posture stability. Our aim is to define fall risk indicators that could routinely be used at home to automatically monitor the evolution of fall risk over time. We used the standard Timed Up and Go (T.U.G.) test to classify 43 individuals into two classes of fall risk, namely high- vs low- risk. Several parameters related to the gait pattern and the sitting position included in the T.U. G. test were automatically extracted using an ambient sensor (Microsoft Kinect sensor). We were able to correctly classify all individuals using machine learning on the combination of two parameters among gait speed, step length and speed to sit down. Coupled to an ambient sensor installed at home to monitor the relevant parameters in daily activities, these algorithms could therefore be used to assess the evolution of fall risk, thereby improving fall prevention.
Cell membrane proteins with high N-glycosylation, high expression and multiple interaction partners are preferred by mammalian viruses as receptors

Motivation: Receptor mediated entry is the first step for viral infection. However, the question of how viruses select receptors remains unanswered. Results: Here, by manually curating a high‐quality database of 268 pairs of mammalian virus‐host receptor interaction, which included 128 unique viral species or sub‐species and 119 virus receptors, we found the viral receptors are structurally and functionally diverse, yet they had several common features when compared to other cell membrane proteins: more protein domains, higher level of N‐glycosylation, higher ratio of self‐interaction and more interaction partners, and higher expression in most tissues of the host. This study could deepen our understanding of virus‐receptor interaction. Availability and implementation: The database of mammalian virus‐host receptor interaction is available at http://www.computationalbiology. cn:5000/viralReceptor. Supplementary information: Supplementary data are available at Bioinformatics online.
Dynamics of child marriage and marital timing in Nigeria: A retrogression or progression?

Abstract The researcher assessed trends and patterns of marital timing and child marriage (CM) among women of reproductive age in Nigeria. Four rounds of Nigeria Demographic and Health Survey data-set were used (1990–2013). Data were analyzed using descriptive statistics and Cox-regression model with time-dependent covariates (α = 0.05). CM (<18 years) falls consistently from 63.8% in 1990 to 56.3% in 2013. The hazard ratio of CM was 1.24 (CI =1.19–1.28, p < .001), 1.24 (CI =1.19–1.29, p < .001), and 1.05 (CI =1.02–1.07, p < .001) times higher in 1990, 2003, and 2008, respectively than 2013. The region, education, religion, and ethnicity are common predictors of CM in all the survey rounds.
Bioinformatics applications on Apache Spark

Abstract With the rapid development of next-generation sequencing technology, ever-increasing quantities of genomic data pose a tremendous challenge to data processing. Therefore, there is an urgent need for highly scalable and powerful computational systems. Among the state-of–the-art parallel computing platforms, Apache Spark is a fast, general-purpose, in-memory, iterative computing framework for large-scale data processing that ensures high fault tolerance and high scalability by introducing the resilient distributed dataset abstraction. In terms of performance, Spark can be up to 100 times faster in terms of memory access and 10 times faster in terms of disk access than Hadoop. Moreover, it provides advanced application programming interfaces in Java, Scala, Python, and R. It also supports some advanced components, including Spark SQL for structured data processing, MLlib for machine learning, GraphX for computing graphs, and Spark Streaming for stream computing. We surveyed Spark-based applications used in next-generation sequencing and other biological domains, such as epigenetics, phylogeny, and drug discovery. The results of this survey are used to provide a comprehensive guideline allowing bioinformatics researchers to apply Spark in their own fields.
Cortisol response to awakening in prepubertal children and adults: Magnitude and variability.

Within the first 30-45 min after awakening, there is a characteristic rise in cortisol that is referred to as cortisol awakening response (CAR). Over the past decades, the CAR has become an important biomarker, mainly because of its reported association with health and disease. Previous research showed that the CAR can already be reliably assessed in infants and children. Yet, earlier findings on the influence of age have been inconsistent, and limited attention has been devoted to prepubertal children. Here, we aimed to contrast the magnitude and stability of the CAR in prepubertal children and adults. To this end, 24 healthy adults between 35 and 50 years of age and 24 healthy children between 6 and 9 years of age collected four salivary cortisol samples within 45 min after awakening on 4 separate days, 2 weekdays, and 2 weekend days. Our results showed that there was a marked CAR on weekdays and weekend days in both adults and children. In children, however, the CAR was overall significantly attenuated relative to adults. Moreover, while the cortisol increases after awakening were, both on weekdays and weekend days, highly correlated in adults, there were no such associations in children. Together, these data suggest that the CAR is less pronounced and less stable in prepubertal children compared to adults. Such age differences need to be taken into account when using the CAR as a biomarker in clinical settings.
Comprehensive systematic review update summary: Disorders of consciousness

Objective To update the 1995 American Academy of Neurology (AAN) practice parameter on persistent vegetative state and the 2002 case definition for the minimally conscious state (MCS) by reviewing the literature on the diagnosis, natural history, prognosis, and treatment of disorders of consciousness lasting at least 28 days. Methods Articles were classified per the AAN evidence-based classification system. Evidence synthesis occurred through a modified Grading of Recommendations Assessment, Development and Evaluation process. Recommendations were based on evidence, related evidence, care principles, and inferences according to the AAN 2011 process manual, as amended. Results No diagnostic assessment procedure had moderate or strong evidence for use. It is possible that a positive EMG response to command, EEG reactivity to sensory stimuli, laser-evoked potentials, and the Perturbational Complexity Index can distinguish MCS from vegetative state/unresponsive wakefulness syndrome (VS/UWS). The natural history of recovery from prolonged VS/UWS is better in traumatic than nontraumatic cases. MCS is generally associated with a better prognosis than VS (conclusions of low to moderate confidence in adult populations), and traumatic injury is generally associated with a better prognosis than nontraumatic injury (conclusions of low to moderate confidence in adult and pediatric populations). Findings concerning other prognostic features are stratified by etiology of injury (traumatic vs nontraumatic) and diagnosis (VS/UWS vs MCS) with low to moderate degrees of confidence. Therapeutic evidence is sparse. Amantadine probably hastens functional recovery in patients with MCS or VS/UWS secondary to severe traumatic brain injury over 4 weeks of treatment. Recommendations are presented separately.
Do health literacy and self‐care behaviours affect quality of life in older persons with lung cancer receiving chemotherapy?

AIM This study aimed at identifying the factors associated with health literacy, self-care behaviours, and quality of life among older persons with lung cancer receiving chemotherapy. METHODS This was a descriptive study. A total of 80 older persons with lung cancer receiving chemotherapy participated in this study. Data were collected from July 21 to November 3, 2016 in Korea. The Short Form of the Korean Functional Health Literacy Test, the Self-Care Behaviours Scale, and the Functional Assessment of Cancer Therapy Scale-Lung were used to measure functional health literacy, self-care behaviours, and quality of life, respectively. Stepwise multiple regression analyses were conducted to analyse the data. RESULTS In the each regression model for the general and disease-related quality of life, performance status, self-care behaviours, and prior lines of treatment were identified as a predictor. However, functional health literacy was found to be a predictor only of disease-related quality of life. Among these predictors, self-care behaviours had the greatest impact. CONCLUSION Health care providers should be aware of the effects of health literacy and self-care behaviours on health-related quality of life and consider the factors associated with quality of life when they take care of older persons with lung cancer receiving chemotherapy.