Miracle-dz/UniFAR-FTUs huggingface dataset:
Between-Population Outbreeding Affects Plant Defence

Between-population crosses may replenish genetic variation of populations, but may also result in outbreeding depression. Apart from direct effects on plant fitness, these outbreeding effects can also alter plant-herbivore interactions by influencing plant tolerance and resistance to herbivory. We investigated effects of experimental within- and between-population outbreeding on herbivore resistance, tolerance and plant fitness using plants from 13 to 19 Lychnis flos-cuculi populations. We found no evidence for outbreeding depression in resistance reflected by the amount of leaf area consumed. However, herbivore performance was greater when fed on plants from between-population compared to within-population crosses. This can reflect outbreeding depression in resistance and/or outbreeding effects on plant quality for the herbivores. The effects of type of cross on the relationship between herbivore damage and plant fitness varied among populations. This demonstrates how between-population outbreeding effects on tolerance range from outbreeding depression to outbreeding benefits among plant populations. Finally, herbivore damage strengthened the observed outbreeding effects on plant fitness in several populations. These results raise novel considerations on the impact of outbreeding on the joint evolution of resistance and tolerance, and on the evolution of multiple defence strategies.
Development of carbapenem resistance in Pseudomonas aeruginosa is associated with OprD polymorphisms, particularly the amino acid substitution at codon 170

Objectives: Pan‐susceptible Pseudomonas aeruginosa (PSPA) clinical isolates carrying an OprD with loop 7 shortening (the group‐1A allele) were found to rapidly develop carbapenem resistance under continuous selection pressure. We further studied whether OprD polymorphisms are associated with the potential to develop carbapenem resistance. Methods: OprD amino acid sequences of 126 PSPA clinical isolates were analysed to determine their STs using P. aeruginosa strain PAO1 as the control strain. Site‐directed mutagenesis was performed in PAO1 to generate polymorphisms of interest. A disc diffusion method was used to select carbapenem‐resistant variants from the mutant strains. Expression levels of oprD were determined by quantitative RT‐PCR. MICs of carbapenems were determined by Etest. Results: Forty‐eight (38.1%) of the tested isolates carried the group‐1A allele. Another two major STs, C1 and C2, both of which harboured an F170L polymorphism, were found in 21 (16.7%) and 39 (31.0%) isolates, respectively. The PAO1 type was also found in 14 (11.1%) isolates. Under continuous selective pressure, isolates of most STs developed carbapenem resistance at different numbers of passaging events; only those belonging to the PAO1 type remained susceptible. However, PAO1 mutants carrying either the oprD group‐1A allele or the OprD‐F170L polymorphism were able to develop carbapenem resistance. Reduced oprD expression triggered by continuous imipenem challenge was found in PAO1 mutants, but not in the PAO1 WT strain. Conclusions: OprD polymorphisms, particularly the F170L substitution and the specific shortening in loop 7, appear to determine the potential for P. aeruginosa to develop carbapenem resistance.
An observational analysis of insulinoma from a single institution

Background Insulinoma is the commonest functioning pancreatic neuroendocrine tumor causing hyperinsulinemic hypoglycemia. Aim This study is aimed to evaluate the clinical features, preoperative laboratory and imaging diagnosis and pathologic findings of insulinoma. Methods Data of the patients from 2001 to 2016 diagnosed as insulinoma in Tongji Hospital, China were retrospectively extracted and analyzed. Results A total of 40 patients were diagnosed as insulinoma with a male/female ratio of 0.68:1. The median onset age was 46.5 years. Nearly all the included patients presented neurological symptoms and 60% presented autonomic symptoms. More than 95% of the patients met the functional European Neuroendocrine Tumor Society criteria including glucose, insulin and C-peptide levels. The preoperative detection rates of ultrasonography, enhanced computed tomography, magnetic resonance imaging, and endoscopic ultrasonography were 60.50%, 84.95%, 80% and 83.3% respectively. The joint imaging examinations can markedly increase the detection rate. The mean tumor size was 1.89 ± 0.72 cm. Ki-67 index by histopathological diagnosis were all less than 20%. The positive rates of insulin, synaptophysin and chromogranin A were close to 100%. Conclusion Laboratory tests of glucose, insulin and C-peptide are reliable for preoperative diagnosis. Combination of the imaging examinations can improve the diagnosis.
Repair of Mandibular Defect by Using Tissue Engineered Bone:A Report of 3 Cases

Objective To explore the feasibility of hBMSCs acting as seeding cell for tissue engineered bone in the repairing of mandibular after tumor surgery.Methods Three patients with mandibular defect were treated by tissue engineered bone after tumor surgery.The hBMSC were isolated by percolling gradient centrifugation from patient's bone marrow aspirated from iliac crest.The hBMSC were cultured in vitro and induced.The osteogenic induced hBMSC were in partly demineralized allogenic bone scaffold and cultured for 1 month.The defects were repaired with the cell-scaffold construct.All cases were followed up for half a month,3 months,2 years postoperatively by PET-CT.Results PET-CT demonstrated that tissue engineered bone was formed in 3 months postoperatively.The tissue engineered bone can repair bone defect,and maintained stable effect.Conclusion The tissue engineered bone from hBMSCS can be formed in human body stably and used for repairing mandibular defect with satisfactory results.
A generalized association test based on U statistics

Motivation: Second generation sequencing technologies are being increasingly used for genetic association studies, where the main research interest is to identify sets of genetic variants that contribute to various phenotypes. The phenotype can be univariate disease status, multivariate responses and even high‐dimensional outcomes. Considering the genotype and phenotype as two complex objects, this also poses a general statistical problem of testing association between complex objects. Results: We here proposed a similarity‐based test, generalized similarity U (GSU), that can test the association between complex objects. We first studied the theoretical properties of the test in a general setting and then focused on the application of the test to sequencing association studies. Based on theoretical analysis, we proposed to use Laplacian Kernel‐based similarity for GSU to boost power and enhance robustness. Through simulation, we found that GSU did have advantages over existing methods in terms of power and robustness. We further performed a whole genome sequencing (WGS) scan for Alzherimer's disease neuroimaging initiative data, identifying three genes, APOE, APOC1 and TOMM40, associated with imaging phenotype. Availability and Implementation: We developed a C ++ package for analysis of WGS data using GSU. The source codes can be downloaded at https://github.com/changshuaiwei/gsu. Contact: weichangshuai@gmail.com; qlu@epi.msu. edu Supplementary information: Supplementary data are available at Bioinformatics online.
Pediatric sleep-disordered breathing: an update on diagnostic testing

Purpose of review Recent advances in diagnostic testing for obstructive sleep apnea in children have refined the standard tests while identifying several new tools that hold promise to radically change how we diagnose sleep apnea. Recent findings Studies have demonstrated that the polysomnogram may be modified to permit home assessment of sleep disturbed breathing in children to ensure more widespread access to the test. Alternately, questionnaires, nocturnal oximetry, and diagnostic urinary biomarkers have shown great promise as both sensitive and specific tools to diagnose sleep apnea in children as well as track the severity of the disease. Summary The gold standard polysomnogram has been refined to permit its application in a modified form at home and for brief examinations in children. This standard has been challenged on several fronts, including questionnaires, nocturnal oximetry, drug-induced sleep endoscopy, and noninvasive urinary biomarkers that may ultimately supplant polysomnography as the gold standard to diagnose obstructive sleep apnea syndrome in children.
Influence of Intimate Partner Violence on Domestic Relocation in Metropolitan and Non-Metropolitan Young Australian Women

Data from a national, population-based longitudinal study of Australian women (26-34 years) were analyzed to investigate the association between domestic relocation and multiple explanatory factors, namely intimate partner violence (IPV), metropolitan versus non-metropolitan residence, education, income, housing tenure, number of children, and changes in relationship status. Experience of IPV in the past 12 months was significantly associated with increased odds of domestic relocation. This association remained significant after controlling for age, social support, area of residence, income, number of children, education, and housing situation. Change in relationship status attenuated the association between recent IPV and domestic relocation. Metropolitan versus non-metropolitan residence had no major influence on these results.
mHealth technologies in the management of obesity: a narrative review

: The global pandemic of obesity requires an urgent response. Obesity results in increased risk of type 2 diabetes, cardiovascular disease and cancer. The need to provide cost-effective treatment to the millions affected is evident but traditional repeated individual face-to-face management would clearly exhaust available health care services. It is for this reason that the use of mobile health (mHealth) to improve population health, diet, and physical activity has become an active area of research. The aim of this review is to give a perspective of where this field of research currently stands using examples from the published literature. Smartphones provide a medium for the delivery of health information, personal coaching, monitoring of eating and physical activity behaviors and to integrate outputs from other sensors. Health and computer researchers have been developing and evaluating mHealth for the management of obesity but their efforts are relatively small. Text messaging, applications (apps) and a number of multicomponent mHealth programs utilizing a variety of Smartphone functions indicate some success in weight management but the results are mixed. Apart from the ubiquitous nature of Smartphones and devices, the real-time delivery of output data provides the potential for continuous adjustment of interventions according to the changes an individual is making after each message they receive from the mHealth program. This ability to optimize interventions for individual weight management in a timely fashion is the big challenge for researchers. Person-alized heath advice is the preferred option of individuals, and cooperation between computer scientists, behavioral scientists, dietitians, exercise physiologists and medical practitioners will be needed to meaningfully integrate data and responses from automated systems. In summary, mHealth shows potential, but we are still in the early stages of being able to harness its full capabilities for making a meaningful contribution to combatting obesity.
Pharmacokinetics of IGF-1 in PAPP-A2-Deficient Patients, Growth Response, and Effects on Glucose and Bone Density

Context The pregnancy-associated plasma protein A2 (PAPP-A2) cleaves insulinlike growth factor binding proteins 3 and 5, releasing free insulinlike growth factor 1 (IGF-1). Homozygous mutations in PAPP-A2 result in growth failure with elevated total but low free IGF-1. Objective To determine the 24-hour pharmacokinetic (PK) profile of free and total IGF-1 after a dose of recombinant human insulinlike growth factor 1 (rhIGF-1). We describe the growth response and effects on glucose metabolism and bone mineral density (BMD) after 1 year of rhIGF-1 therapy. Design and Patients Three affected siblings, their heterozygous parents, and two healthy controls participated. The subjects received a dose of rhIGF-1, followed by serial blood samples collected over 24 hours. The two younger siblings were started on rhIGF-1 treatment. An oral glucose tolerance test and dual-energy X-ray absorptiometry scans were obtained at baseline and after 1 year of treatment. Results Subcutaneous administration of rhIGF-1 increased the concentration of free and total IGF-1 in patients with PAPP-A2 deficiency. The PK profile was comparable in all participants. At baseline, all three subjects demonstrated insulin resistance and below-average BMD. Treatment with rhIGF-1 is ongoing in the youngest patient but was discontinued in his brother because of the development of pseudotumor cerebri. The treated patient had an increase in height velocity from 3.0 to 6.2 cm/y, resolution of insulin resistance, and an increase in total body BMD. Conclusions rhIGF-1 at standard dosages resulted in similar PK characteristics in patients with PAPP-A2 deficiency, heterozygous relatives, and healthy controls. The youngest affected patient experienced a modest growth response to therapy with rhIGF-1, as well as beneficial effects on glucose metabolism and bone mass.
Incidence and prognosis of patients with brain metastases at diagnosis of systemic malignancy: a population-based study

Background Brain metastases are associated with significant morbidity and mortality. Population-level data describing the incidence and prognosis of patients with brain metastases are lacking. The aim of this study was to characterize the incidence and prognosis of patients with brain metastases at diagnosis of systemic malignancy using recently released data from the Surveillance, Epidemiology, and End Results (SEER) program. Methods We identified 1302166 patients with diagnoses of nonhematologic malignancies originating outside of the CNS between 2010 and 2013 and described the incidence proportion and survival of patients with brain metastases. Results We identified 26430 patients with brain metastases at diagnosis of cancer. Patients with small cell and non-small cell lung cancer displayed the highest rates of identified brain metastases at diagnosis; among patients presenting with metastatic disease, patients with melanoma (28.2%), lung adenocarcinoma (26.8%), non-small cell lung cancer not otherwise specified/other lung cancer (25.6%), small cell lung cancer (23.5%), squamous cell carcinoma of the lung (15.9%), bronchioloalveolar carcinoma (15.5%), and renal cancer (10.8%) had an incidence proportion of identified brain metastases of >10%. Patients with brain metastases secondary to prostate cancer, bronchioloalveolar carcinoma, and breast cancer displayed the longest median survival (12.0, 10.0, and 10.0 months, respectively). Conclusions In this study we provide generalizable estimates of the incidence and prognosis for patients with brain metastases at diagnosis of a systemic malignancy. These data may allow for appropriate utilization of brain-directed imaging as screening for subpopulations with cancer and have implications for clinical trial design and counseling of patients regarding prognosis.
Minimizing the Maximum Delay in Wireless Sensor Networks by Intelligent Sink Placement

Research activity in the area of wireless sensor networks(WSNs) has grown dramatically in the past few years, driven by advances in miniaturized hardware, and motivated by a vast array of potential applications. Typical scenarios for large-scale WSNs contain multiple sources and multiple sinks. In WSNs, energy is the most critical resource constraint and the lifetime of a WSNs is dependent on limited battery although there are several promising methods for energy scavenging which need additional circuitry and cost. Besides, performance issues in WSNs play a vital role in some applications as for example message transfer delay for detection systems. Therefore, in this research, we focus on the sink placement problem for minimizing the maximum worst-case delay as well as maximizing the lifetime of a WSN. Di(cid:27)erent sink placement strategies are introduced and their advantages and disadvantages are discussed. A random sink placment (RSP) strategy is used as a lower bound for other strategies. A geographic sink placement (GSP) strategy is proposed as a benchmark sink placement in WSNs whereas an intelligent sink placement (ISP) strategy is introduced as an optimal sink placement. Due to the computational expensiveness of ISP, a Genetic Algorithm-based sink placement (GASP) strategy is discussed and is demonstrated to represent a good approximation for the optimal sink placement. During the performance analysis of the sink placement strategies, the question of a (cid:16)good(cid:17) number of sinks given a certain number of sensor nodes is also discussed. To calculate the maximum worst-case delay, sensor network calculus (introduced in [8]), a recent methodology, is applied in this research work. The core of this research work is to give a framework for sink placement in real-time WSNs applications with two GSP and GASP strategies. The GSP strategies are suited for WSNs in which sensor nodes positions are unknown, whereas the GASP strategies are designated for WSNs when given sensor nodes’ positions. Finally, numerical results are obtained us-ing DISCO network calculator [7] for di(cid:27)erent scenarios.
A screen for deeply conserved non-coding GWAS SNPs uncovers a MIR-9-2 functional mutation associated to retinal vasculature defects in human

Abstract Thousands of human disease-associated single nucleotide polymorphisms (SNPs) lie in the non-coding genome, but only a handful have been demonstrated to affect gene expression and human biology. We computationally identified risk-associated SNPs in deeply conserved non-exonic elements (CNEs) potentially contributing to 45 human diseases. We further demonstrated that human CNE1/rs17421627 associated with retinal vasculature defects showed transcriptional activity in the zebrafish retina, while introducing the risk-associated allele completely abolished CNE1 enhancer activity. Furthermore, deletion of CNE1 led to retinal vasculature defects and to a specific downregulation of microRNA-9, rather than MEF2C as predicted by the original genome-wide association studies. Consistent with these results, miR-9 depletion affects retinal vasculature formation, demonstrating MIR-9-2 as a critical gene underpinning the associated trait. Importantly, we validated that other CNEs act as transcriptional enhancers that can be disrupted by conserved non-coding SNPs. This study uncovers disease-associated non-coding mutations that are deeply conserved, providing a path for in vivo testing to reveal their cis-regulated genes and biological roles.
Quality of anticoagulation control and hemorrhage risk among African American and European American warfarin users

Objective We evaluated whether percent time in target range (PTTR), risk of over-anticoagulation [international normalized ratio (INR)>4], and risk of hemorrhage differ by race. As PTTR is a strong predictor of hemorrhage risk, we also determined the influence of PTTR on the risk of hemorrhage by race. Participants and methods Among 1326 warfarin users, PTTR was calculated as the percentage of interpolated INR values within the target range of 2.0–3.0. PTTR was also categorized as poor (PTTR<60%), good (60⩽PTTR<70%), or excellent (PTTR≥70%) anticoagulation control. Over-anticoagulation was defined as INR more than 4 and major hemorrhages included serious, life-threatening, and fatal bleeding episodes. Logistic regression and survival analyses were carried out to evaluate the association of race with PTTR (≥60 vs. <60) and major hemorrhages, respectively. Results Compared with African Americans, European Americans had higher PTTR (57.6 vs. 49.1%; P<0.0001) and were more likely to attain 60⩽PTTR<70% (22.9 vs. 13.1%; P<0.001) or PTTR of at least 70% (26.9 vs. 18.2%; P=0.001). Older (>65 years) patients without venous thromboembolism indication and chronic kidney disease were more likely to attain PTTR of at least 60%. After accounting for clinical and genetic factors, and PTTR, African Americans had a higher risk of hemorrhage [hazard ratio (HR)=1.58; 95% confidence interval (CI): 1.04–2.41; P=0.034]. Patients with 60⩽PTTR<70% (HR=0.62; 95% CI: 0.38–1.02; P=0.058) and PTTR of at least 70% (HR=0.27; 95% CI: 0.15–0.49; P<0.001) had a lower risk of hemorrhage compared with those with PTTR less than 60%. Conclusion Despite the provision of warfarin management through anticoagulation clinics, African Americans achieve a lower overall PTTR and have a significantly higher risk of hemorrhage. Personalized medicine interventions tailored to African American warfarin users need to be developed.
Capturing the Diversity of Successful Aging: An Operational Definition Based on 16-Year Trajectories of Functioning

Purpose of the Study To determine the prevalence and extent of successful aging (SA) when various suggestions proposed in the previous literature for improving models of SA are incorporated into one holistic operational definition. These suggestions include defining and measuring SA as a developmental process, including subjective indicators alongside more objective ones, and expressing SA on a continuum. Design and Methods Data were used from 2,241 respondents in the Longitudinal Aging Study Amsterdam, a multidisciplinary study in a nationally representative sample of older adults in the Netherlands. Latent class growth analysis was used to identify successful 16-year trajectories within nine indicators of physical, cognitive, emotional, and social functioning. SA was quantified as the number of indicators in which individual respondents showed successful trajectories (range 0-9). Results Successful trajectories were characterized by stability, limited decline, or even improvement of functioning over time. Of the respondents, 39.6% of men and 29.3% of women were successful in at least seven indicators; 7% of men and 11% of women were successful in less than three indicators. Proportions of successful respondents were largest in life satisfaction (>85%) and smallest in social activity (<25%). Correlations of success between separate indicators were low to moderate (range r = .02-.37). Implications Many older adults age relatively successfully, but the character of successful functioning over time varies between indicators, and the combinations of successful indicators vary between individuals.
10b 150MS/s 0.4mm2 45nm CMOS ADC based on process-insensitive amplifiers

A 10b 150MS/s 0.4mm2 pipeline ADC is implemented in a 45nm CMOS process. The input SHA, employing four charge-redistributed capacitors, converts single-ended or differential input signals of 1.2Vpp to differential outputs of 0.8Vpp for a low supply voltage of 1.1V. The process-insensitive high-gain amplifiers in the SHA and MDACs are based on gain-boosting, pseudo-differential output pair, and continuous-time common-mode feedback circuits to overcome various performance limitations that are observed in deep nanometer CMOS technologies. The MDAC2 and MDAC3 share a single high-gain amplifier to reduce the input memory effect, chip area, and power dissipation. The measured DNL and INL are within 1.06 and 1.29LSB, respectively. At 150MS/s, the prototype ADC shows a maximum SNDR of 51.8dB and a maximum SFDR of 63.7dB with a 1.2Vpp sinusoidal input and consumes 47.3mW.