Miracle-dz/UniFAR-FTUs huggingface dataset:
Phenotypic and Transcriptional Analysis of Divergently Selected Maize Populations Reveals the Role of Developmental Timing in Seed Size Determination1[W][OPEN]

The onset and rate of seed development are key determinates of seed size and are regulated by coexpression networks for this trait. Seed size is a component of grain yield and an important trait in crop domestication. To understand the mechanisms governing seed size in maize (Zea mays), we examined transcriptional and developmental changes during seed development in populations divergently selected for large and small seed size from Krug, a yellow dent maize cultivar. After 30 cycles of selection, seeds of the large seed population (KLS30) have a 4.7-fold greater weight and a 2.6-fold larger size compared with the small seed population (KSS30). Patterns of seed weight accumulation from the time of pollination through 30 d of grain filling showed an earlier onset, slower rate, and earlier termination of grain filling in KSS30 relative to KLS30. This was further supported by transcriptome patterns in seeds from the populations and derived inbreds. Although the onset of key genes was earlier in small seeds, similar maximum transcription levels were observed in large seeds at later stages, suggesting that functionally weaker alleles, rather than transcript abundance, may be the basis of the slow rate of seed filling in KSS30. Gene coexpression networks identified several known genes controlling cellularization and proliferation as well as novel genes that will be useful candidates for biotechnological approaches aimed at altering seed size in maize and other cereals.
Neonatal mouse cortical but not isogenic human astrocyte feeder layers enhance the functional maturation of induced pluripotent stem cell‐derived neurons in culture

Human induced pluripotent stem (iPS) cell‐derived neurons and astrocytes are attractive cellular tools for nervous system disease modeling and drug screening. Optimal utilization of these tools requires differentiation protocols that efficiently generate functional cell phenotypes in vitro. As nervous system function is dependent on networked neuronal activity involving both neuronal and astrocytic synaptic functions, we examined astrocyte effects on the functional maturation of neurons from human iPS cell‐derived neural stem cells (NSCs). We first demonstrate human iPS cell‐derived NSCs can be rapidly differentiated in culture to either neurons or astrocytes with characteristic cellular, molecular and physiological features. Although differentiated neurons were capable of firing multiple action potentials (APs), few cells developed spontaneous electrical activity in culture. We show spontaneous electrical activity was significantly increased by neuronal differentiation of human NSCs on feeder layers of neonatal mouse cortical astrocytes. In contrast, co‐culture on feeder layers of isogenic human iPS cell‐derived astrocytes had no positive effect on spontaneous neuronal activity. Spontaneous electrical activity was dependent on glutamate receptor‐channel function and occurred without changes in INa, IK, Vm, and AP properties of iPS cell‐derived neurons. These data demonstrate co‐culture with neonatal mouse cortical astrocytes but not human isogenic iPS cell‐derived astrocytes stimulates glutamatergic synaptic transmission between iPS cell‐derived neurons in culture. We present RNA‐sequencing data for an immature, fetal‐like status of our human iPS cell‐derived astrocytes as one possible explanation for their failure to enhance synaptic activity in our co‐culture system.
Excipients for Oral Liquid Formulations

Compared to conventional tablets and capsules, oral liquid dosage forms including solutions, syrups, suspensions, elixirs, or concentrates offer unique advantages to many patients. For example, liquids may provide better patient compliance for those with swallowing difficulties and better dosage control versus a fixed tablet dose. However, there are also a number of ‘‘challenges’’ surrounding the formulation and development of these forms. This chapter presents a brief description of some of the typical areas of challenges and opportunities for liquid formulations, the market justification for overcoming these challenges, and some of the typical excipients used to develop solutions, syrups, and suspensions.
Quantitatve Arthroscopic Ultrasonic Assessment of Articular Cartilage The Potential of Intravascular Ultrasound (IVUS)

In this study we introduced the intravascular ultrasound (IVUS) as a potential arthroscopic tool for the quantitative assessment of articular cartilage. An IVUS system with a catheter-based probe (φ ≈ 1 mm) was used to measure the thickness and surface acoustical reflection amplitude of normal bovine patellar articular cartilages before and after degeneration induced by two enzyme treatments. Similar measurement was performed using another high frequency ultrasound system (Vevo) with a conventional hand-held probe and the results were compared between the two systems. The thickness measured using IVUS was highly correlated (r = 0.985, p < 0.001) with that obtained by Vevo. Surface acoustical reflection amplitude was found to be significantly reduced (p < 0.05) after two enzyme treatments. However, no significant change of thickness was found after enzyme treatments. The measurement results obtained from IVUS were confirmed with those obtained from Vevo. It is concluded that IVUS can be potentially used for the quantitative assessment of articular cartilage, with its ready-to- use arthroscopic feature.
Prediction of skin sensitization potency using machine learning approaches

The replacement of animal use in testing for regulatory classification of skin sensitizers is a priority for US federal agencies that use data from such testing. Machine learning models that classify substances as sensitizers or non‐sensitizers without using animal data have been developed and evaluated. Because some regulatory agencies require that sensitizers be further classified into potency categories, we developed statistical models to predict skin sensitization potency for murine local lymph node assay (LLNA) and human outcomes. Input variables for our models included six physicochemical properties and data from three non‐animal test methods: direct peptide reactivity assay; human cell line activation test; and KeratinoSens™ assay. Models were built to predict three potency categories using four machine learning approaches and were validated using external test sets and leave‐one‐out cross‐validation. A one‐tiered strategy modeled all three categories of response together while a two‐tiered strategy modeled sensitizer/non‐sensitizer responses and then classified the sensitizers as strong or weak sensitizers. The two‐tiered model using the support vector machine with all assay and physicochemical data inputs provided the best performance, yielding accuracy of 88% for prediction of LLNA outcomes (120 substances) and 81% for prediction of human test outcomes (87 substances). The best one‐tiered model predicted LLNA outcomes with 78% accuracy and human outcomes with 75% accuracy. By comparison, the LLNA predicts human potency categories with 69% accuracy (60 of 87 substances correctly categorized). These results suggest that computational models using non‐animal methods may provide valuable information for assessing skin sensitization potency. Copyright © 2017 John Wiley & Sons, Ltd.
Measuring Psychological Insulin Resistance

PURPOSE The purpose of this study is to explore the attitudes that contribute to psychological insulin resistance (PIR) in insulin-naive patients with type 2 diabetes and to identify predictors of PIR. METHODS A prospective study using 2 self-report surveys and incorporating demographic and health variables was conducted to determine the prevalence of PIR among a sample of 100 adult, insulin-naive patients with type 2 diabetes at an outpatient diabetes center in a university-affiliated teaching hospital. RESULTS Thirty-three percent of patients with type 2 diabetes were unwilling to take insulin. The most commonly expressed negative attitudes were concern regarding hypoglycemia, permanent need for insulin therapy, less flexibility, and feelings of failure. Less than 40% expressed fear of self-injection or thought that injections were painful. However, compared with willing subjects, unwilling subjects were more likely to fear injections and thought injections would be painful, life would be less flexible, and taking insulin meant health would deteriorate (P< .005 for all comparisons). Poorer general health and higher depression scores also correlated with PIR. CONCLUSIONS The results of the surveys, which were generally consistent, identified several remediable misconceptions regarding insulin therapy and suggest targets for educational interventions.
Association Between Marginal Jawbone Loss and Onset of Rheumatoid Arthritis and Relationship to Plasma Levels of RANKL

Objective. To investigate whether periodontitis, characterized by marginal jawbone loss, precedes the onset of symptoms of rheumatoid arthritis (RA), and to analyze plasma levels of RANKL (a cytokine that is crucial for bone resorption) and anti–citrullinated peptide antibodies (ACPAs) in presymptomatic individuals compared with matched referent controls. Methods. Marginal jawbone loss was measured on dental radiographs of the premolar/molar regions in the jaws in 176 subjects, 93 of whom subsequently developed RA. Among these participating subjects, 46 had documented radiographs predating symptom onset, and 45 cases could be matched to controls, according to sex, age, and smoking status. Plasma RANKL concentrations were analyzed using enzyme-linked immunosorbent assay. A receiver operating characteristic curve was used to define the cutoff value for RANKL positivity. Results. Bone loss was significantly greater in presymptomatic subjects classified as never smokers compared with that in controls, and increasing levels of bone loss were associated with a higher risk of the subsequent development of RA (hazard ratio 1.03, 95% confidence interval 1.01–1.05). No association between jawbone loss and RA was observed in smokers. A significantly greater extent of marginal jawbone loss was detected in RANKL-positive presymptomatic subjects, and even more pronounced jawbone loss was observed in those who were positive for both RANKL and ACPA. Conclusion. Marginal jawbone loss preceded the clinical onset of RA symptoms, but this was observed only in nonsmokers. Moreover, marginal jawbone loss was significantly greater in RANKL-positive presymptomatic subjects compared with RANKL-negative presymptomatic subjects and was highest in presymptomatic subjects positive for both ACPA and RANKL.
Impact of Chronic Cannabis Use on Auditory Mismatch Negativity Generation in Schizophrenia Patients

Abstract Introduction Cannabis use disorders (CUD) are highly prevalent among patients with schizophrenia (SCZ). Deficient mismatch negativity (MMN) generation is a characteristic finding in SCZ patients and cannabis users. This study therefore examined the effects of CUD on MMN generation in SCZ patients. Methods Twenty SCZ − CUD patients, 21 SCZ+CUD patients, and 20 healthy controls (HC) were included in this study. MMN to frequency and duration deviants was elicited within an auditory oddball paradigm and recorded by 32 channel EEG. Results As expected, SCZ − CUD patients showed reduced frontocentral MMN amplitudes to duration deviants compared to HC. Interestingly, SCZ+CUD patients demonstrated greater MMN amplitudes to duration deviants compared to SCZ − CUD patients at central electrodes with no differences compared to HC. Discussion These results demonstrate that comorbid cannabis use in SCZ patients might be associated with superior cognitive functioning. It can be assumed that the association between cannabis use and better cognitive performance may be due to a subgroup of cognitively less impaired SCZ patients characterized by lower genetic vulnerability for psychosis.
Rheological Characterization of Ethanolamine Gel Propellants

Ethanolamine is considered to be an environmentally friendly propellant system because it has low toxicity and is noncarcinogenic in nature. In this article, efforts are made to formulate and prepare ethanolamine gel systems, using pure agarose and hybrids of paired gelling agents (agarose + polyvinylpyrrolidine (PVP), agarose + SiO2, and PVP + SiO2), that exhibit a measurable yield stress, thixotropic behavior under shear rate ranges of 1–1,000 s−1 and a viscoelastic nature. To achieve these goals, multiple rheological experiments (including flow and dynamic studies) are performed. In this article, results are presented from experiments measuring the apparent viscosity, yield stress, thixotropy, dynamic strain, frequency sweep, and tan δ behaviors, as well as the effects of the test temperature, in the gel systems. The results show that the formulated ethanolamine gels are thixotropic in nature with yield stress between 30 and 60 Pa. The apparent viscosity of the gel decreases as the test temperature increases, and the apparent activation energy is the lowest for the ethanolamine-(PVP + SiO2) gel system. The dynamic rheology study shows that the type of gellant, choice of hybrid gelling materials and their concentration, applied frequencies, and strain all vitally affect the viscoelastic properties of the ethanolamine gel systems. In the frequency sweep experiment, the ethanolamine gels to which agarose, agarose + PVP, and agarose + SiO2 were added behave like linear frequency-dependent viscoelastic liquids, whereas the ethanolamine gel to which PVP + SiO2 was added behaves like a nearly frequency-independent viscoelastic solid. The variation in the tan δ of these gelled propellants as a function of frequency is also discussed.
Online Learning of Joint-Muscle Mapping Using Vision in Tendon-Driven Musculoskeletal Humanoids

The body structures of tendon-driven musculoskeletal humanoids are complex, and accurate modeling is difficult, because they are made by imitating the body structures of human beings. For this reason, we have not been able to move them accurately like ordinary humanoids driven by actuators in each axis, and large internal muscle tension and slack of tendon wires have emerged by the model error between its geometric model and the actual robot. Therefore, we construct a joint-muscle mapping (JMM) using a neural network (NN), which expresses a nonlinear relationship between joint angles and muscle lengths, and aim to move tendon-driven musculoskeletal humanoids accurately by updating the JMM online from data of the actual robot. In this study, the JMM is updated online by using the vision of the robot so that it moves to the correct position (Vision Updater). Also, we execute another update to modify muscle antagonisms correctly (Antagonism Updater). By using these two updaters, the error between the target and actual joint angles decrease to about 40% in 5 min, and we show through a manipulation experiment that the tendon-driven musculoskeletal humanoid Kengoro becomes able to move as intended. This novel system can adapt to the state change and growth of robots, because it updates the JMM online successively.
Incomplete Recovery of CD4 Cell Count, CD4 Percentage, and CD4/CD8 Ratio in Patients With Human Immunodeficiency Virus Infection and Suppressed Viremia During Long-term Antiretroviral Therapy

Background The extent and duration of long-term recovery of CD4 count, CD4 percentage (CD4%), and CD4/CD8 ratio after initiation of combination antiretroviral therapy (cART) in patients with a suppressed viral load (VL) are largely unknown. Methods Patients infected with human immunodeficiency virus type 1 who started cART between January 2004 and January 2012 and showed persistent viral suppression (VL, <200 copies/mL) for ≥4 years were followed up at the AIDS Clinical Center in Tokyo. Change point analysis was used to determine the time point when CD4 count recovery shows a plateau, and a linear mixed model was applied to estimate the CD4 count at this change point. Results Data were analyzed from 752 patients (93% male; median age, 38 years; median baseline CD4 cell count, 172/µL [interquartile range CD4%, 13.8%]; CD4/CD8 ratio, 0.23). The median follow-up period was 81.2 months, and 91 patients (12.1%) were followed up for >10 years. Change point analysis showed that CD4 count, CD4%, and CD4/CD8 ratio continued to increase until 78.6, 62.2, and 64.3 months, respectively, with adjusted means of 590/µL (95% confidence interval, 29.5%, and 0.89, respectively, at the change point. Although CD4 counts ≥500/μL were achieved in 73.8% of the study patients, they were not achieved in 48.2% of those with a baseline CD4 count <100/μL. Neither the CD4% nor the CD4/CD8 ratio were normalized in a majority of patients. Conclusions The results showed lack of normalization of CD4 count, CD4%, and CD4/CD8 ratio to the levels seen in healthy individuals even after long-term successful cART in patients with a suppressed VL.
Voltage-Mode Highpass, Bandpass, Lowpass and Notch Biquadratic Filters Using Single DDCC

A new voltage-mode multifunction biquadratic filter using one differential difference current conveyor (DDCC), two grounded capacitors and three resistors is presented. The proposed circuit offers the following attrac- tive advantages: realizing highpass, bandpass, lowpass and notch filter functions, simultaneously, from the same circuit configuration; employing grounded capacitors, which is ideal for integration and simpler circuit configu- ration.
Randomized study between radical surgery and radiotherapy for the treatment of stage IB–IIA cervical cancer: 20-year update

Objective Stage IB–IIA cervical carcinoma can be equally cured either by radical surgery or radiotherapy (RT). Albeit such policies show the same efficacy, they carry a different morbidity. This is an update after 20 years of a previously published randomized trial of RT vs. surgery in the treatment of stage IB–IIA cervical cancers to assess long-term survival and morbidity and the different pattern of relapse between the 2 modalities. Methods Between September 1986 and December 1991, women referred for a newly diagnosed stage IB and IIA cervical carcinoma were randomized to radical surgery or RT. The primary outcome measures were long-term survival and complications rate. The secondary outcome was recurrence of the disease. Results Three-hundred forty-three eligible women were randomized: 172 to radical surgery and 171 to external RT. Minimum follow-up was 19 years. Thirty-three patients (10%) died of intercurrent disease (31 cases) or fatal complications (2 cases). Twenty-year overall survival is 72% and 77% in the 2 treatment groups (p=0.280), respectively. As a whole, 94 recurrences (28%) were observed. Median time to relapse was 13.5 (surgery group) and 11.5 months (radiotherapy group) (p=0.100), respectively. Multivariate analysis confirms that risk factors for survival are histotype (p=0.020), tumor diameter (p=0.008), and lymph node status (p<0.001). Conclusion The results of the present study seem to suggest that there is no treatment of choice for early stage cervical carcinoma in terms of survival. Long term follow-up confirms that the best treatment for the individual patient should take into account clinical factors such as menopausal status, comorbidities, histological type, and tumor diameter.
Association between GWAS-identified lung adenocarcinoma susceptibility loci and EGFR mutations in never-smoking Asian women, and comparison with findings from Western populations

To evaluate associations by EGFR mutation status for lung adenocarcinoma risk among never-smoking Asian women, we conducted a meta-analysis of 11 loci previously identified in genome-wide association studies (GWAS). Genotyping in an additional 10,780 never-smoking cases and 10,938 never-smoking controls from Asia confirmed associations with eight known single nucleotide polymorphisms (SNPs). Two new signals were observed at genome-wide significance (P < 5 × 10-8), namely, rs7216064 (17q24.3, BPTF), for overall lung adenocarcinoma risk, and rs3817963 (6p21.3, BTNL2) which is specific to cases with EGFR mutations. In further sub-analyses by EGFR status, rs9387478 (ROS1/DCBLD1) and rs2179920 (HLA-DPB1) showed stronger estimated associations in EGFR-positive compared to EGFR-negative cases. Comparison of the overall associations with published results in Western populations revealed that the majority of these findings were distinct, underscoring the importance of distinct contributing factors for smoking and non-smoking lung cancer. Our results extend the catalogue of regions associated with lung adenocarcinoma in non-smoking Asian women and highlight the importance of how the germline could inform risk for specific tumour mutation patterns, which could have important translational implications.
Continuous Glucose Monitoring in Very Preterm Infants: A Randomized Controlled Trial

Continuous subcutaneous glucose monitoring and a computer-based algorithm guide the titration of glucose infusion reducing both hypoglycemia and hyperglycemia and glucose variability of very preterm infants. BACKGROUND AND OBJECTIVES: Impaired glucose control in very preterm infants is associated with increased morbidity, mortality, and poor neurologic outcome. Strategies based on insulin titration have been unsuccessful in achieving euglycemia in absence of an increase in hypoglycemia and mortality. We sought to assess whether glucose administration guided by continuous glucose monitoring (CGM) is more effective than standard of care blood glucose monitoring in maintaining euglycemia in very preterm infants. METHODS: Fifty newborns ≤32 weeks’ gestation or with birth weight ≤1500 g were randomly assigned (1:1) within 48-hours from birth to receive computer-guided glucose infusion rate (GIR) with or without CGM. In the unblinded CGM group, the GIR adjustments were driven by CGM and rate of glucose change, whereas in the blinded CGM group the GIR was adjusted by using standard of care glucometer on the basis of blood glucose determinations. Primary outcome was percentage of time spent in euglycemic range (72–144 mg/dL). Secondary outcomes were percentage of time spent in mild (47–71 mg/dL) and severe (<47 mg/dL) hypoglycemia; percentage of time in mild (145–180 mg/dL) and severe (>180 mg/dL) hyperglycemia; and glucose variability. RESULTS: Neonates in the unblinded CGM group had a greater percentage of time spent in euglycemic range (median, 84% vs 68%, P < .001) and decreased time spent in mild (P = .04) and severe (P = .007) hypoglycemia and in severe hyperglycemia (P = .04) compared with the blinded CGM group. Use of CGM also decreased glycemic variability (SD: 21.6 ± 5.4 mg/dL vs 27 ± 7.2 mg/dL, P = .01; coefficient of variation: 22.8% ± 4.2% vs 27.9% ± 5.0%; P < .001). CONCLUSIONS: CGM-guided glucose titration can successfully increase the time spent in euglycemic range, reduce hypoglycemia, and minimize glycemic variability in preterm infants during the first week of life.