Miracle-dz/UniFAR-FTUs huggingface dataset:
The Quantitative Genetics of Phenotypic Robustness

Phenotypic robustness, or canalization, has been extensively investigated both experimentally and theoretically. However, it remains unknown to what extent robustness varies between individuals, and whether factors buffering environmental variation also buffer genetic variation. Here we introduce a quantitative genetic approach to these issues, and apply this approach to data from three species. In mice, we find suggestive evidence that for hundreds of gene expression traits, robustness is polymorphic and can be genetically mapped to discrete genomic loci. Moreover, we find that the polymorphisms buffering genetic variation are distinct from those buffering environmental variation. In fact, these two classes have quite distinct mechanistic bases: environmental buffers of gene expression are predominantly sex-specific and trans-acting, whereas genetic buffers are not sex-specific and often cis-acting. Data from studies of morphological and life-history traits in plants and yeast support the distinction between polymorphisms buffering genetic and environmental variation, and further suggest that loci buffering different types of environmental variation do overlap with one another. These preliminary results suggest that naturally occurring polymorphisms affecting phenotypic robustness could be abundant, and that these polymorphisms may generally buffer either genetic or environmental variation, but not both.
Patients’ Acceptance of Smartphone Health Technology for Chronic Disease Management: A Theoretical Model and Empirical Test

Background Chronic disease patients often face multiple challenges from difficult comorbidities. Smartphone health technology can be used to help them manage their conditions only if they accept and use the technology. Objective The aim of this study was to develop and test a theoretical model to predict and explain the factors influencing patients’ acceptance of smartphone health technology for chronic disease management. Methods Multiple theories and factors that may influence patients’ acceptance of smartphone health technology have been reviewed. A hybrid theoretical model was built based on the technology acceptance model, dual-factor model, health belief model, and the factors identified from interviews that might influence patients’ acceptance of smartphone health technology for chronic disease management. Data were collected from patient questionnaire surveys and computer log records about 157 hypertensive patients’ actual use of a smartphone health app. The partial least square method was used to test the theoretical model. Results The model accounted for . 412 of the variance in patients’ intention to adopt the smartphone health technology. Intention to use accounted for . 111 of the variance in actual use and had a significant weak relationship with the latter. Perceived ease of use was affected by patients’ smartphone usage experience, relationship with doctor, and self-efficacy. Although without a significant effect on intention to use, perceived ease of use had a significant positive influence on perceived usefulness. Relationship with doctor and perceived health threat had significant positive effects on perceived usefulness, countering the negative influence of resistance to change. Perceived usefulness, perceived health threat, and resistance to change significantly predicted patients’ intentions to use the technology. Age and gender had no significant influence on patients’ acceptance of smartphone technology. The study also confirmed the positive relationship between intention to use and actual use of smartphone health apps for chronic disease management. Conclusions This study developed a theoretical model to predict patients’ acceptance of smartphone health technology for chronic disease management. Although resistance to change is a significant barrier to technology acceptance, careful management of doctor-patient relationship, and raising patients’ awareness of the negative effect of chronic disease can negate the effect of resistance and encourage acceptance and use of smartphone health technology to support chronic disease management for patients in the community.
Magnitude of Clinical Benefit of Cancer Drugs Approved by the US Food and Drug Administration

Background It is uncertain whether drugs approved by the US Food and Drug Administration (FDA) have clinically meaningful benefit as determined by validated scales such as the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). Methods We searched the Drugs@FDA website for applications of anticancer drugs from January 2006 to December 2016. Study characteristics, outcomes, and regulatory pathways were collected from drug labels and reports of registration trials. For randomized controlled trials (RCTs), ESMO-MCBS grades were applied. Meaningful benefit was defined as a grade of A or B for (neo)adjuvant intent and 4 or 5 for palliative intent. All statistical tests were two-sided. Results We identified 63 individual drugs for 118 indications. These were supported by 135 studies, among which were 105 RCTs for which ESMO-MCBS could be applied. Only 46 (43.8%) met the ESMO-MCBS meaningful benefit threshold (100% of (neo)adjuvant trials and 38.8% of palliative trials). In palliative therapy trials, meaningful ESMO-MCBS grades were associated with phase III trials (compared with phase II; odds ratio [OR] = 38.45, 95% confidence interval [CI] = 3.27 to 452.00, P = .004), those with overall survival as their primary end point (compared with intermediate end points; OR = 8.28, 95% CI = 2.49 to 27.50, P = .001) and trials of targeted drugs with companion diagnostics (OR = 11.62, 95% CI = 2.95 to 45.78, P < .001). Over time, there has been an increase in the number of trials meeting the ESMO-MCBS threshold (Ptrend = .04). There were insufficient (neo)adjuvant studies to perform statistical analysis. Conclusions The number of trials meeting the ESMO-MCBS threshold for clinical benefit has improved over time. However, fewer than half of RCTs supporting FDA approval meet the threshold for clinically meaningful benefit.
A nomogram to predict the probability of axillary lymph node metastasis in female patients with breast cancer in China: A nationwide, multicenter, 10-year epidemiological study

Axillary lymph node dissection (ALND) or sentinel lymph node biopsy (SLNB) alone may lead to postoperative complications. Among patients with positive ALN in the preoperative examination, approximately 40% patients do not have SLN metastasis. Herein, we aimed to develop a model to predict the probability of ALN metastasis as a preoperative tool to support clinical decision-making. We retrospectively analyzed the clinicopathological features of 4211 female patients with breast cancer who were diagnosed in seven breast cancer centers representing entire China, over 10 years (1999-2008). The patients were randomly categorized into a training cohort or validation cohort (3:1 ratio). Multivariate logistic regression analysis was performed for 1869 patients with complete information on the study variables. Age at diagnosis, tumor size, tumor quadrant, clinical nodal status, local invasion status, pathological type, and molecular subtypes were the independent predictors of ALN metastasis. The nomogram was then developed using the seven variables. Further, it was subsequently validated in 642 patients with complete data on variables in the validation cohort. Coefficient of determination (R2) and the area under the receiver-operating characteristic (ROC) curve (AUC) were calculated to be 0.979 and 0.7007, showing good calibration and discrimination of the model, respectively. The false-negative rates of the nomogram were 0 and 6.9% for the predicted risk cut-off values of 14.03% and 20%, respectively. Therefore, when the predicted risk is less than 20%, SLNB may be avoided. After further validation in various patient populations, this model may support increasingly limited axillary surgery in breast cancer.
1/f2 Characteristics and Isotropy in the Fourier Power Spectra of Visual Art, Cartoons, Comics, Mangas, and Different Categories of Photographs

Art images and natural scenes have in common that their radially averaged (1D) Fourier spectral power falls according to a power-law with increasing spatial frequency (1/f2 characteristics), which implies that the power spectra have scale-invariant properties. In the present study, we show that other categories of man-made images, cartoons and graphic novels (comics and mangas), have similar properties. Further on, we extend our investigations to 2D power spectra. In order to determine whether the Fourier power spectra of man-made images differed from those of other categories of images (photographs of natural scenes, objects, faces and plants and scientific illustrations), we analyzed their 2D power spectra by principal component analysis. Results indicated that the first fifteen principal components allowed a partial separation of the different image categories. The differences between the image categories were studied in more detail by analyzing whether the mean power and the slope of the power gradients from low to high spatial frequencies varied across orientations in the power spectra. Mean power was generally higher in cardinal orientations both in real-world photographs and artworks, with no systematic difference between the two types of images. However, the slope of the power gradients showed a lower degree of mean variability across spectral orientations (i.e., more isotropy) in art images, cartoons and graphic novels than in photographs of comparable subject matters. Taken together, these results indicate that art images, cartoons and graphic novels possess relatively uniform 1/f2 characteristics across all orientations. In conclusion, the man-made stimuli studied, which were presumably produced to evoke pleasant and/or enjoyable visual perception in human observers, form a subset of all images and share statistical properties in their Fourier power spectra. Whether these properties are necessary or sufficient to induce aesthetic perception remains to be investigated.
Intelligent Digital Learning: Agent-Based Recommender System

In the context of intelligent digital learning, we propose an agent-based recommender system that aims to help learners overcome their gaps by suggesting relevant learning resources. The main idea is to provide them with appropriate support in order to make their learning experience more effective. To this end we design an agent-based cooperative system where autonomous agents are able to update recommendation data and to improve the recommender outcome on behalf of their past experiences in the learning platform.
PLGA nanoparticles for intravitreal peptide delivery: statistical optimization, characterization and toxicity evaluation

Abstract Frequent intravitreal injections are currently used to overcome the ocular barriers and provide sufficient drug to the posterior eye segment. However, intravitreal injections have been associated with a number of complications and high treatment costs. To overcome these limitations, peptide-loaded poly(d,l-lactic-co-glycolic acid) nanoparticles (PLGA NPs) were developed using the nanoprecipitation technique and were optimized via Box–Behnken Design (BBD) and Response Surface Methodology (RSM). Developed NPs were evaluated for potential toxicity and cell apoptosis using the zebrafish embryo toxicity (ZET) model with titanium dioxide NPs and ethanol (1% v/v) serving as positive controls. Developed NPs had a size of 75.6–153.8 nm, a polydispersity index between 0.11 and 0.25 and a zeta potential of −9.4 to −46.0 mV. Loaded peptide was found to be stable under various experimental conditions tested. BBD and RSM were validated through the characterization of optimized formulations. Survival and hatching rates of NP-treated zebrafish 0–144 h post-fertilization were found to be normal with no significant malformations. Cellular apoptosis studies also endorsed the non-cytotoxic nature of the NPs. The overall results indicate that optimized PLGA nanoparticles could be a promising platform for efficient peptide delivery to the posterior segment of the eye.
'Sustaining the DOTS': stakeholders' experience of a social protection intervention for TB in Nigeria.

Background Social protection for TB patients can lower patient costs and improve adherence. The aim of this study was to explore patients' and health workers' experiences of a social protection intervention for TB in order to inform a more patient-centred approach for the Nigeria National TB Programme strategy. Methods This was a qualitative study consisting of 103 in-depth interviews and two focus group discussions with patients who received the intervention, and 10 key informant interviews with health workers. A thematic content analysis of the interviews was performed. Results Of those who completed the interviews, 53 (51.5%) were male, and 69 (67.0%) were below 40 years. Most of the participants received care and support from their families but delayed access to TB services due to lack of funds for transportation, nutritional supplementation and non-TB drugs. The intervention had a high level of acceptability and uptake; particularly clear benefits emerged for most patients who used the social protection funds to purchase food and supplements, other drugs, transportation and additional personal necessities. Some patients assert that the financial incentive package increased their awareness of timing of their follow-up visits. In addition, health workers observed increased enthusiasm to treatment and improvement in adherence among participants. Conclusions Patients and health workers reported positive experiences with the financial incentives provided for TB treatment.
The 4E-BP–eIF4E axis promotes rapamycin-sensitive growth and proliferation in lymphocytes

Lymphocyte reliance on 4E-BP2 and eIF4E for growth and proliferation underlies their exquisite sensitivity to the drug rapamycin. 4E-BP, the key to lymphocyte sensitivity In most cells, the mammalian (mechanistic) target of rapamycin complex 1 (mTORC1) regulates cell growth through the ribosomal S6 kinases (S6Ks) and cell proliferation through translation-regulating proteins of the eIF4E-binding protein (4E-BP) family, respectively. Although mTORC1 is present in all cells, the mTORC1 inhibitor rapamycin is an effective immunosuppressant that blocks lymphocyte proliferation (see the Focus by Abraham). But, why are lymphocytes so exquisitely sensitive? So et al. found that lymphocytes did not depend on S6K signaling to promote growth or proliferation in response to antigen receptor stimulation. Instead, these cells relied on 4E-BP proteins for both processes. Unlike in nonlymphoid cells, the 4E-BP2 isoform was more abundant than the 4E-BP1 isoform in lymphocytes, and its phosphorylation by mTORC1 was more sensitive to rapamycin. These data suggest that the exquisite sensitivity of lymphocytes to rapamycin may be due to their complete reliance on 4E-BP2 for both growth and proliferation. Rapamycin has been used as a clinical immunosuppressant for many years; however, the molecular basis for its selective effects on lymphocytes remains unclear. We investigated the role of two canonical effectors of the mammalian target of rapamycin (mTOR): ribosomal S6 kinases (S6Ks) and eukaryotic initiation factor 4E (eIF4E)–binding proteins (4E-BPs). S6Ks are thought to regulate cell growth (increase in cell size), and 4E-BPs are thought to control proliferation (increase in cell number), with mTORC1 signaling serving to integrate these processes. However, we found that the 4E-BP–eIF4E signaling axis controlled both the growth and proliferation of lymphocytes, processes for which the S6Ks were dispensable. Furthermore, rapamycin disrupted eIF4E function selectively in lymphocytes, which was due to the increased abundance of 4E-BP2 relative to that of 4E-BP1 in these cells and the greater sensitivity of 4E-BP2 to rapamycin. Together, our findings suggest that the 4E-BP–eIF4E axis is uniquely rapamycin-sensitive in lymphocytes and that this axis promotes clonal expansion of these cells by coordinating growth and proliferation.
Placebo Effects Across Self-Report, Clinician Rating, and Objective Performance Tasks Among Women With Post-Traumatic Stress Disorder: Investigation of Placebo Response in a Pharmacological Treatment Study of Post-Traumatic Stress Disorder

Purpose/Background For a drug to acquire Food and Drug Administration approval, it must significantly outperform placebo treatment. In recent years, the placebo effect seems to be increasing in neuropsychiatric conditions. Here, we examine placebo effects across self-reported, clinically rated, and performance-based data from a trial using a corticotropin-releasing hormone receptor type 1 (CRHR1) antagonist for treatment of post-traumatic stress disorder (PTSD). Methods/Procedures Women with chronic PTSD were randomized to treatment with either GSK561679, a CRHR1 antagonist, or placebo. Before randomization, participants completed self-report scales, clinician-rated measures of PTSD and depression symptoms, and objective tests of cognition and functioning. Differences in change scores on measures were compared between GSK561679 and placebo-treated participants. Findings/Results GSK561679 failed to produce any significant improvement in the participants. A substantial placebo effect was observed in both self-report and clinical rating scales, with effect sizes up to 1.5 SD. No single variable predicted placebo-related changes. Notably, there was an improvement on objective performance measures of cognition that exceeded previous standards for practice effects. Implications/Conclusions Participants in this trial manifested retest effects on performance-based measures of cognition. Notably, they had minimal prior experience with performance-based assessments. Experiencing the structure and support of a clinical trial may have contributed to significant reductions in subject-reported and clinician-rated PTSD symptom levels. The improvement seen across all assessment domains was consistent with that seen in previous studies where the active treatments separated from placebo. Investigators conducting clinical trials treating PTSD patients should expect placebo effects and design studies accordingly.
The effect of moisture content and bending rate on the work required to bend solid red oak

Sixty red oak (Quercus rubra) specimens were divided into three bending rate and two initial moisture content (MC) categories. The specimens were pre-steamed and then bent at 185° to 190°F in an environment where steam was sprayed around the samples continuously. After bending, the work required to produce each bend was calculated and comparisons were made. It was hypothesized that decreasing the rate of strain and increasing the MC would decrease the level of work required to produce the bend and decrease the probability of failure. An overall comparison of the effects of rate and MC showed both to be significant factors affecting the work input. As the rate increased, the amount of work required to bend the wood increased, as expected. The work required to bend the samples also decreased as the MC increased from 12 to 15 percent, as hypothesized. Comparisons of these test results with the work to maximum load from conventional bending experiments show that a slower bending rate than is currently used in commercial practice combined with an MC of about 15 percent would probably be efficacious for producing high-quality bentwood.
Strength in the midst of pain: Abuse as a predictor of sexual relationship power among substance-abusing Black women

ABSTRACT The aim of this research was to explore the association of abuse experiences (child sexual abuse and adult physical/sexual violence) to sexual relationship power among Black substance-abusing women. The study was a secondary analysis of baseline data collected from 124 Black women in 12 drug treatment programs across the United States who initially participated in an HIV risk reduction trial conducted within the National Drug Abuse Treatment Clinical Trials Network of the National Institute on Drug Abuse (NIDA). The findings revealed that adult sexual abuse, but not childhood sexual or adult physical abuse, was associated with lower relationship control and decision-making dominance as measured by the Sexual Relationship Power Scale. The findings suggest that designing and implementing sexual risk reduction interventions that address adult sexual violence may enhance the relationship power of Black substance-abusing women and in turn may promote safer sex practices.
A relational logic for higher-order programs

Relational program verification is a variant of program verification where one can reason about two programs and as a special case about two executions of a single program on different inputs. Relational program verification can be used for reasoning about a broad range of properties, including equivalence and refinement, and specialized notions such as continuity, information flow security or relative cost. In a higher-order setting, relational program verification can be achieved using relational refinement type systems, a form of refinement types where assertions have a relational interpretation. Relational refinement type systems excel at relating structurally equivalent terms but provide limited support for relating terms with very different structures. We present a logic, called Relational Higher Order Logic (RHOL), for proving relational properties of a simply typed λ-calculus with inductive types and recursive definitions. RHOL retains the type-directed flavour of relational refinement type systems but achieves greater expressivity through rules which simultaneously reason about the two terms as well as rules which only contemplate one of the two terms. We show that RHOL has strong foundations, by proving an equivalence with higher-order logic (HOL), and leverage this equivalence to derive key meta-theoretical properties: subject reduction, admissibility of a transitivity rule and set-theoretical soundness. Moreover, we define sound embeddings for several existing relational type systems such as relational refinement types and type systems for dependency analysis and relative cost, and we verify examples that were out of reach of prior work.