Miracle-dz/UniFAR-FTUs huggingface dataset:
HMGA2 and Bach‐1 cooperate to promote breast cancer cell malignancy

During breast cancer progression, tumor cells acquire multiple malignant features. The transcription factors and cell cycle regulators high mobility group A2 (HMGA2) and BTB and CNC homology 1 (Bach‐1) are overexpressed in several cancers, but the mechanistic understanding of how HMGA2 and Bach‐1 promote cancer development has been limited. We found that HMGA2 and Bach‐1 are overexpressed in breast cancer tissues and their expression correlates positively in tumors but not in normal tissues. Individual HMGA2 or Bach‐1 knockdown downregulates expression of both proteins, suggesting a mutual stabilizing effect between the two proteins. Importantly, combined HMGA2 and Bach‐1 knockdown additively decrease cell proliferation, migration, epithelial‐to‐mesenchymal transition, and colony formation, while promoting apoptotic cell death via upregulation of caspase‐3 and caspase‐9. First the first time, we show that HMGA2 and Bach‐1 overexpression in tumors correlate positively and that the proteins cooperatively suppress a broad range of malignant cellular properties, such as proliferation, migration, clonogenicity, and evasion of apoptotic cell death. Thus, our observations suggest that combined targeting of HMGA2 and Bach1 may be an effective therapeutic strategy to treat breast cancer.
Flight muscle protein damage during endurance flight is related to energy expenditure but not dietary polyunsaturated fatty acids in a migratory bird

ABSTRACT Migration poses many physiological challenges for birds, including sustaining high intensity aerobic exercise for hours or days. A consequence of endurance flight is the production of reactive oxygen species (ROS). ROS production may be influenced by dietary polyunsaturated fatty acids (PUFA), which, although prone to oxidative damage, may limit mitochondrial ROS production and increase antioxidant capacity. We examined how flight muscles manage oxidative stress during flight, and whether dietary long-chain PUFA influence ROS management or damage. Yellow-rumped warblers were fed diets low in PUFA, or high in long-chain n-3 or n-6 PUFA. Flight muscle was sampled from birds in each diet treatment at rest or immediately after flying for up to a maximum of 360 min in a wind tunnel. Flight increased flight muscle superoxide dismutase activity but had no effect on catalase activity. The ratio of glutathione to glutathione disulphide decreased during flight. Oxidative protein damage, indicated by protein carbonyls, increased with flight duration (Pearson r=0.4). Further examination of just individuals that flew for 360 min (N=15) indicates that oxidative damage was related more to total energy expenditure (Pearson r=0.86) than to flight duration itself. This suggests that high quality individuals with higher flight efficiency have not only lower energy costs but also potentially less oxidative damage to repair after arrival at the destination. No significant effects of dietary long-chain PUFA were observed on antioxidants or damage. Overall, flight results in oxidative stress and the degree of damage is likely driven more by energy costs than fatty acid nutrition. Summary: Migration is oxidatively challenging for birds, and in yellow-rumped warblers, the oxidative challenge is strongly related to energy expenditure during flight but not dietary long-chain PUFA.
Microstructure Evolution and Orientation Relationship of Reverted Austenite in 13Cr Supermartensitic Stainless Steel During the Tempering Process

The transformation mechanism of reverted austenite and the amount of reverted austenite during the tempering process in supermartensitic stainless steel have been investigated by X-ray diffraction (XRD), electron backscattered diffraction (EBSD), and a high-temperature laser scanning confocal microscope (HTLSCM). The results indicate that the microstructure mainly consists of tempered martensite and reverted austenite. The reverted austenite nucleates uniformly at the sub-block boundary and prior grain austenite boundary. The amount of reverted austenite strongly relies on the tempering time, showing a positive correlation in the supermartensitic stainless steel. The crystallographic orientation relationship between reverted austenite and martensite meets the Kurdjumov-Sachs(K-S) relationship and the deviation angle is mainly concentrated at about 2 degrees. The mechanism of reverted austenite transformed from martensite is a diffusion mechanism. The growth kinetics of the reverted austenite are dominated by diffusion of the Ni element and there is no shear deformation of the martensite matrix in the in situ observation. It can be deduced that the reverted austenite is formed by nickel diffusion during tempering at 620 °C for different tempering times.
Measurement of the refractive index of whole blood and its components for a continuous spectral region

Abstract. The refractive index of blood is a key biophysical parameter, which can reflect the physiological state. We measured the refractive index of whole blood and other components, such as serum, plasma, and hemoglobin, based on internal reflection by using a homemade apparatus in the spectral range of 400 to 750 nm. In addition to the hemoglobin solution, which has a Soret band about 420 nm and two Q-bands between 500 and 600 nm, the measurements of other samples are the normal dispersion curve. The results are approximated by the Cauchy equation and Sellmeier equation, and the correlation coefficients are more than 0.997.
NAA10 polyadenylation signal variants cause syndromic microphthalmia

Background A single variant in NAA10 (c.471+2T>A), the gene encoding N-acetyltransferase 10, has been associated with Lenz microphthalmia syndrome. In this study, we aimed to identify causative variants in families with syndromic X-linked microphthalmia. Methods Three families, including 15 affected individuals with syndromic X-linked microphthalmia, underwent analyses including linkage analysis, exome sequencing and targeted gene sequencing. The consequences of two identified variants in NAA10 were evaluated using quantitative PCR and RNAseq. Results Genetic linkage analysis in family 1 supported a candidate region on Xq27-q28, which included NAA10. Exome sequencing identified a hemizygous NAA10 polyadenylation signal (PAS) variant, chrX:153,195,397T>C, c. *43A>G, which segregated with the disease. Targeted sequencing of affected males from families 2 and 3 identified distinct NAA10 PAS variants, chrX:g.153,195,401T>C, c. *39A>G and chrX:g.153,195,400T>C, c. *40A>G. All three variants were absent from gnomAD. Quantitative PCR and RNAseq showed reduced NAA10 mRNA levels and abnormal 3′ UTRs in affected individuals. Targeted sequencing of NAA10 in 376 additional affected individuals failed to identify variants in the PAS. Conclusion These data show that PAS variants are the most common variant type in NAA10-associated syndromic microphthalmia, suggesting reduced RNA is the molecular mechanism by which these alterations cause microphthalmia/anophthalmia. We reviewed recognised variants in PAS associated with Mendelian disorders and identified only 23 others, indicating that NAA10 harbours more than 10% of all known PAS variants. We hypothesise that PAS in other genes harbour unrecognised pathogenic variants associated with Mendelian disorders. The systematic interrogation of PAS could improve genetic testing yields.
Functionalized magnetic nanoparticles attenuate cancer cells proliferation: Transmission electron microscopy analysis

The penetration and transportation of nanoparticles (NPs) inside the cancer cells is critical to study. In this article, cancer cells (HCT‐116) were treated with functionalized magnetic NPs for the period of 48 hr and studied their ultrastructure by transmission electron microscopy (TEM). The NPs‐treated cells were prepared by chemical fixation and sliced into electron‐transparent arbitrary sections (200 × 200 μm2) by ultramicrotome. Major events of NPs–cell interaction, such as penetration of NPs, encapsulation of NPs into the intracellular compartments, transportation of NPs, and NPs exit, were examined by TEM to understand the mechanism of cell death. The NPs showed the uniform spherical shape with broad size distribution (100–400 nm), while cells displayed irregular morphology with average diameter ~5 μm. Our results showed the successful penetration of NPs deep into the cell, encapsulation, transportation, and exocytosis. Furthermore, we tested the different concentrations (0, 1.5, 12.5, and 50 μg/ml) of NPs on cancer cells and evaluated the cell viability. Laser confocal microscopy and colorimetric analysis together demonstrated that the cell viability is a dose‐dependent phenomenon, where 50 μg/ml specimen showed the highest killing of cancer cells compared to other dosages.
Sleep Mediates the Relationship Between Depression and Cognitive Impairment in Older Men

Sleep and depression are strongly associated with cognitive impairment. The role of sleep disturbances in the adverse effect of depression on cognitive dysfunction in older adults remains unclear. This study explored the mediating effect of self-reported sleep disturbances on the relationship between depression and cognitive impairment in older adults according to sex differences. This study derived data from the 2009 Taiwan National Health Interview Survey and included 2,175 community-dwelling adults aged 65 years and older (men = 991; women = 1,184). Sleep disturbances were measured using self-reported survey questions. The Center for Epidemiological Studies Depression scale was used to assess depression. The Mini-Mental State Examination was used to evaluate cognitive impairment. A higher proportion of female older persons had cognitive impairment and depression than male older persons (cognition: 24.4% vs. 11.5%; depression: 17.0% vs. 10.8%). The meditating effect of sleep was detected in only men. Difficulty in initiating sleep was a complete mediator of the adverse effect of depression on cognitive impairment (Sobel test: p = .03). In summary, difficultly in initiating sleep may be a crucial, treatable mediator of the adverse effect of depression on cognitive impairment in older men.
Disparity tuning of binocular facilitation and suppression after normal versus abnormal visual development.

PURPOSE To study the pattern of facilitatory and suppressive binocular interactions in stereodeficient patients with strabismus and in healthy controls. METHODS Visual evoked potentials were recorded in response to a Vernier onset/offset pattern presented to one eye, either monocularly or paired dichoptically with a straight vertical square-wave grating, which, when fused with the target in the other eye, gave rise to a percept of a series of bands appearing in depth from an otherwise uniform plane or with a grating that contained offsets that produced a standing disparity and the appearance of a constantly segmented image, portions of which moved in depth. RESULTS Participants with normal stereopsis showed facilitative and suppressive binocular interactions that depended on which dichoptic target was presented. Patients with longstanding, constant strabismus lacked normal facilitative binocular interactions. The response to a normally facilitative stimulus was reduced below the monocular level when it was presented to the dominant eye of patients without anisometropia, consistent with classical strabismic suppression of the nondominant eye. The dominant eye of strabismic patients without anisometropia retained suppressive input from crossed but not uncrossed disparity stimuli presented to the nondominant eye. CONCLUSIONS Abnormal disparity processing can be detected with the dichoptic VEP method we describe. Our results suggest that suppression in stereoblind, nonamblyopic observers is determined by a binocular mechanism responsive to disparity. In some cases, the sign of the disparity is important, and this suggests a mechanism that can explain diplopia in patients made exotropic after surgery for esotropia.
A Test of the Null Hypothesis Significance Testing Procedure Correlation Argument

Some supporters of the null hypothesis significance testing procedure recognize that the logic on which it depends is invalid because it only produces the probability of the data if given the null hypothesis and not the probability of the null hypothesis if given the data (e.g., J. Krueger, 2001). However, the supporters argue that the procedure is good enough because they believe that the probability of the data if given the null hypothesis correlates with the probability of the null hypothesis if given the data. The present authors' main goal was to test the size of the alleged correlation. To date, no other researchers have done so. The present findings indicate that the correlation is unimpressive and fails to provide a compelling justification for computing p values. Furthermore, as the significance rule becomes more stringent (e.g., .01, .001), the correlation decreases.
Insulin pump therapy, pre‐pump hemoglobin A1c and metabolic improvement in children with type 1 diabetes at a tertiary Canadian children's hospital

Indications for insulin pump therapy (IPT) in children with type 1 diabetes (T1D) are relatively non‐specific and therefore subject to provider discretion. Health professionals' perceptions of which people will have difficulty with IPT, for example, those with higher hemoglobin A1c (HbA1c), may not be correct. This study examined the effect of IPT on HbA1c, and the role of pre‐pump HbA1c on this effect.
Two E3 ligases antagonistically regulate the UV-B response in Arabidopsis

Significance Plant seedlings encounter increasing levels of UV-B irradiation during their emergence from soil as they undergo a light-induced developmental process termed photomorphogenesis. However, less is known about the molecular mechanisms underlying plant responses to this invisible part of the light spectrum. Here, we reveal that the UV-B light signal is interpreted coordinately by two sets of E3 ligases and a transcription factor in Arabidopsis. The UV-B–inducible E3 CUL4-DDB1–RUP1/RUP2 complex targets the master transcription factor HY5 for proteolysis. COP1 directly interacts with and degrades RUP1/RUP2 to stabilize HY5, ultimately promoting photomorphogenesis under UV-B light. These findings uncover the mechanism of plant responses to UV-B irradiation, and are critical to develop methods to improve plant growth and light energy utilization. Photomorphogenesis is a pivotal developmental strategy used by plants to respond to environmental light levels. During emergence from the soil and the establishment of photomorphogenesis, seedlings encounter increasing levels of UV-B irradiation and develop adaptive responses accordingly. However, the molecular mechanisms that orchestrate UV-B signaling cascades remain elusive. Here, we provide biochemical and genetic evidence that the prolonged signaling circuits of UV-B–induced photomorphogenesis involve two sets of E3 ligases and a transcription factor in Arabidopsis thaliana. The UV-B–inducible protein RUP1/RUP2 associates with the CUL4-DDB1 scaffold to form an E3 ligase, which represses photomorphogenesis by mediating the degradation of HY5, the hub transcription factor in the light signaling pathway. Conversely, COP1 directly targets RUP1/RUP2 for ubiquitination and degradation, leading to balanced RUP1/RUP2 accumulation, alleviation of the COP1–HY5 interaction, and stabilization of HY5 protein. Therefore, our study reveals that these two E3-substrate modules, CUL4-DDB1-RUP1/RUP2-HY5 and COP1-RUP1/RUP2, constitute the repression and derepression machinery by which plants respond to prolonged UV-B irradiation in photomorphogenic development.
Cost-effectiveness analysis of utidelone plus capecitabine for metastatic breast cancer in China

Abstract Objective: To estimate the cost-effectiveness of utidelone plus capecitabine therapy compared to capecitabine alone in patients with metastatic breast cancer (MBC) resistant to anthracyclines and taxanes treatment in the Chinese context and provide a reference for the marketing of utidelone in China. Methods: A Markov model was developed based on the NCT02253459 clinical trial to simulate the clinical course of patients with metastatic breast cancer who had received taxanes and anthracycline therapy. The quality-adjusted life years (QALYs) and Incremental Cost Effectiveness Ratio (ICER) were then analyzed to evaluate the benefits. Two-parametric Weibull distribution was conducted to fit PFS and OS curves by using R. Sensitivity analyses were performed to evaluate the stability of the model designed. Results: The addition of utidelone increased the cost and QALYs by $13,370.25 and 0.1961, respectively, resulting in an increased ICER of $68,180.78 per QALY. The most sensitive influential parameter on ICER was the price of utidelone. At the threshold of willingness-to-pay (WTP) of $24,380 (3 per capita GDP of China), the cost of utidelone per 30 mg of less than $18.5, $33.7, and greater than $48.8 resulted in a 100%, 50%, and 0% possibility of cost-effectiveness, respectively. The addition of utidelone was not cost-effective when it was $115.4 per 30 mg—the price of its analog paclitaxel. In consideration of varied economics levels across China, cost-effectiveness could be achieved with the price of utidelone ranging from $5.2 to $35.9. Limitations: The survival curves extended beyond the follow-up time horizon, of which data were generated not from the real analyses but from our established two-parameter Weibull survival model. Conclusion: It is recommended that the price of utidelone would be less than $18.5 per 30 mg in order to obtain cost-effectiveness for metastatic breast cancer patients resistant to anthracyclines and taxanes treatment in China.
Contributing factors to high prevalence of hearing impairment in the Elias Motsoaledi Local Municipal area, South Africa: A rural perspective

Background There is evidence that the factors contributing to the prevalence and aetiology of hearing impairment vary widely from one country to another. In South Africa, as in other low-income and middle-income countries, more context-specific information on the estimated prevalence of hearing impairment and the factors that contribute to its onset is required. Aim The aim of this study was to provide decision-makers and hearing health professionals with local and accurate information on the prevalence of ear and hearing disorders in the Elias Motsoaledi Local Municipal (EMLM) area of the Limpopo province, South Africa. Methods The World Health Organization (WHO) protocol for population-based surveys of prevalence and causes of deafness, hearing impairment and other ear diseases was utilised. A random multi-stage cluster sampling strategy, two-stage sampling, was utilised to select the seven municipal wards and 357 households through the probability proportional to size method. A total of 850 participants were included in the study. Results The overall prevalence of hearing impairment was 19.88% (95% confidence interval [CI]: 0.15–0.2) and 8.94 (95% CI: 0.08–0.12) for disabling hearing impairment. The prevalence of ear disease was 13.19% (95% CI: 0.10–0.15), with impacted cerumen and otitis media reported most often. Associations with hearing impairment were established for age, gender and hypertension. Conclusion The study has shown a higher prevalence of disabling hearing impairment in the rural EMLM area of the Limpopo province compared to global prevalence rates. In addition, known factors associated with hearing impairment were confirmed.
Animal-assisted activity improves social behaviors in psychiatrically hospitalized youth with autism

There is preliminary research suggesting that animal-assisted activities can improve social interactions of children with autism spectrum disorder. This pilot study sought to investigate the benefits of animal-assisted activities with dogs and psychiatrically hospitalized youth with autism spectrum disorder. Participants were recruited from a specialized inpatient psychiatric hospital unit for youth with autism spectrum disorder and other developmental disabilities. Utilizing a crossover design, participants served as their own control by engaging in two 10-min conditions: an experimental dog and handler interaction (animal-assisted activities) and a novel toy and handler control (control). Of the 142 youth aged 6-–8 years screened for participation, 47 completed both conditions. Participants’ behavioral data were captured via video and coded using the Observation of Human-Animal Interaction for Research, a tool specifically developed to capture human behavioral interactions in the presence of animals. Overall, social-communication behaviors significantly improved in the animal-assisted activities experimental condition compared to the control condition (p = 0.0001). Specifically, participants in the animal-assisted activities experimental condition displayed more positive emotional facial expressions (p ⩽ 0.0001), talking (p = 0.0408), use of gestures (p = 0.032), and looking at both adults and peers (p ⩽ 0.0001). In addition, a higher frequency of constant motion (p = 0.003) was observed in the animal-assisted activities experimental condition. Results suggest that animal-assisted activities with a dog may promote social-communication behaviors in psychiatrically hospitalized youth with autism spectrum disorder. Given the fact that social and communication behaviors can facilitate treatment engagement for this population, we recommend future studies examine how such improvements can positively affect the psychiatric treatment of this population.
Sensitivity of stress and strain calculations to passive material parameters in cardiac mechanical models using unloaded geometries

Abstract Cardiac stress (load) and strain (stretch) are widely studied indicators of cardiac function and outcome, but are difficult or impossible to directly measure in relation to the cardiac microstructure. An alternative approach is to estimate these states using computer methods and image-based measurements, but this still requires knowledge of the tissue material properties and the unloaded state, both of which are difficult to determine. In this work, we tested the sensitivity of these two interdependent unknowns (reference geometry and material parameters) on stress and strain calculations in cardiac tissue. Our study used a finite element model of the human ventricle, with a hyperelastic passive material model, and was driven by a cell model mediated active contraction. We evaluated 21 different published parameter sets for the five parameters of the passive material model, and for each set we optimised the corresponding unloaded geometry and contractility parameter to model a single pressure-volume loop. The resulting mechanics were compared, and calculated systolic stresses were largely insensitive to the chosen parameter set when an unloading algorithm was used. Meanwhile, material strain calculations varied substantially depending on the choice of material parameters. These results indicate that determining the correct material and unloaded configuration may be highly important to understand strain driven processes, but less so for calculating stress estimates.