Miracle-dz/UniFAR-FTUs huggingface dataset:
YAP1 and TAZ negatively control bone angiogenesis by limiting hypoxia-inducible factor signaling in endothelial cells

Blood vessels are integrated into different organ environments with distinct properties and physiology (Augustin and Koh, 2017). A striking example of organ-specific specialization is the bone vasculature where certain molecular signals yield the opposite effect as in other tissues (Glomski et al., 2011; Kusumbe et al., 2014; Ramasamy et al., 2014). Here, we show that the transcriptional coregulators Yap1 and Taz, components of the Hippo pathway, suppress vascular growth in the hypoxic microenvironment of bone, in contrast to their pro-angiogenic role in other organs. Likewise, the kinase Lats2, which limits Yap1/Taz activity, is essential for bone angiogenesis but dispensable in organs with lower levels of hypoxia. With mouse genetics, RNA sequencing, biochemistry, and cell culture experiments, we show that Yap1/Taz constrain hypoxia-inducible factor 1α (HIF1α) target gene expression in vivo and in vitro. We propose that crosstalk between Yap1/Taz and HIF1α controls angiogenesis depending on the level of tissue hypoxia, resulting in organ-specific biological responses.
Effects of smartphone application education combined with hands-on practice in breast self-examination on junior nursing students in South Korea.

BACKGROUND Breast self-examination is a convenient and effective way to detect breast abnormalities. Based on Dale's Cone of Experience theory, we hypothesized that the combination of a smartphone application with hands-on practice would have a greater impact than using a smartphone application alone. The purpose of this study was to compare the effects of different educational methods on (a) knowledge, (b) attitudes, (c) skills, and (d) students' satisfaction with the learning methods. METHODS We conducted a pre- and post-test quasi-experimental design and developed a smartphone application using a video clip. One experimental group received smartphone-based education, another group received smartphone-based education combined with hands-on practice, and the control group received a one-time classroom lecture. We administered a pre-test, provided intervention, and conducted a post-test. RESULTS Among the three groups, the knowledge and attitude of the experimental groups were significantly higher than that of the control group. In addition, the group using the combination of the smartphone application and hands-on practice showed the highest score changes in skills and satisfaction with the learning methods. CONCLUSIONS Smartphone application use combined with hands-on practice could be an effective education method for breast self-examination.
Association between Single Nucleotide Polymorphisms and Glioma Risk: A Systematic Literature Review

Abstract This study aimed to determine the main single nucleotide polymorphisms (SNPs) that are associated with an increased or decreased risk of glioma development in healthy individuals. We conducted a systematic review of the articles published in English on the PUBMED database between January 2008 and December 2017. Our search resulted in a total of 743 articles; however, only 56 were included in this review. A total of 148 polymorphisms were found, which involved 64 different genes. The polymorphisms that were most associated with an increased risk of glioma development were polymorphic variants rs179782, rs13181, and rs3791679 of the genes XRCC1, ERCC2, and EFEMP1, respectively.
Circulating branched‐chain amino acids and incident heart failure in type 2 diabetes: The Hong Kong Diabetes Register

Levels of branched‐chain amino acids (BCAAs, namely, isoleucine, leucine, and valine) are modulated by dietary intake and metabolic/genetic factors. BCAAs are associated with insulin resistance and increased risk of type 2 diabetes (T2D). Although insulin resistance predicts heart failure (HF), the relationship between BCAAs and HF in T2D remains unknown.
CCL5 mediates target‐kinase independent resistance to FLT3 inhibitors in FLT3‐ITD‐positive AML

FLT3‐ITD tyrosine kinase inhibitors (TKI) show limited clinical activity in acute myeloid leukemia (AML) due to emerging resistance. TKI resistance is mediated by secondary FLT3‐ITD mutations only in a minority of cases. We hypothesize that the cytokine CCL5 protects AML cells from TKI‐mediated cell death and contributes to treatment resistance. We generated PKC412‐ and sorafenib‐resistant MOLM‐13 cell lines as an in vitro model to study TKI resistance in AML. Increased CCL5 levels were detected in supernatants from PKC412‐resistant cell lines compared to TKI‐sensitive cells. Moreover, CCL5 treatment of TKI‐sensitive cells induced resistance to PKC412. In resistant cell lines with high CCL5 release, we observed a significant downregulation of the CCL5‐receptor CCR5 and CXCR4. In these cell lines, TKI resistance could be partly overcome by addition of the CXCR4‐receptor antagonist plerixafor. Microarray and intracellular flow cytometry analyses revealed increased p‐Akt or p‐Stat5 levels in PKC412‐resistant cell lines releasing high amounts of CCL5. Treatment with the CXCR4 antagonist plerixafor, αCCL5, or CCR5‐targeting siRNA led to a decrease of p‐Akt‐positive cells. Transient transfection of sensitive MOLM‐13 cells with a CCL5‐encoding vector mediated resistance against PKC412 and led to an increase in p‐Akt‐positive and p‐Stat5‐positive cells. Isolated AML blasts from patients treated with PKC412 revealed that CCL5 transcript levels increase significantly at relapse. Taken together, our findings indicate that CCL5 mediates resistance to FLT3‐TKIs in FLT3‐ITD‐mutated AML and could possibly serve as a biomarker to predict drug resistance.
The Role of Free and Cued Selective Reminding Test in Predicting [18F]Florbetaben PET Results in Mild Cognitive Impairment and Mild Dementia.

BACKGROUND Free and Cued Selective Reminding Test (FCSRT) is a reliable cognitive marker for Alzheimer's disease (AD), and the identification of neuropsychological tests sensitive to the early signs of AD pathology is crucial both in research and clinical practice. OBJECTIVE The study aimed to ascertain the ability of FCSRT in predicting the amyloid load as determined from amyloid PET imaging (Amy-PET) in patients with cognitive disorders. METHODS For our purpose, 79 patients (71 MCI, 8 mild dementia) underwent a complete workup for dementia, including the FCSRT assessment and a [18F]florbetaben PET scan. FCSRT subitem scores were used as predictors in different binomial regression models. RESULTS Immediate free recall and delayed free recall were the best predictors overall in the whole sample; whereas in patients <76 years, all models further improved with immediate total recall (ITR) and Index of Sensitivity of Cueing (ISC) resulting in the most accurate in anticipating Amy-PET results, with a likelihood of being Amy-PET positive greater than 85% for ITR and ISC scores of less than 25 and 0.5, respectively. CONCLUSION FCSRT proved itself to be a valid tool in dementia diagnosis, also being able to correlate with amyloid pathology. The possibility to predict Amy-PET results through a simple and reliable neuropsychological test might be helpful for clinicians in the dementia field, adding value to a paper and pencil tool compared to most costly biomarkers.
Paradise lost: End‐of‐century warming and acidification under business‐as‐usual emissions have severe consequences for symbiotic corals

Despite recent efforts to curtail greenhouse gas emissions, current global emission trajectories are still following the business‐as‐usual representative concentration pathway (RCP) 8.5 emission pathway. The resulting ocean warming and acidification have transformative impacts on coral reef ecosystems, detrimentally affecting coral physiology and health, and these impacts are predicted to worsen in the near future. In this study, we kept fragments of the symbiotic corals Acropora intermedia (thermally sensitive) and Porites lobata (thermally tolerant) for 7 weeks under an orthogonal design of predicted end‐of‐century RCP8.5 conditions for temperature and pCO2 (3.5°C and 570 ppm above present‐day, respectively) to unravel how temperature and acidification, individually or interactively, influence metabolic and physiological performance. Our results pinpoint thermal stress as the dominant driver of deteriorating health in both species because of its propensity to destabilize coral–dinoflagellate symbiosis (bleaching). Acidification had no influence on metabolism but had a significant negative effect on skeleton growth, particularly when photosynthesis was absent such as in bleached corals or under dark conditions. Total loss of photosynthesis after bleaching caused an exhaustion of protein and lipid stores and collapse of calcification that ultimately led to A. intermedia mortality. Despite complete loss of symbionts from its tissue, P. lobata maintained small amounts of photosynthesis and experienced a weaker decline in lipid and protein reserves that presumably contributed to higher survival of this species. Our results indicate that ocean warming and acidification under business‐as‐usual CO2 emission scenarios will likely extirpate thermally sensitive coral species before the end of the century, while slowing the recovery of more thermally tolerant species from increasingly severe mass coral bleaching and mortality. This could ultimately lead to the gradual disappearance of tropical coral reefs globally, and a shift on surviving reefs to only the most resilient coral species.
MLH1‐mediated recruitment of FAN1 to chromatin for the induction of apoptosis triggered by O6‐methylguanine

O6‐Methylguanines (O6‐meG), which are produced in DNA by the action of alkylating agents, are mutagenic and cytotoxic, and induce apoptosis in a mismatch repair (MMR) protein‐dependent manner. To understand the molecular mechanism of O6‐meG‐induced apoptosis, we performed functional analyses of FANCD2 and FANCI‐associated nuclease 1 (FAN1), which was identified as an interacting partner of MLH1. Immunoprecipitation analyses showed that FAN1 interacted with both MLH1 and MSH2 after treatment with N‐methyl‐N‐nitrosourea (MNU), indicating the formation of a FAN1‐MMR complex. In comparison with control cells, FAN1‐knockdown cells were more resistant to MNU, and the appearances of a sub‐G1 population and caspase‐9 activation were suppressed. FAN1 formed nuclear foci in an MLH1‐dependent manner after MNU treatment, and some were colocalized with both MLH1 foci and single‐stranded DNA (ssDNA) created at damaged sites. Under the same condition, FANCD2 also formed nuclear foci, although it was dispensable for the formation of FAN1 foci and ssDNA. MNU‐induced formation of ssDNA was dramatically suppressed in FAN1‐knockdown cells. We therefore propose that FAN1 is loaded on chromatin through the interaction with MLH1 and produces ssDNA by its exonuclease activity, which contributes to the activation of the DNA damage response followed by the induction of apoptosis triggered by O6‐meG.
Virtual reality and music therapy as distraction interventions to alleviate anxiety and improve mood states in breast cancer patients during chemotherapy

Psychological distress is a common consequence of breast cancer diagnosis and treatment and could further exacerbate therapy side effects. Interventions increasing treatment tolerance are crucial to improve both patients' quality of life and adherence to therapies. Virtual reality (VR) has emerged as an effective distraction tool for different medical procedures. Here, we assessed the efficacy of immersive and interactive VR in alleviating chemotherapy‐related psychological distress in a cohort of Italian breast cancer patients, also comparing its effects with those of music therapy (MT). Thirty patients were included in the VR group, 30 in the MT group, and 34 in the control group, consisting of patients receiving standard care during chemotherapy. Our data suggest that both VR and MT are useful interventions for alleviating anxiety and for improving mood states in breast cancer patients during chemotherapy. Moreover, VR seems more effective than MT in relieving anxiety, depression, and fatigue.
Ultra-High Mass Resolving Power, Mass Accuracy, and Dynamic Range MALDI Mass Spectrometry Imaging by 21-T FT-ICR MS

Detailed characterization of complex biological surfaces by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) requires instrumentation that is capable of high mass resolving power, mass accuracy, and dynamic range. Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) offers the highest mass spectral performance for MALDI MSI experiments, and often reveals molecular features that are unresolved on lower performance instrumentation. Higher magnetic field strength improves all performance characteristics of FT-ICR; mass resolving power improves linearly, while mass accuracy and dynamic range improve quadratically with magnetic field strength. Here, MALDI MSI at 21T is demonstrated for the first time: mass resolving power in excess of 1 600 000 (at m/z 400), root-mean-square mass measurement accuracy below 100 ppb, and dynamic range per pixel over 500:1 were obtained from the direct analysis of biological tissue sections. Molecular features with m/z differences as small as 1.79 mDa were resolved and identified with high mass accuracy. These features allow for the separation and identification of lipids to the underlying structures of tissues. The unique molecular detail, accuracy, sensitivity, and dynamic range combined in a 21T MALDI FT-ICR MSI experiment enable researchers to visualize molecular structures in complex tissues that have remained hidden until now. The instrument described allows for future innovative, such as high-end studies to unravel the complexity of biological, geological, and engineered organic material surfaces with an unsurpassed detail.
Topical niacinamide does not stimulate hair growth based on the existing body of evidence

This letter is intended to clarify misconceptions in the consumer world on the alleged side effects of niacinamide (Nam) on hair growth properties. It is important that the overall body of evidence related to Nam and hair biology be reviewed so as not to confuse consumers and patients on Nam impact on facial and body hair. We have reviewed the published literature and provide new data to demonstrate that Nam has a neutral, if any, impact on hair growth properties.
Generalized parametric cure models for relative survival

Cure models are used in time‐to‐event analysis when not all individuals are expected to experience the event of interest, or when the survival of the considered individuals reaches the same level as the general population. These scenarios correspond to a plateau in the survival and relative survival function, respectively. The main parameters of interest in cure models are the proportion of individuals who are cured, termed the cure proportion, and the survival function of the uncured individuals. Although numerous cure models have been proposed in the statistical literature, there is no consensus on how to formulate these. We introduce a general parametric formulation of mixture cure models and a new class of cure models, termed latent cure models, together with a general estimation framework and software, which enable fitting of a wide range of different models. Through simulations, we assess the statistical properties of the models with respect to the cure proportion and the survival of the uncured individuals. Finally, we illustrate the models using survival data on colon cancer, which typically display a plateau in the relative survival. As demonstrated in the simulations, mixture cure models which are not guaranteed to be constant after a finite time point, tend to produce accurate estimates of the cure proportion and the survival of the uncured. However, these models are very unstable in certain cases due to identifiability issues, whereas LC models generally provide stable results at the price of more biased estimates.
Real-time chemical analysis of root filling materials with heating; guidelines for safe temperature levels.

AIM To investigate the chemical changes affecting different types of gutta-percha and endodontic sealers during heating, and correlate changes with the heating capacity of different heat carriers. METHODOLOGY The heating capacity of three endodontic heat carriers were evaluated using thermocouples to produce heat profiles. The devices were activated at different temperature set-ups, in continuous or cut-out modes. Chemical changes of six brands of gutta-percha and four types of sealers were assessed in real-time during heating using micro-Raman spectroscopy equipped with a heating stage. Raman spectra of each tested material were averaged and compared at different temperature levels. The sealers were further assessed by Fourier transform infrared (FTIR) spectroscopy. RESULTS None of the tested heat carriers achieved the temperature levels that were set by the devices and recommended by the manufacturer. The use of continuous heating mode resulted in higher rises in temperature than the 4s cut-out mode that reached 110 °C. The various brands of gutta-percha exhibited different chemical changes in response to heat. Some changes even occurred below temperature levels generated by the heating devices. All sealers revealed changes in their chemical composition upon heating. Changes in epoxy resin- and zinc oxide eugenol-based sealers were detectable at 100 °C, with structural alterations beyond that temperature and irreversible changes after cooling. Water loss was irreversible in BioRoot, but its chemical structure was stable as well as for the TotalFill. CONCLUSIONS The heating capacity of endodontic heat carriers needs to be standardized, so that the temperatures delivered by the tips is the same as that set on the dial. Practitioners should be aware of the actual temperatures generated by these devices, and the suitability of sealers to be used at the temperature levels achieved.
Adaptation of the Accommodation among Romantic Couples Scale (ARCS) to the Spanish Population.

BACKGROUND The different conflict resolution strategies that couples use are crucial in preserving or ending their relationships. Despite the importance of these strategies, no instrument for measuring them has been adequately adapted to Spanish culture. The goal of this study is to adapt the Accommodation among Romantic Couples Scale to Spanish culture, filling this gap by providing a rigorous instrument to evaluate the construct. METHOD A total of 489 participants from the general population responded to the instrument after adaptation. The scale's psychometric properties were then evaluated from a classical perspective. RESULTS The indexes of fit from confirmatory factor analysis indicated good fit to the four-factor structure proposed by the authors of the original scale: voice, loyalty, exit, and neglect. The reliability of these dimensions was similar to that obtained in the original version. Evidence of validity relative to other variables indicated good convergent and discriminant validity. CONCLUSIONS The Spanish version of the Accommodation among Romantic Couples Scale is a reliable instrument with sufficient valid evidence to provide accurate measurement of conflict resolution strategies in couple relationships.
Reorganized functional connectivity of language centers as a possible compensatory mechanism for basal ganglia aphasia

ABSTRACT Primary Object: To investigate the functional connectivity (FC) of cortical language centers in patients who have regained fluent speech after basal ganglia aphasia and identify the possible compensatory mechanism. Methods & Procedures: A retrospective cohort of 12 patients and 17 healthy controls were studied using resting-state functional MRI (rs-fMRI). All patients suffered from an ischemic stroke with lesions confined to the basal ganglia and showed impaired language functions at admission. Seven patients had lesions in the left basal ganglia, three in the right, and two in both sides. The rs-fMRI was performed after the patients regained fluent speech. Broca’s area, Wernicke’s area, and their contralateral homologues were selected as the region-of-interest (ROI) for both voxel-wise and ROI-wise FC studies. Results: We discovered that the interhemispheric FC of the language centers (i.e. Broca’s area and Wernicke’s area) decreased and the intrahemispheric FC of the language centers increased in these patients who regained fluent speech after basal ganglia aphasia. Conclusions: We speculated that damages to the basal ganglia disrupted the cortico-subcortical circuits that facilitated the transhemispheric communications of language functions, resulting in decreased interhemispheric FC. Consequently, the intrahemispheric FC increased as a possible compensatory mechanism to restore the language functions.
Cryo-EM structures of cardiac thin filaments reveal the 3D architecture of troponin

Troponin is an essential component of striated muscle and it regulates the sliding of actomyosin system in a calcium-dependent manner. Despite its importance, the structure of troponin has been elusive due to its high structural heterogeneity. In this study, we analyzed the 3D structures of murine cardiac thin filaments using a cryo-electron microscope equipped with a Volta phase plate (VPP). Contrast enhancement by a VPP enabled us to reconstruct the entire repeat of the thin filament. We determined the orientation of troponin relative to F-actin and tropomyosin, and characterized the interactions between troponin and tropomyosin. This study provides a structural basis for understanding the molecular mechanism of actomyosin system.
Productive Activity Patterns and Functional Health: A Comparison of Urban and Rural Chinese Older Adults

This study examines the association between productive activity patterns and functional health trajectories of Chinese older adults and whether this association varies by urban/rural residence. Using three waves of the China Health and Retirement Longitudinal Study from a sample of 7,503 older adults, we first performed latent class analysis (LCA) to identify productive activity patterns based on four activities (work, caregiving, informal help, and formal volunteering). Next, multilevel regression analyses were conducted to assess the association between the identified productive activity patterns and functional health trajectories among older adults. Four productive activity patterns are identified from LCA: nonengagers, working-caregivers, workers, and helpers. We find that participation in productive activities is associated with slower functional health decline. The moderation effects of urban/rural differences are prominent across identified groups. Our findings highlight the importance of the urban/rural context in understanding productive aging and its health consequences among Chinese older adults.