Miracle-dz/UniFAR-FTUs huggingface dataset:
Histone H3K27 demethylase KDM6A is an epigenetic gatekeeper of mTORC1 signalling in cancer

Objective Large-scale genome sequencing efforts of human tumours identified epigenetic modifiers as one of the most frequently mutated gene class in human cancer. However, how these mutations drive tumour development and tumour progression are largely unknown. Here, we investigated the function of the histone demethylase KDM6A in gastrointestinal cancers, such as liver cancer and pancreatic cancer. Design Genetic alterations as well as expression analyses of KDM6A were performed in patients with liver cancer. Genetic mouse models of liver and pancreatic cancer coupled with Kdm6a-deficiency were investigated, transcriptomic and epigenetic profiling was performed, and in vivo and in vitro drug treatments were conducted. Results KDM6A expression was lost in 30% of patients with liver cancer. Kdm6a deletion significantly accelerated tumour development in murine liver and pancreatic cancer models. Kdm6a-deficient tumours showed hyperactivation of mTORC1 signalling, whereas endogenous Kdm6a re-expression by inducible RNA-interference in established Kdm6a-deficient tumours diminished mTORC1 activity resulting in attenuated tumour progression. Genome-wide transcriptional and epigenetic profiling revealed direct binding of Kdm6a to crucial negative regulators of mTORC1, such as Deptor, and subsequent transcriptional activation by epigenetic remodelling. Moreover, in vitro and in vivo genetic epistasis experiments illustrated a crucial function of Deptor and mTORC1 in Kdm6a-dependent tumour suppression. Importantly, KDM6A expression in human tumours correlates with mTORC1 activity and KDM6A-deficient tumours exhibit increased sensitivity to mTORC1 inhibition. Conclusion KDM6A is an important tumour suppressor in gastrointestinal cancers and acts as an epigenetic toggle for mTORC1 signalling. Patients with KDM6A-deficient tumours could benefit of targeted therapy focusing on mTORC1 inhibition.
Seeing is Believing: Advances in Plant Imaging Technologies.

Biological systems are dynamic in space and time at all levels of organization, from single molecules to complex multicellular organisms. Being able to see and quantify how biological processes unfold allows us to understand the mechanisms of life. Imaging methods across the full scale of biological organi-zation are constantly being developed and they revolutionize we visualize the inner workings of cells, tissues, organs and whole organisms. Many advances in imaging techniques were ﬁrst made in animal systems, and their beneﬁts to the ﬁeld of plant imaging countless Yet, plants differ from animals in many ways: their development is typically slower, cells do not migrate and their cell walls, plas-tids and vacuoles provide speciﬁc challenges for imaging. Thus plant-optimized techniques have been developed to enable the functional imaging of plant processes on different scales, which provides a deeper insight into how plants function as unique multicellular organisms (Kierzkowski
Early and Standard Urinary Catheter Removal After Gynecological Surgery for Benign Lesions: A Quasi-Experimental Study

Patients undergoing gynecological surgery commonly receive indwelling transurethral Foley catheters, however duration of catheterization is associated with risk of urinary tract infections and other adverse effects. Early removal of catheters is encouraged, however optimal timing postsurgery remains unclear. This quasi-experimental study compared outcomes for women after removal of a Foley catheter at two different times following benign gynecological surgery. Participants received either early catheter removal, within 6 hours of surgery (n = 38) or standard catheter removal, within 12 to 24 hours of surgery (n = 45). There were no significant differences in outcomes for discomfort scores or re-catheterization rates between groups. However, the early removal group had a significantly shorter time to first ambulation and shorter hospital stays. Early removal of Foley catheters in patients who underwent gynecological surgery did not increase adverse events. Early removal of catheters after gynecological surgery may decrease re-catheterization rates and increase patient satisfaction.
Longitudinal Assessment of Prognostic Understanding in Advanced Lung Cancer Patients and Its Association with Their Psychological Distress.

BACKGROUND Accurate prognostic understanding in advanced cancer patients is essential for shared decision making; however, they may experience psychological burden through knowing the incurable nature of advanced cancer. It has been unclear how their prognostic understanding fluctuates and whether accurate prognostic understanding is associated with psychological distress from the time of diagnosis over time. METHODS We longitudinally investigated prognostic understanding in a total of 225 patients with newly diagnosed advanced lung cancer at 16 hospitals in Japan until 24 months after diagnosis. We examined associated factors with being consistently accurate in prognostic understanding, especially focusing on its association with psychological well-being. RESULTS The proportions of patients with inaccurate prognostic understanding kept around 20 % over time with the presence of patients with inconsistent understanding. Patients with consistently accurate prognostic understanding showed significantly lower Emotional Well-Being subscale score at both 3 and 6 months after diagnosis (P= 0.010 and P= 0.014, respectively). In multivariate analyses, being consistently accurate in prognostic understanding was significantly associated with female gender and higher lung cancer-specific symptom burden at 3 months (P= 0.008 and P= 0.005, respectively) and lower emotional well-being at 6 months (P= 0.006). CONCLUSION While substantial proportions of advanced lung cancer patients had inaccurate prognostic understanding from the time of diagnosis over time, patients with consistently accurate prognostic understanding experienced greater psychological burden. Our findings highlight the importance of continuous psychological care and support for patients that understand their severe prognosis accurately. IMPLICATIONS FOR PRACTICE This study demonstrated that approximately 20% of patients with advanced lung cancer had inaccurate understanding about their prognosis not only at the time of diagnosis but also at the later time points. Being consistently accurate in prognostic understanding was significantly associated with elevated levels of psychological distress. While accurate prognostic understanding is essential for decision making for treatment and advance care planning, health care providers should be aware of psychological burdens in patients that accept their severe prognosis accurately. Appropriate care and support for such patients are warranted from diagnosis over time.
Sex and Cardiovascular Function in Relation to Vascular Brain Injury in Patients with Cognitive Complaints.

BACKGROUND Emerging evidence shows sex differences in manifestations of vascular brain injury in memory clinic patients. We hypothesize that this is explained by sex differences in cardiovascular function. OBJECTIVE To assess the relation between sex and manifestations of vascular brain injury in patients with cognitive complaints, in interaction with cardiovascular function. METHODS 160 outpatient clinic patients (68.8±8.5 years, 38% female) with cognitive complaints and vascular brain injury from the Heart-Brain Connection study underwent a standardized work-up, including heart-brain MRI. We calculated sex differences in vascular brain injury (lacunar infarcts, non-lacunar infarcts, white matter hyperintensities [WMHs], and microbleeds) and cardiovascular function (arterial stiffness, cardiac index, left ventricular [LV] mass index, LV mass-to-volume ratio and cerebral blood flow). In separate regression models, we analyzed the interaction effect between sex and cardiovascular function markers on manifestations of vascular brain injury with interaction terms (sex*cardiovascular function marker). RESULTS Males had more infarcts, whereas females tended to have larger WMH-volumes. Males had higher LV mass indexes and LV mass-to-volume ratios and lower CBF values compared to females. Yet, we found no interaction effect between sex and individual cardiovascular function markers in relation to the different manifestations of vascular brain injury (p-values interaction terms > 0.05). CONCLUSION Manifestations of vascular brain injury in patients with cognitive complaints differed by sex. There was no interaction between sex and cardiovascular function, warranting further studies to explain the observed sex differences in injury patterns.
SphereFace Revived: Unifying Hyperspherical Face Recognition

This paper addresses the deep face recognition problem under an open-set protocol, where ideal face features are expected to have smaller maximal intra-class distance than minimal inter-class distance under a suitably chosen metric space. To this end, hyperspherical face recognition, as a promising line of research, has attracted increasing attention and gradually become a major focus in face recognition research. As one of the earliest works in hyperspherical face recognition, SphereFace explicitly proposed to learn face embeddings with large inter-class angular margin. However, SphereFace still suffers from severe training instability which limits its application in practice. In order to address this problem, we introduce a unified framework to understand large angular margin in hyperspherical face recognition. Under this framework, we extend the study of SphereFace and propose an improved variant with substantially better training stability – SphereFace-R. Specifically, we propose two novel ways to implement the multiplicative margin, and study SphereFace-R under three different feature normalization schemes (no feature normalization, hard feature normalization and soft feature normalization). We also propose an implementation strategy – “characteristic gradient detachment” – to stabilize training. Extensive experiments on SphereFace-R show that it is consistently better than or competitive with state-of-the-art methods.
Prediction of dementia using diffusion tensor MRI measures: the OPTIMAL collaboration

Objectives It has been suggested that diffusion tensor imaging (DTI) measures sensitive to white matter (WM) damage may predict future dementia risk not only in cerebral small vessel disease (SVD), but also in mild cognitive impairment. To determine whether DTI measures were associated with cognition cross-sectionally and predicted future dementia risk across the full range of SVD severity, we established the International OPtimising mulTImodal MRI markers for use as surrogate markers in trials of Vascular Cognitive Impairment due to cerebrAl small vesseL disease collaboration which included six cohorts. Methods Among the six cohorts, prospective data with dementia incidences were available for three cohorts. The associations between six different DTI measures and cognition or dementia conversion were tested. The additional contribution to prediction of other MRI markers of SVD was also determined. Results The DTI measure mean diffusivity (MD) median correlated with cognition in all cohorts, demonstrating the contribution of WM damage to cognition. Adding MD median significantly improved the model fit compared to the clinical risk model alone and further increased in all single-centre SVD cohorts when adding conventional MRI measures. Baseline MD median predicted dementia conversion. In a study with severe SVD (SCANS) change in MD median also predicted dementia conversion. The area under the curve was best when employing a multimodal MRI model using both DTI measures and other MRI measures. Conclusions Our results support a central role for WM alterations in dementia pathogenesis in all cohorts. DTI measures such as MD median may be a useful clinical risk predictor. The contribution of other MRI markers varied according to disease severity.
Exosomal-miR-1184 derived from mesenchymal stem cells alleviates cisplatin-associated acute kidney injury

Acute kidney injury (AKI) poses a severe threat to human health. MicroRNAs (miRNAs/miRs) are known to be involved in the progression of AKI; however, the function of miR-1184 in AKI remains unclear. Thus, the aim of the present study was to examine the role of this miRNA in kidney injury. In order to mimic AKI in vitro, HK-2 cells were treated with cisplatin. Bioinformatics analysis was performed to explore the differentially expressed miRNAs in AKI. A Cell Counting Kit-8 assay and flow cytometry were performed to examine cell viability and apoptosis, respectively. mRNA expression levels were detected via reverse transcription-quantitative PCR, and protein levels were investigated by western blot analysis. ELISA was performed to examine the levels of IL-1β and TNF-α in the cell supernatants. The results revealed that miR-1184 expression was downregulated in AKI. Exosomes derived from miR-1184 agomir-treated mesenchymal stem cells (MSCs) significantly reversed cisplatin-induced cell growth inhibition by inhibiting apoptosis. Moreover, forkhead box O4 (FOXO4) was found to be the direct target of miR-1184, and exosomes expressing miR-1184 notably inhibited cisplatin-induced inflammatory responses in HK-2 cells via the mediation of IL-1β and TNF-α. Furthermore, exosomes derived from miR-1184 agomir-treated MSCs significantly induced G1 phase arrest in HK-2 cells via the regulation of FOXO4, p27 Kip1 and CDK2. In conclusion, the present study demonstrated that exosomal-miR-1184 derived from MSCs alleviates cisplatin-associated AKI. Thus, the findings presented herein may shed new light onto the exploration of novel strategies for the treatment of AKI.
Topology-Informed Model Predictive Control for Anticipatory Collision Avoidance on a Ballbot

—We focus on the problem of planning safe and efﬁcient motion for a ballbot (i.e., a dynamically balancing mobile robot), navigating in a crowded environment. The ballbot’s design gives rise to human-readable motion which is valuable for crowd navigation. However, dynamic stabilization introduces kinematic constraints that severely limit the ability of the robot to execute aggressive maneuvers, complicating collision avoidance and respect for human personal space. Past works reduce the need for aggressive maneuvering by motivating anticipatory collision avoidance through the use of human motion prediction models. However, multiagent behavior prediction is hard due to the combinatorial structure of the space. Our key insight is that we can accomplish anticipatory multiagent collision avoidance without high-ﬁdelity prediction models if we capture fundamental features of multiagent dynamics. To this end, we build a model predictive control architecture that employs a constant-velocity model of human motion prediction but monitors and proactively adapts to the unfolding homotopy class of crowd-robot dynamics by taking actions that maximize the pairwise winding numbers between the robot and each human agent. This results in robot motion that accomplishes statistically signiﬁcantly higher clearances from the crowd compared to state-of-the-art baselines while maintaining similar levels of efﬁciency, across a variety of challenging physical scenarios and crowd simulators.
Therapeutic targeting of hepatic ACSL4 ameliorates NASH in mice

Globally, NAFLD is one of the most common liver disorders, with an estimated prevalence rate of more than 30% in men and 15% in women and an even higher prevalence in people with type 2 diabetes mellitus. Optimal pharmacologic therapeutic approaches for NAFLD are an urgent necessity.
Image enhancement to leverage the 3D morphological reconstruction of single-cell neurons

MOTIVATION To digitally reconstruct the 3D neuron morphologies has long been a major bottleneck in neuroscience. One of the obstacles to automate the procedure is the low signal-background contrast and the large dynamic range of signal and background both within and across images. RESULTS We developed a pipeline to enhance the neurite signal and to suppress the background, with the goal of high signal-background contrast and better within- and between image homogeneity. The performance of the image enhancement was quantitatively verified according to the different figures of merit benchmarking the image quality. Additionally, the method could improve the neuron reconstruction in approximately 1/3 of the cases, with very few cases of degrading the reconstruction. This significantly outperformed three other approaches of image enhancement. Moreover, the compression rate was increased 5 times by average comparing the enhanced to the raw image. All results demonstrated the potential of the proposed method in leveraging the neuroscience providing better 3D morphological reconstruction and lower cost of data storage and transfer. AVAILABILITY The study is conducted based on the Vaa3D platform and python 3.7. 9. The Vaa3D platform is available on the GitHub (https://github.com/Vaa3D). The source code of the proposed image enhancement as a Vaa3D plugin, the source code to benchmark the image quality, and the example image blocks are available under the repository of vaa3d_tools/hackathon/SGuo/imPreProcess. The original fMost images of mouse brains can be found at the BICCN's Brain Image Library (BIL) (https://www.brainimagelibrary.org). SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Changes in Cancer Patients' and Caregivers' Disease Perceptions While Receiving Early Palliative Care: A Qualitative and Quantitative Analysis

Abstract Background Little is known about the underlying mechanisms through which early palliative care (EPC) improves multiple outcomes in patients with cancer and their caregivers. The aim of this study was to qualitatively and quantitatively analyze patients’ and caregivers’ thoughts and emotional and cognitive perceptions about the disease prior to and during the EPC intervention, and in the end of life, following the exposure to EPC. Materials and Methods Seventy‐seven patients with advanced cancer and 48 caregivers from two cancer centers participated in semistructured interviews. Their reports were qualitatively and quantitatively analyzed by the means of the grounded theory and a text‐analysis program. Results Participants reported their past as overwhelmed by unmanaged symptoms, with detrimental physical and psychosocial consequences. The EPC intervention allowed a prompt resolution of symptoms and of their consequences and empowerment, an appreciation of its multidimensional approach, its focus on the person and its environment, and the need for EPC for oncologic populations. Patients reported that conversations with the EPC team increased their acceptance of end of life and their expectation of a painless future. Quantitative analysis revealed higher use of Negative Affects (p < .001) and Biological Processes words (p < .001) when discussing the past; Agency words when discussing the present (p < .001); Positive Affects (p < .001), Optimism (p = .002), and Insight Thinking words (p < .001) when discussing the present and the future; and Anxiety (p = .002) and Sadness words (p = .003) when discussing the future. Conclusion Overall, participants perceived EPC to be beneficial. Our findings suggest that emotional and cognitive processes centered on communication underlie the benefits experienced by participants on EPC. Implications for Practice By qualitative and quantitative analyses of the emotional and cognitive perceptions of cancer patients and their caregivers about their experiences before and during EPC interventions, this study may help physicians/nurses to focus on the disease perception by patients/caregivers and the benefits of EPC, as a standard practice. The analysis of words used by patients/caregivers provides a proxy for their psychological condition and support in tailoring an EPC intervention, based on individual needs. This study highlights that the relationship of the triad EPC team/patients/caregivers may rise as a therapeutic tool, allowing increasing awareness and progressive acceptance of the idea of death.
Adherence and persistence in the use of statins and ezetimibe over 8 years in a real-life study

Abstract Background Adherence and persistence to treatment are crucial in statin therapy as they are synonymous with efficacy and quality of care. The aim of this study was the real-life assessment of adherence and persistence over eight years in treatment-naive patients receiving atorvastatin, lovastatin, simvastatin, pravastatin, ezetimibe. Methods Adherence to treatment was calculated using the ‘proportion of days covered’ method and persistence as the difference between the start and end of the therapy under study. Results Treatment adherence was consistently above 85% for all drugs under study in each year. Treatment persistence was shown to half halved already from the first year. Conclusion Adherent patients had a higher persistence than non-adherent patients.
Normal anthropometry does not equal normal body composition in paediatric intestinal failure.

BACKGROUND Published reports on abnormal body composition in paediatric patients with intestinal failure have been in patients with poor growth. The goal of the current study was to report the body composition of normally growing patients with intestinal failure. METHODS Children aged 8-18 years old with a Dual-energy x-ray absorptiometry (DXA) between January 1, 2013, and July 15, 2018, were included in the study. Data were retrospectively collected from the medical charts and included demographics, residual bowel anatomy, nutritional support, height, and weight. DXA data including total body less head bone mineral density (BMD), fat mass (FM), and fat-free mass (FFM) were collected and compared to published literature controls matched for age and sex. RESULTS: :Thirty-four children met inclusion criteria. Mean age at the time of DXA was 9.6±1.8 years. Weight- and height-for-age z-scores were -0.4±0.9 and -0.5±1.0, respectively. Mean BMD z-score was -1.0 ±1.3. Twenty six percent of patients (n = 9) had reduced BMD. Patients with intestinal failure had higher FM (p = 0.02) and lower FFM (p = 0.02) compared to controls. CONCLUSIONS: : This data shows that despite normal range z-scores for height and weight, children with intestinal failure are at risk for abnormal body composition. Body composition should be routinely measured in children with intestinal failure to direct nutritional interventions. This article is protected by copyright. All rights reserved.
Breathing rate estimation based on multiple linear regression

Abstract The breathing rate is a key clinical parameter that can now be estimated using photoplethysmographic methods. Here, we present an indirect method of breathing rate estimation that does not require bulky and uncomfortable sensors. Breathing modulates a pulsed wave; we extracted the maximum and minimum values, and first-order derivatives thereof, to measure breathing amplitude, frequency, and baseline drift. Demodulation was used to obtain multiple breathing waveforms, from which peak values are extracted to obtain breathing rates. Multiple linear regression was used to combine the breathing rates of different feature points. We used a breathing dataset for 53 subjects, and divided the data into training and test sets when calculating the regression coefficients. We also assessed the generalizability of our linear model. We found that breathing rate estimation was more accurate when using a multivariate signal method with multiple versus a single feature point. The mean absolute error, mean error, and standard deviation of the error were 1.28, −0.07, and 1.60 breaths per minute, respectively.