Miracle-dz/UniFAR-FTUs huggingface dataset:
Deep learning for image analysis: Personalizing medicine closer to the point of care

Abstract The precision-based revolution in medicine continues to demand stratification of patients into smaller and more personalized subgroups. While genomic technologies have largely led this movement, diagnostic results can take days to weeks to generate. Management at, or closer to, the point of care still heavily relies on the subjective qualitative interpretation of clinical and diagnostic imaging findings. New and emerging technological advances in artificial intelligence (AI) now appear poised to help bring objectivity and precision to these traditionally qualitative analytic tools. In particular, one specific form of AI, known as deep learning, is achieving expert-level disease classifications in many areas of diagnostic medicine dependent on visual and image-based findings. Here, we briefly review concepts of deep learning, and more specifically recent developments in convolutional neural networks (CNNs), to highlight their transformative potential in personalized medicine and, in particular, diagnostic histopathology. Understanding the opportunities and challenges of these quantitative machine-based decision support tools is critical to their widespread introduction into routine diagnostics.
A Compassionate Self Is a True Self? Self-Compassion Promotes Subjective Authenticity

Theory and research converge to suggest that authenticity predicts positive psychological adjustment. Given these benefits of authenticity, there is a surprising dearth of research on the factors that foster authenticity. Five studies help fill this gap by testing whether self-compassion promotes subjective authenticity. Study 1 found a positive association between trait self-compassion and authenticity. Study 2 demonstrated that on days when people felt more self-compassionate, they also felt more authentic. Study 3 discovered that people experimentally induced to be self-compassionate reported greater state authenticity relative to control participants. Studies 4 and 5 recruited samples from multiple cultures and used a cross-sectional and a longitudinal design, respectively, and found that self-compassion predicts greater authenticity through reduced fear of negative evaluation (Study 4) and heightened optimism (Study 5). Across studies, self-compassion’s effects on authenticity could not be accounted for by self-esteem. Overall, the results suggest that self-compassion can help cultivate subjective authenticity.
Jeopardized Myocardium Defined by Late Gadolinium Enhancement Magnetic Resonance Imaging Predicts Survival in Patients With Ischemic Cardiomyopathy: Impact of Revascularization

Background The prognostic impact of jeopardized myocardium (JM) in patients with advanced ischemic cardiomyopathy (ICM) is unclear. We hypothesized that JM is an independent predictor of mortality in patients with advanced ICM. Methods and Results Patients with ICM who underwent cardiac magnetic resonance imaging between January 2002 and January 2013 were included in our study. JM was identified as a vascular territory with <50% myocardial scarring on cardiac magnetic resonance imaging and with >70% stenosis in a major coronary vessel that was not subsequently revascularized. A propensity score was developed for revascularization. A multivariable Cox proportional hazards model was used to evaluate the association of JM with all‐cause mortality. We evaluated 631 patients over a mean follow‐up of 5.1 years. Overall, 336 patients underwent subsequent revascularization during the follow‐up period, among whom 23% had remaining JM, while 295 patients were medically treated (57% with JM). There were 204 deaths (32%). On multivariable analysis, JM (hazard ratio, 1.88; 95% confidence interval, 1.38–2.55 [P<0.001]) was independently associated with all‐cause mortality after adjusting for multiple other factors. The risk associated with the presence of JM increased by 5% for every 10‐unit increase in left ventricular end‐systolic volume index. Conclusions JM is an independent and incremental predictor of mortality in patients with advanced ICM. Patients undergoing revascularization with residual JM had similar risk of mortality compared with medically treated patients with JM. The risk associated with JM significantly increased in the presence of worsening adverse left ventricular remodeling. Cardiac magnetic resonance viability assessment may provide important risk stratification in patients with ICM.
Effect of hydraulic retention time on electricity generation using a solid plain-graphite plate microbial fuel cell anoxic/oxic process for treating pharmaceutical sewage

Abstract Treatment efficiency and electricity generation were evaluated using a solid plain-graphite plate microbial fuel cell (MFC) anoxic/oxic (A/O) process that treated pharmaceutical sewage using different hydraulic retention times (HRT). Short HRTs increased the volumetric organic loading rate, thereby reducing the MFC performance due to rapid depletion of the substrate (carbon/nitrogen source). The COD removal efficiency decreased from 96.28% at a HRT of 8 h to 90.67% at a HRT of 5 h. The removal efficiency of total nitrogen was reduced from 74.16% at a HRT of 8 h to 53.42% at a HRT of 5 h. A shorter HRT decreased the efficiency in treatment of the pharmaceutical products (PPs), which included acetaminophen, ibuprofen and sulfamethoxazole in an aerobic reactor because these antibiotic compounds inhibited the microbial activity of the aerobic activated sludge in the MFC A/O system. The average power density and coulombic efficiency values were 162.74 mW m−2 and 7.09% at a HRT of 8 h and 29.12 mW m−2 and 2.23% at a HRT of 5 h, respectively. The dominant bacterial species including Hydrogenophaga spp. , Rubrivivax spp. and Leptothrix spp. , which seem to be involved in PP biodegradation; these were identified in the MFC A/O system under all HRT conditions for the first time using next generation sequencing. Bacterial nanowires were involved in accelerating the transfer of electrons and served as mediators in the SPGRP biofilm. In conclusion, a SPGRP MFC A/O system at a HRT of 8 h gave better removal of COD, T-N and PPs, as well as generated more electricity.
Dodecameric structure of a small heat shock protein from Mycobacterium marinum M

Small heat shock proteins (sHSPs) are ATP‐independent molecular chaperones present ubiquitously in all kingdoms of life. Their low molecular weight subunits associate to form higher order structures. Under conditions of stress, sHSPs prevent aggregation of substrate proteins by undergoing rapid changes in their conformation or stoichiometry. Polydispersity and dynamic nature of these proteins have made structural investigations through crystallography a daunting task. In pathogens like Mycobacteria, sHSPs are immuno‐dominant antigens, enabling survival of the pathogen within the host and contributing to disease persistence. We characterized sHSPs from Mycobacterium marinum M and determined the crystal structure of one of these. The protein crystallized in three different conditions as dodecamers, with dimers arranged in a tetrahedral fashion to form a closed cage‐like architecture. Interestingly, we found a pentapeptide bound to the dodecamers revealing one of the modes of sHSP‐substrate interaction. Further, we have observed that ATP inhibits the chaperoning activity of the protein.
P53 ICE CRIM mouse: a tool to generate mutant allelic series in somatic cells and germ lines for cancer studies

The clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 technology facilitates somatic genome editing to reveal cooperative genetic interactions at the cellular level without extensive breeding between different mutant animals. Here we propose a transgenic inducible Cas9 effector‐CRISPR mutagen (ICE CRIM) mouse model in which CRISPR/Cas9–mediated somatic mutagenesis events can occur in response to Cre expression. The well‐known tumor suppressor gene, Trp53, and 2 important DNA mismatch repair genes, Mlh1 and Msh2, were selected to be our somatic mutagenesis targets. Amplicon‐based sequencing was performed to validate the editing efficiency and to identify the mutant allelic series. Crossed with various Cre lines, the Trp53 ICE CRIM alleles were activated to generate targeted cancer gene somatic or germ line mutant variants. We provide experimental evidence to show that an activated ICE CRIM can mutate both targeted alleles within a cell. Simultaneous disruption of multiple genes was also achieved when there were multiple single‐guide RNA expression cassettes embedded within an activated ICE CRIM. Our mouse model can be used to generate mutant pools in vivo, which enables a functional screen to be performed in situ. Our results also provide evidence to support a monoclonal origin of hematopoietic neoplasms and to indicate that DNA mismatch repair deficiency accelerates tumorigenesis in Trp53 mutant genetic background. —Fan, H. ‐H. , Yu, I. ‐S. , Lin, Y. ‐H. , Wang, S. ‐Y. , Liaw, Y. ‐H. , Chen, P.‐L. , Yang, T. ‐L. , Lin, S. ‐W. , Chen, Y. ‐T. P53 ICE CRIM mouse: a tool to generate mutant allelic series in somatic cells and germ lines for cancer studies. FASEB J. 33, 5571–5584 (2019). www.fasebj. org
Genetic Variation/Evolution and Differential Host Responses Resulting from In-Patient Adaptation of Mycobacterium avium

Members of the Mycobacterium avium complex (MAC) are characterized as nontuberculosis mycobacteria and are pathogenic mainly in immunocompromised individuals. MAC strains show a wide genetic variability, and there is growing evidence suggesting that genetic differences may contribute to a varied immune response that may impact the infection outcome. ABSTRACT Members of the Mycobacterium avium complex (MAC) are characterized as nontuberculosis mycobacteria and are pathogenic mainly in immunocompromised individuals. MAC strains show a wide genetic variability, and there is growing evidence suggesting that genetic differences may contribute to a varied immune response that may impact the infection outcome. The current study aimed to characterize the genomic changes within M. avium isolates collected from single patients over time and test the host immune responses to these clinical isolates. Pulsed-field gel electrophoresis and whole-genome sequencing were performed on 40 MAC isolates isolated from 15 patients at the Department of Medical Microbiology at St. Olavs Hospital in Trondheim, Norway. Isolates from patients (patients 4, 9, and 13) for whom more than two isolates were available were selected for further analysis. These isolates exhibited extensive sequence variation in the form of single-nucleotide polymorphisms (SNPs), suggesting that M. avium accumulates mutations at higher rates during persistent infections than other mycobacteria. Infection of murine macrophages and mice with sequential isolates from patients showed a tendency toward increased persistence and the downregulation of inflammatory cytokines by host-adapted M. avium strains. The study revealed the rapid genetic evolution of M. avium in chronically infected patients, accompanied by changes in the virulence properties of the sequential mycobacterial isolates.
Of Discomfort and Disagreement: Unclaimed Bodies in Anatomy Laboratories at United States Medical Schools

Use of unclaimed bodies for anatomy teaching in undergraduate medical education continues, but is ethically controversial. The purposes of this study were to estimate the proportion of United States (US) medical schools using unclaimed bodies in first‐year anatomy laboratories, to determine whether schools inform students of this use, and to explore anatomy course leaders’ attitudes toward unclaimed body use. Anatomy course leaders from 146 US medical schools that had independent preclinical programs including anatomy were surveyed. Survey results were analyzed with descriptive statistics and statistical tests of association. Free text responses were analyzed using a thematic editing style of qualitative content analysis. Of 89 responses (response rate, 61.0%), 11 schools (12.4%) reported possible use of unclaimed bodies. Course leaders from these schools reported greater comfort with using unclaimed bodies compared to leaders from other schools (P < 0.01). Although most course leaders (49/76, or 64.5%) believed it was important or very important to inform students about use of unclaimed bodies, respondents from schools where unclaimed bodies could be used were more neutral (P < 0.01). Qualitative findings revealed deep disagreement and contradictory views about how unclaimed body use relates to ethical principles of respect for persons and justice. Continued use of unclaimed bodies, varying levels of comfort with their use, and disagreement about the practices’ underlying morality suggest a need for greater ethical reflection about the permissibility of unclaimed body use in clinical anatomy and for educational interventions that teach students about its history, ethics, and contemporary practice.
Melatonin restricts the viability and angiogenesis of vascular endothelial cells by suppressing HIF-1α/ROS/VEGF

Angiogenesis is an essential process involved in various physiological, including placentation, and pathological, including cancer and endometriosis, processes. Melatonin (MLT), a well-known natural hormone secreted primarily in the pineal gland, is involved in regulating neoangiogenesis and inhibiting the development of a variety of cancer types, including lung and breast cancer. However, the specific mechanism of its anti-angiogenesis activity has not been systematically elucidated. In the present study, the effect of MLT on viability and angiogenesis of human umbilical vein endothelial cells (HUVECs), and the production of vascular endothelial growth factor (VEGF) and reactive oxygen species (ROS), under normoxia or hypoxia was analyzed using Cell Counting kit 8, tube formation, flow cytometry, ELISA and western blot assays. It was determined that the secretion of VEGF by HUVECs was significantly increased under hypoxia, while MLT selectively obstructed VEGF release as well as the production of ROS under hypoxia. Furthermore, MLT inhibited the viability of HUVECs in a dose-dependent manner and reversed the increase in cell viability and tube formation that was induced by hypoxia/VEGF/H2O2. Additionally, treatment with an inhibitor of hypoxia inducible factor (HIF)-1α (KC7F2) and MLT synergistically reduced the release of ROS and VEGF, and inhibited cell viability and tube formation of HUVECs. These observations demonstrate that MLT may serve dual roles in the inhibition of angiogenesis, as an antioxidant and a free radical scavenging agent. MLT suppresses the viability and angiogenesis of HUVECs through the downregulation of HIF-1α/ROS/VEGF. In summary, the present data indicate that MLT may be a potential anticancer agent in solid tumors with abundant blood vessels, particularly combined with KC7F2.
Evaluación de la actividad fungicida e identificación de compuestos orgánicos volátiles liberados por Trichoderma viride

The secondary metabolites produced by fungi widely vary in structure and function, providing a rich source of biologically active compounds with applications in farming, pharmacology and food processing.Volatile organic compounds (VOCs) are a biologically relevant class ofsecondary metabolites, since they are suspected of playing a crucial role in the communication between microorganisms. In this work, we use a test headspace chamber to evaluate the VOCs mediated antifungal activity of T. viride against Fusarium sp. and Colletotricum gloeosporiodes. We observed that VOCs produced by T. viride interact with both fungi affecting the growth halos of Fusarium sp. and modifying the colour of Colletotricum gloeosporiodes . The VOCs responsible for this activity were identified using three extraction techniques: Dynamical Headspace (DHS), Static Headspace (SHS) and liquid-liquid extraction (LLE), all of them analyzed via gas chromatography coupled to mass spectrometry (GCMS). DHS and SHS identified alcohols and lactones as VOCs, while with LLE we found a large number of alcohol components and several organic acids. All three techniques identified benzyl alcohol, 2-phenylethyl alcohol, 6-pentyl-2H-pyran-2-one and , for the first time associated to T. viride , gama-butirolactone. After comparison between these extraction techniques, we established that DHS provides the most accurate simulation of biological activity in the test chamber, which reflects in a reliable identification of the VCOs with antifungal activity.
27.2: Invited Paper: True 3D displays for AR applications

Augmented reality (AR) technology, which integrates virtual computer‐generated information into the real world scene, is believed to be the next‐generation human‐machine interface. However, most AR products adopt stereoscopic 3D display technique, which causes the accommodation‐vergence conflict. To solve this problem, we have proposed two approaches. The first is a multi‐planar volumetric display using fast switching polymer‐stabilized liquid crystal (PSLC) films. By rapidly switching the films between scattering and transparent states while synchronizing with a high‐speed projector, the 2D slices of a 3D volume could be displayed in time sequence. We delved into the research on developing high‐performance PSLC films in both normal mode and reverse mode; moreover, we also realized the demonstration of four‐depth AR images with correct accommodation cues. For the second approach, we realized a holographic AR display using digital blazed gratings and a 4f system to eliminate zero‐order and higher‐order noise. With a 4k liquid crystal on silicon device, we achieved a field of view (FOV) of 32 deg. Moreover, we designed a compact waveguide‐based holographic 3D display. In the design, there are two holographic optical elements (HOEs), each of which functions as a diffractive grating and a Fresnel lens. Because of the grating effect, holographic 3D image light is coupled into and decoupled out of the waveguide by modifying incident angles. Because of the lens effect, the collimated zero order light is focused at a point, and got filtered out. The optical power of the second HOE also helps enlarge FOV.
Retinal Deficits Precede Cognitive and Motor Deficits in a Rat Model of Type II Diabetes.

Purpose To investigate the temporal appearance of retinal, cognitive, and motor deficits in Goto-Kakizaki (GK) rats, a spontaneously occurring, polygenic model of type II diabetes. GK rats develop impaired insulin secretion at 2 weeks and fasting hyperglycemia at 4 weeks. Methods In male and female GK rats and Wistar controls, glucose tolerance test (hyperglycemia) and electroretinogram (ERG, retinal function) were performed at 4 and 8 weeks of age. Spectral domain-optical coherence tomography (retinal structure) was assessed at 6 weeks. Spatial alternation (cognitive function) and number of entries (exploratory behavior) were assessed via Y-maze at 4, 5, 6, 7, and 8 weeks. Rotarod (motor function) was performed at 4, 6, and 8 weeks. Results By 4 weeks, the GK rats exhibited significant glucose intolerance (P < 0.001) and retinal deficits, including delays in ERG implicit times (flicker, P < 0.01; oscillatory potentials, P < 0.001). In addition, the GK rats showed greater ERG amplitudes (P < 0.001) and thinner retinas (P < 0.001). At 7 weeks, the GK rats showed deficits in cognitive function (P < 0.001) and exploratory behavior (P < 0.01). However, no motor function deficits were observed by 8 weeks. Interestingly, the male GK rats showed greater hyperglycemia (P < 0.05), but the female rats showed greater ERG delays (P < 0.001). Conclusions In GK rats, retinal function deficits developed prior to cognitive or motor deficits. Future studies will investigate common mechanistic links, long-term functional and vascular changes, and whether early retinal deficits can predict cognitive dysfunction or late-stage retinal disease.
Methods for RNA Modification Mapping Using Deep Sequencing: Established and New Emerging Technologies

New analytics of post-transcriptional RNA modifications have paved the way for a tremendous upswing of the biological and biomedical research in this field. This especially applies to methods that included RNA-Seq techniques, and which typically result in what is termed global scale modification mapping. In this process, positions inside a cell’s transcriptome are receiving a status of potential modification sites (so called modification calling), typically based on a score of some kind that issues from the particular method applied. The resulting data are thought to represent information that goes beyond what is contained in typical transcriptome data, and hence the field has taken to use the term “epitranscriptome”. Due to the high rate of newly published mapping techniques, a significant number of chemically distinct RNA modifications have become amenable to mapping, albeit with variegated accuracy and precision, depending on the nature of the technique. This review gives a brief overview of known techniques, and how they were applied to modification calling.
Autologous transplantation as consolidation for high risk aggressive T-cell non-Hodgkin lymphoma: a SWOG 9704 intergroup trial subgroup analysis

Abstract Phase II data suggest a benefit to autotransplantation for aggressive T-cell non-Hodgkin lymphoma (T-NHL) in first remission; randomized trials have yet to validate this. We performed a retrospective analysis of aggressive T-NHL patients in the intergroup randomized consolidative autotransplant trial (SWOG 9704). Of the 370 enrolled, 40 had T-NHL: 12 were not randomized due to ineligibility (n = 1), choice (n = 2), or progression (n = 9), leaving 13 randomized to control and 15 to autologous stem cell transplantation (ASCT). Two ASCT patients refused transplant and one failed mobilization. The 5-year landmark PFS/OS estimates for ASCT vs. control groups were 40% vs. 38% (p = .56), and 40% vs. 45% (p = .98), respectively. No difference was seen based on IPI, or histologic subtype. Only 1/7 receiving BCNU-based therapy survived vs. 4/5 receiving TBI. Aggressive T-NHL autotransplanted in first remission did not appear to benefit from consolidative ASCT. This and the 30% who dropped out pre-randomization mostly to progression, suggests that improved induction regimens be developed.
Loss of the deglutamylase CCP5 perturbs multiple steps of spermatogenesis and leads to male infertility

ABSTRACT Sperm cells are highly specialized mammalian cells, and their biogenesis requires unique intracellular structures. Perturbation of spermatogenesis often leads to male infertility. Here, we assess the role of a post-translational modification of tubulin, glutamylation, in spermatogenesis. We show that mice lacking the tubulin deglutamylase CCP5 (also known as AGBL5) do not form functional sperm. In these mice, spermatids accumulate polyglutamylated tubulin, accompanied by the occurrence of disorganized microtubule arrays, in particular in the sperm manchette. Spermatids further fail to re-arrange their intracellular space and accumulate organelles and cytosol, while nuclei condense normally. Strikingly, spermatids lacking CCP5 show supernumerary centrioles, suggesting that glutamylation could control centriole duplication. We show that most of these observed defects are also present in mice in which CCP5 is deleted only in the male germ line, strongly suggesting that they are germ-cell autonomous. Our findings reveal that polyglutamylation is, beyond its known importance for sperm flagella, an essential regulator of several microtubule-based functions during spermatogenesis. This makes enzymes involved in glutamylation prime candidates for being genes involved in male sterility. Summary: Perturbation of post-translational polyglutamylation affects early stages of spermatogenesis in mice: loss of the deglutamylase CCP5 completely prevents the formation of functional spermatocytes.