Miracle-dz/UniFAR-FTUs huggingface dataset:
Prognostic factors in progressive high-grade glial tumors treated with systemic approach: A single center experience

Purpose Malignant high-grade gliomas are the most common and aggressive type of primary brain tumor, and the prognosis is generally extremely poor. In this retrospective study, we analyzed the outcome of systemic treatment in recurrent high-grade glioma patients and the impact of prognostic factors on survivals. Methods Data from 114 patients with recurrent high-grade glioma who received systemic treatment and followed in our clinic between 2012 and 2018 were retrospectively analyzed. Eastern Cooperative Oncology Group (ECOG) performance status, age, gender, histology, type of surgical resection, side effects after systemic treatment (deep vein thrombosis, hypertension, proteinuria), IDH1 and alpha thalassemia/mental retardation syndrome X-linked (ATRX) mutation status were investigated as prognostic factors for progression-free survival and overall survival. Results At the time of diagnosis, the median age was 48 (17–77) and 68% of the patients were male. Most common pathologic subtype was glioblastoma multiforme (68%). Median follow-up duration was 9.1 months (1–68 months). Median progression-free survival and overall survival were 6.2 months and 8 months, respectively. In multivariate analysis, ECOG PS, deep venous thrombosis and the presence of ATRX and IDH1 mutation were found to be independent prognostic factors for progression-free survival (p < 0.05) and, ECOG PS, the presence of ATRX and IDH1 mutation for overall survival (p < 0.05). Conclusion Our study is real life data and the median progression-free survival and overall survival rates are similar to the literature. We have found ECOG PS, presence of ATRX and IDH1 mutation to be independent prognostic factors for both progression-free survival and overall survival.
Multiplex generation, tracking, and functional screening of substitution mutants using a CRISPR/retron system

We developed a clustered regularly interspaced short palindromic repeats (CRISPR)/retron system for multiplexed generation of substitution mutations by co-utilization of a retron system that continuously expresses donor DNA and a CRISPR/Cas9 cassette that induces cleavage at target genomic loci. Our system efficiently introduces substitution mutation in the Escherichia coli genome in a high-throughput manner. These substitution mutations can be tracked by analysis of retron plasmid sequences without laborious amplification of individual edited loci. We demonstrated that our CRISPR/retron system can introduce thousands of mutations in a single experiment and be used for screening phenotypes related to chemical responses or fitness changes. We expect that our system could facilitate genome-scale substitution screenings.
Telomere and Centromere Staining Followed by M-FISH Improves Diagnosis of Chromosomal Instability and Its Clinical Utility

Dicentric chromosomes are a relevant marker of chromosomal instability. Their appearance is associated with telomere dysfunction, leading to cancer progression and a poor clinical outcome. Here, we present Telomere and Centromere staining followed by M-FISH (TC+M-FISH) for improved detection of telomere dysfunction and the identification of dicentric chromosomes in cancer patients and various genetic syndromes. Significant telomere length shortening and significantly higher frequencies of telomere loss and deletion were found in the peripheral lymphocytes of patients with cancer and genetic syndromes relative to similar age-matched healthy donors. We assessed our technique against conventional cytogenetics for the detection of dicentric chromosomes by subjecting metaphase preparations to both approaches. We identified dicentric chromosomes in 28/50 cancer patients and 21/44 genetic syndrome patients using our approach, but only 7/50 and 12/44, respectively, using standard cytogenetics. We ascribe this discrepancy to the identification of the unique configuration of dicentric chromosomes. We observed significantly higher frequencies of telomere loss and deletion in patients with dicentric chromosomes (p < 10−4). TC+M-FISH analysis is superior to classical cytogenetics for the detection of chromosomal instability. Our approach is a relatively simple but useful tool for documenting telomere dysfunction and chromosomal instability with the potential to become a standard additional diagnostic tool in medical genetics and the clinic.
The gravitational imprint on sensorimotor planning and control.

Humans excel at learning complex tasks and elite performers such as musicians or sportsmen develop motor skills that defy biomechanical constraints. All actions require the movement of massive bodies. Of particular interest in the process of sensorimotor learning and control is the impact of gravitational forces on the body. Indeed, efficient control and accurate internal representations of the body configuration in space depend on our ability to feel and anticipate the action of gravity. Here we review studies on perception and sensorimotor control in both normal and altered gravity. Behavioral and modeling studies together suggested that the nervous system develops efficient strategies to take advantage of gravitational forces across a wide variety of tasks. However, when exposed to altered gravity, the rate of strategy updating exhibited substantial variations from one experiment to another and sometimes led to partial adjustment only. Overall, these results support the hypothesis that the brain uses a multimodal and flexible representation of gravity effects on our body and movements. Future work is necessary to better characterize the nature of this internal representation and the extent to which it can adapt to novel contexts.
A Novel Analog Front End with Voltage-Dependent Input Impedance and Bandpass Amplification for Capacitive Biopotential Measurements

This paper proposes a novel analogue front end (AFE) that has three features: voltage-dependent input impedance, bandpass amplification, and stray capacitance reduction. With a view to applying the AFE to capacitive biopotential measurements (CBMs), the three features were investigated separately in a schematic and mathematical manner. Capacitive electrocardiogram (cECG) or capacitive electromyogram (cEMG) measurements using the AFE were performed in low-humidity conditions (below 35% relative humidity) for a total of seven human subjects. Performance evaluation of the AFE revealed the following: (1) the proposed AFE in cECG measurement with 1.70-mm thick clothing reduced the baseline recovery time and root mean square voltage of respiratory interference in subjects with healthy-weight body mass index (BMI), and increased R-wave amplitude for overweight-BMI subjects; and (2) the proposed AFE in cEMG measurement of biceps brachii muscle yielded stable electromyographic waveforms without the marked DC component for all subjects and a significant (p < 0.01) increase in the signal-to-noise ratio. These results indicate that the proposed AFE can provide a feasible balance between sensitivity and stability in CBMs, and it could be a versatile replacement for the conventional voltage follower used in CBMs.
Effect of Different Shear Rates on Particle Microstructure of Cementitious Materials in a Wide Gap Vane-in-cup Rheometer

Rheological properties of cementitious suspensions are affected not only by their mixture composition but also by process-related factors such as shear history. To enable a model-based description, investigations were carried out on the effect of shear history (shear rate variation over time) on the cement paste agglomeration state. Therefore, a Focused Beam Reflectance Measurement (FBRM) system and a wide gap rheometer were coupled to study the relation between shear history and in-situ chord length distribution simultaneously, indicating particle agglomeration. Hence, the effect of average shear rates (resulting from the applied shear profile), as well as shear rate distribution within the gap (local shear rates) on the particle agglomeration state have been investigated. The rheological properties of cement paste were evaluated with the Reiner–Riwlin approach. Furthermore, the agglomeration state of the particles was compared for different average shear rates and local shear rates at various positions of the FBRM probe. The results show that the median chord length increases in all positions when the average shear rate is decreased, indicating increasing particle agglomeration. Moreover, due to variable local shear rates at different FBRM probe positions, different agglomeration states are observed, resulting from two factors, shear rate dependent particle agglomeration and shear-induced particle migration.
Regulation of Clathrin-Mediated Endocytosis by Dynamic Ubiquitination/Deubiquitination of Ede1

Clathrin-mediated endocytosis in budding yeast requires the regulated recruitment and disassociation of over 60 proteins at discreet plasma membrane puncta. Post-translational modifications, such as phosphorylation and ubiquitination, may play important regulatory roles in this highly processive and ordered process. However, while ubiquitination plays an important role in cargo selection, functions for ubiquitination of the endocytic machinery are not known. We identified the deubiquitinase (DUB) Ubp7p as a late arriving endocytic protein. Deletion of the DUBs Ubp2p and Ubp7p resulted in elongation of the lifetimes of endocytic coat proteins at the plasma membrane and recruitment of endocytic proteins to internal membranes. These phenotypes could be replicated by expressing a permanently ubiquitinated version of the early endocytic adaptor Ede1p, the yeast Eps15 homolog, which is implicated in the initiation of endocytic sites. However, Ede1p absence did not fully suppress the deubiquitinase deletion phenotype, suggesting that Ede1p is not the only endocytic target whose deubiquitination affects coat formation and disassembly.
The role of the telomere bouquet in controlling spindle pole body composition in fission yeast meiosis

The telomere bouquet is a highly conserved structure specific to meiotic prophase in which the telomeres are gathered to a limited region of the nuclear periphery. In a number of organisms including fission yeast, the bouquet is tethered to the spindle pole body (SPB) or centrosome. The meiosis-specific factors Bqt1/Bqt2 function as a bridge to connect the telomere proteins Taz1/Rap1 to the SPB. Deletion of any of these elements disrupts the bouquet, leading to defective spindle formation and aberrant meiosis (Tomita and Cooper, 2007). The aim of this thesis was to determine the molecular basis for control of the meiotic spindle by the telomere bouquet. We asked the question: how does the meiotic SPB differ in the presence and absence of bouquet function? Using methods to quantify SPB component levels via fluorescence microscopy in live cells, we found that bouquet-defective strains show a slight elevation of the level of Pcp1, an SPB component, but such elevation is not enough to confer bouquet-mutant phenotypes in bouquet-proficient backgrounds. Indeed, our data suggest that in the absence of the bouquet, SPB duplication occurs properly and with normal timing. However, we observed that the separation of the duplicated SPBs is markedly abnormal, as the duplicated SPBs fail to remain apart and at least one of them often becomes dislodged from the nucleus. Moreover, the γ-tubulin complex fails to localise to both spindle poles. Hence, the duplicated SPBs fail to properly recruit the γ-tubulin complex. We thus investigated the molecular mechanism underlying control of γ-tubulin complex recruitment by the bouquet. Our findings allow us to propose a model that explains the different types of spindle defects seen in the absence of the bouquet.
Two Cases of Hepatocellular Carcinoma Arising Over 20 Years after a Sustained Virologic Response Following Interferon Therapy for Chronic Hepatitis C

The development of hepatocellular carcinoma (HCC) after a sustained virologic response (SVR) due to interferon (IFN) therapy for hepatitis C virus infection remains a serious problem. We herein report 2 cases of HCC that developed more than 20 years after SVR with IFN therapy for chronic hepatitis C. The patients were 89- and 72-year-old men with HCC that developed 24-25 years after an SVR with IFN therapy. These patients regularly underwent imaging examinations; therefore, the HCC was detected in the early stage, when it was still curable. Both cases suggest that long-term surveillance after an SVR is effective for the detection of HCC, and radical treatment is possible.
Pediatric alopecia areata.

BACKGROUND Alopecia areata (AA) is a non-scarring hair loss disorder of autoimmune etiology. OBJECTIVE To familiarize physicians with the clinical presentation, diagnosis, evaluation, and management of pediatric alopecia areata. METHODS The search term 'Alopecia areata' was entered into a Pubmed search. A narrow scope was applied to the categories of 'epidemiology', 'clinical diagnosis', 'investigations', 'comorbidities', and 'treatment'. Meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews were included. Only papers published in the English language were included. A descriptive, narrative synthesis was provided of the retrieved articles. RESULTS AA is an autoimmune disease of unknown etiology. It is the third most common dermatologic presentation in children with a lifetime risk of 1-2%. Diagnosing AA can be made on the basis of the history and clinical findings. Patients will often present with patchy, non-scarring hair loss generally affecting the scalp. History may reveal a personal or family medical history of autoimmune or atopic disease or a recent stressful event. Tricoscopic examination will classically show "exclamation point hairs" and "yellow dots". Nonspecific nail changes may be present. Other clinical variants include alopecia totalis, alopecia universalis, ophiasis, sisaipho, and Canitis subita. There are multiple treatment options for AA including conservative treatment, and topical, oral, and injectable medications. CONCLUSION AA is an autoimmune disease with a heterogenous presentation and unpredictable clinical course. Although there is no cure for AA, there are many current treatment options available to help manage this disfiguring disease.
Independent evolution of song diversity and song motor performance in canaries, goldfinches and allies indicates clade‐specific trade‐offs in birdsong

The diversity and the motor performance of birdsongs can both be sexually selected. In wood warblers, most species with high motor performance sing a greater proportion of trills, presumably to advertise performance, and thus have lower syllable diversity. We tested if this trade‐off between motor performance and syllable diversity extends to canaries, goldfinches and allies, a clade with much longer and more varied songs. We assembled a molecular phylogeny and inferred song motor performance based on the speed of frequency modulation either in trills or in within‐song intervals. The two metrics of performance were positively, but only mildly, related across species. While performance evaluated in intervals had high phylogenetic signal, performance evaluated in trills changed independently of phylogeny and was constrained by body size. Species in densely vegetated habitats sang fewer trills, but did not differ in motor performance. Contrary to wood warblers, song motor performance did not predict the proportion of trilled syllables nor within‐song syllable diversity, perhaps because large differences in the song duration of canaries, goldfinches and allies prevent trills from severely compromising syllable diversity. Opposed results in wood warblers and in these finches indicate the existence of clade‐specific trade‐offs in the evolution of birdsong.
Gene-Wise Burden of Coding Variants Correlates to Noncoding Pharmacogenetic Risk Variants

Genetic variability can modulate individual drug responses. A significant portion of pharmacogenetic variants reside in the noncoding genome yet it is unclear if the noncoding variants directly influence protein function and expression or are present on a haplotype including a functionally relevant genetic variation (synthetic association). Gene-wise variant burden (GVB) is a gene-level measure of deleteriousness, reflecting the cumulative effects of deleterious coding variants, predicted in silico. To test potential associations between noncoding and coding pharmacogenetic variants, we computed a drug-level GVB for 5099 drugs from DrugBank for 2504 genomes of the 1000 Genomes Project and evaluated the correlation between the long-known noncoding variant-drug associations in PharmGKB, with functionally relevant rare and common coding variants aggregated into GVBs. We obtained the area under the receiver operating characteristics curve (AUC) by comparing the drug-level GVB ranks against the corresponding pharmacogenetic variants-drug associations in PharmGKB. We obtained high overall AUCs (0.710 ± 0.022–0.734 ± 0.018) for six different methods (i.e., SIFT, MutationTaster, Polyphen-2 HVAR, Polyphen-2 HDIV, phyloP, and GERP++), and further improved the ethnicity-specific validations (0.759 ± 0.066–0.791 ± 0.078). These results suggest that a significant portion of the long-known noncoding variant-drug associations can be explained as synthetic associations with rare and common coding variants burden of the corresponding pharmacogenes.
Methods for the study of strictly anaerobic microorganisms

Most anaerobic extremophiles are obligate anaerobes that require strictly anoxic environment, and an extracellular milieu that is poised at a low redox potential. Despite their requirement for fastidiously anoxic conditions, these anaerobic microorganisms are ubiquitous in the environment and occur in a large range of ‘‘extreme’’ habitats that include anoxic sewage digestors, mammalian, ruminant and termite digestive tracts, polar lakes and tundra, geothermal submarine vents, calderas and hot springs, deep sea sediments, and deep subsurface rock. The combined processes of aerobic and anaerobic degradation ensures that CO2 ‘‘fixed’’ as cell carbon by photosynthetic organisms and consumed by heterotrophs, is eventually restored to the atmosphere as CO2, thus completing the global carbon cycle in even the most antianthropomorphic environments. Geological hydrogen-utilizing, CO2-reducing extremophiles such as the methanogenic Archaea can also serve as primary producers of reduced carbon compounds in the absence of photosynthesis, which has significant implications for research in astrobiology and the search for extraterrestrial life. Unlike facultative anaerobes and oxygen-tolerant anaerobes, many obligate anaerobes require stringent anaerobic conditions to maintain viability. This is achieved by using anaerobic gases to prepare anoxic medium with the addition of chemical reducing agents to achieve a low redox potential. Specialized glassware and vessels are utilized to maintain reduced anoxic conditions during growth. This chapter describes the apparatus and methodology for growth, isolation, scale-up of the most stringent anaerobes and the isolation of oxygen-labile biomolecules. Methods described herein are applicable to methanogenic Euryarchaeota, non-methanogenic hyperthermophiles within both the Euryarchaeota and Crenarchaeota, and hyperthemophilic eubacteria within the Thermotogales. These methods are also applicable to ‘‘nonextremophiles’’ such as the iron-reducing and sulfate-reducing bacteria as well as other obligate anaerobes within the eubacteria.
Multicopper Oxidases in Saccharomyces cerevisiae and Human Pathogenic Fungi

Multicopper oxidases (MCOs) are produced by microscopic and macroscopic fungal species and are involved in various physiological processes such as morphogenesis, lignin degradation, and defense mechanisms to stress inducing environmental conditions as well as fungal virulence. This review will summarize our current understanding regarding the functions of MCOs present in Saccharomyces cerevisiae and in different human fungal pathogens. Of the two main MCO groups, the first group of MCOs is involved in iron homoeostasis and the second includes laccases. This review will also discuss their role in the pathogenesis of human fungal pathogens.
The impact of post-harvest treatments of transgenic eggplant residues on soil quality and microbial diversity

A lot of literature concerning the impacts of genetically modified (GM) plants to the environment is available but actually there is the need to assess the impact of post-harvest treatments of transgenic plant residues on soil quality and microbial communities, as requested by European Directive 2001/18. In this study a multidisciplinary approach was used to assess the effects of GM eggplants on soil quality and microbial diversity after two different treatments: cutting up and extirpation. Classical biochemical, ecophysiological (BIOLOG) and molecular methods (DGGE) were used. Samplings were performed just before treatments (Tl), with plants still in the field, after 6 months (T2) and 12 months (T3). A significant difference in microbial respiration and diversity among GM plots and controls was observed in Tl but after 6 and 12 months such differences disappeared, suggesting a strong correlation between plants and microorganisms, as well as a short-term impact.
Individual participant data meta‐analysis to examine interactions between treatment effect and participant‐level covariates: Statistical recommendations for conduct and planning

Precision medicine research often searches for treatment‐covariate interactions, which refers to when a treatment effect (eg, measured as a mean difference, odds ratio, hazard ratio) changes across values of a participant‐level covariate (eg, age, gender, biomarker). Single trials do not usually have sufficient power to detect genuine treatment‐covariate interactions, which motivate the sharing of individual participant data (IPD) from multiple trials for meta‐analysis. Here, we provide statistical recommendations for conducting and planning an IPD meta‐analysis of randomized trials to examine treatment‐covariate interactions. For conduct, two‐stage and one‐stage statistical models are described, and we recommend: (i) interactions should be estimated directly, and not by calculating differences in meta‐analysis results for subgroups; (ii) interaction estimates should be based solely on within‐study information; (iii) continuous covariates and outcomes should be analyzed on their continuous scale; (iv) nonlinear relationships should be examined for continuous covariates, using a multivariate meta‐analysis of the trend (eg, using restricted cubic spline functions); and (v) translation of interactions into clinical practice is nontrivial, requiring individualized treatment effect prediction. For planning, we describe first why the decision to initiate an IPD meta‐analysis project should not be based on between‐study heterogeneity in the overall treatment effect; and second, how to calculate the power of a potential IPD meta‐analysis project in advance of IPD collection, conditional on characteristics (eg, number of participants, standard deviation of covariates) of the trials (potentially) promising their IPD. Real IPD meta‐analysis projects are used for illustration throughout.