julilili42/papers huggingface dataset:
Display Sets of Normal and Tree-Child Networks
2021-01-14

Phylogenetic networks are leaf-labelled directed acyclic graphs that are used in computational biology to analyse and represent the evolutionary relationships of a set of species or viruses. In contrast to phylogenetic trees, phylogenetic networks have vertices of in-degree at least two that represent reticulation events such as hybridisation, lateral gene transfer, or reassortment. By systematically deleting various combinations of arcs in a phylogenetic network , one derives a set of phylogenetic trees that are embedded in . We recently showed that the problem of deciding if two binary phylogenetic networks embed the same set of phylogenetic trees is computationally hard, in particular, we showed it to be -complete. In this paper, we establish a polynomial-time algorithm for this decision problem if the initial two networks consist of a normal network and a tree-child network; two well-studied topologically restricted subclasses of phylogenetic networks, with normal networks being more structurally constrained than tree-child networks. The running time of the algorithm is quadratic in the size of the leaf sets.
Posterior Uveal Effusion after Cataract Surgery
2021-01-14

We report a case of posterior uveal effusion (UE) with a long-term follow-up that has occurred following cataract surgery. A 64-year-old woman presented with diminished vision of the right eye (RE) 3 weeks after an uneventful phacoemulsification and intraocular lens implantation. Complete ophthalmic examination including fluorescein angiography (FA), indocyanine green angiography (ICGA), echography and optical coherence tomography (OCT) were performed. Best corrected visual acuity (BCVA) of the RE was 20/50. Anterior segment and intraocular pressure were unremarkable. OCT revealed prominent folds of the choroid and retina, subretinal fluid and darkening of the choroid with reduced visibility of the choroidal vessels and the scleral border. The left eye (LE) was unremarkable. BCVA of the LE was: 20/20. After topical anti-inflammatory and systemic corticosteroid therapy for 5 months, no morphological change of the macula was seen. The patient was observed without any treatment. Forty-three months after the cataract surgery and 38 months after cessation of the corticosteroid therapy, OCT revealed a normal macular morphology and the BCVA improved to 20/25. Even though rare, UE at the posterior pole may occur after modern cataract surgery. OCT examination is a reliable tool in monitoring the macular morphology. Since morphological and functional improvement can be seen in long-term, observation may be considered for some cases of posterior UE with resistance to the therapy.
PharmVar GeneFocus: CYP2B6
2021-01-15

The Pharmacogene Variation Consortium (PharmVar) catalogs star (*) allele nomenclature for the polymorphic human CYP2B6 gene. Genetic variation within the CYP2B6 gene locus impacts the metabolism or bioactivation of clinically important drugs. Of particular importance are efficacy and safety concerns regarding: efavirenz, which is used for the treatment of HIV type‐1 infection; methadone, a mainstay in the treatment of opioid use disorder and as an analgesic; ketamine, used as an antidepressant and analgesic; and bupropion, which is prescribed to treat depression and for smoking cessation. This GeneFocus provides a comprehensive overview and summary of CYP2B6 and describes how haplotype information catalogued by PharmVar is utilized by the Pharmacogenomics Knowledgebase (PharmGKB) and the Clinical Pharmacogenetics Implementation Consortium (CPIC).
Synthesis and Hydrogenation of Heavy Homologues of Rhodium Carbynes: [(Me3P)2(Ph3P)Rh≡E‐Ar*] (E=Sn, Pb)
2021-01-15

Abstract Tetrylidynes [(Me 3 P) 2 (Ph 3 P)Rh≡SnAr*] ( 10 ) and [(Me 3 P) 2 (Ph 3 P)Rh≡PbAr*] ( 11 ) are accessed for the first time via dehydrogenation of dihydrides [(Ph 3 P) 2 RhH 2 SnAr*] ( 3 ) and [(Ph 3 P) 2 RhH 2 PbAr*] ( 7 ) (Ar*=2,6‐Trip 2 C 6 H 3 , Trip=2,4,6‐triisopropylphenyl), respectively. Tin dihydride 3 was either synthesized in reaction of the dihydridostannate [Ar*SnH 2 ] − with [(Ph 3 P) 3 RhCl] or via reaction between hydrides [(Ph 3 P) 3 RhH] and [(Ar*SnH) 2 ]. Homologous lead hydride [(Ph 3 P) 2 RhH 2 PbAr*] ( 7 ) was synthesized analogously from [(Ph 3 P) 3 RhH] and [(Ar*PbH) 2 ]. Abstraction of hydrogen from 3 and 7 supported by styrene and trimethylphosphine addition yields tetrylidynes 10 and 11 . Stannylidyne 10 was also characterized by 119 Sn Mössbauer spectroscopy. Hydrogenation of the triple bonds at room temperature with excess H 2 gives the cis ‐dihydride [(Me 3 P) 2 (Ph 3 P)RhH 2 PbAr*] ( 12 ) and the tetrahydride [(Me 3 P) 2 (Ph 3 P)RhH 2 SnH 2 Ar*] ( 14 ). Complex 14 eliminates spontaneously one equivalent of hydrogen at room temperature to give the dihydride [(Me 3 P) 2 (Ph 3 P)RhH 2 SnAr*] ( 13 ). Hydrogen addition and elimination at stannylene tin between complexes 13 and 14 is a reversible reaction at room temperature.
Intensity and Dose of Neuromuscular Electrical Stimulation Influence Sensorimotor Cortical Excitability
2021-01-15

Neuromuscular electrical stimulation (NMES) of the nervous system has been extensively used in neurorehabilitation due to its capacity to engage the muscle fibers, improving muscle tone, and the neural pathways, sending afferent volleys toward the brain. Although different neuroimaging tools suggested the capability of NMES to regulate the excitability of sensorimotor cortex and corticospinal circuits, how the intensity and dose of NMES can neuromodulate the brain oscillatory activity measured with electroencephalography (EEG) is still unknown to date. We quantified the effect of NMES parameters on brain oscillatory activity of 12 healthy participants who underwent stimulation of wrist extensors during rest. Three different NMES intensities were included, two below and one above the individual motor threshold, fixing the stimulation frequency to 35 Hz and the pulse width to 300 μs. Firstly, we efficiently removed stimulation artifacts from the EEG recordings. Secondly, we analyzed the effect of amplitude and dose on the sensorimotor oscillatory activity. On the one hand, we observed a significant NMES intensity-dependent modulation of brain activity, demonstrating the direct effect of afferent receptor recruitment. On the other hand, we described a significant NMES intensity-dependent dose-effect on sensorimotor activity modulation over time, with below-motor-threshold intensities causing cortical inhibition and above-motor-threshold intensities causing cortical facilitation. Our results highlight the relevance of intensity and dose of NMES, and show that these parameters can influence the recruitment of the sensorimotor pathways from the muscle to the brain, which should be carefully considered for the design of novel neuromodulation interventions based on NMES.
Characterization of cytochrome P450 (CYP) 2D6 drugs as substrates of human organic cation transporters and multidrug and toxin extrusion proteins
2021-01-15

Background and Purpose The metabolic activity of cytochrome P450 (CYP) 2D6 is highly variable and CYP2D6 genotypes insufficiently explain the extensive and intermediate metabolic phenotypes, limiting the prediction of drug response plus adverse drug reactions. Since CYP2D6 prototypic substrates are positively charged, the aim of this study was to evaluate the organic cation transporters (OCTs) and multidrug and toxin extrusion proteins (MATEs) as potential contributors to the variability of CYP2D6 hydroxylation of debrisoquine, dextromethorphan, diphenhydramine, perhexiline and sparteine. Experimental Approach OCT1/ SLC22A1 ‐, OCT2/ SLC22A2 ‐, OCT3/ SLC22A3 ‐, MATE1/ SLC47A1 ‐, and MATE2K/ SLC47A2 ‐overexpressing cell lines were used to investigate the transport of the selected drugs. Individuals from a study cohort, well defined with respect to CYP2D6 genotype and sparteine pharmacokinetics, were genotyped for the common OCT1 variants rs12208357 (OCT1‐R61C), rs34130495 (OCT1‐G401S), rs202220802 (OCT1‐Met420del), rs34059508 (OCT1‐G465R), OCT2 variant rs316019 (OCT2‐A270S) and MATE1 variant rs2289669. Sparteine pharmacokinetics was stratified according to CYP2D6 and OCT1 , OCT2 or MATE1 genotype. Key Results OCTs and MATE1 transport sparteine and debrisoquine with high affinity in vitro, but OCT‐ and MATE1‐dependent transport of dextromethorphan, diphenhydramine and perhexiline was not detected. Sparteine and debrisoquine transport depends on OCT1 genotype; however, sparteine pharmacokinetics is independent from OCT1 genotype. Conclusions and Implications Some drugs that are substrates of CYP2D6 are also substrates of OCTs and MATE1, suggesting overlapping specificities. Variability in sparteine hydroxylation in extensive and intermediate metabolizers cannot be explained by OCT1 genetic variants indicating presence of other factors. Dose‐dependent toxicities of dextromethorphan, diphenhydramine and perhexiline appear to be independent from OCTs and MATEs.
Reversible Iodine Intercalation into Tungsten Ditelluride
2021-01-15

The new compound WTe<sub>2</sub>I was prepared by a reaction of WTe<sub>2</sub> with iodine in a fused silica ampule at temperatures between 40 and 200 °C. Iodine atoms are intercalated into the van der Waals gap between tungsten ditelluride layers. As a result, the WTe<sub>2</sub> layer separation is significantly increased. Iodine atoms form planar layers between each tungsten ditelluride layer. Due to oxidation by iodine the semimetallic nature of WTe<sub>2</sub> is changed, as shown by comparative band structure calculations for WTe<sub>2</sub> and WTe<sub>2</sub>I based on density functional theory. The calculated phonon band structure of WTe<sub>2</sub>I indicates the presence of phonon instabilities related to charge density waves, leading to an observed incommensurate modulation of the iodine position within the layers.
Emergent Goal-Anticipatory Gaze in Infants via Event-Predictive Learning and Inference
2021-01-15

From about 7 months of age onwards, infants start to reliably fixate the goal of an observed action, such as a grasp, before the action is complete. The available research has identified a variety of factors that influence such goal-anticipatory gaze shifts, including the experience with the shown action events and familiarity with the observed agents. However, the underlying cognitive processes are still heavily debated. We propose that our minds (i) tend to structure sensorimotor dynamics into probabilistic, generative event-predictive and event-boundary-predictive models, and, meanwhile, (ii) choose actions with the objective to minimize predicted uncertainty. We implement this proposition by means of event-predictive learning and active inference. The implemented learning mechanism induces an inductive, event-predictive bias, thus developing schematic encodings of experienced events and event boundaries. The implemented active inference principle chooses actions by aiming at minimizing expected future uncertainty. We train our system on multiple object-manipulation events. As a result, the generation of goal-anticipatory gaze shifts emerges while learning about object manipulations: the model starts fixating the inferred goal already at the start of an observed event after having sampled some experience with possible events and when a familiar agent (i.e., a hand) is involved. Meanwhile, the model keeps reactively tracking an unfamiliar agent (i.e, a mechanical claw) that is performing the same movement. We qualitatively compare these modeling results to behavioral data of infants and conclude that event-predictive learning combined with active inference may be critical for eliciting goal-anticipatory gaze behavior in infants.
1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans
2021-01-15

Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown.We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48 % male) derived from 15 distinct MRI scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers – the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.
Protocol for a Systematic Review of Outcomes From Microsurgical Free Tissue Transfer Performed on Short-term Surgical Missions in Low-income and Middle-income Countries
2021-01-15

<title>Abstract</title> <bold>Background: </bold>In many units around the world, microsurgical free tissue transfer represents the gold standard for reconstruction of significant soft tissue defects following cancer, trauma or infection. However, many reconstructive units in low-income and middle-income countries (LMICs) do not yet have access to the resources, infrastructure or training required to perform any microsurgical procedures. Long-term international collaborations have been formed with annual short-term reconstructive missions conducting microsurgery. In the first instance, these provide reconstructive surgery to those who need it. In the longer-term, they offer an opportunity for teaching and the development of sustainable local services.<bold>Methods:</bold> A PRISMA-compliant systematic review and meta-analysis will be performed. A comprehensive, predetermined search strategy will be applied to the MEDLINE and Embase electronic databases from inception to December 2020. All clinical studies presenting sufficient data on free tissue transfer performed on short-term surgical missions (STSMs) in LMICs will be eligible for inclusion. The primary outcomes are rate of free flap failure, rate of emergency return to theatre for free flap salvage and successful salvage rate. The secondary outcomes include postoperative complications and any functional or patient reported outcome measures. Screening of studies, data extraction and assessments of study quality and bias will be conducted by two authors. Individual study quality will be assessed according to the Oxford Evidence-based Medicine Scales of Evidence 2, and risk of bias using either the ‘Revised Cochrane risk of bias tool for randomized trials’ (Rob2), or the ‘Risk of bias in non-randomized studies of interventions’ (ROBINS-I) tools. Overall strength of evidence will be assessed according to the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach.<bold>Discussion:</bold> To-date the outcomes of microsurgical procedures performed on STSMs to LMICs are largely unknown. Improved education, funding and allocation of resources are needed to support surgeons in LMICs to perform free tissue transfer. STSMs provide a vehicle for sustainable collaboration and training. Disseminating microsurgical skills could improve the care received by patients living with reconstructive pathology in LMICs, but this is poorly established. This study sets out a robust protocol for a systematic review designed to critically analyse outcomes. <bold>Systematic review registration: </bold>Submitted to PROSPERO (15/12/20 ID: 225613)
Pulling the Brakes on Fast and Furious Multiple Drug-Resistant (MDR) Bacteria
2021-01-16

Life-threatening bacterial infections have been managed by antibiotics for years and have significantly improved the wellbeing and lifetime of humans. However, bacteria have always been one step ahead by inactivating the antimicrobial agent chemically or by producing certain enzymes. The alarming universal occurrence of multidrug-resistant (MDR) bacteria has compelled researchers to find alternative treatments for MDR infections. This is a menace where conventional chemotherapies are no longer promising, but several novel approaches could help. Our current review article discusses the novel approaches that can combat MDR bacteria: starting off with potential nanoparticles (NPs) that efficiently interact with microorganisms causing fatal changes in the morphology and structure of these cells; nanophotothermal therapy using inorganic NPs like AuNPs to destroy pathogenic bacterial cells; bacteriophage therapy against which bacteria develop less resistance; combination drugs that act on dissimilar targets in distinctive pathways; probiotics therapy by the secretion of antibacterial chemicals; blockage of quorum sensing signals stopping bacterial colonization, and vaccination against resistant bacterial strains along with virulence factors. All these techniques show us a promising future in the fight against MDR bacteria, which remains the greatest challenge in public health care.
The longevity gene Klotho and its cerebrospinal fluid protein profiles as a modifier for Parkinson´s disease
2021-01-16

Abstract Background Parkinson ́s disease (PD) has a large phenotypic variability, which may, at least partly, be genetically driven including alterations of gene products. Candidates might not only be proteins associated with disease risk but also pathways that play a role in aging. Objective To evaluate phenotype‐modifying effects of genetic variants in Klotho , a longevity gene. Methods We analyzed two longitudinal cohorts: one local cohort comprising 459 PD patients who underwent genotyping for the KL‐VS haplotype in Klotho including a subgroup of 125 PD patients and 50 healthy controls who underwent biochemical cerebrospinal fluid (CSF) analyses of Klotho and fibroblast growth factor 23 as well as vitamin D metabolites. The second cohort comprised 297 patients from the Parkinsonʼs Progression Markers Initiative (PPMI) for validation of genetic−clinical findings. Results PD patients carrying the KL‐VS haplotype demonstrated a shorter interval between PD onset and onset of cognitive impairment (both cohorts) and higher Unified Parkinson ́s Disease Rating Scale part III (UPDRS III) scores (PPMI). CSF protein levels of Klotho and fibroblast growth factor 23 were lower in PD patients irrespective of gender compared to controls. Moreover, low CSF levels of Klotho were associated with higher scores in the UPDRS III and Hoehn and Yahr Scale. Conclusions Our results indicate that genetic variants in Klotho together with its corresponding CSF protein profiles are associated with aspects of disease severity in PD. These findings suggest that pathways associated with aging might be targets for future biomarker research in PD.
Long‐term effects of pallidal and thalamic deep brain stimulation in myoclonus dystonia
2021-01-16

Abstract Objective Observational study to evaluate long‐term effects of deep brain stimulation (DBS) of the globus pallidus internus (GPi) and the ventral intermediate thalamic nucleus (VIM) on patients with medically refractory myoclonus dystonia (MD). Background More recently, pallidal as well as thalamic DBS have been applied successfully in MD but long‐term data are sparse. Methods We retrospectively analyzed a cohort of seven MD patients with either separate (n = 1, VIM) or combined GPi‐ DBS and VIM‐DBS (n = 6). Myoclonus, dystonia and disability were rated at baseline (BL), short‐term (ST‐FU) and long‐term follow‐up (LT‐FU) using the United Myoclonus Rating Scale, Burke−Fahn−Marsden Dystonia Rating Scale (BFMDRS) and Tsui rating scale, respectively. Quality of life (QoL) and mood were evaluated using the SF‐36 and Beck Depression Inventory questionnaires, respectively. Results Patients reached a significant reduction of myoclonus at ST‐FU (62% ± 7.3%; mean ± SE) and LT‐FU (68% ± 3.4%). While overall motor BFMDRS changes were not significant at LT‐FU, patients with GPi‐DBS alone responded better and predominant cervical dystonia ameliorated significantly up to 54% ± 9.7% at long‐term. Mean disability scores significantly improved by 44% ± 11.4% at ST‐FU and 58% ± 14.8% at LT‐FU. Mood and QoL remained unchanged between 5 and up to 20 years postoperatively. No serious long‐lasting stimulation‐related adverse events were observed. Conclusions We present a cohort of MD patients with very long follow‐up of pallidal and/or thalamic DBS that supports the GPi as the favourable stimulation target in MD with safe and sustaining effects on motor symptoms (myoclonus&gt;dystonia) and disability.
Polymorphism and structure formation in copper phthalocyanine thin films
2021-01-16

Many polymorphic crystal structures of copper phthalocyanine (CuPc) have been reported over the past few decades, but despite its manifold applicability, the structure of the frequently mentioned α polymorph remained unclear. The base-centered unit cell (space group C 2/ c ) suggested in 1966 was ruled out in 2003 and was replaced by a primitive triclinic unit cell (space group P 1 ). This study proves unequivocally that both α structures coexist in vacuum-deposited CuPc thin films on native silicon oxide by reciprocal space mapping using synchrotron radiation in grazing incidence. The unit-cell parameters and the space group were determined by kinematic scattering theory and provide possible molecular arrangements within the unit cell of the C 2/ c structure by excluded-volume considerations. In situ X-ray diffraction experiments and ex situ atomic force microscopy complement the experimental data further and provide insight into the formation of a smooth thin film by a temperature-driven downward diffusion of CuPc molecules during growth.
X-Linked Retinitis Pigmentosa Caused by Non-Canonical Splice Site Variants in RPGR
2021-01-16

We aimed to validate the effect of non-canonical splice site variants in the RPGR gene in five patients from four families diagnosed with retinitis pigmentosa. Four variants located in intron 2 (c.154 + 3_154 + 6del), intron 3 (c.247 + 5G&gt;A), intron 7 (c.779-5T&gt;G), and intron 13 (c.1573-12A&gt;G), respectively, were analyzed by means of in vitro splice assays. Splicing analysis revealed different aberrant splicing events, including exon skipping and intronic nucleotide addition, which are predicted to lead either to an in-frame deletion affecting relevant protein domains or to a frameshift of the open reading frame. Our data expand the landscape of pathogenic variants in RPGR, thereby increasing the genetic diagnostic rate in retinitis pigmentosa and allowing patients harboring the analyzed variants to be enrolled in clinical trials.