julilili42/papers huggingface dataset:
Optimized testing strategy for the diagnosis of GAA-FGF14 ataxia/spinocerebellar ataxia 27B
2023-06-15

Abstract Dominantly inherited GAA repeat expansions in FGF14 are a common cause of spinocerebellar ataxia (GAA- FGF14 ataxia; spinocerebellar ataxia 27B). Molecular confirmation of FGF14 GAA repeat expansions has thus far mostly relied on long-read sequencing, a technology that is not yet widely available in clinical laboratories. We developed and validated a strategy to detect FGF14 GAA repeat expansions using long-range PCR, bidirectional repeat-primed PCRs, and Sanger sequencing. We compared this strategy to targeted nanopore sequencing in a cohort of 22 French Canadian patients and next validated it in a cohort of 53 French index patients with unsolved ataxia. Method comparison showed that capillary electrophoresis of long-range PCR amplification products significantly underestimated expansion sizes compared to nanopore sequencing (slope, 0.87 [95% CI, 0.81 to 0.93]; intercept, 14.58 [95% CI, − 2.48 to 31.12]) and gel electrophoresis (slope, 0.84 [95% CI, 0.78 to 0.97]; intercept, 21.34 [95% CI, − 27.66 to 40.22]). The latter techniques yielded similar size estimates. Following calibration with internal controls, expansion size estimates were similar between capillary electrophoresis and nanopore sequencing (slope: 0.98 [95% CI, 0.92 to 1.04]; intercept: 10.62 [95% CI, − 7.49 to 27.71]), and gel electrophoresis (slope: 0.94 [95% CI, 0.88 to 1.09]; intercept: 18.81 [95% CI, − 41.93 to 39.15]). Diagnosis was accurately confirmed for all 22 French Canadian patients using this strategy. We also identified 9 French patients (9/53; 17%) and 2 of their relatives who carried an FGF14 (GAA) ≥250 expansion. This novel strategy reliably detected and sized FGF14 GAA expansions, and compared favorably to long-read sequencing.
Lexical phylogenetics of the Tupí-Guaraní family: Language, archaeology, and the problem of chronology
2023-06-15

Tupí-Guaraní is one of the largest branches of the Tupían language family, but despite its relevance there is no consensus about its origins in terms of age, homeland, and expansion. Linguistic classifications vary significantly, with archaeological studies suggesting incompatible date ranges while ethnographic literature confirms the close similarities as a result of continuous inter-family contact. To investigate this issue, we use a linguistic database of cognate data, employing Bayesian phylogenetic methods to infer a dated tree and to build a phylogeographic expansion model. Results suggest that the branch originated around 2500 BP in the area of the upper course of the Tapajós-Xingu basins, with a split between Southern and Northern varieties beginning around 1750 BP. We analyse the difficulties in reconciling archaeological and linguistic data for this group, stressing the importance of developing an interdisciplinary unified model that incorporates evidence from both disciplines.
Practice walking on a treadmill-mounted balance beam modifies beam walking sacral movement and alters performance in other balance tasks
2023-06-15

The goals of this study were to determine if a single 30-minute session of practice walking on a treadmill mounted balance beam: 1) altered sacral marker movement kinematics during beam walking, and 2) affected measures of balance during treadmill walking and standing balance. Two groups of young, healthy human subjects practiced walking on a treadmill mounted balance beam for thirty minutes. One group trained with intermittent visual occlusions and the other group trained with unperturbed vision. We hypothesized that the subjects would show changes in sacrum movement kinematics after training and that there would be group differences due to larger improvements in beam walking performance by the visual occlusions group. We also investigated if there was any balance transfer from training on the beam to treadmill walking (margin of stability) and to standing static balance (center of pressure excursion). We found significant differences in sacral marker maximal velocity after training for both groups, but no significant differences between the two groups from training. There was limited evidence of balance transfer from beam-walking practice to gait margin of stability for treadmill walking and for single leg standing balance, but not for tandem stance balance. The number of step-offs while walking on a narrow beam had the largest change with training (partial η 2 = 0.7), in accord with task specificity. Other balance metrics indicative of transfer had lower effect sizes (partial η 2 &lt;0.5). Given the limited transfer across balance training tasks, future work should examine how intermittent visual occlusions during multi-task training improve real world functional outcomes.
Platelet formation and activation are influenced by neuronal guidance proteins
2023-06-15

Platelets are anucleate blood cells derived from megakaryocytes. They link the fundamental functions of hemostasis, inflammation and host defense. They undergo intracellular calcium flux, negatively charged phospholipid translocation, granule release and shape change to adhere to collagen, fibrin and each other, forming aggregates, which are key to several of their functions. In all these dynamic processes, the cytoskeleton plays a crucial role. Neuronal guidance proteins (NGPs) form attractive and repulsive signals to drive neuronal axon navigation and thus refine neuronal circuits. By binding to their target receptors, NGPs rearrange the cytoskeleton to mediate neuron motility. In recent decades, evidence has indicated that NGPs perform important immunomodulatory functions and influence platelet function. In this review, we highlight the roles of NGPs in platelet formation and activation.
Long-Term Degradation Mechanisms in Application-Implemented Radical Thin Films
2023-06-15

Blatter radical derivatives are very attractive due to their potential applications, ranging from batteries to quantum technologies. In this work, we focus on the latest insights regarding the fundamental mechanisms of radical thin film (long-term) degradation, by comparing two Blatter radical derivatives. We find that the interaction with different contaminants (such as atomic H, Ar, N, and O and molecular H<sub>2</sub>, N<sub>2</sub>, O<sub>2</sub>, H<sub>2</sub>O, and NH<sub>2</sub>) affects the chemical and magnetic properties of the thin films upon air exposure. Also, the radical-specific site, where the contaminant interaction takes place, plays a role. Atomic H and NH<sub>2</sub> are detrimental to the magnetic properties of Blatter radicals, while the presence of molecular water influences more specifically the magnetic properties of the diradical thin films, and it is believed to be the major cause of the shorter diradical thin film lifetime in air.
The Historical School and German International Legal Thought in the 19th Century
2023-06-15

Abstract This article traces the influence of the German Historical School of Law around Friedrich Carl von Savigny has had on various fundamental concepts of international law during the 19th and into the beginning of the 20th century in a detailed manner. During this time, the Historical School’s radical reformulation of the notion of law as a peoples’ spiritual essence unfolding through its habitual social action allowed 19th century scholars to redefine international law as customary law and, together with notably Hegelian teleological thought, laid conceptual groundwork for the integration of themes of European cultural superiority into the doctrines and philosophy of international law. Its conceptual legacy can further be traced in the later German positivism à la Jellinek or Oppenheim with its theories on ‘common civilised consent’ as foundation of international law.
Decoding Mental Effort in a Quasi-Realistic Scenario: A Feasibility Study on Multimodal Data Fusion and Classification
2023-06-15

Humans’ performance varies due to the mental resources that are available to successfully pursue a task. To monitor users’ current cognitive resources in naturalistic scenarios, it is essential to not only measure demands induced by the task itself but also consider situational and environmental influences. We conducted a multimodal study with 18 participants (nine female, M = 25.9 with SD = 3.8 years). In this study, we recorded, respiratory, ocular, cardiac, and brain activity using functional near-infrared spectroscopy (fNIRS) while participants performed an adapted version of the warship commander task with concurrent emotional speech distraction. We tested the feasibility of decoding the experienced mental effort with a multimodal machine learning architecture. The architecture comprised feature engineering, model optimisation, and model selection to combine multimodal measurements in a cross-subject classification. Our approach reduces possible overfitting and reliably distinguishes two different levels of mental effort. These findings contribute to the prediction of different states of mental effort and pave the way toward generalised state monitoring across individuals in realistic applications.
Oral Nano-Delivery Systems for Colon-Targeted Drug Delivery of Traditional Chinese Medicine in Ulcerative Colitis
2023-06-15

Ulcerative colitis (UC) is a type of inflammatory bowel disease with a high recurrence rate. In this regard, sulfasalazine and immunosuppressive medications are often used for an extended period in clinical practice, but their effectiveness is limited, and they are prone to side effects. Modern research has shown that herbal active ingredients of Traditional Chinese Medicine (TCM), such as polyphenols, alkaloids, quinones, and terpenes, have a promising impact on treating UC via a multi-target mechanism and with low side effects. Poor water solubility and low bioavailability of these agents in the gastrointestinal tract are the most challenging issues in delivering these agents to the target tissues. Researchers have created a variety of oral colon-targeted nano-systems of TCM active ingredients in response to the above formulation issues, which significantly improve the treatment of UC by avoiding gastrointestinal damage, prolonging intestinal retention, and achieving controlled drug release at the lesion site. In order to provide ideas for the oral-targeted treatment of UC with active ingredients from TCM, the research progress of an oral colon-targeted nano-system for the treatment of UC is reviewed in the current study, as well as the research progress of an oral colon-targeted nano-system for the treatment of UC. Keywords: Medicine, Chinese Traditional, Colitis, Ulcerative, Nanoparticle Drug Delivery System.
Spatially Tunable Spin Interactions in Neutral Atom Arrays
2023-06-16

Analog quantum simulations with Rydberg atoms in optical tweezers routinely address strongly correlated many-body problems due to the hardware-efficient implementation of the Hamiltonian. Yet, their generality is limited, and flexible Hamiltonian-design techniques are needed to widen the scope of these simulators. Here we report on the realization of spatially tunable interactions for XYZ models implemented by two-color near-resonant coupling to Rydberg pair states. Our results demonstrate the unique opportunities of Rydberg dressing for Hamiltonian design in analog quantum simulators.
Drug repurposing—a promising approach for patients with angina but non-obstructive coronary artery disease (ANOCA)
2023-06-16

In today’s era of individualized precision medicine drug repurposing represents a promising approach to offer patients fast access to novel treatments. Apart from drug repurposing in cancer treatments, cardiovascular pharmacology is another attractive field for this approach. Patients with angina pectoris without obstructive coronary artery disease (ANOCA) report refractory angina despite standard medications in up to 40% of cases. Drug repurposing also appears to be an auspicious option for this indication. From a pathophysiological point of view ANOCA patients frequently suffer from vasomotor disorders such as coronary spasm and/or impaired microvascular vasodilatation. Consequently, we carefully screened the literature and identified two potential therapeutic targets: the blockade of the endothelin-1 (ET-1) receptor and the stimulation of soluble guanylate cyclase (sGC). Genetically increased endothelin expression results in elevated levels of ET-1, justifying ET-1 receptor blockers as drug candidates to treat coronary spasm. sGC stimulators may be beneficial as they stimulate the NO-sGC-cGMP pathway leading to GMP-mediated vasodilatation.
A basidomycetous hydroxynaphthalene-prenylating enzyme exhibits promiscuity toward prenyl donors
2023-06-16

Abstract The fungal prenyltransferase ShPT from Stereum hirsutum was believed to prenylate 4-hydroxybenzyl alcohol and thereby be involved in the vibralactone biosynthesis. In this study, we demonstrate that hydroxynaphthalenes instead of benzyl alcohol or aldehyde were accepted by ShPT for regular C-prenylation in the presence of both dimethylallyl and geranyl diphosphate. Although the natural substrate of ShPT remains unknown, our results provide one additional prenyltransferase from basidiomycetes, which are less studied, in comparison to those from other sources. Furthermore, this study expands the chemical toolbox for regioselective production of prenylated naphthalene derivatives. Key points • Basidiomycetous prenyltransferase • Biochemical characterization • A DMATS prenyltransferase prenylating hydroxynaphthalene derivatives
Time Series of Electrical Conductivity Fluctuations Give Insights Into Long‐Term Solute Transport Dynamics of an Urban Stream
2023-06-16

Abstract Artificial tracers are often used for quantitative estimates of solute transport properties in rivers. However, single‐injection tracer tests give insights in transport characteristics limited to the ecohydrological conditions at the testing time. Series of time‐consuming and laborious tracer tests would be required to properly capture seasonal changes. The present study uses intrinsic diurnal fluctuations of electrical conductivity (EC) caused by discharge of treated wastewater as a tracer to evaluate solute transport processes along a 4.7‐km reach of the River Erpe, Germany. By reproducing the fluctuations recorded along the river using the solute transport model one‐dimensional transport with inflow and storage, this study investigated the long‐term dynamics in solute transport properties. Individual 48‐hr curves of EC were used in the steady state configuration of the model to gain 48‐hr‐integrated estimates of selected transport parameters. Using a sliding window approach in 1‐hr steps along the 2,270‐hr time series of EC the temporal variability of solute transport between April and June 2016 was assessed. To test the identifiability of parameters using the proposed method, sensitivity analyses and a breakthrough curve analysis of selected 48‐hr windows were implemented. With time advancing into the summer, a significant rising trend (Mann‐Kendall test p ‐value &lt; 0.05) of the cross sectional area of the channel was observed and attributed to the growth of macrophytes and a significant slightly decreasing trend for the storage rate was found. The presented method is of high value for river management, as promoting transient storage enhances biogeochemical cycling and benefits water quality.
Patients’ well-being during the transition period after psychiatric hospitalization to school: insights from an intensive longitudinal assessment of patient–parent–teacher triads
2023-06-16

Abstract Background The transition period after psychiatric hospitalization back to school is accompanied by various challenges, including a substantial risk for rehospitalization. Self-efficacy and self-control, as transdiagnostic variables and important predictors of coping with school demands, should be crucial factors for successful adaptation processes as well as an overall high well-being during school reentry. The present study therefore investigates how patients’ well-being develops during this period, and how it is related to patients’ self-control and academic self-efficacy, as well as parents’ and teachers’ self-efficacy in dealing with the patient. Methods In an intensive longitudinal design, daily ambulatory assessment measures via smartphone were collected with self-reports from the triadic perspective of 25 patients ( M age = 10.58 years), 24 parents, and 20 teachers on 50 consecutive school days, starting 2 weeks before discharge from a psychiatric day hospital (mean compliance rate: 71% for patients, 72% for parents and 43% for teachers). Patients answered daily questions between five and nine o'clock in the evening about their well-being, self-control, academic self-efficacy and about positive and negative events at school, as well as parents and teachers about their self-efficacy in dealing with the patient. Results Multilevel modeling revealed that on average, patients’ well-being and self-control decreased during the transition period, with trends over time differing significantly between patients. While patients’ academic self-efficacy did not systematically decrease over time, it did show considerable intra-individual fluctuation. Importantly, patients experienced higher well-being on days with higher self-control and academic self-efficacy as well as with higher parental self-efficacy. Daily teacher self-efficacy did not show a significant within-person relationship to daily patients’ well-being. Conclusions Well-being in the transition period is related to self-control and self-efficacy of patients and their parents. Thus, addressing patients’ self-control and academic self-efficacy, as well as parental self-efficacy, seems promising to enhance and stabilize well-being of patients during transition after psychiatric hospitalization. Trial registration Not applicable, as no health care intervention was conducted.
Non-equilibrium quantum probing through linear response
2023-06-16

The formalism of linear response theory can be extended to encompass physical situations where an open quantum system evolves towards a non-equilibrium steady-state. Here, we use the framework put forward by Konopik and Lutz [Phys. Rev. Research {\\bf 1}, 033156 (2019)] to go beyond unitary perturbations of the dynamics. Considering an open system comprised of two coupled quantum harmonic oscillators, we study the system's response to unitary perturbations, affecting the Hamiltonian dynamics, as well as non-unitary perturbations, affecting the properties of the environment, e.g., its temperature and squeezing. We show that linear response, combined with a quantum probing approach, can effectively provide valuable quantitative information about the perturbation and characteristics of the environment, even in cases of non-unitary dynamics.
Targeting SARS-CoV-2 Main Protease (MPro) with Kinase Inhibitors: A Promising Approach for Discovering Antiviral and Anti-inflammatory Molecules against SARS-CoV-2
2023-06-17

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus infected over 688 million people worldwide, causing public health concern and approximately 6.8 million deaths due to COVID-19. COVID-19, especially severe cases, is characterized by exacerbated lung inflammation with an increase of pro-inflammatory cytokines. In addition to antiviral drugs, there is a need for anti-inflammatory therapies to treat all phases of COVID-19. One of the most attractive drug targets for COVID-19 is the SARS-CoV-2 main protease (MPro), an enzyme responsible for cleaving polyproteins formed after the translation of viral RNA, which is essential for viral replication. MPro inhibitors, therefore, have the potential to stop viral replication and act as antiviral drugs. Considering that several kinase inhibitors are known for their action in inflammatory pathways, this could also be investigated toward a potential anti-inflammatory treatment for COVID-19. Therefore, the use of kinase inhibitors against SARS-CoV-2 MPro may be a promising strategy to find molecules with dual activity─antiviral and anti-inflammatory. Considering this, the potential of six kinase inhibitors against SARS-CoV-2 MPro were evaluated in silico and in vitro, including Baricitinib, Tofacitinib, Ruxolitinib, BIRB-796, Skepinone-L, and Sorafenib. To assess the inhibitory potential of the kinase inhibitors, a continuous fluorescent-based enzyme activity assay was optimized with SARS-CoV-2 MPro and MCA-AVLQSGFR-K(Dnp)-K-NH2 (substrate). BIRB-796 and Baricitinib were identified as inhibitors of SARS-CoV-2 MPro, presenting IC<sub>50</sub> values of 7.99 and 25.31 μM, respectively. As they are also known for their anti-inflammatory action, both are prototype compounds with the potential to present antiviral and anti-inflammatory activity against SARS-CoV-2 infection.
Two different isoforms of osteopontin modulate myelination and axonal integrity
2023-06-17

Abstract Abnormal myelination underlies the pathology of white matter diseases such as preterm white matter injury and multiple sclerosis. Osteopontin (OPN) has been suggested to play a role in myelination. Murine OPN mRNA is translated into a secreted isoform (sOPN) or an intracellular isoform (iOPN). Whether there is an isoform‐specific involvement of OPN in myelination is unknown. Here we generated mouse models that either lacked both OPN isoforms in all cells (OPN‐KO) or lacked sOPN systemically but expressed iOPN specifically in oligodendrocytes (OLs‐iOPN‐KI). Transcriptome analysis of isolated oligodendrocytes from the neonatal brain showed that genes and pathways related to increase of myelination and altered cell cycle control were enriched in the absence of the two OPN isoforms in OPN‐KO mice compared to control mice. Accordingly, adult OPN‐KO mice showed an increased axonal myelination, as revealed by transmission electron microscopy imaging, and increased expression of myelin‐related proteins. In contrast, neonatal oligodendrocytes from OLs‐iOPN‐KI mice compared to control mice showed differential regulation of genes and pathways related to the increase of cell adhesion, motility, and vasculature development, and the decrease of axonal/neuronal development. OLs‐iOPN‐KI mice showed abnormal myelin formation in the early phase of myelination in young mice and signs of axonal degeneration in adulthood. These results suggest an OPN isoform‐specific involvement, and a possible interplay between the isoforms, in myelination, and axonal integrity. Thus, the two isoforms of OPN need to be separately considered in therapeutic strategies targeting OPN in white matter injury and diseases.