julilili42/papers huggingface dataset:
Spatial gene expression profile of Wnt-signaling components in the murine enteric nervous system
2024-01-18

Introduction Wnt-signaling is a key regulator of stem cell homeostasis, extensively studied in the intestinal crypt and other metazoan tissues. Yet, there is hardly any data available on the presence of Wnt-signaling components in the adult enteric nervous system (ENS) in vivo . Methods Therefore, we employed RNAscope HiPlex-assay, a novel and more sensitive in situ hybridization technology. By amplifying target specific signals, this technique enables the detection of low abundance, tightly regulated RNA content as is the case for Wnt-signaling components. Additionally, we compared our data to previously published physiological single cell RNA and RiboTag-based RNA sequencing analyses of enteric gliosis using data-mining approaches. Results Our descriptive analysis shows that several components of the multidi-mensional regulatory network of the Wnt-signaling pathway are present in the murine ENS. The transport and secretion protein for Wnt-ligands Wntless as well as canonical (Wnt3a and Wnt2b) and non-canonical Wnt-ligands (Wnt5a, Wnt7a, Wnt8b and Wnt11) are detectable within submucosal and myenteric plexus. Further, corresponding Frizzled receptors (Fzd1, Fzd3, Fzd6, and Fzd7) and regulatory signaling mediators like R-Spondin/DKK ligands are present in the ENS of the small and large intestine. Further, data mining approaches revealed, that several Wnt-related molecules are expressed by enteric glial cell clusters and are dynamically regulated during the inflammatory manifestation of enteric gliosis. Discussion Our results suggest, that canonical and non-canonical Wnt-signaling has a much broader impact on the mature ENS and its cellular homeostasis in health and inflammation, than previously anticipated.
Mini-Implant Insertion Using a Guide Manufactured with Computer-Aided Design and Computer-Aided Manufacturing in an Adolescent Patient Suffering from Tooth Eruption Disturbance
2024-01-18

Due to dental diseases, anatomical restrictions, and mixed dentition, the reduction in the number of teeth and the displacement of tooth germs pose challenges in orthodontic treatment, limiting anchorage options. The presented case demonstrates an advanced treatment solution using digital CAD/CAM-technologies and medical imaging for the creation of a mini-implant template. A 12-year-old male patient experiencing delayed tooth eruption, multiple impacted germs, and maxillary constriction underwent intraoral scanning and CBCT. Utilizing coDiagnostiXTM Version 10.2 software, the acquired data were merged to determine the mini-implant placement and to design the template. The template was then manufactured through stereolithography using surgical-guide material. Mini-implants were inserted using the produced appliance, enabling safe insertion by avoiding vital structures. Surgically exposed displaced teeth were aligned using a Hyrax screw appliance anchored on the mini-implants for rapid palatal expansion (RPE) and subsequently used as fixed orthodontics to align impacted teeth. The screw was activated daily for 10 weeks, resulting in a 7 mm posterior and 5 mm anterior maxillary transversal increase. Skeletal anchorage facilitated simultaneous RPE and tooth alignment, ensuring accuracy, patient safety, and appliance stability. The presented case shows a scenario in which computer-aided navigation for mini-implant positioning can enhance precision and versatility in challenging anatomical cases.
A pathogenic variant in RAB32 causes autosomal dominant Parkinson’s disease andactivates LRRK2 kinase
2024-01-18

Summary Background Parkinson’s disease (PD) is a progressive neurodegenerative disorder. Mendelian forms have revealed multiple genes, with a notable emphasis on membrane trafficking; RAB GTPases play an important role in PD as a subset are both regulators and substrates of LRRK2 protein kinase. To explore the role of RAB GTPases in PD, we undertook a comprehensive examination of their genetic variability in familial PD. Methods Affected probands from 130 multi-incident PD families underwent whole-exome sequencing and genotyping, Potential pathogenic variants in 61 RAB GTPases were genotyped in relatives to assess disease segregation. These variants were also genotyped in a larger case-control series, totaling 3,078 individuals (2,734 with PD). The single most significant finding was subsequently validated within genetic data (6,043 with PD). Clinical and pathologic findings were summarized for gene-identified patients, and haplotypes were constructed. In parallel, wild-type and mutant RAB GTPase structural variation, protein interactions, and resultant enzyme activities were assessed. Findings We found RAB32 c.213C&gt;G (Ser71Arg) to co-segregate with autosomal dominant parkinsonism in three multi-incident families. RAB32 Ser71Arg was also significantly associated with PD in case-control samples: genotyping and database searches identified thirteen more patients with the same variant that was absent in unaffected controls. Notably, RAB32 Ser71Arg heterozygotes share a common haplotype. At autopsy, one patient had sparse neurofibrillary tangle pathology in the midbrain and thalamus, without Lewy body pathology. In transfected cells the RAB32 Arg71 was twice as potent as Ser71 wild type to activate LRRK2 kinase. Interpretation Our study provides unequivocal evidence to implicate RAB32 Ser71Arg in PD. Functional analysis demonstrates LRRK2 kinase activation. We provide a mechanistic explanation to expand and unify the etiopathogenesis of monogenic PD. Funding National Institutes of Health, the Canada Excellence Research Chairs program, Aligning Science Across Parkinson’s, the Michael J. Fox Foundation for Parkinson’s Research, and the UK Medical Research Council.
Odor cueing of declarative memories during sleep enhances coordinated spindles and slow oscillations
2024-01-18

Long-term memories are formed by repeated reactivation of newly encoded information during sleep. This process can be enhanced by using memory-associated reminder cues like sounds and odors. While auditory cueing has been researched extensively, few electrophysiological studies have exploited the various benefits of olfactory cueing. We used high-density electroencephalography in an odor-cueing paradigm that was designed to isolate the neural responses specific to the cueing of declarative memories. We show widespread cueing-induced increases in the duration and rate of sleep spindles. Higher spindle rates were most prominent over centro-parietal areas and largely overlapping with a concurrent increase in the amplitude of slow oscillations (SOs). Interestingly, greater SO amplitudes were linked to a higher likelihood of coupling a spindle and coupled spindles expressed during cueing were more numerous in particular around SO up states. We thus identify temporally and spatially coordinated enhancements of sleep spindles and slow oscillations as a candidate mechanism behind cueing-induced memory processing. Our results further demonstrate the feasibility of studying neural activity patterns linked to such processing using olfactory cueing during sleep.
Continuous Newton-like Methods Featuring Inertia and Variable Mass
2024-01-18

We introduce a new dynamical system, at the interface between second-order\\ndynamics with inertia and Newton's method. This system extends the class of\\ninertial Newton-like dynamics by featuring a time-dependent parameter in front\\nof the acceleration, called variable mass. For strongly convex optimization, we\\nprovide guarantees on how the Newtonian and inertial behaviors of the system\\ncan be non-asymptotically controlled by means of this variable mass. A\\nconnection with the Levenberg--Marquardt (or regularized Newton's) method is\\nalso made. We then show the effect of the variable mass on the asymptotic rate\\nof convergence of the dynamics, and in particular, how it can turn the latter\\ninto an accelerated Newton method. We provide numerical experiments supporting\\nour findings. This work represents a significant step towards designing new\\nalgorithms that benefit from the best of both first- and second-order\\noptimization methods.\\n
West African Monsoon dynamics and its control on stable oxygen isotopic composition of precipitation in the Late Cenozoic
2024-01-18

This study presents an overview of the Late Cenozoic evolution of the West African Monsoon (WAM), and the associated changes in atmospheric dynamics and oxygen isotopic composition of precipitation (δ18Op). This evolution is established by using the high-resolution isotope-enabled GCM ECHAM5-wiso to simulate the climatic responses to paleoenvironmental changes during the Mid-Holocene (MH), Last Glacial Maximum (LGM), and Mid-Pliocene (MP). The simulated responses are compared to a set of GCM outputs from Paleoclimate Model Intercomparison Project phase 4 (PMIP4) to assess the added value of a high resolution and model consistency across different time periods. Results show WAM magnitudes and pattern changes that are consistent with PMIP4 models and proxy reconstructions. ECHAM5-wiso estimates the highest WAM intensification in the MH, with a precipitation increase of up to 150 mm/month reaching 25°N during the monsoon season. The WAM intensification in the MP estimated by ECHAM5-wiso (up to 80 mm/month) aligns with the mid-range of the PMIP4 estimates, while the LGM dryness magnitude matches most of the models. Despite an enhanced hydrological cycle in MP, MH simulations indicate a ~50% precipitation increase and a greater northward extent of WAM than the MP simulations. Strengthened conditions of the WAM in the MH and MP result from a pronounced meridional temperature gradient driving low-level westerly, Sahel-Sahara vegetation expansion, and a northward shift of the Africa Easterly Jet. The simulated δ18Op values patterns and their relationship with temperature and precipitation are non-stationarity over time, emphasising the implications of assuming stationarity in proxy reconstruction transfer functions.
The Anti-Pornography Act and gender relations in Uganda: an analysis of how patriarchy and legislation interact
2024-01-18

This article analyses how the Ugandan Anti-Pornography Act interacted with gender relations in Uganda from a critical-feminist point of view. Relying on interview data, media reports, and secondary sources and using a practice-theoretic approach to gender relations and changes therein, the article traces how the APA legitimised, encouraged, and enabled violent and misogynist practices. Yet, it also informed feminist and radical practices pushing for bodily self-determination. Thus, the Anti-Pornography Act reinforced patriarchal gender relations and, simultaneously, contributed to the re-politicisation of the feminist movement in Uganda. In a time of global backlashes against feminism and equality, this article details the far-reaching retrogressive and progressive ramifications anti-feminist legislation can have and thus contributes to current and necessary debates.
Volatile Organic Compound Sensing with WO3-Based Gas Sensors: Surface Chemistry Basics
2024-01-19

The sensing properties of WO3-based gas sensors were evaluated at an operating temperature of 150 °C in the presence of different volatile organic compounds (VOCs). Simultaneously to the sensing tests, operando diffuse-reflectance infrared Fourier transform spectra were acquired. Remarkably, no CO2 generation was observed under gas exposure for any of the target VOCs. Catalytic combustion properties of the WO3 toward acetone and ethanol at temperatures from 150 to 400 °C, both in dry and humid atmospheres, were additionally performed. Such measurements confirmed that no combustion occurred for ethanol (up to at least 300 °C) while it became detectable for acetone only starting from 250 °C. The reaction products are acetaldehyde and acetate in the case of ethanol exposure and acetate and formate in the case of acetone exposure. The oxidation catalytic effect of WO3 was confirmed for both toluene, where benzaldehyde and benzoate modes were observed, and acetylene (where acetaldehyde and ethenol were detected). The systematic absence of CO2 as a product and the identification of oxidized species are the basis of the proposed reaction mechanisms.
Cathepsin-Targeting SARS-CoV-2 Inhibitors: Design, Synthesis, and Biological Activity
2024-01-19

Cathepsins (Cats) are proteases that mediate the successful entry of SARS-CoV-2 into host cells. We designed and synthesized a tailored series of 21 peptidomimetics and evaluated their inhibitory activity against human cathepsins L, B, and S. Structural diversity was realized by combinations of different C-terminal warhead functions and N-terminal capping groups, while a central Leu-Phe fragment was maintained. Several compounds were identified as promising cathepsin L and S inhibitors with <i>K</i><sub>i</sub> values in the low nanomolar to subnanomolar range, for example, the peptide aldehydes <b>9a</b> and <b>9b</b> (<b>9a</b>, 2.67 nM, CatL; 0.455 nM, CatS; <b>9b</b>, 1.76 nM, CatL; 0.512 nM, CatS). The compounds' inhibitory activity against the main protease of SARS-CoV-2 (M<sup>pro</sup>) was additionally investigated. Based on the results at CatL, CatS, and M<sup>pro</sup>, selected inhibitors were subjected to investigations of their antiviral activity in cell-based assays. In particular, the peptide nitrile <b>11e</b> exhibited promising antiviral activity with an EC<sub>50</sub> value of 38.4 nM in Calu-3 cells without showing cytotoxicity. High metabolic stability and favorable pharmacokinetic properties make <b>11e</b> suitable for further preclinical development.
NfL reliability across laboratories, stage-dependent diagnostic performance and matrix comparability in genetic FTD: a large GENFI study
2024-01-19

Background Blood neurofilament light chain (NfL) is increasingly considered as a key trial biomarker in genetic frontotemporal dementia (gFTD). We aimed to facilitate the use of NfL in gFTD multicentre trials by testing its (1) reliability across labs; (2) reliability to stratify gFTD disease stages; (3) comparability between blood matrices and (4) stability across recruiting sites. Methods Comparative analysis of blood NfL levels in a large gFTD cohort (GENFI) for (1)–(4), with n=344 samples (n=148 presymptomatic, n=11 converter, n=46 symptomatic subjects, with mutations in C9orf72 , GRN or MAPT ; and n=139 within-family controls), each measured in three different international labs by Simoa HD-1 analyzer. Results NfL revealed an excellent consistency (intraclass correlation coefficient (ICC) 0.964) and high reliability across the three labs (maximal bias (pg/mL) in Bland-Altman analysis: 1.12±1.20). High concordance of NfL across laboratories was moreover reflected by high areas under the curve for discriminating conversion stage against the (non-converting) presymptomatic stage across all three labs. Serum and plasma NfL were largely comparable (ICC 0.967). The robustness of NfL across 13 recruiting sites was demonstrated by a linear mixed effect model. Conclusions Our results underline the suitability of blood NfL in gFTD multicentre trials, including cross-lab reliable stratification of the highly trial-relevant conversion stage, matrix comparability and cross-site robustness.
Focal Pulsed Field Ablation for Atrial Arrhythmias: Efficacy and Safety under Deep Sedation
2024-01-19

Focal pulsed field ablation (PFA) is a novel technique for treating cardiac arrhythmias. It has demonstrated positive results in initial studies and has a good safety profile. In recent studies, PFA was often utilized for first-time pulmonary vein isolation (PVI) and was performed under general anesthesia. In our study, we assessed the feasibility, safety, acute procedural efficacy, and efficiency of focal PFA under deep sedation in patients, 80% of whom had undergone at least one left atrial ablation previously. We treated 30 patients (71 ± 7, 46% male) using the CENTAURI system for various atrial arrhythmias, including atrial fibrillation, typical and atypical atrial flutter, and focal atrial tachycardia. The average procedure and fluoroscopy times were 122 ± 43 min and 9 ± 7 min, respectively. A total of 83.33% of patients received additional line ablations beyond PVI, specifically targeting the posterior box and anterior mitral line. All ablations were successfully performed in deep sedation with only one major and one minor complication observed. The major complication was a vasospasm of the right coronary artery during ablation of the cavotricuspid isthmus, which was treated successfully with intracoronary nitroglycerin. All patients could be discharged in sinus rhythm. Moreover, adenosine appears effective in identifying dormant conduction in some patients after focal PFA. In conclusion, focal PFA is an effective approach for complex left atrial ablations under deep sedation, offering both high efficacy and efficiency with a reliable safety profile. Studies on long-term outcomes are needed.
Predictive value of facial motor–evoked potential and electromyography for facial motor function in vestibular schwannoma surgery
2024-01-19

Abstract Purpose Intraoperative neuromonitoring (IONM) aims to preserve facial nerve (FN) function during vestibular schwannoma (VS) surgery. However, current techniques such as facial nerve motor evoked potentials (FNMEP) or electromyography (fEMG) alone are limited in predicting postoperative facial palsy (FP). The objective of this study was to analyze a compound fEMG/FNMEP approach. Methods Intraoperative FNMEP amplitude and the occurrence of fEMG-based A-trains were prospectively determined for the orbicularis oris (ORI) and oculi (OCU) muscle in 322 VS patients. Sensitivity and specificity of techniques to predict postoperative FN function were calculated. Confounding factors as tumor size, volume of intracranial air, or IONM duration were analyzed. Results A relevant immediate postoperative FP was captured in 105/322 patients with a significant higher risk in large VS. While fEMG demonstrated a high sensitivity (77% and 86% immediately and 15 month postoperative, respectively) for identifying relevant FP, specificity was low. In contrast, FNMEP have a significantly higher specificity of 80.8% for predicting postoperative FP, whereas the sensitivity is low. A retrospective combination of techniques demonstrated still an incorrect prediction of FP in ~ 1/3 of patients. Conclusions FNMEP and fEMG differ in sensitivity and specificity to predict postoperative FP. Although a combination of IONM techniques during VS surgery may improve prediction of FN function, current techniques are still inaccurate. Further development is necessary to improve IONM approaches for FP prediction.
Now they accept it, now they don’t : Acceptability judgements of nontypical multiword units in Russian as a native and a heritage language
2024-01-19

Aims/objectives/research questions: Heritage speakers have been shown to use multiword units, which merge structural elements of both their languages, which do not conform to the combinability patterns of the monolingual variety. However, it is not clear to what extent heritage speakers actually have the knowledge of the corresponding monolingual sequences. The present study on Russian heritage speakers in Germany addresses the question of whether heritage speakers have receptive knowledge of monolingual multiword units that they do not command in production. Design/methodology/approach: The study followes a mixed methods design by combining corpus and experimental methodology. Data/analyses: First, language production data of heritage speakers from two corpora were analysed for nontypical multiword units with prepositional phrases. In the second step, these nontypical multiword units as well as their typical monolingual equivalents served as test items in an acceptability judgement task performed by 53 Russian-German heritage speakers and 56 Russian native speakers. Findings/conclusions: The results show that heritage and native speakers rate nontypical multiword units as less acceptable than their monolingual equivalents. However, the acceptability of typical and the unacceptability of nontypical expressions were more salient for native speakers, whereas heritage speakers in many cases tended to equally accept typical and nontypical items. Acceptability ratings varied according to test items in both groups, but there was no overlap between nontypical multiword units most acceptable to monolinguals and those most acceptable to heritage speakers. Originality: Our paper applies an innovative mixed method approach in investigating the receptive knowledge of monoloigual multiword units in heritage speakers. Additionally, it is one of the first studies looking at the reactions of native spekaers to novel multiword units produced by heritage speakers. Implications: The findings support the idea of a unified multilingual construction, suggesting that heritage speakers do have some receptive knowledge of monolingual multiword units but this knowledge differs from that of monolingual speakers.
#picturesofchange: Physical self-representations in social media as a sign of change in sports- and movement culture
2024-01-19

The mediatization of communicative action is a process that centrally moderates social change. Changes in communication (e.g., through new kinds of media) thus have momentous consequences for social forms and processes. As essential cultural signs, social bodies, their medial representation, and areas of society in which bodies play a role are interrelated with changes in communication. Currently, physical self-representations in digital media play a key role and hold strong possibilities of influence on the culture of sports and movement. The aim of this study was to identify the effects of visual self-representations in social media on this culture. Following an integrative review methodology, we systematically organised the current state of empirical evidence and identified the implications that digital self-representations in social media (esp., Instagram, Facebook) have on sports and movement culture and therefore possibly on physical education (PE). Six electronic databases, reference lists, and citations of full-text articles were searched for English and German language peer-reviewed articles. The search string combined different terms relating to social media and sports culture. Two independent reviewers screened all identified studies for eligibility and assessed the methodological quality of the included studies. The results point to direct changes in some sports and movement cultures such as the prosumtion (consumption and production) of videos in skateboarding or the perpetuation of body ideals in the fitness culture. Other sports and movement cultures are changed indirectly via different new use cases for the athletes, as they can use social media to either build communities or gain visibility. As the practice of prosuming bodily self-representations is a growing part of the lifeworld of adolescents, such practices could become content within PE. Therewith, students could acquire competencies that allow them to intellectually relate to these practices, which could help them in understanding, changing or transcending their existing realities.