julilili42/papers huggingface dataset:
Unusual plesiosaur vertebrae from the Lower Jurassic Posidonia Shale of Germany
2023-08-17

ABSTRACTThe Toarcian (upper Lower Jurassic) strata of the world-renowned Posidonia Shale of Central Europe have yielded diverse assemblages of marine vertebrates. Some of them, such as those of the Holzmaden area in southwestern Germany, are among the best-preserved specimens of Lower Jurassic vertebrate taxa. Here, we provide a reassessment of ‘Plesiosaurus’ bavaricus, a long-overlooked plesiosaur taxon from the Posidonia Shale of northern Bavaria (southern Germany), established based upon two isolated cervical centra and a caudal vertebra. The cervical material exhibits an intriguing character combination, providing evidence for the presence of a distinct plesiosaur taxon in the upper Lower Jurassic of the Posidonia Shale of Germany. Additionally, we report another isolated cervical vertebra, likewise from the Posidonia Shale of Bavaria, that shows striking similarities to the type cervicals of ‘P’. bavaricus. Following our study of the Bavarian specimens, we hypothesise that, despite their substantial incompleteness, it seems likely that the material belonged to the same taxon, either species or a group of species, distinct from other plesiosaurs known from the Posidonia Shale.KEYWORDS: PlesiosauriaPosidonia shaleToarcianJurassicGermany AcknowledgmentsWe would like to express our gratitude to Thomas Voigt (IGJ) for access to specimens under his care and to Stefan Eggmaier (Urwelt-Museum Oberfranken, Bayreuth, Germany) for information about the historical fossil locality Creez. Oliver Rauhut (BSPHG) is thanked for providing details on the lost syntype specimens of ‘Plesiosaurus’ bavaricus and Glenn Storrs (Cincinnati Museum Center, Cincinnati, Ohio, USA) kindly provided a copy of Zarnik's (1925) rare publication. We also thank Cristian David Benavides-Cabra and an anonymous reviewer for their helpful comments.Disclosure statementNo potential conflict of interest was reported by the author(s).
Development of an optimized, non-stem cell line for intranasal delivery of therapeutic cargo to the central nervous system
2023-08-17

Abstract Neural stem cells (NSC) are considered to be valuable candidates for delivering a variety of anti-cancer agents to brain tumors, including oncolytic viruses. However, owing to the previously reported tumorigenic potential of NSC cell line after intranasal administration (INA), here we identified the human hepatic stellate cell line (LX-2) as a cell type capable of longer resistance to replication of oncolytic adenoviruses (OAV) as therapeutic cargo, and being non-tumorigenic after INA. Our data show that LX-2 cells can longer withstand the OAV XVir-N-31 replication and oncolysis than NSCs. By selecting the highly migratory cell population out of LX-2, an offspring cell line with a higher and more stable capability to migrate was generated. Additionally, as a safety backup, we applied genomic HSV-TK integration into LX-2 leading to the high vulnerability to Ganciclovir. Histopathological analyses confirmed the absence of neoplasia in the respiratory tracts and brains of immuno-compromised mice 3 months after INA of LX-2 cells. Our data suggest that LX-2 is a novel robust and safe cell line for delivering anti-cancer and other therapeutic agents to the brain.
Fall-related ocular trauma in patients over 90 years in tertiary ophthalmic center in Germany: 90-TOSG Report 1
2023-08-17

Abstract Purpose To investigate the clinical characteristics of fall-related ocular trauma in patients over 90 years of age. Methods Retrospective, medical record reviews. Patients over the age of 90 years treated in a tertiary center with fall-related ocular trauma were included in the study. Results Fifty consecutive patients (fifty eyes) were analyzed. The mean age was 93.6 ± 1.8 years and 41 patients (82%) were female. The most common site of the injuries was orbital fracture (18 patients, 36%), accompanied with open globe rupture (OGR) in three patients, and globe contusion in two patients. Seventeen patients (34%) presented with OGR. Ocular trauma score in those patients was category 1 in 10 patients (58.8%) and category 2 in the others. Conjunctival hemorrhage and/or periocular contusion was seen in 14 patients (28%) and globe contusion in six patients (12%). At the presentation, the mean best corrected visual acuity (BCVA) was 2.82 ± 0.24 logMAR in patients with OGR and 1.98 ± 0.81 logMAR in six patients with globe contusion. Three of the patients with OGR had a final vision of 20/200 or better whereas the remaining patients had hand movements or less. The most common risk factors were female gender (82%) and use of antihypertensive drugs (46%). Conclusion Patients with OGR had a poor visual outcome despite the early treatment. It is important to raise public awareness about of the poor prognosis of ocular injuries due to falls in the elderly population in order to establish preventive measures.
Predicting the three-dimensional age-depth field of an ice rise
2023-08-17

Ice rises situated around the perimeter of Antarctica buttress ice flow and contain information about the past climate and changes in flow regime. Moreover, ice rises contain convergent and divergent flow regimes, and both floating and grounded ice over comparatively small spatial scales, meaning they are ideal locations to study ice-flow dynamics. Here, we introduce a new modelling framework that permits the comparison between modelled and observed stratigraphy. A thermo-mechanically coupled, isotropic, full Stokes ice flow model with a dynamic grounding line is used (Elmer/Ice). The result is the simulated age-depth field of a three-dimensional, steady-state ice rise which is dynamically coupled to the surrounding ice shelf. Applying the model to Derwael Ice Rise, results show a good match between observed and modelled stratigraphy over most of the ice rise and predict approximately year old ice at a depth of \\%. Differences in the prediction of age between simulations using Glen’s flow law exponents of and are generally small ( \\% over most areas). In the ice rise shear zones, large differences in shear strain rates in the velocity direction are found between the and the simulations. Our simulations indicate that a Glen’s flow law exponent of may be better suited when modelling ice rises due to a steady-state geometry which is closer to the observed geometry. Our three-dimensional modelling framework can easily be transferred to other ice rises and has relevance for researchers interested in ice core dating and understanding ice-flow re-organisation.
Family and literature analysis demonstrates phenotypic effect of two variants in the calpain-3 gene
2023-08-17

Abstract Both, recessive (LGMD R1) and dominant (LGMD D4) inheritance occur in calpain 3-related muscular dystrophy. We report a family with calpain-related muscular dystrophy caused by two known variants in the calpain 3 gene ( CAPN3 , NM_000070.3; (I) c.700G&gt;A, p.Gly234Arg and (II) c.1746-20C&gt;G, p.?). Three family members are compound heterozygous and exhibit a relatively homogeneous phenotype characterized by progressive proximal weakness starting in the third to fourth decade of life in the shoulder girdle and spreading to the legs. Two family members affected only by the p.Gly234Arg heterozygous missense variants show a different phenotype characterized by severe exertional myalgia without overt pareses. We conclude that in our family, the missense variant causes a severe myalgic phenotype without pareses that is aggravated by the second intronic variant and put these findings in the context of previous studies of the same variants.
Dental eruption and adult dentition of the enigmatic ptolemaiid Qarunavus meyeri from the Oligocene of the Fayum Depression (Egypt) revealed by micro-computed tomography clarifies its phylogenetic position
2023-08-17

Abstract The Palaeogene is a very important time period for mammalian evolution because it documents the first occurrence of many groups. One such group is the enigmatic Ptolemaiida, best known from the Early Oligocene of the Fayum Depression in Egypt, where it is represented by three genera, Ptolemaia, Qarunavus, and Cleopatrodon, including five species. Among these, Qarunavus meyeri is especially rare, as it is only known from two partial juvenile mandibles. Herein, the affinities of this taxon are re-investigated by applying micro-computed tomography (μCT), thus enabling the study and comparison of its unerupted permanent dentition with that of other ptolemaiidans. The μCT analysis confirms that Q. meyeri is a valid species, distinct from all other ptolemaiidans. Both the comparison and a phylogenetic analysis suggest a closer relationship of Qarunavus to the genus Cleopatrodon than to Ptolemaia; thereby, placing Qarunavus in the family Ptolemaiidae. Furthermore, the μCT analysis enabled the assessment of the dental morphology of Q. meyeri revealing an unusual combination of traits, such as a very small single incisor next to a large canine. The eruption sequence of the permanent dentition in Q. meyeri implies a late dental eruption for the species, which would support the hypothesis of Ptolemaiida belonging to Afrotheria.
Exploring the Binding Affinity of the ARR2 GARP DNA Binding Domain via Comparative Methods
2023-08-17

Plants have evolved signaling mechanisms such as the multi-step phosphorelay (MSP) to respond to different internal and external stimuli. MSP responses often result in gene transcription regulation that is modulated through transcription factors such as B-type Arabidopsis response regulator (ARR) proteins. Among these proteins, ARR2 is a key component that is expressed ubiquitously and is involved in many aspects of plant development. Although it has been noted that B-type ARRs bind to their cognate genes through a DNA-binding domain termed the GARP domain, little is known about the structure and function of this type of DNA-binding domain; thus, how ARRs bind to DNA at a structural level is still poorly understood. In order to understand how the MSP functions in planta, it is crucial to unravel both the kinetics as well as the structural identity of the components involved in such interactions. For this reason, this work focusses on resolving how the GARP domain of ARR2 (GARP2) binds to the promoter region of ARR5, one of its native target genes in cytokinin signaling. We have established that GARP2 specifically binds to the ARR5 promoter with three different bi-molecular interaction systems—qDPI-ELISA, FCS, and MST—and we also determined the KD of this interaction. In addition, structural modeling of the GARP2 domain confirms that GARP2 entails a HTH motif, and that protein–DNA interaction most likely occurs via the α3-helix and the N-terminal arm of this domain since mutations in this region hinder ARR2’s ability to activate transcription.
Interaction Styles in Context: Comparing Drag-and-Drop, Point-and-Touch, and Touch in a Mobile Spelling Game
2023-08-17

The choice of appropriate interaction style for children's application has been a divisive subject of debate. For example, drag-and-drop is often said to perform worse than point-and-click in educational applications -- and vice versa. In this paper, we argue for the need to choose the interaction style in context, considering a range of factors. We compare drag-and-drop, point-and-touch, and simple touch for selecting letters to form words in a spelling line as part of an educational spelling game. We evaluate the perceived workload, user experience, preference, and writing times of twenty-five children (8-11 years), eight of whom were dyslexic. We found that touch received better ratings and was ranked highest most often on all subscales compared to drag-and-drop and point-and-touch. Children needed less time using touch and 68% chose it as their favorite interaction style. We also found small advantages for drag-and-drop over point-and-touch, which runs counter to some recent recommendations. This becomes particularly clear when using ranking responses, which support a particularly fine-grained picture.
Viral Genome Sequencing to Decipher In-Hospital SARS-CoV-2 Transmission Events
2023-08-17

Abstract Background: The SARS-CoV-2 pandemic has highlighted the need to better define in-hospital transmissions, a need that extends to all other common infectious diseases encountered in clinical settings. Objectives: To evaluate how whole viral genome sequencing can contribute to deciphering nosocomial SARS-CoV-2 transmission Methods: 926 SARS-CoV-2 viral genomes from 622 staff members and patients were collected between February 2020 and January 2021 at a university hospital in Munich, Germany, and analysed along with the place of work, duration of hospital stay and ward transfers. Bioinformatically defined transmission clusters inferred from viral genome sequencing were compared to those inferred from interview-based contact tracing. An additional dataset collected at the same time at another university hospital in the same city was used to account for multiple independent introductions. Results: Clustering analysis of 619 viral genomes generated 18 clusters ranging from 3 to 29 individuals. Sequencing-based transmission clusters showed little overlap to those based on contact tracing data. The viral genomes were significantly more closely related to each other than comparable genomes collected simultaneously at other hospitals in the same city (n=681), suggesting nosocomial transmission. Longitudinal sampling from individual patients suggested possible cross-infection events during the hospital stay in 19.2% of individuals (14 of 73 individuals). Conclusion: Clustering analysis of SARS-CoV-2 whole genome sequences can reveal cryptic transmission events missed by classical, interview-based contact tracing, helping to decipher in-hospital transmissions. These results, in line with other studies across the world, advocate for viral genome sequencing as pathogen transmission surveillance tools in hospitals.
Phase I/II trial of a peptide-based COVID-19 T-cell activator in patients with B-cell deficiency
2023-08-18

Abstract T-cell immunity is central for control of COVID-19, particularly in patients incapable of mounting antibody responses. CoVac-1 is a peptide-based T-cell activator composed of SARS-CoV-2 epitopes with documented favorable safety profile and efficacy in terms of SARS-CoV-2-specific T-cell response. We here report a Phase I/II open-label trial (NCT04954469) in 54 patients with congenital or acquired B-cell deficiency receiving one subcutaneous CoVac-1 dose. Immunogenicity in terms of CoVac-1-induced T-cell responses and safety are the primary and secondary endpoints, respectively. No serious or grade 4 CoVac-1-related adverse events have been observed. Expected local granuloma formation has been observed in 94% of study subjects, whereas systemic reactogenicity has been mild or absent. SARS-CoV-2-specific T-cell responses have been induced in 86% of patients and are directed to multiple CoVac-1 peptides, not affected by any current Omicron variants and mediated by multifunctional T-helper 1 CD4 + T cells. CoVac-1-induced T-cell responses have exceeded those directed to the spike protein after mRNA-based vaccination of B-cell deficient patients and immunocompetent COVID-19 convalescents with and without seroconversion. Overall, our data show that CoVac-1 induces broad and potent T-cell responses in patients with B-cell/antibody deficiency with a favorable safety profile, which warrants advancement to pivotal Phase III safety and efficacy evaluation. ClinicalTrials.gov identifier NCT04954469.
Breast cancer patient-derived microtumors resemble tumor heterogeneity and enable protein-based stratification and functional validation of individualized drug treatment
2023-08-18

Abstract Despite tremendous progress in deciphering breast cancer at the genomic level, the pronounced intra- and intertumoral heterogeneity remains a major obstacle to the advancement of novel and more effective treatment approaches. Frequent treatment failure and the development of treatment resistance highlight the need for patient-derived tumor models that reflect the individual tumors of breast cancer patients and allow a comprehensive analyses and parallel functional validation of individualized and therapeutically targetable vulnerabilities in protein signal transduction pathways. Here, we introduce the generation and application of breast cancer patient-derived 3D microtumors (BC-PDMs). Residual fresh tumor tissue specimens were collected from n = 102 patients diagnosed with breast cancer and subjected to BC-PDM isolation. BC-PDMs retained histopathological characteristics, and extracellular matrix (ECM) components together with key protein signaling pathway signatures of the corresponding primary tumor tissue. Accordingly, BC-PDMs reflect the inter- and intratumoral heterogeneity of breast cancer and its key signal transduction properties. DigiWest®-based protein expression profiling of identified treatment responder and non-responder BC-PDMs enabled the identification of potential resistance and sensitivity markers of individual drug treatments, including markers previously associated with treatment response and yet undescribed proteins. The combination of individualized drug testing with comprehensive protein profiling analyses of BC-PDMs may provide a valuable complement for personalized treatment stratification and response prediction for breast cancer.
Increased Levels of BAMBI Inhibit Canonical TGF-β Signaling in Chronic Wound Tissues
2023-08-18

Chronic wounds affect more than 2% of the population worldwide, with a significant burden on affected individuals, healthcare systems, and societies. A key regulator of the entire wound healing cascade is transforming growth factor beta (TGF-β), which regulates not only inflammation and extracellular matrix formation but also revascularization. This present work aimed at characterizing wound tissues obtained from acute and chronic wounds regarding angiogenesis, inflammation, as well as ECM formation and degradation, to identify common disturbances in the healing process. Serum and wound tissues from 38 patients (N = 20 acute and N = 18 chronic wounds) were analyzed. The patients’ sera suggested a shift from VEGF/VEGFR to ANGPT/TIE2 signaling in the chronic wounds. However, this shift was not confirmed in the wound tissues. Instead, the chronic wound tissues showed increased levels of MMP9, a known activator of TGF-β. However, regulation of TGF-β target genes, such as CTGF, COL1A1, or IL-6, was absent in the chronic wounds. In wound tissues, all three TGF-β isoforms were expressed with increased levels of TGF-β1 and TGF-β3 and a reporter assay confirmed that the expressed TGF-β was activated. However, Western blots and immunostaining showed decreased canonical TGF-β signaling in the respective chronic wound tissues, suggesting the presence of a TGF-β inhibitor. As a potential regulatory mechanism, the TGF-β proteome profiler array suggested elevated levels of the TGF-β pseudo-receptor BAMBI. Also, tissue expression of BAMBI was significantly increased not only in chronic wounds (10.6-fold) but also in acute wounds that had become chronic (9.5-fold). In summary, our data indicate a possible regulatory role of BAMBI in the development of chronic wounds. The available few in vivo studies support our findings by postulating a therapeutic potential of BAMBI for controlling scar formation.
More than annealing: RNAi is not alone in the fight against plant viruses
2023-08-18

Cellular organisms have evolved different strategies to defend themselves against the invasion by viruses. In plants, RNA interference (RNAi) or RNA silencing, which is triggered by virus‐derived double‐stranded (ds)RNA, is considered the main antiviral defence mechanism. Martínez‐Pérez et al have now uncovered an additional plant antiviral pathway, termed by the authors “m 6 A‐YTHDF axis,” which relies on the modification and subsequent recognition of the viral RNA.
Modelling the expected very high energy γ-ray emission from accreting neutron stars in X-ray binaries
2023-08-18

ABSTRACT The detection of γ-ray emission from accreting pulsars in X-ray binaries (XRBs) has long been sought after. For some high-mass X-ray binaries (HMXBs), marginal detections have recently been reported. Regardless of whether these will be confirmed or not, future telescopes operating in the γ-ray band could offer the sensitivity needed to achieve solid detections and possibly spectra. In view of future observational advances, we explored the expected emission above 10 GeV from XRBs, based on the Cheng &amp; Ruderman model, where γ-ray photons are produced by the decay of π0 originated by protons accelerated in the magnetosphere of an accreting pulsar fed by an accretion disc. We improved this model by considering, through Monte Carlo simulations, the development of cascades inside of and outside the accretion disc, taking into account pair and photon production processes that involve interaction with nuclei, X-ray photons from the accretion disc, and the magnetic field. We produced grids of solutions for different input parameter values of the X-ray luminosity (Lx), magnetic field strength (B), and for different properties of the region where acceleration occurs. We found that the γ-ray luminosity spans more than five orders of magnitude, with a maximum of ∼1035 erg s−1. The γ-ray spectra show a large variety of shapes: some have most of the emission below ∼100 GeV, others are harder (emission up to 10–100 TeV). We compared our results with Fermi/LAT and VERITAS detections and upper limits of two HMXBs: A0535+26 and GRO J1008−57. More consequential comparisons will be possible when more sensitive instruments will be operational in the coming years.
Intrapartum time intervals and transfer of nulliparae from community births to maternity care units in Germany
2023-08-18

Abstract Background Over one‐third of nulliparae planning births either at home or in freestanding midwife‐led birthing centers (community births) in high‐income countries are transferred during labor. Perinatal data are reported each year in Germany for women planning community birth. So far, data sets have not been linked to describe time‐related factors associated with nulliparous transfer to hospital. Objectives To describe the prevalence of referral for nulliparae and assess maternal and labor characteristics associated with intrapartum transfer. Methods Perinatal data from 2010 to 2015 were linked ( n = 26,115). Women were reviewed with respect to international eligibility criteria for community birth; 1997 women were excluded (7.6%). Descriptive statistics were reported; unadjusted and adjusted odds ratios with 95% confidence intervals (CI) tested the predictive effect of demographic and labor factors on rates of intrapartum transfer. Results One in three nulliparous women (30.6%) were transferred to hospital. Compared with community births, transferred women were significantly more likely to experience longer time intervals during labor: from rupture of membranes (ROM) until birth lasting 5 to 18 h (OR 6.05, CI 5.53–6.61) and 19 to 24 h (OR 10.83, CI 9.45–12.41) compared to one to 4 h; and from onset of labor until birth 11 to 24 h (OR 6.72, CI 6.24–7.23) and 25 to 29 h (OR 26.62, CI 22.77–31.11) compared to one to 10 h. When entering all factors into the model, we found the strongest predictors of transfer to be fetal distress, longer time intervals between ROM until birth and onset of labor until birth. Conclusions Nulliparous transfer rates were similar to rates in other high‐income countries; 94% of referrals were non‐urgent. Time was found to be an independent risk factor for the transfer of nulliparae planning community birth.