julilili42/papers huggingface dataset:
3D geometric morphometrics analysis of mandibular fragments of Ouranopithecus macedoniensis from the late Miocene deposits of Central Macedonia, Greece
2021-10-19

Abstract Objectives To explore mandibular shape differences between Ouranopithecus macedoniensis and a comparative sample of extant great apes using three‐dimensional (3D) geometrics morphometrics. Other objectives are to assess mandibular shape variation and homogeneity within Ouranopithecus , explore the effects of size on mandibular shape, and explore the degree of mandibular sexual size dimorphism in Ouranopithecus . Materials and methods The comparative sample comprises digitized mandibles from adult extant great apes. The 3D analysis includes three datasets: one with landmarks registered on the mandibular corpus and symphysis of mandibles preserving both sides, one on hemimandibles only, and one focused on the ramus and gonial area. Multivariate statistical analyses were conducted, such as ordination analyses (PCA), intra‐specific Procrustes distances pairs, pairwise male–female centroid size differences, and correlation analyses. Results The male and female specimens of Ouranopithecus have mandibular shapes that are quite similar, although differences exist. The Procrustes distances results suggest more shape variation in Ouranopithecus than in the extant great apes. Ouranopithecus shows some similarities in mandibular shape to the larger great apes, Gorilla and Pongo . Moreover, the degree of sexual dimorphism in the small Ouranopithecus sample is greater than any of the great apes. Based on our correlation analyses of principal components (PC) with size, some PCs are significantly correlated with size, with correlation varying from moderate to substantial. Discussion This study attempted to understand better the variation within the mandibles of O . macedoniensis and the expression of sexual dimorphism in this taxon in more detail than has been done previously. The overall mandibular morphology of Ouranopithecus shows some similarities to those of the larger great apes, which likely reflects similarities in size. Compared to Gorilla and Pongo , O . macedoniensis shows an elevated degree of morphological variation, although limitations relating to sample size apply. Sexual dimorphism in the mandibles of O . macedoniensis appears to be relatively high, seemingly greater than in Gorilla and high even in comparison to Pongo , but this again is possibly in part an artifact of a small sample size.
PEGASOS - A New Linking Mechanism for Modular Osteosynthesis Plates in Minimally Invasive Acetabular Surgery
2021-10-19

Abstract Background: Recently presented minimally invasive endoscopic surgical techniques demonstrated the feasibility of implanting standard osteosynthesis plates for pelvic fractures. The reconstruction and internal fixation of complex acetabular fractures is still challenging. The goal of this study is to introduce a divisible implant, with a positive-locking in situ linking mechanism for plate osteosynthesis, making it possible to stabilize large and complex acetabular fractures with involvement of the quadrilateral surface. Method: Standard implants were used to recreate a base design. Using computer aided design (CAD), a three-dimensional standard implant was divided into two parts, so they could be re-allocated in situ. A critical objective was to reduce the cross-section of each part (clearance gauge). To connect the separated parts in situ, a new linking mechanism (cone in cone) was created. The new construct also features self-stabilization, self-centering, reinforced positional movement and preloading effects. Results: A linking system for plate osteosynthesis was developed entitled PEGASOS ("Percutaneous Endoscopic Guided Acetabulum-Stabilizing Osteosynthesis System"). Endoscopic implantation and in-situ-linking could be performed in a human cadaver. Therefore, we could demonstrate, that buttressing the quadrilateral surface of the acetabulum could be performed minimally invasive using a divisible suprapectineal buttress plate. Conclusion: We created a linking mechanism to couple two plates in situ. This mechanism enables an extremely strong, positive-locking connection, whereas its geometric shape allows for different relative movements during the locking procedure, with a single screw.
Structural network alterations in focal and generalized epilepsy follow axes of epilepsy risk gene expression: An ENIGMA study
2021-10-19

Epilepsy is associated with genetic risk factors and cortico-subcortical network alterations, but associations between neurobiological mechanisms and macroscale connectomics remain unclear. This multisite ENIGMA-Epilepsy study examined whole-brain structural covariance networks in patients with epilepsy and related findings to postmortem co-expression patterns of epilepsy risk genes. Brain network analysis included 578 adults with temporal lobe epilepsy (TLE), 288 adults with idiopathic generalized epilepsy (IGE), and 1,328 healthy controls from 18 centres worldwide. Graph theoretical analysis of structural covariance networks revealed increased clustering and path length in orbitofrontal and temporal regions in TLE, suggesting a shift towards network regularization. Conversely, people with IGE showed decreased clustering and path length in fronto-temporo-parietal cortices, indicating a random network configuration. Syndrome-specific topological alterations reflected expression patterns of risk genes for hippocampal sclerosis in TLE and for generalized epilepsy in IGE. These imaging-genetic signatures could guide diagnosis, and ultimately, tailor therapeutic approaches to specific epilepsy syndromes.
Diffuse large B-cell lymphomas in adults with aberrant coexpression of CD10, BCL6, and MUM1 are enriched in IRF4 rearrangements
2021-10-20

Abstract Diffuse large B-cell lymphoma (DLBCL) with aberrant coexpression of CD10+BCL6+MUM1+ (DLBCL-AE), classified as germinal center B cell (GCB) type by the Hans algorithm (HA), was genetically characterized. To capture the complexity of DLBCL-AE, we used an integrated approach that included gene expression profiling (GEP), fluorescence in situ hybridization, targeted gene sequencing, and copy number (CN) arrays. According to GEP, 32/54 (59%) cases were classified as GCB-DLBCL, 16/54 (30%) as activated B-cell (ABC) DLBCL, and 6/54 (11%) as unclassifiable. The discrepancy between HA and GEP was 41%. Three genetic subgroups were identified. Group 1 included 13/50 (26%) cases without translocations and mainly showing and ABC/MCD molecular profile. Group 2 comprised 11/50 (22%) cases with IRF4 alterations (DLBCL-IRF4), frequent mutations in IRF4 (82%) and NF-κB pathway genes (MYD88, CARD11, and CD79B), and losses of 17p13.2. Five cases each were classified as GCB- or ABC-type. Group 3 included 26/50 (52%) cases with 1 or several translocations in BCL2/BCL6/MYC/IGH, and GCB/EZB molecular profile predominated. Two cases in this latter group showed complex BCL2/BCL6/IRF4 translocations. DLBCL-IRF4 in adults showed a similar copy number profile and shared recurrent CARD11 and CD79B mutations when compared with LBCL-IRF4 in the pediatric population. However, adult cases showed higher genetic complexity, higher mutational load with frequent MYD88 and KMT2D mutations, and more ABC GEP. IRF4 mutations were identified only in IRF4-rearranged cases, indicating its potential use in the diagnostic setting. In conclusion, DLBCL-AE is genetically heterogeneous and enriched in cases with IRF4 alterations. DLBCL-IRF4 in adults has many similarities to the pediatric counterpart.
Design of a “Two-in-One” Mutant-Selective Epidermal Growth Factor Receptor Inhibitor That Spans the Orthosteric and Allosteric Sites
2021-10-20

Inhibitors targeting the epidermal growth factor receptor (EGFR) are an effective therapy for patients with non-small cell lung cancer harboring drug-sensitive activating mutations in the EGFR kinase domain. Drug resistance due to treatment-acquired mutations has motivated the development of successive generations of inhibitors that bind in the ATP site. The third-generation agent osimertinib is now a first-line treatment for this disease. Recently, allosteric inhibitors have been developed to overcome drug-resistant mutations that confer a resistance to osimertinib. Here, we present the structure-guided design and synthesis of a mutant-selective lead compound, which consists of a pyridinyl imidazole-fused benzylisoindolinedione scaffold that simultaneously occupies the orthosteric and allosteric sites. The compound potently inhibits enzymatic activity in L858R/T790M/C797S mutant EGFR (4.9 nM), with a significantly lower activity for wild-type EGFR (47 nM). Additionally, this compound achieves modest cetuximab-independent and mutant-selective cellular efficacies on the L858R (1.2 μM) and L858R/T790M (4.4 μM) variants.
Unfolding Trade Effect in Two Margins of Informality: The Peruvian Case
2021-10-20

This paper studies the effect of an increase in import competition on informality along two margins. It considers the extensive margin, where workers are hired by unregistered employers, and the intensive margin, where even though jobs are carried out by registered firms, employees are off the books. Peru's relentless informal employment and its unprecedented trade-driven growth provides an ideal case study. Using a rich household survey, this study finds that exposure to trade impacts on informality through two competing and contrasting mechanisms. On the one hand, extensive-informal employment declines as unregistered employers shrink or exit due to their low productivity. On the other hand, intensive-informal employment rises as registered employers reduce costs by hiring informal workers. Furthermore, results suggest that the intensive margin drives the overall effect. Hence, trade liberalization increases informality.
Can supermassive black hole shadows test the Kerr metric?
2021-10-20

The unprecedented image of the M87* supermassive black hole has sparked some\\ncontroversy over its usefulness as a test of the general relativistic Kerr\\nmetric. The criticism is mainly related to the black hole's quasi-circular\\nshadow and advocates that its radius depends not only on the black hole's true\\nspacetime properties but also on the poorly known physics of the illuminating\\naccretion flow. In this paper we take a sober view of the problem and argue\\nthat our ability to probe gravity with a black hole shadow is only partially\\nimpaired by the matter degrees of freedom and the number of non-Kerr parameters\\nused in the model. As we show here, a more intriguing situation arises from the\\nmass scaling of the dimensional coupling constants that typically appear in\\nnon-GR theories of gravity. Existing limits from gravitational wave\\nobservations imply that supermassive systems like the M87* black hole would\\nsuffer a suppression of all non-GR deviation parameters in their metric, making\\nthe spacetime and the produced shadow virtually Kerr. Therefore, a supermassive\\nblack hole shadow is likely to probe only those extensions of General\\nRelativity which are endowed with dimensionless coupling constants or other\\nspecial cases with a screening mechanism for black holes or certain types of\\nspontaneous scalarisation.\\n
Formation of low-gradient bedrock chutes by dry rockfall on planetary surfaces
2021-10-20

Abstract Channel-like forms are ubiquitous on steep hillslopes on Earth, Mars, and other planetary bodies. On Earth and Mars, these landforms are commonly attributed to water activity, especially for slopes below the angle of repose (∼30°) where dry granular flows are considered ineffective. While the angle of repose characterizes loose sediment stability, it is unclear whether dry rockfall can traverse and erode channels in bedrock or cemented substrates. We used a large-scale experiment to show that bedrock chutes can form spontaneously at low gradients from dry rockfall. Our results, combined with observations of rocky outcrops and boulders on Mars, indicate that rockfall can be an important bedrock degradation process that can produce low-gradient channels in the absence of water.
Significant reduced loss of bone mineral density after four vs. six cycles of R-CHOP: an analysis of the FLYER-trial
2021-10-20

Patients with diffuse large B-cell lymphoma (DLBCL) treated with the R-CHOP regime receive a high cumulative dose of prednisone. We used computer tomography-ascertained Hounsfield units (HU) as a surrogate parameter for bone mineral density (BMD) in three different locations of the L3 vertebral body at baseline and post-treatment. HU were measured in 50 patients with DLBCL of the previously published FLYER-trial which compared four cycles of R-CHOP + 2 × rituximab infusion to six cycles of R-CHOP in young, favorable DLBCL patients. In total, median loss was 26.8 HU in all patients over time. The median HU loss was significantly lower in the four cycles arm (21.3 HU vs. 41.3 HU, <i>p</i> = 0.023). In conclusion, young patients with DLBCL receiving R-CHOP have significant HU/BMD loss under treatment with R-CHOP. Patients receiving four cycles of R-CHOP had less HU/BMD loss than patients receiving six cycles.
Non-Invasive Physical Plasma Enhances the Membrane Permeability to Low Molecular Weight Compounds and Subsequently Leads to the Loss of Cellular ATP and the Devitalization of Epithelial Cancer Cells
2021-10-20

Non-invasive physical plasma (NIPP) achieves biomedical effects primarily through the formation of reactive oxygen and nitrogen species. In clinical use, these species interact with cells of the treated tissue, affecting the cytoplasmic membrane first. The present study investigated the permeability of the cytoplasmic membrane of breast cancer cells with different fluorescent dyes after NIPP treatment and determined the subsequent effects on cell viability. After NIPP treatment and the associated formation of reactive oxygen species, low molecular weight compounds were able to pass through the cytoplasmic membrane in both directions to a higher extent. Consequently, a loss of cellular ATP into the extracellular space was induced. Due to these limitations in cell physiology, apoptosis was induced in the cancer cells and the entire cell population exhibited decreased cell growth. It can be concluded that NIPP treatment disturbs the biochemical functionality of the cytoplasmic membrane of cancer cells, which massively impairs their viability. This observation opens a vast application horizon of NIPP therapy to treat precancerous and malignant diseases beyond breast cancer therapy.
Magnetic resonance imaging validation of medial transthyroid ultrasound‐guided stellate ganglion block: A pilot study
2021-10-20

Abstract Objective Ultrasound‐guided stellate ganglion block (usSGB) facilitates improved accuracy of needle position and application of lesser volumes of local anesthetic (LA). Approaches of usSGB, however, have not fully been optimized with respect to efficacy and technical convenience. This pilot study examined the anatomical position and spatial distribution of a small volume of LA injectate dispensed by medial transthyroid usSGB via magnetic resonance imaging (MRI) and assessment of its effect on cervical sympathetic nerves. Methods Twelve healthy males were tested in a double‐blinded within‐subject design. In a total of 37 usSGB, 3 ml of LA and saline 0.9% solution were injected intramuscularly into the longus colli muscle (LCM) preventing uncontrollable spread of LA within cervical structures. Immediately after injection, distribution of injectate was traced by MRI. Twenty‐four out of the 37 usSGB‐injections with 3 ml ropivacaine 1% (verum) and saline 0.9% (placebo) were compared. Efficacy of usSGB was assessed by the appearance of oculosympathetic paresis and increases in skin temperature. Results All usSGBs were positioned in the proximity of the LCM muscle belly. Most of the axial injectate was distributed within the transversal plane between the middle section of C5 and the upper section of T1 vertebra. Signs of oculosympathetic paresis and skin temperature increase were found exclusively under verum conditions. Conclusion This pilot study demonstrated the feasibility of medial transthyroid usSGB using an out‐of‐plane technique and a volume of 3 ml of LA. Further studies are required to establish the relative value and safety of this technique compared to other published approaches.
Visual Motion Coherence Responses in Human Visual Cortex
2021-10-20

1 Abstract Random dot kinematograms (RDKs) have recently been used to train subjects with cortical scotomas to perform direction of motion discrimination, partially restoring visual motion perception. To study recovery of visual perception, it is important to understand how visual areas in normal subjects and subjects with cortical scotomas respond to RDK stimuli. Studies in normal subjects have shown that Blood Oxygen Level Dependent (BOLD) responses in human area hV5/MT+ increase monotonically with coherence, in general agreement with electrophysiology studies in primates. However, RDK responses in prior studies were obtained while the subject was performing fixation, not a motion discrimination condition. Furthermore, BOLD responses were gauged against a baseline condition of uniform illumination or static dots, potentially decreasing the specificity of responses for the spatial integration of local motion signals (motion coherence). Here we revisit this question starting from a baseline RDK condition of no coherence, thereby isolating the component of BOLD response due specifically to the spatial integration of local motion signals. In agreement with prior studies, we found that responses in area hV5/MT+ of healthy subjects were monotonically increasing when subjects fixated without performing a motion discrimination task. In contrast, when subjects were performing an RDK direction of motion discrimination task, responses in area hV5/MT+ remained flat, changing minimally, if at all, as a function of motion coherence. A similar pattern of responses was seen in area hV5/MT+ of subjects with dense cortical scotomas performing direction of motion discrimination for RDKs presented inside the scotoma. Passive RDK presentation within the scotoma elicited no significant hV5/MT+ responses. These observations shed further light on how visual cortex responses behave as a function of motion coherence, helping to prepare the ground for future studies using these methods to study visual system recovery after injury.
Laparoscopic Excision of Solitary Dysontogenetic Liver Cysts in Young Children: Technical Aspects and Outcome
2021-10-20

<b><i>Background:</i></b> Solitary dysontogenetic liver cysts are rare in young children. However, large cysts can cause symptoms and require therapy. Cyst excision is the therapeutic method least associated with cyst recurrence. Only limited data are available on cyst excision performed laparoscopically in this age group. We present our experience using this surgical approach. <b><i>Methods:</i></b> Since 2005, 7 children including 5 newborns and infants with solitary dysontogenetic liver cysts have undergone minimally invasive excision of the cyst at our institution. Patient data were analyzed retrospectively. <b><i>Results:</i></b> Median age of the patients at surgery was 8 months (3 days to 6 years); 5 of them were younger than 1 year. The cysts had varying locations in the segments IV-VIII, and median size was 5.4 cm (3.8-7.9). Complete excision was realized in all cases. Median duration of surgery was 120 minutes (60-171). All procedures could be completed laparoscopically. One intraoperative complication occurred (injury of a bile duct that could be sutured laparoscopically). Median follow-up was 29 months (14-173). Cyst recurrence was not observed in any of the cases. <b><i>Conclusion:</i></b> Laparoscopic excision of solitary dysontogenetic liver cysts is an effective treatment in young children. Resection is not limited to cysts in anterior and lateral liver segments.
Bare Root Infinitives in German
2021-10-20

The aim of this paper is to show how linguistic and literary studies can benefit from a joint work about linguistic structures in poetry. Firstly, the analysis of poetry has an important impact on linguistic theory as it leads our attention to specific structures and meanings that so far have not been considered. Secondly, a close linguistic analysis can reveal hitherto overlooked facets of meaning which have a great significance for the overall interpretation of a poem. We focus on Bare Root Infinitives (BRIs) in German. As they lack the features for tense, mood, person and number, they are more flexible in meaning than finite forms. When looking at poetry, besides the well-known deontic and bouleticmeanings (cf. Reis 1995, 2003; Gärtner 2014) a third meaning that we call reactive meaning stands out. Remarkably, this reactive meaning can also be found in everyday language. Its specific semantic properties show that a semantic analysis of BRIs in the style of Kaufmann (2012) is adequate: modality, but not non-referentiality, is a “hard-wired” semantic property of BRIs. The specific case study of the poem ‘muster fixieren’ (‘fixating patterns’) by Nico Bleutge reveals how the restricted context of the poem interacts with the different interpretations of BRIs to arrive at a complex text interpretation. Keywords: bare root infinitives, semantic-pragmatic interface, poetry, modality, pragmatic enrichment, semantics
Light-triggered and phosphorylation-dependent 14-3-3 association with NON-PHOTOTROPIC HYPOCOTYL 3 is required for hypocotyl phototropism
2021-10-21

Abstract NON-PHOTOTROPIC HYPOCOTYL 3 (NPH3) is a key component of the auxin-dependent plant phototropic growth response. We report that NPH3 directly binds polyacidic phospholipids, required for plasma membrane association in darkness. We further demonstrate that blue light induces an immediate phosphorylation of a C-terminal 14-3-3 binding motif in NPH3. Subsequent association of 14-3-3 proteins is causal for the light-induced release of NPH3 from the membrane and accompanied by NPH3 dephosphorylation. In the cytosol, NPH3 dynamically transitions into membraneless condensate-like structures. The dephosphorylated state of the 14-3-3 binding site and NPH3 membrane recruitment are recoverable in darkness. NPH3 variants that constitutively localize either to the membrane or to condensates are non-functional, revealing a fundamental role of the 14-3-3 mediated dynamic change in NPH3 localization for auxin-dependent phototropism. This regulatory mechanism might be of general nature, given that several members of the NPH3-like family interact with 14-3-3 via a C-terminal motif.
Causal decoding of individual cortical excitability states
2021-10-21

Brain responsiveness to stimulation fluctuates with rapidly shifting cortical excitability state, as reflected by oscillations in the electroencephalogram (EEG). For example, the amplitude of motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) of motor cortex changes from trial to trial. To date, individual estimation of the cortical processes leading to this excitability fluctuation has not been possible. Here, we propose a data-driven method to derive individually optimized EEG classifiers in healthy humans using a supervised learning approach that relates pre-TMS EEG activity dynamics to MEP amplitude. Our approach enables considering multiple brain regions and frequency bands, without defining them a priori, whose compound phase-pattern information determines the excitability. The individualized classifier leads to an increased classification accuracy of cortical excitability states from 57% to 67% when compared to μ-oscillation phase extracted by standard fixed spatial filters. Results show that, for the used TMS protocol, excitability fluctuates predominantly in the μ-oscillation range, and relevant cortical areas cluster around the stimulated motor cortex, but between subjects there is variability in relevant power spectra, phases, and cortical regions. This novel decoding method allows causal investigation of the cortical excitability state, which is critical also for individualizing therapeutic brain stimulation.