julilili42/papers huggingface dataset:
Sagittal suture morphological variation in human archaeological populations
2021-03-27

Abstract Cranial sutures join the many bones of the skull. They are therefore points of weakness and consequently subjected to the many mechanical stresses affecting the cranium. However, the way in which this impacts their morphological complexity remains unclear. We examine the intrinsic and extrinsic mechanisms of human sagittal sutures by quantifying the morphology from 107 individuals from archaeological populations spanning the Mesolithic to Middle ages, using standardized two‐dimensional photographs. Results show that the most important factor determining sutural complexity appears to be the position along the cranial vault from the junction with the coronal suture at its anterior‐most point to the junction with the lambdoid suture at its posterior‐most point. Conversely, factors such as age and lifeways show few trends in complexity, the most significant of which is a lower complexity in the sutures of Mesolithic individuals who consumed a tougher diet. The simple technique used in this study therefore allowed us to identify that, taken together, structural aspects play a more important role in defining the complexity of the human sagittal suture than extrinsic factors such as the mechanical forces imposed on the cranium by individuals' diet.
Intravenous Immunoglobulin Therapy in Livedoid Vasculopathy: Retrospective Observation of Clinical Outcome and Patient’s Activity Level
2021-03-28

Background Livedoid vasculopathy (LV) is a rare disease characterized by livedo racemosa, atrophie blanche, ulcerations, and severe pain. Low molecular weight heparins and rivaroxaban can be used in LV-patients. In addition, intravenous immunoglobulins (IVIG) have been described as treatment-option. Objectives Objective was to investigate the therapeutic effect of IVIG on ulcer, pain and restrictions in daily life. Methods Thirty-two LV-patients who received IVIG at the Department of Dermatology Tübingen between 01/2014 and 06/2019 were identified. Twenty-five of these patients were available for further follow up and were included in the study. Patients were interviewed using a questionnaire focusing on the course of the disease, symptoms, and subjective response to IVIG-treatment. Results Twenty-five patients were included in the study (mean follow up: 28.9 months). Patients received an average of 6.8 cycles (range 1-45) of IVIG during the observed period. Significant improvements were seen regarding skin findings, pain, and limitation of daily activities. Complete remission of symptoms was observed in 68% of patients. Good tolerability of IVIG was shown in 92%. Conclusions A good therapy response regarding ulceration, pain, and daily life restrictions with good tolerability was demonstrated for IVIG (2 g/kg bodyweight over 5 days).
Lunar periodic modulation of the circadian activity rhythm in a wild North Colombian night monkey (Aotus griseimembra)
2021-03-28

South American night monkeys (genus Aotus) are the only nocturnal simian primates. Early activity recordings in North Colombian A. griseimembra monkeys kept under semi-natural conditions and extensive chronobiological studies carried out in laboratory settings revealed a strictly nocturnal behavior and strong activity enhancing (disinhibiting) effects of moonlight or corresponding luminosities during the dark time. To check whether the results from captive individuals correspond to the behavior of wild monkeys, we carried out long-term activity recordings of a wild female A. griseimembra in a tropical rainforest near San Juan de Carare, Northern Colombia. Our data from about 150 days of continuous activity records with an "Actiwatch Mini" (CamNtech, UK) accelerometer-data logger device, confirmed: (1) strictly nocturnal behavior, (2) a pronounced bimodal activity pattern with prominent peaks during dusk and dawn, and (3) a lunar periodic modulation (masking) of the night monkey's circadian activity rhythm due to distinct activity inhibiting effects of the absence of moonlight throughout the night. The results from this wild-living tropical night monkey are consistent with those from captive conspecifics studied decades earlier.
A Goal Scoring Probability Model for Shots Based on Synchronized Positional and Event Data in Football (Soccer)
2021-03-29

Due to the low scoring nature of football (soccer), shots are often used as a proxy to evaluate team and player performances. However, not all shots are created equally and their quality differs significantly depending on the situation. The aim of this study is to objectively quantify the quality of any given shot by introducing a so-called expected goals (xG) model. This model is validated statistically and with professional match analysts. The best performing model uses an extreme gradient boosting algorithm and is based on hand-crafted features from synchronized positional and event data of 105, 627 shots in the German Bundesliga. With a ranked probability score (RPS) of 0.197, it is more accurate than any previously published expected goals model. This approach allows us to assess team and player performances far more accurately than is possible with traditional metrics by focusing on process rather than results.
The Subcortical Atlas of the Rhesus Macaque (SARM) for neuroimaging
2021-03-29

Digitized neuroanatomical atlases that can be overlaid onto functional data are crucial for localizing brain structures and analyzing functional networks identified by neuroimaging techniques. To aid in functional and structural data analysis, we have created a comprehensive parcellation of the rhesus macaque subcortex using a high-resolution ex vivo structural imaging scan. This anatomical scan and its parcellation were warped to the updated NIMH Macaque Template (NMT v2), an in vivo population template, where the parcellation was refined to produce the Subcortical Atlas of the Rhesus Macaque (SARM) with 210 primary regions-of-interest (ROIs). The subcortical parcellation and nomenclature reflect those of the 4<sup>th</sup> edition of the Rhesus Monkey Brain in Stereotaxic Coordinates (Paxinos et al., in preparation), rather than proposing yet another novel atlas. The primary ROIs are organized across six spatial hierarchical scales from small, fine-grained ROIs to broader composites of multiple ROIs, making the SARM suitable for analysis at different resolutions and allowing broader labeling of functional signals when more accurate localization is not possible. As an example application of this atlas, we have included a functional localizer for the dorsal lateral geniculate (DLG) nucleus in three macaques using a visual flickering checkerboard stimulus, identifying and quantifying significant fMRI activation in this atlas region. The SARM has been made openly available to the neuroimaging community and can easily be used with common MRI data processing software, such as AFNI, where the atlas has been embedded into the software alongside cortical macaque atlases.
Mutations in BRCA1/2 and Other Panel Genes in Patients With Metastatic Breast Cancer —Association With Patient and Disease Characteristics and Effect on Prognosis
2021-03-29

PURPOSE Among patients with metastatic breast cancer (mBC), the frequency of germline mutations in cancer susceptibility genes and the clinical relevance of these mutations are unclear. In this study, a prospective cohort of patients with mBC was used to determine mutation rates for breast cancer (BC) predisposition genes, to evaluate the clinical characteristics of patients with mutations, and to assess the influence of mutations on patient outcome. PATIENTS AND METHODS Germline DNA from 2,595 patients with mBC enrolled in the prospective PRAEGNANT registry was evaluated for mutations in cancer predisposition genes. The frequencies of mutations in known BC predisposition genes were compared with results from a prospective registry of patients with nonmetastatic BC sequenced using the same QIAseq method and with public reference controls. Associations between mutation status and tumor characteristics, progression-free survival, and overall survival were assessed. RESULTS Germline mutations in 12 established BC predisposition genes (including BRCA1 and BRCA2) were detected in 271 (10.4%) patients. A mutation in BRCA1 or BRCA2 was seen in 129 patients (5.0%). BRCA1 mutation carriers had a higher proportion of brain metastasis (27.1%) compared with nonmutation carriers (12.8%). Mutations were significantly enriched in PRAEGNANT patients with mBC compared with patients with nonmetastatic BC (10.4% v 6.6%, P &lt; .01). Mutations did not significantly modify progression-free survival or overall survival for patients with mBC. CONCLUSION Multigene panel testing may be considered in all patients with mBC because of the high frequency of germline mutations in BRCA1/2 and other BC predisposition genes. Although the prognosis of mutation carriers and nonmutation carriers with mBC was similar, differences observed in tumor characteristics have implications for treatment and for future studies of targeted therapies.
Modeling the nonaxisymmetric structure in the HD 163296 disk with planet-disk interaction
2021-03-29

\\nContext. High-resolution ALMA observations such as the DSHARP campaign have revealed a variety of rich substructures in numerous protoplanetary disks. These structures consist of rings, gaps, and asymmetric features. It has been debated whether planets can be accounted for among these substructures in the dust continuum. Characterizing the origin of asymmetries, as seen in HD 163296, might lead to a better understanding of planet formation and the underlying physical parameters of the system.\\nAims. We test the possibility that the formation of the crescent-shaped asymmetry in the HD 163296 disk can be attributed to planet-disk interaction. The goal is to obtain constraints on planet masses, eccentricities, and disk viscosities. Furthermore, we test the reproducibility of the two prominent rings in the HD 163296 disk at 67 and 100 au.\\nMethods. We performed two-dimensional, multi-fluid, hydrodynamical simulations with the FARGO3D code, including three embedded planets in the setup. Dust is described via the pressureless fluid approach and distributed over eight size bins. The resulting grids were post-processed with the radiative transfer code RADMC-3D and CASA software to model the synthetic observations.\\nResults. We find that the crescent-shaped asymmetry can be qualitatively modeled with a Jupiter mass planet at a radial distance of 48 au. Dust is trapped in the trailing Lagrange point L5, preferably, with a mass of between 10 and 15 earth masses. The observation of such a feature constrains the level of viscosity and planetary mass. Increased values of eccentricity of the innermost Jupiter mass planet negatively impacts the stability of the crescent-shaped feature and does not reproduce the observed radial proximity to the first prominent ring in the system. Generally, a low level of viscosity (α ≤ 2 × 10−3) is necessary to allow for the existence of such a feature. Including dust feedback in the leading point, L4, can dominantly capture dust for dust grains with an initial Stokes number ≤ 3.6 × 10−2. In the synthetic ALMA observation of the model with dust feedback, two crescent-shaped features are visible. The observational results suggest a negligible effect on the part of dust feedback since only one such feature has been detected so far. The dust-to-gas ratio may thus be overestimated in the models. Additionally, the planet mass growth time scale does not strongly affect the formation of such asymmetries in the co-orbital region. \\n
The Method of Local Restriction: in search of potential great ape culture‐dependent forms
2021-03-29

ABSTRACT Humans possess a perhaps unique type of culture among primates called cumulative culture. In this type of culture, behavioural forms cumulate changes over time, which increases their complexity and/or efficiency, eventually making these forms culture‐dependent. As changes cumulate, culture‐dependent forms become causally opaque, preventing the overall behavioural form from being acquired by individuals on their own; in other words, culture‐dependent forms must be copied between individuals and across generations. Despite the importance of cumulative culture for understanding the evolutionary history of our species, how and when cumulative culture evolved is still debated. One of the challenges faced when addressing these questions is how to identify culture‐dependent forms that result from cumulative cultural evolution. Here we propose a novel method to identify the most likely cases of culture‐dependent forms. The ‘Method of Local Restriction’ is based on the premise that as culture‐dependent forms are repeatedly transmitted via copying, these forms will unavoidably cumulate population‐specific changes (due to copying error) and therefore must be expected to become locally restricted over time. When we applied this method to our closest living relatives, the great apes, we found that most known ape behavioural forms are not locally restricted (across domains and species) and thus are unlikely to be acquired via copying. Nevertheless, we found 25 locally restricted forms across species and domains, three of which appear to be locally unique (having been observed in a single population of a single species). Locally unique forms represent the best current candidates for culture‐dependent forms in non‐human great apes. Besides these rare exceptions, our results show that overall, ape cultures do not rely heavily on copying, as most ape behaviours appear across sites and/or species, rendering them unlikely to be culture‐dependent forms resulting from cumulative cultural evolution. Yet, the locally restricted forms (and especially the three locally unique forms) identified by our method should be tested further for their potential reliance on copying social learning mechanisms (and in turn, for their potential culture‐dependence). Future studies could use the Method of Local Restriction to investigate the existence of culture‐dependent forms in other animal species and in the hominin archaeological record to estimate how widespread copying is in the animal kingdom and to postulate a timeline for the emergence of copying in our lineage.
TGF‐β activates pericytes via induction of the epithelial‐to‐mesenchymal transition protein SLUG in glioblastoma
2021-03-29

Abstract Aims In primary central nervous system tumours, epithelial‐to‐mesenchymal transition (EMT) gene expression is associated with increased malignancy. However, it has also been shown that EMT factors in gliomas are almost exclusively expressed by glioma vessel‐associated pericytes (GA‐Peris). In this study, we aimed to identify the mechanism of EMT in GA‐Peris and its impact on angiogenic processes. Methods In glioma patients, vascular density and the expression of the pericytic markers platelet derived growth factor receptor (PDGFR)‐β and smooth muscle actin (αSMA) were examined in relation to the expression of the EMT transcription factor SLUG and were correlated with survival of patients with glioblastoma (GBM). Functional mechanisms of SLUG regulation and the effects on primary human brain vascular pericytes (HBVP) were studied in vitro by measuring proliferation, cell motility and growth characteristics. Results The number of PDGFR‐β‐ and αSMA‐positive pericytes did not change with increased malignancy nor showed an association with the survival of GBM patients. However, SLUG‐expressing pericytes displayed considerable morphological changes in GBM‐associated vessels, and TGF‐β induced SLUG upregulation led to enhanced proliferation, motility and altered growth patterns in HBVP. Downregulation of SLUG or addition of a TGF‐β antagonising antibody abolished these effects. Conclusions We provide evidence that in GA‐Peris, elevated SLUG expression is mediated by TGF‐β, a cytokine secreted by most glioma cells, indicating that the latter actively modulate neovascularisation not only by modulating endothelial cells, but also by influencing pericytes. This process might be responsible for the formation of an unstructured tumour vasculature as well as for the breakdown of the blood–brain barrier in GBM.
Distinct Lugdunins from a New Efficient Synthesis and Broad Exploitation of Its MRSA-Antimicrobial Structure
2021-03-29

A new solid-phase peptide synthesis and bioprofiling of the antimicrobial activity of lugdunin, a fibupeptide, enable a comprehensive structure-activity relationship (SAR) study (MRSA <i>Staphylococcus aureus</i>). Distinct lugdunin analogues with variation of the three important amino acids Val<sup>2</sup>, Trp<sup>3</sup>, and Leu<sup>4</sup> are readily available based on the established high-output synthesis. This efficient synthesis concept takes advantage of the presynthesized thiazolidine building block. To gain further knowledge of SAR, d-Val<sup>2</sup>, and d-Leu<sup>4</sup> were replaced with aliphatic amino acids. For l-Trp<sup>3</sup> derivatization, a set of non-natural aromatic amino acids with manifold substitution and annulation patterns precisely shows structural imperatives, starting from the exchange of d-Val<sup>6</sup> → d-Trp<sup>6</sup> with a 2-fold improved biological activity. d-Trp<sup>6</sup>-lugdunin analogues with additional variation of d-Val<sup>2</sup> and d-Leu<sup>4</sup> residues were designed and synthesized followed by antimicrobial profiling. For the first time, these SAR studies deliver valuable information on the tolerance of other amino acids to d-Val<sup>2</sup>, l-Trp<sup>3</sup>, and d-Leu<sup>4</sup> in the sequence of lugdunin.
Integrin Activation Enables Sensitive Detection of Functional CD4+ and CD8+ T Cells: Application to Characterize SARS-CoV-2 Immunity
2021-03-29

We have previously shown that conformational change in the β 2 -integrin is a very early activation marker that can be detected with fluorescent multimers of its ligand intercellular adhesion molecule (ICAM)-1 for rapid assessment of antigen-specific CD8 + T cells. In this study, we describe a modified protocol of this assay for sensitive detection of functional antigen-specific CD4 + T cells using a monoclonal antibody (clone m24 Ab) specific for the open, high-affinity conformation of the β 2 -integrin. The kinetics of β 2 -integrin activation was different on CD4 + and CD8 + T cells (several hours vs. few minutes, respectively); however, m24 Ab readily stained both cell types 4–6 h after antigen stimulation. With this protocol, we were able to monitor ex vivo effector and memory CD4 + and CD8 + T cells specific for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), cytomegalovirus (CMV), Epstein–Barr virus (EBV), and hepatitis B virus (HBV) in whole blood or cryopreserved peripheral blood mononuclear cells (PBMCs) of infected or vaccinated individuals. By costaining β 2 -integrin with m24 and CD154 Abs, we assessed extremely low frequencies of polyfunctional CD4 + T cell responses. The novel assay used in this study allows very sensitive and simultaneous screening of both CD4 + and CD8 + T cell reactivities, with versatile applicability in clinical and vaccination studies.
Singlet Fission in Dideuterated Tetracene and Pentacene
2021-03-29

Abstract The impact of molecular vibrations on singlet fission, which is the spontaneous fission of a singlet exciton into two triplet excitons, is studied using ultrafast optical spectroscopy for the prototypical singlet fission chromophores tetracene and pentacene. We modify the frequency of intramolecular vibrations by deuteration, without impacting thin film structure and molecular arrangement, and study the resulting changes in exo‐ and endothermic singlet fission rates by comparing the deuterated and parent chromophores. We find that changes in the frequency of the C−C deformation modes of Δω=6 cm −1 and the occurrence of C−D vibrational modes do not lead to significant modifications in the singlet fission time constants. We conclude that the changes in the frequency of phonon modes induced by deuteration are too small to significantly impact the electron–phonon coupling that drives the singlet fission process.
Cellular Immune Phenotypes and Worsening Scores of Frailty-Associated Parameters Over an 18-Month Period in the Very Old
2021-03-29

Abstract Frailty has been related to inflammaging and certain immune parameters. In previous analyses of participants older than 80 years of age in the longitudinal BELFRAIL cohort study, the main focus was on T-cell phenotypes and the association with cytomegalovirus (CMV) serostatus and survival, finding that a CD4:CD8 ratio greater than 5 was associated with frailty, impaired activities of daily living (ADLs), and mortality (but only in women). Here, we phenotyped peripheral blood immune cells via multicolor flow cytometry and correlated these with the dynamics of changes in ADL, geriatric depression score, Mini-Mental State Examination, and Short Physical Performance Battery from baseline values over 18 months follow-up. We found that higher frequencies of B cells and late-differentiated CD8+ T cells at 18 months from baseline were associated with ADL impairment that had worsened over the preceding 18 months. There were no significant associations with monocyte, dendritic cell, or natural killer (NK) cell phenotypes. No associations with the Geriatric Depression Scale, the Mini-Mental State Examination, or the Short Physical Performance Battery were found. Thus, while these results do not establish causality, they suggest that certain adaptive immune, but not innate immune, parameters are associated with a worsened ADL in the very old.
Acute vagus nerve stimulation does not affect liking or wanting ratings of food in healthy participants
2021-03-29

Abstract The vagus nerve plays a vital role in the regulation of food intake and vagal afferent signals may help regulate food cue reactivity by providing negative homeostatic feedback. Despite strong evidence from preclinical studies on vagal afferent “satiety” signals in guiding food intake, evidence from human studies is largely inconclusive to date. Here, we investigated the acute effects of left or right transcutaneous auricular vagus nerve stimulation (taVNS) on subjective ratings of wanting and liking of various food and non-food items in 82 healthy participants (46 women, M BMI = 23.1 kg/m 2 ). In contrast to previous reports in patients with depression, we found moderate to anecdotal evidence supporting the absence of taVNS-induced changes in food ratings. To test whether the absence of taVNS effects on food ratings is due to heterogeneity in the sample, we conducted post hoc subgroup analyses by splitting the data according to stimulation side and sex (between-subject factors) as well as caloric density, perceived healthiness, and flavor (sweet vs. savory) of the food (within-subject factors). This multiverse analysis largely supported the absence of taVNS-induced changes since the strongest subgroup effects provided only anecdotal evidence in favor of taVNS-induced changes. We conclude that acute taVNS only has a marginal effect on subjective ratings of food, suggesting that it is an unlikely mechanism for the reported long-term effects of VNS on body weight. In light of an absence of acute taVNS effects on food craving, our results call for future research on the correspondence between acute and chronic effects of vagal afferent stimulation.