julilili42/papers huggingface dataset:
Anyskop Blowout Prehistoric Dataset, Western Cape, South Africa
2023-12-06

&amp;lt;p&amp;gt;These Stone Age archaeological datasets were collected in 2001 and 2002 by a team from the Department of Early Prehistory and Quaternary Ecology of the University of T&amp;uuml;bingen (Germany) headed by Nicholas J. Conard. Many South African researchers collaborated on this project, with Pippa Haarhoff, John Compton, Dave Roberts, and Stephan Woodborne deserving special mention.&amp;lt;/p&amp;gt;\\n&amp;lt;p&amp;gt;The field work took place at the Anyskop Blowout (ANY1) located within the West Coast Fossil Park near Langebaanweg, Western Cape, South Africa. The field work was conducted with the help of students from the universities of T&amp;uuml;bingen and Cape Town. The datasets are predominantly in English (with some German as well) and include field data in the MAIN table. Further analytical data for many classes of artifacts include: LITHICS, FAUNA, POTTERY, MODERN, BUCKETS, REFITS.&amp;lt;/p&amp;gt;\\n&amp;lt;p&amp;gt;All collected materials are curated by the Iziko South African Museums in Cape Town under accession numbers SAM-AA-8903 (finds collected by other teams before 2001) and SAM-AA-9007 (finds from this study, 2001-2002). Some of the finds are exhibited in the museum at the West Coast Fossil Park.&amp;lt;/p&amp;gt;\\n&amp;lt;p&amp;gt;Funding for this research project came mainly from the German Research Foundation (DFG - CO 226/5-1, 5-2, 5-5 and 5-6) and the University of T&amp;uuml;bingen. Significant support was provided by the Iziko South African Museums, the West Coast Fossil Park, and the University of Cape Town.&amp;lt;/p&amp;gt;
Toward a Cenozoic history of atmospheric CO 2
2023-12-07

The geological record encodes the relationship between climate and atmospheric carbon dioxide (CO 2 ) over long and short timescales, as well as potential drivers of evolutionary transitions. However, reconstructing CO 2 beyond direct measurements requires the use of paleoproxies and herein lies the challenge, as proxies differ in their assumptions, degree of understanding, and even reconstructed values. In this study, we critically evaluated, categorized, and integrated available proxies to create a high-fidelity and transparently constructed atmospheric CO 2 record spanning the past 66 million years. This newly constructed record provides clearer evidence for higher Earth system sensitivity in the past and for the role of CO 2 thresholds in biological and cryosphere evolution.
Promising applications of nanotechnology in inhibiting chemo-resistance in solid tumors by targeting epithelial-mesenchymal transition (EMT)
2023-12-07

The resistance of cancer cells to chemotherapy, also known as chemo-resistance, poses a significant obstacle to cancer treatment and can ultimately result in patient mortality. Epithelial-mesenchymal transition (EMT) is one of the many factors and processes responsible for chemo-resistance. Studies have shown that targeting EMT can help overcome chemo-resistance, and nanotechnology and nanomedicine have emerged as promising approaches to achieve this goal. This article discusses the potential of nanotechnology in inhibiting EMT and proposes a viable strategy to combat chemo-resistance in various solid tumors, including breast cancer, lung cancer, pancreatic cancer, glioblastoma, ovarian cancer, gastric cancer, and hepatocellular carcinoma. While nanotechnology has shown promising results in targeting EMT, further research is necessary to explore its full potential in overcoming chemo-resistance and discovering more effective methods in the future.
DNA methylation in the wild: epigenetic transgenerational inheritance can mediate adaptation in clones of wild strawberry (Fragaria vesca)
2023-12-07

Summary Due to the accelerating climate change, it is crucial to understand how plants adapt to rapid environmental changes. Such adaptation may be mediated by epigenetic mechanisms like DNA methylation, which could heritably alter phenotypes without changing the DNA sequence, especially across clonal generations. However, we are still missing robust evidence of the adaptive potential of DNA methylation in wild clonal populations. Here, we studied genetic, epigenetic and transcriptomic variation of Fragaria vesca , a predominantly clonally reproducing herb. We examined samples from 21 natural populations across three climatically distinct geographic regions, as well as clones of the same individuals grown in a common garden. We found that epigenetic variation was partly associated with climate of origin, particularly in non‐CG contexts. Importantly, a large proportion of this variation was heritable across clonal generations. Additionally, a subset of these epigenetic changes affected the expression of genes mainly involved in plant growth and responses to pathogen and abiotic stress. These findings highlight the potential influence of epigenetic changes on phenotypic traits. Our findings indicate that variation in DNA methylation, which can be environmentally inducible and heritable, may enable clonal plant populations to adjust to their environmental conditions even in the absence of genetic adaptation.
Therapeutic Consequences of Targeting the IGF-1/PI3K/AKT/FOXO3 Axis in Sarcopenia: A Narrative Review
2023-12-07

The high prevalence of sarcopenia in an aging population has an underestimated impact on quality of life by increasing the risk of falls and subsequent hospitalization. Unfortunately, the application of the major established key therapeutic—physical activity—is challenging in the immobile and injured sarcopenic patient. Consequently, novel therapeutic directions are needed. The transcription factor Forkhead-Box-Protein O3 (FOXO3) may be an option, as it and its targets have been observed to be more highly expressed in sarcopenic muscle. In such catabolic situations, Foxo3 induces the expression of two muscle specific ubiquitin ligases (Atrogin-1 and Murf-1) via the PI3K/AKT pathway. In this review, we particularly evaluate the potential of Foxo3-targeted gene therapy. Foxo3 knockdown has been shown to lead to increased muscle cross sectional area, through both the AKT-dependent and -independent pathways and the reduced impact on the two major downstream targets Atrogin-1 and Murf-1. Moreover, a Foxo3 reduction suppresses apoptosis, activates satellite cells, and initiates their differentiation into muscle cells. While this indicates a critical role in muscle regeneration, this mechanism might exhaust the stem cell pool, limiting its clinical applicability. As systemic Foxo3 knockdown has also been associated with risks of inflammation and cancer progression, a muscle-specific approach would be necessary. In this review, we summarize the current knowledge on Foxo3 and conceptualize a specific and targeted therapy that may circumvent the drawbacks of systemic Foxo3 knockdown. This approach presumably would limit the side effects and enable an activity-independent positive impact on skeletal muscle.
Human WIPI β‐propeller function in autophagy and neurodegeneration
2023-12-07

The four human WIPI β‐propellers, WIPI1 through WIPI4, belong to the ancient PROPPIN family and fulfill scaffold functions in the control of autophagy. In this context, WIPI β‐propellers function as PI3P effectors during autophagosome formation and loss of WIPI function negatively impacts autophagy and contributes to neurodegeneration. Of particular interest are mutations in WDR45 , the human gene that encodes WIPI4. Sporadic WDR45 mutations are the cause of a rare human neurodegenerative disease called BPAN, hallmarked by high brain iron accumulation. Here, we discuss the current understanding of the functions of human WIPI β‐propellers and address unanswered questions with a particular focus on the role of WIPI4 in autophagy and BPAN.
Reproducibility of diffusion-weighted magnetic resonance imaging in head and neck cancer assessed on a 1.5 T MR-Linac and comparison to parallel measurements on a 3 T diagnostic scanner
2023-12-07

ADC values, measured on the 1.5 T MRL, showed reasonable reproducibility with an ADC underestimation in contrast to the DS. This ADC shift must be validated in further experiments and considered for future translation of QIB candidates from DS to MRL for response adaptive RT.
We don't know what you did last summer. On the importance of transparent reporting of reaction time data pre-processing
2023-12-07

In behavioral, cognitive, and social sciences, reaction time measures are an important source of information. However, analyses on reaction time data are affected by researchers' analytical choices and the order in which these choices are applied. The results of a systematic literature review, presented in this paper, revealed that the justification for and order in which analytical choices are conducted are rarely reported, leading to difficulty in reproducing results and interpreting mixed findings. To address this methodological shortcoming, we created a checklist on reporting reaction time pre-processing to make these decisions more explicit, improve transparency, and thus, promote best practices within the field. The importance of the pre-processing checklist was additionally supported by an expert consensus survey and a multiverse analysis. Consequently, we appeal for maximal transparency on all methods applied and offer a checklist to improve replicability and reproducibility of studies that use reaction time measures.
Impact of specialist ataxia centres on health service resource utilisation and costs across Europe: cross-sectional survey
2023-12-07

Abstract Background Little is known about the costs of treating ataxia and whether treatment at a specialist ataxia centre affects the cost of care. The aim of this study was to investigate whether patients who attended specialist ataxia centres in three European countries reported differences in their health care use and costs compared with patients who did not attend a specialist ataxia centre. We compared mean resource use and health service costs per patient affected by ataxia in the United Kingdom, Italy and Germany over a 12-month period. Data were obtained from a survey distributed to people with ataxia in the three countries. We compared mean resource use for each contact type and costs, stratifying patients by whether they were currently attending a specialist ataxia centre or had never attended one. Results Responses were received from 181 patients from the United Kingdom, 96 from Italy and 43 from Germany. Differences in the numbers of contacts for most types of health service use between the specialist ataxia centre and non-specialist ataxia centre groups were non-significant. In the United Kingdom the mean total cost per patient was €2209 for non-specialist ataxia centre patients and €1813 for specialist ataxia centre patients ( P = 0.59). In Italy these figures were €2126 and €1971, respectively ( P = 0.84). In Germany they were €2431 and €4087, respectively ( P = 0.19). Inpatient stays made the largest contribution to total costs. Conclusions Within each country, resource use and costs were broadly similar for specialist ataxia centre and non-specialist ataxia centre groups. There were differences between countries in terms of health care contacts and costs.
Development of Ligands for the Super Conserved Orphan G Protein-Coupled Receptor GPR27 with Improved Efficacy and Potency
2023-12-07

The orphan G protein-coupled receptor GPR27 appears to play a role in insulin production, secretion, lipid metabolism, neuronal plasticity, and l-lactate homeostasis. However, investigations on the function of GPR27 are impaired by the lack of potent and efficacious agonists. We describe herein the development of di- and trisubstituted benzamide derivatives <b>4a</b>-<b>e</b>, <b>7a</b>-<b>z</b>, and <b>7aa</b>-<b>ai</b>, which display GPR27-specific activity in a β-arrestin 2 recruitment-based assay. Highlighted compounds are PT-91 (<b>7p</b>: pEC<sub>50</sub> 6.15; <i>E</i><sub>max</sub> 100%) and <b>7ab</b> (pEC<sub>50</sub> 6.56; <i>E</i><sub>max</sub> 99%). A putative binding mode was revealed by the docking studies of <b>7p</b> and <b>7ab</b> with a GPR27 homology model. The novel active compounds exhibited no GPR27-mediated activation of G proteins, indicating that the receptor may possess an atypical profile. Compound <b>7p</b> displays high metabolic stability and brain exposure in mice. Thus, <b>7p</b> represents a novel tool to investigate the elusive pharmacology of GPR27 and assess its potential as a drug target.
Turkish correlatives in monolingual Turkish and bilingual Turkish-German grammar
2023-12-07

Our paper presents an experimental study on multiple correlatives in Turkish. The research questions that guided our study are twofold: (a) What are the presuppositions of multiple correlatives in Turkish? (b) Is there a difference between monolingual Turkish speakers and bilingual Turkish-German speakers with respect to multiple correlatives? Question (a) targets the presuppositions of interrogative-based correlatives. Since the presuppositions of multiple questions are crosslinguistically variable, are the presuppositions of correlatives based on them variable in a parallel way? Question (b) targets crosslinguistic variability in the acceptability of multiple correlatives. While Turkish permits them, German does not. Does this variability affect bilingual speakers’ grammars? Our results indicate that (a) multiple correlatives share the presuppositions of the questions they contain and (b) bilingual speakers’ grammar of correlatives is different from that of monolingual speakers. The paper sheds a new light on crosslinguistic variation in the domain of questions and correlatives and on bilingual grammar.
Age, preoperative tumor volume and widening of the internal acoustic meatus are independent factors associated with poor preoperative hearing in vestibular schwannoma patients – results of a single-center retrospective analysis
2023-12-07

<title>Abstract</title> Background: Preoperative hearing function shows wide variations among patients diagnosed with vestibular schwannoma. In addition to the obvious role of tumor size other factors that influence hearing function are frequently discussed. Methods: We analyzed clinical factors, imaging data and the expression of the proliferation marker MIB1 as potential influencing factors on the preoperative hearing function in a retrospective cohort of 523 primary sporadic vestibular schwannomas. The results of the preoperative audiometry were quantified using the Gardner-Robertson Score. Uni- and multivariate analyses were performed. Results: Serviceable hearing (Gardner-Robertson class 1 or 2) was documented in 391 patients (74.8%). Factors associated with non-serviceable hearing (Gardner-Robertson class 3–5) were patients of older age (p &lt; 0.0001), larger preoperative tumor volume (p = 0.0013) and widening of the internal acoustic meatus compared to the healthy side (p = 0.0353). Gender and the expression of the proliferation marker MIB1 were no significant factors. In the multivariate nominal logistic regression older age (OR 27.60 (CI 9.17–87.18), p &lt; 0.0001), larger preoperative tumor volume (OR 20.20 (CI 3.43–128.58), p = 0.0011) and widening of the internal acoustic canal (OR 7.86 (CI 1.77–35.46), p = 0.0079) remained independent factors associated with non-serviceable hearing. Conclusions. Widening of the internal acoustic canal is an independent factor for non-serviceable preoperative hearing in vestibular schwannoma patients together with older age and larger preoperative tumor volume.
eROSITA studies of the Carina Nebula
2023-12-07

During the first four all-sky surveys eRASS:4 carried out from December 2019 to 2021, the extended Roentgen Survey with an Imaging Telescope Array (eROSITA) on board Spektrum-Roentgen-Gamma (Spektr-RG, SRG) observed the Galactic HII region Carina nebula. We analysed the eRASS:4 data to study the distribution and the spectral properties of the hot interstellar plasma and the bright stellar sources in the Carina nebula. Spectral extraction regions of the diffuse emission were defined based on X-ray spectral morphology and multi-wavelength data. The spectra were fit with a combination of thermal and non-thermal emission models. X-ray bright point sources in the Carina nebula are the colliding wind binary Car, several O stars, and Wolf-Rayet (WR) stars. We extracted the spectrum of the brightest stellar sources, which can be well fit with a multi-component thermal plasma model. The spectra of the diffuse emission in the brighter parts of the Carina nebula is well reproduced by two thermal models, a lower-temperature component ( 0.2 keV) and a higher-temperature component (0.6 - 0.8 keV). An additional non-thermal component dominates the emission above 1 keV in the central region around Car and the other massive stars. Significant orbital variation of the X-ray flux was measured for Car, WR22 and WR25. Car requires an additional time-variable thermal component in the spectral model, which is associated to the wind-wind-collision zone. Properties like temperature, pressure, and luminosity of the X-ray emitting plasma in the Carina nebula derived from the eROSITA data are consistent with theoretical calculations of emission from superbubbles. It confirms that the X-ray emission is caused by the hot plasma inside the Carina nebula which has been shocked-heated by the stellar winds of the massive stars, in particular, of Car.
Cone Density Is Correlated to Outer Segment Length and Retinal Thickness in the Human Foveola
2023-12-08

Using optical coherence tomography-derived measurements of OSL enables to estimate CDC cone density and two-dimensional foveal cone density maps for example in patient eyes unsuitable for adaptive optics imaging. Furthermore, the observation of a fixed relationship between the normalized OSL and cone density points to a conserved mechanism shaping the foveal pit.
mitoBKCa is functionally expressed in murine and human breast cancer cells and potentially contributes to metabolic reprogramming
2023-12-08

Alterations in the function of K + channels such as the voltage- and Ca 2+ -activated K + channel of large conductance (BK Ca ) reportedly promote breast cancer (BC) development and progression. Underlying molecular mechanisms remain, however, elusive. Here, we provide electrophysiological evidence for a BK Ca splice variant localized to the inner mitochondrial membrane of murine and human BC cells (mitoBK Ca ). Through a combination of genetic knockdown and knockout along with a cell permeable BK Ca channel blocker, we show that mitoBK Ca modulates overall cellular and mitochondrial energy production, and mediates the metabolic rewiring referred to as the ‘Warburg effect’, thereby promoting BC cell proliferation in the presence and absence of oxygen. Additionally, we detect mitoBK Ca and BK Ca transcripts in low or high abundance, respectively, in clinical BC specimens. Together, our results emphasize, that targeting mitoBK Ca could represent a treatment strategy for selected BC patients in future.
Day care availability and awareness of gendered economic risks: How they shape work and care norms
2023-12-08

Family policies not only provide money, time and infrastructure to families, but also convey normative assumptions about what is considered desirable or acceptable in paid work and family care. This study conceptualises and empirically investigates how priming respondents with brief media report-like information on existing day care policy entitlements and economic consequences of maternal employment interruptions may change personal normative judgements about parental work–care arrangements. Furthermore, we analyse whether these effects differ between groups of respondents assumed to vary in their degree of affectedness by the information as well as previous knowledge. The theoretical framework builds on the concept of normative policy feedback effects combined with social norm theory and human cognition theories. The study is based on a fully randomized survey experiment combined with a vignette experiment in Wave 12 of the German Family Panel (pairfam). It applies linear and ordinal logistic regressions with cluster-robust standard errors to a sample of 5,783 respondents. Our results suggest that priming respondents with information on day care policy and long-term economic risks of maternal employment interruptions increases acceptance of intensive day care use across the full sample and especially for mothers with children below school entry age. It further increases support for longer maternal hours spent in paid work among childless women and mothers with school-aged children. Norms regarding paternal working hours are largely unaffected by the information given in this survey experiment.
Probing invisible vector meson decay mode with the hadronic beam in the NA64 experiment at SPS CERN
2023-12-08

We test a novel idea of using a beam in the fixed-target experiments to search for new physics in the events with missing energy. Bounds for invisible vector meson decay were derived, analyzed, and compared with the current limits on searching dark matter in the accelerator based experiments. We demonstrate that the new approach can be effective tool to probe sub-GeV dark matter parameter space.
Discovery of Lead 2-Thiazolylhydrazones with Broad-Spectrum and Potent Antifungal Activity
2023-12-08

Opportunistic fungal infections represent a global health problem, mainly for immunocompromised individuals. New therapeutical options are needed since several fungal strains show resistance to clinically available antifungal agents. 2-Thiazolylhydrazones are well-known as potent compounds against <i>Candida</i> and <i>Cryptococcus</i> species. A scaffold-focused drug design using machine-learning models was established to optimize the 2-thiazolylhydrazone skeleton and obtain novel compounds with higher potency, better solubility in water, and enhanced absorption. Twenty-nine novel compounds were obtained and most showed low micromolar MIC values against different species of <i>Candida</i> and <i>Cryptococcus</i> spp., including <i>Candida auris</i>, an emerging multidrug-resistant yeast. Among the synthesized compounds, 2-thiazolylhydrazone <b>28</b> (MIC value ranging from 0.8 to 52.17 μM) was selected for further studies: cytotoxicity evaluation, permeability study in Caco-2 cell model, and <i>in vivo</i> efficacy against <i>Cryptococcus neoformans</i> in an invertebrate infection model. All results obtained indicate the great potential of <b>28</b> as a novel antifungal agent.
Imaging of Pathologies of the Temporal Bone and Middle Ear: Inflammatory Diseases, Their Mimics and Potential Complications—Pictorial Review
2023-12-08

Imaging of the temporal bone and middle ear is challenging for radiologists due to the abundance of distinct anatomical structures and the plethora of possible pathologies. The basis for a precise diagnosis is knowledge of the underlying anatomy as well as the clinical presentation and the individual patient’s otological status. In this article, we aimed to summarize the most common inflammatory lesions of the temporal bone and middle ear, describe their specific imaging characteristics, and highlight their differential diagnoses. First, we introduce anatomical and imaging fundamentals. Additionally, a point-to-point comparison of the radiological and histological features of the wide spectrum of inflammatory diseases of the temporal bone and middle ear in context with a review of the current literature and current trends is given.