julilili42/papers huggingface dataset:
14th century Yersinia pestis genomes support emergence of pestis secunda within Europe
2023-07-18

Pestis secunda (1356–1366 CE) is the first of a series of plague outbreaks in Europe that followed the Black Death (1346–1353 CE). Collectively this period is called the Second Pandemic. From a genomic perspective, the majority of post-Black Death strains of Yersinia pestis thus far identified in Europe display diversity accumulated over a period of centuries that form a terminal sub-branch of the Y . pestis phylogeny. It has been debated if these strains arose from local evolution of Y . pestis or if the disease was repeatedly reintroduced from an external source. Plague lineages descended from the pestis secunda , however, are thought to have persisted in non-human reservoirs outside Europe, where they eventually gave rise to the Third Pandemic (19 th and 20 th centuries). Resolution of competing hypotheses on the origins of the many post-Black Death outbreaks has been hindered in part by the low representation of Y . pestis genomes in archaeological specimens, especially for the pestis secunda . Here we report on five individuals from Germany that were infected with lineages of plague associated with the pestis secunda . For the two genomes of high coverage, one groups within the known diversity of genotypes associated with the pestis secunda , while the second carries an ancestral genotype that places it earlier. Through consideration of historical sources that explore first documentation of the pandemic in today’s Central Germany, we argue that these data provide robust evidence to support a post-Black Death evolution of the pathogen within Europe rather than a re-introduction from outside. Additionally, we demonstrate retrievability of Y . pestis DNA in post-cranial remains and highlight the importance of hypothesis-free pathogen screening approaches in evaluations of archaeological samples.
Development of an airfoil-based passive volumetric air sampling and flow control system for fixed-wing UAS
2023-07-18

Abstract This study aims to develop a concept of a passive volumetric flow control system for gas sampling applications onboard fixed-wing UAS based on the pressure field around airfoils. The passive flow control system utilizes the aerodynamics of a UAS to create a vacuum pump effect that ensures constant gas sampling, which can be used to facilitate airborne aerosol and gas measurements. The pump effect is achieved by short-circuiting the pressure field’s minima and maxima points around an airfoil through pipes and 3D printed structures that could function both as a pump system and a gas measurement chamber. The design of this structurally integrated functionality brings many advantages for scientific applications, especially onboard small research UAS, which would dispense entirely with complex active pump systems, thus reducing weight and ensuring gas sampling at a constant volumetric flow rate independent of altitude and atmospheric variance. In favor of developing further applications, this paper outlines the development steps of the passive pump concept starting from the theory and numerical modeling of the effect to the implementation on board a fixed-wing UAS. Finally, possible improvements based on numerical models and flight measurements are discussed.
Chinese monks, dragons, and reincarnation: the hand of Juan Cobo in the cultural translation of Mingxin baojian 明心寶鑑 (Precious Mirror for Enlightening the Mind), circa 1590
2023-07-18

Abstract This article examines the relationship between the manuscript translation of Mingxin baojian 明心寶鑑 ( Precious Mirror for Enlightening the Mind ) ( circa 1590) by Juan Cobo ( circa 1546–1592) and the Fujian book market in China. It explores the cultural implications of Cobo's translation by focusing on the commentary he provided in the marginalia of the manuscript. By investigating Cobo's translation and marginalia notes on three Chinese concepts—Chinese monks, dragons, and reincarnation—this article highlights the complex cultural issues present when the early Spanish missionaries in the Philippines negotiated with Chinese culture in their writings and publications.
Inherited retinal degeneration: T-type voltage-gated channels, Na+/Ca2+-exchanger and calpain-2 promote photoreceptor cell death
2023-07-18

ABSTRACT Inherited retinal degeneration (IRD) refers to a group of untreatable blinding diseases characterized by a progressive loss of photoreceptors. IRD pathology is often linked to an excessive activation of cyclic nucleotide-gated channels (CNGC) leading to Na + – and Ca 2+ -influx, subsequent activation of voltage-gated Ca 2+ -channels (VGCC), and further Ca 2+ influx. However, whether and how exactly intracellular Ca 2+ overload contributes to photoreceptor degeneration is still controversial. Here, we used whole-retina and single-cell RNA-sequencing to compare gene expression between the rd1 mouse model for IRD and wild-type ( wt ) mice. Differentially expressed genes were linked to several Ca 2+ –signalling related pathways. To explore this further, organotypic retinal explant cultures derived from rd1 and wt mice were treated with the intracellular Ca 2+ -chelator BAPTA-AM and with inhibitors for different Ca 2+ -permeable channels, including CNGC, L-type VGCC, T-type VGCC, Ca 2+ -release-activated channel (CRAC), and Na + /Ca 2+ exchanger (NCX). Moreover, we employed the compound NA-184 to selectively inhibit the Ca 2+ -dependent protease calpain-2. The overall activity of poly(ADP-ribose) polymerases (PARPs), sirtuin-type histone-deacetylases, calpains, as well as the activation of calpain-1, and –2 were analysed in situ on retinal tissue sections. Cell viability was assessed via the TUNEL assay. While rd1 photoreceptor cell death was reduced by BAPTA-AM, the effects of Ca 2+ -channel blockers were ambiguous, with T-type VGCC and NCX inhibition showing protection, while blocking CNGC and CRAC was detrimental. Activity of calpains and PARPs generally followed similar trends as cell death. Remarkably, sirtuin activity and calpain-1 activation was associated with photoreceptor protection, while calpain-2 activity was linked to degeneration. Accordingly, the calpain-2 inhibitor NA-184 protected rd1 photoreceptors. Together, these results indicate that Ca 2+ overload in rd1 photoreceptors may be triggered by T-type VGCC in conjunction with NCX. High Ca 2+ -levels likely suppress the protective activity of calpain-1 and promote neurodegeneration via activation of calpain-2. Our study details the complexity of Ca 2+ -signalling in photoreceptors and emphasizes the importance of identifying and targeting degenerative processes to achieve a therapeutic benefit for IRD.
BakedSDF: Meshing Neural SDFs for Real-Time View Synthesis
2023-07-19

We present a method for reconstructing high-quality meshes of large unbounded real-world scenes suitable for photorealistic novel view synthesis. We first optimize a hybrid neural volume-surface scene representation designed to have well-behaved level sets that correspond to surfaces in the scene. We then bake this representation into a high-quality triangle mesh, which we equip with a simple and fast view-dependent appearance model based on spherical Gaussians. Finally, we optimize this baked representation to best reproduce the captured viewpoints, resulting in a model that can leverage accelerated polygon rasterization pipelines for real-time view synthesis on commodity hardware. Our approach outperforms previous scene representations for real-time rendering in terms of accuracy, speed, and power consumption, and produces high quality meshes that enable applications such as appearance editing and physical simulation.
T Cells in Colorectal Cancer: Unravelling the Function of Different T Cell Subsets in the Tumor Microenvironment
2023-07-19

Therapeutic options for metastatic colorectal cancer (mCRC) are very limited, and the prognosis using combination therapy with a chemotherapeutic drug and a targeted agent, e.g., epidermal growth factor receptor or tyrosine kinase, remains poor. Therefore, mCRC is associated with a poor median overall survival (mOS) of only 25–30 months. Current immunotherapies with checkpoint inhibitor blockade (ICB) have led to a substantial change in the treatment of several cancers, such as melanoma and non-small cell lung cancer. In CRC, ICB has only limited effects, except in patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) tumors, which comprise about 15% of sporadic CRC patients and about 4% of patients with metastatic CRC. The vast majority of sporadic CRCs are microsatellite-stable (MSS) tumors with low levels of infiltrating immune cells, in which immunotherapy has no clinical benefit so far. Immunotherapy with checkpoint inhibitors requires the presence of infiltrating T cells into the tumor microenvironment (TME). This makes T cells the most important effector cells in the TME, as evidenced by the establishment of the immunoscore—a method to estimate the prognosis of CRC patients. The microenvironment of a tumor contains several types of T cells that are anti-tumorigenic, such as CD8+ T cells or pro-tumorigenic, such as regulatory T cells (Tregs) or T helper 17 (Th17) cells. However, even CD8+ T cells show marked heterogeneity, e.g., they can become exhausted, enter a state of hyporesponsiveness or become dysfunctional and express high levels of checkpoint molecules, the targets for ICB. To kill cancer cells, CD8+ T cells need the recognition of the MHC class I, which is often downregulated on colorectal cancer cells. In this case, a population of unconventional T cells with a γδ T cell receptor can overcome the limitations of the conventional CD8+ T cells with an αβT cell receptor. γδ T cells recognize antigens in an MHC-independent manner, thus acting as a bridge between innate and adaptive immunity. Here, we discuss the effects of different T cell subsets in colorectal cancer with a special emphasis on γδ T cells and the possibility of using them in CAR-T cell therapy. We explain T cell exclusion in microsatellite-stable colorectal cancer and the possibilities to overcome this exclusion to enable immunotherapy even in these “cold” tumors.
Goethite Formed in the Periplasmic Space of Pseudomonas sp. JM-7 during Fe Cycling Enhances Its Denitrification in Water
2023-07-19

Denitrification-driven Fe(II) oxidation is an important microbial metabolism that connects iron and nitrogen cycling in the environment. The formation of Fe(III) minerals in the periplasmic space has a significant effect on microbial metabolism and electron transfer, but direct evidence of iron ions entering the periplasm and resulting in periplasmic mineral precipitation and electron conduction properties has yet to be conclusively determined. Here, we investigated the pathways and amounts of iron, with different valence states and morphologies, entering the periplasmic space of the denitrifier <i>Pseudomonas</i> sp. JM-7 (<i>P.</i> JM-7), and the possible effects on the electron transfer and the denitrifying ability. When consistently provided with Fe(II) ions (from siderite (FeCO<sub>3</sub>)), the dissolved Fe(II) ions entered the periplasmic space and were oxidized to Fe(III), leading to the formation of a 25 nm thick crystalline goethite crust, which functioned as a semiconductor, accelerating the transfer of electrons from the intracellular to the extracellular matrix. This consequently doubled the denitrification rate and increased the electron transport capacity by 4-30 times (0.015-0.04 μA). However, as the Fe(II) concentration further increased to above 4 mM, the Fe(II) ions tended to preferentially nucleate, oxidize, and crystallize on the outer surface of <i>P.</i> JM-7, leading to the formation of a densely crystallized goethite layer, which significantly slowed down the metabolism of <i>P.</i> JM-7. In contrast to the Fe(II) conditions, regardless of the initial concentration of Fe(III), it was challenging for Fe(III) ions to form goethite in the periplasmic space. This work has shed light on the likely effects of iron on environmental microorganisms, improved our understanding of globally significant iron and nitrogen geochemical cycles in water, and expanded our ability to study and control these important processes.
Scalable and efficient DNA sequencing analysis on different compute infrastructures aiding variant discovery
2023-07-19

Abstract DNA variation analysis has become indispensable in many aspects of modern biomedicine, most prominently in the comparison of normal and tumor samples. Thousands of samples are collected in local sequencing efforts and public databases requiring highly scalable, portable, and automated workflows for streamlined processing. Here, we present nf-core/sarek 3, a well-established, comprehensive variant calling and annotation pipeline for germline and somatic samples. It is suitable for any genome with a known reference. We present a full rewrite of the original pipeline showing a significant reduction of storage requirements by using the CRAM format and runtime by increasing intra-sample parallelization. Both are leading to a 70% cost reduction in commercial clouds enabling users to do large-scale and cross-platform data analysis while keeping costs and CO 2 emissions low. The code is available at https://nf-co.re/sarek .
Inhibition of p90 ribosomal S6 kinases disrupts melanoma cell growth and immune evasion
2023-07-19

Abstract Background The mitogen-activated protein kinase (MAPK) signaling pathway is frequently hyperactivated in malignant melanoma and its inhibition has proved to be an efficient treatment option for cases harboring BRAF V600 mutations (BRAF Mut ). However, there is still a significant need for effective targeted therapies for patients with other melanoma subgroups characterized by constitutive MAPK activation, such as tumors with NRAS or NF-1 alterations (NRAS Mut , NF-1 LOF ), as well as for patients with MAPK pathway inhibitor-resistant BRAF Mut melanomas, which commonly exhibit a reactivation of this pathway. p90 ribosomal S6 kinases (RSKs) represent central effectors of MAPK signaling, regulating cell cycle progression and survival. Methods RSK activity and the functional effects of its inhibition by specific small molecule inhibitors were investigated in established melanoma cell lines and patient-derived short-term cultures from different MAPK pathway-hyperactivated genomic subgroups (NRAS Mut , BRAF Mut , NF-1 LOF ). Real-time qPCR, immunoblots and flow cytometric cell surface staining were used to explore the molecular changes following RSK inhibition. The effect on melanoma cell growth was evaluated by various two- and three-dimensional in vitro assays as well as with melanoma xenograft mouse models. Co-cultures with gp100- or Melan-A-specific cytotoxic T cells were used to assess immunogenicity of melanoma cells and associated T-cell responses. Results In line with elevated activity of the MAPK/RSK signaling axis, growth and survival of not only BRAF Mut but also NRAS Mut and NF-1 LOF melanoma cells were significantly impaired by RSK inhibitors. Intriguingly, RSK inhibition was particularly effective in three-dimensional growth settings with long-term chronic drug exposure and suppressed tumor cell growth of in vivo melanoma models. Additionally, our study revealed that RSK inhibition simultaneously promoted differentiation and immunogenicity of the tumor cells leading to enhanced T-cell activation and melanoma cell killing. Conclusions Collectively, RSK inhibitors exhibited both multi-layered anti-tumor efficacy and broad applicability across different genomic melanoma subgroups. RSK inhibition may therefore represent a promising novel therapeutic strategy for malignant melanoma with hyperactivated MAPK signaling.
Comprehensive reversed‐phase×chiral two‐dimensional liquid chromatography coupled to quadrupole‐time‐of‐flight tandem mass spectrometry with post‐first dimension flow splitting for untargeted enantioselective amino acid analysis
2023-07-19

This work describes a comprehensive achiral × chiral two‐dimensional liquid chromatography separation for enantioselective amino acid analysis coupled to electrospray ionization‐tandem mass spectrometry detection using data‐independent acquisition. Flow splitting after the first and second dimension separation was utilized for volumetric flow reduction and for enabling a multi‐detector approach (with ultraviolet, fluorescence, charged aerosol, and MS detection), respectively. Derivatization with 6‐aminoquinolyl‐ N ‐hydroxysuccinimidyl carbamate provided a chromophore, a fluorophore, and an efficient mass tag for efficient ionization in positive electrospray ionization‐mass spectrometry. Chiral columns often have limitations in terms of their chemoselectivity, which may be a problem when complex sample mixtures with structurally related compounds need to be separated. It can be alleviated by a reversed‐phase×chiral two‐dimensional‐liquid chromatography setup, in which the first dimension provides the chemoselectivity and a chiral tandem column constituted of quinine‐carbamate derived weak anion‐exchanger and zwitterionic ion‐exchanger in the second dimension separation of D‐ and L‐amino acid enantiomers. The method was used to control the stereointegrity of the therapeutic peptide octreotide. After hydrolysis, all amino acid constituents were detected with the correct configuration and composition. Some options for flow splitting and integration of destructive detectors in the first dimension separation are outlined.
Alternatives to traditional outcome modelling approaches in applied linguistics: A primer on propensity score matching
2023-07-19

Observational studies and quasi-experiments are commonplace in applied linguistics. Causal inference based on such a design hinges on different assumptions, one of which is commonly referred to as the assumption of no unmeasured confounding. To address this assumption, researchers typically consider different confounders using regression adjustment methods (i.e., entering the confounders into the model as covariates). Although these methods are theoretically sound procedures, they are not without criticism, for instance, regarding potentially extrapolated effect estimates or implausible linear functional form assumptions. In this article, we introduce an alternative statistical method, known as propensity score matching (PSM), which can help address the limitations of traditional regression adjustment methods. We use an example case study, where we first discuss the challenges applied linguists face when they intend to investigate causal effects. We illustrate how PSM can be used with applied linguistics data and examine theoretical and practical issues around each analytical step, including electing relevant covariates, estimating the propensity score, performing matching, assessing the matches, and estimating the treatment effects. Our overall goal is to provide applied linguists with an alternative method (PSM), which might be beneficial and reasonably applied in several practical situations.
Hyperthermia in the treatment of high-risk soft tissue sarcomas: a systematic review
2023-07-19

The gathered data strengthen the beneficial role of RHT in the multimodal setting. Further expert consensus and clinical trials are required to determine the optimal integration of RHT in treating STS.
Rhamnolipid Biosurfactants Enhance Microbial Oil Biodegradation in Surface Seawater from the North Sea
2023-07-19

Biosurfactants are promising alternatives to chemical dispersants for combating marine oil spills; however, the impacts of biosurfactants on microbial community composition and oil biodegradation activities remain largely unknown. Here, we conducted a time-course microcosm experiment mimicking oil spill scenarios with surface seawater from the North Sea, amended with either the biosurfactant rhamnolipid or a dispersant (Corexit 9500 or Slickgone NS). Radioactive tracer assays to track hexadecane and naphthalene oxidation as well as bacterial production revealed the highest hydrocarbon oxidation rates and general microbial activities in the rhamnolipid-amended oil microcosms, followed by oil microcosms with Slickgone and Corexit. Impacts on the microbial community composition differed among treatments, and growth of oil-degrading Colwellia was stimulated remarkably in Corexit-amended oil and oil-only microcosms, while potential oil-degrading Oleispira were highly enriched in the presence of oil in combination with rhamnolipid or Slickgone. Furthermore, increased abundances of Colwellia and Oleispira, and stimulated bacterial production in microcosms with only rhamnolipid, Corexit, or Slickgone, indicated their involvement in biosurfactant/dispersant biodegradation. Our findings highlight varying microbial impacts resulting from rhamnolipid and chemical dispersants and suggest great promise for the application of biosurfactants in future marine oil spills.
Possible Advantages of Minimal-Invasive Approaches in Rectal Cancer Surgery: A Nationwide Analysis
2023-07-19

(1) Background: Laparoscopic resection for colon and rectal cancer was introduced in the early 1990s; the aim of this analysis was to show possible advantages of minimal-invasive approaches in rectal cancer surgery. (2) Methods: From 2016 to 2020, all patients undergoing open, laparoscopic or robotic-assisted rectal cancer surgery in Germany were retrospectively analyzed regarding sex distribution, conversion rates and in-hospital mortality rates according to nationwide hospital billing data based on diagnosis-related groups (DRGs). (3) Results: In total, 68,112 patients were analyzed, and most commonly, low anterior rectal resections with primary anastomosis (n = 25,824) were performed with an increase of minimal-invasive procedures over the years (open: 51% to 27%; laparoscopic: 47% to 63% and robotic: 2% to 10%). In-hospital mortality rate was 2.95% (n = 2012). In total, 4.61%, 1.77%, 1.14% and 3.95% of patients with open, laparoscopic, robotic and converted-to-open surgery died during hospital stay, respectively (open vs. laparoscopic p &lt; 0.0001; open vs. robotic p &lt; 0.00001; laparoscopic vs. robotic p = 0.001). Conversion rates were significantly more favorable in the robotic compared to the laparoscopic group. (11.94% vs. 2.53%; p &lt; 0.0001). (4) Conclusion: Minimal-invasive rectal cancer surgery might have some advantages in terms of a reduced in-hospital mortality, and an improved conversion rate for the robotic approach.
Unique Evolution Patterns of Hepatitis B and C Viruses Revealed by Continuous Genetic Surveillance from 2015 to 2021 in Gabon, Central Africa
2023-07-19

Viral hepatitis remains one of the largest public health concerns worldwide. Especially in Central Africa, information on hepatitis virus infections has been limited, although the prevalence in this region has been reported to be higher than the global average. To reveal the current status of hepatitis B and C viruses (HBV and HCV) infections and the genetic diversity of the viruses, we conducted longitudinal surveillance in Gabon. We detected 22 HBV and 9 HCV infections in 2,047 patients with febrile illness. Genetic analyses of HBV identified subgenotype A1 for the first time in Gabon and an insertion generating a frameshift to create an X-preC/C fusion protein. We also revealed that most of the detected HCVs belonged to the &amp;ldquo;Gabon-specific&amp;rdquo; HCV subtype 4e (HCV-4e), and the entire nucleotide sequence of the HCV-4e polyprotein was determined to establish the first reference sequence. HCV-4e strains possessed resistance-associated substitutions similar to those of other HCV-4 strains, indicating that the use of direct-acting antiviral therapy may be complex. These results provide a better understanding of the current situation of hepatitis B and C virus infections in Central Africa, and will help public health organizations develop effective countermeasures to eliminate chronic viral hepatitis in this region.