julilili42/papers huggingface dataset:
Genome-Scale Modeling ofRothia mucilaginosaReveals Insights into Metabolic Capabilities and Therapeutic Strategies for Cystic Fibrosis
2023-11-21

ABSTRACT Background Cystic fibrosis (CF) is an inherited genetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, resulting in the production of sticky and thick mucosal fluids. This leads to an environment that facilitates the colonization of various microorganisms, some of which can cause acute and chronic lung infections, while others may have a positive influence on the disease process. Rothia mucilaginosa , an oral commensal, is relatively abundant in the lungs of CF patients. Recent studies have unveiled the anti-inflammatory properties of R. mucilaginosa using in vitro three-dimensional (3-D) lung epithelial cell cultures and in vivo mouse models relevant to chronic lung diseases. Apart from a potentially beneficial anti-inflammatory role in chronic lung diseases, R. mucilaginosa has been associated with severe infections. This dual nature highlights the bacterium’s complexity and diverse impact on health and disease. However, its metabolic capabilities and genotype-phenotype relationships remain largely unknown. Results To gain insights into the cellular metabolism and genetic content of R. mucilaginosa , we developed the first manually curated genome-scale metabolic model, i RM23NL. Through growth kinetic experiments and high-throughput phenotypic microarray testings, we defined its complete catabolic phenome. Subsequently, we assessed the model’s effectiveness in accurately predicting growth behaviors and utilizing multiple substrates. We used constraint-based modeling techniques to formulate novel hypotheses that could expedite the development of antimicrobial strategies. More specifically, we detected putative essential genes and assessed their effect on metabolism under varying nutritional conditions. These predictions could offer novel potential antimicrobial targets without laborious large-scale screening of knock-outs and mutant transposon libraries. Conclusion Overall, i RM23NL demonstrates a solid capability to predict cellular phenotypes and holds immense potential as a valuable resource for accurate predictions in advancing antimicrobial therapies. Moreover, it can guide metabolic engineering to tailor R. mucilaginosa ’s metabolism for desired performance.
Minimizing Interfacial Recombination in 1.8 eV Triple‐Halide Perovskites for 27.5% Efficient All‐Perovskite Tandems
2023-11-22

Abstract All‐perovskite tandem solar cells show great potential to enable the highest performance at reasonable costs for a viable market entry in the near future. In particular, wide‐bandgap (WBG) perovskites with higher open‐circuit voltage ( V OC ) are essential to further improve the tandem solar cells’ performance. Here, a new 1.8 eV bandgap triple‐halide perovskite composition in conjunction with a piperazinium iodide (PI) surface treatment is developed. With structural analysis, it is found that the PI modifies the surface through a reduction of excess lead iodide in the perovskite and additionally penetrates the bulk. Constant light‐induced magneto‐transport measurements are applied to separately resolve charge carrier properties of electrons and holes. These measurements reveal a reduced deep trap state density, and improved steady‐state carrier lifetime (factor 2.6) and diffusion lengths (factor 1.6). As a result, WBG PSCs achieve 1.36 V V OC , reaching 90% of the radiative limit. Combined with a 1.26 eV narrow bandgap (NBG) perovskite with a rubidium iodide additive, this enables a tandem cell with a certified scan efficiency of 27.5%.
The Cycling Mechanism of Manganese‐Oxide Cathodes in Zinc Batteries: A Theory‐Based Approach
2023-11-22

Abstract Zinc‐based batteries offer good volumetric energy densities and are compatible with environmentally friendly aqueous electrolytes. Zinc‐ion batteries (ZIBs) rely on a lithium‐ion‐like Zn 2+ ‐shuttle, which enables higher roundtrip efficiencies and better cycle life than zinc‐air batteries. Manganese‐oxide cathodes in near‐neutral zinc sulfate electrolytes are the most prominent candidates for ZIBs. Zn 2+ ‐insertion, H + ‐insertion, and Mn 2+ ‐dissolution are proposed to contribute to the charge‐storage mechanism. During discharge and charge, two distinct phases are observed. Notably, the pH‐driven precipitation of zinc‐sulfate‐hydroxide is detected during the second discharge phase. However, a complete and consistent understanding of the two‐phase mechanism of these ZIBs is still missing. This paper presents a continuum full cell model supported by density functional theory (DFT) calculations to investigate the implications of these observations. The complex‐formation reactions of near‐neutral aqueous electrolytes are integrated into the battery model and, in combination with the DFT calculations, draw a consistent picture of the cycling mechanism. The interplay between electrolyte pH and reaction mechanisms is investigated at the manganese‐oxide cathodes and the dominant charge‐storage mechanism is identified. The model is validated with electrochemical cycling data, cyclic voltammograms, and in situ pH measurements. This allows to analyze the influence of cell design and electrolyte composition on cycling and optimize the battery performance.
Peripheral vision is mainly for looking rather than seeing
2023-11-22

Vision includes looking and seeing. Looking, mainly via gaze shifts, selects a fraction of visual input information for passage through the brain's information bottleneck. The selected input is placed within the attentional spotlight, typically in the central visual field. Seeing decodes, i.e., recognizes and discriminates, the selected inputs. Hence, peripheral vision should be mainly devoted to looking, in particular, deciding where to shift the gaze. Looking is often guided exogenously by a saliency map created by the primary visual cortex (V1), and can be effective with no seeing and limited awareness. In seeing, peripheral vision not only suffers from poor spatial resolution, but is also subject to crowding and is more vulnerable to illusions by misleading, ambiguous, and impoverished visual inputs. Central vision, mainly for seeing, enjoys the top-down feedback that aids seeing in light of the bottleneck which is hypothesized to starts from V1 to higher areas. This feedback queries for additional information from lower visual cortical areas such as V1 for ongoing recognition. Peripheral vision is deficient in this feedback according to the Central-peripheral Dichotomy (CPD) theory. The saccades engendered by peripheral vision allows looking to combine with seeing to give human observers the impression of seeing the whole scene clearly despite inattentional blindness.
Reinforcing the idea of an early dispersal of Hippopotamus amphibius in Europe: Restoration and multidisciplinary study of the skull from the Middle Pleistocene of Cava Montanari (Rome, central Italy)
2023-11-22

A skull of Hippopotamus recovered from the area of Tor di Quinto, within the urban area of Rome (central Italy) is here redescribed. Despite being one of the most complete specimens of hippopotamuses of the European Pleistocene, the Tor di Quinto skull did not attract much research interest, due to long-standing uncertainties on its provenance. This work begun in 2021, when the skull was restored, within a large renovation project on the vertebrate exposed at the Earth Science University Museum of Sapienza University of Rome. Original sediments were found inside the cranial and mandible cavities during the restoration work, which were sampled for petrographic analyses. By combining a review of the old paleontological, archeological and geological literature published during the 19 th and 20 th century on the Rome basin and the correlation of these new sedimentological and petrographic information with the lithostratigraphic and synthemic units of the national geological cartography, we clarify that the Hippopotamus skull was most likely to have been collected from a quarry called Cava Montanari, from a formation dated between 560 and 460 ka. Morphological and biometric analyses clearly support an attribution of the Cava Montanari specimen to the extant species Hippopotamus amphibius . The reassessment of the stratigraphic and geological data on Cava Montanari implies that the studied specimen is the earliest confirmed occurrence of Hippopotamus amphibius in the European fossil record.
Predictive Value of Minimal Residual Disease for Efficacy of Rituximab Maintenance in Mantle Cell Lymphoma: Results From the European Mantle Cell Lymphoma Elderly Trial
2023-11-22

PURPOSE The outcome of older patients with mantle cell lymphoma (MCL) has improved by the introduction of immunochemotherapy, followed by rituximab (R)-maintenance. Assessment of minimal residual disease (MRD) represents a promising tool for individualized treatment decisions and was a prospectively planned part of the European MCL Elderly trial. We investigated how MRD status influenced the efficacy of R-maintenance and how MRD can enable tailored consolidation strategies. PATIENTS AND METHODS Previously untreated patients with MCL age 60 years or older have been randomly assigned to R versus interferon-alpha maintenance after response to rituximab, fludarabine, cyclophosphamide (R-FC) versus rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP). MRD monitoring was performed by real-time quantitative polymerase chain reaction (qPCR) following EuroMRD guidelines. RESULTS A qPCR assay with a median sensitivity of 1 × 10 −5 could be generated in 80% of 288 patients in an international, multicenter, multilaboratory setting. More extensive tumor dissemination facilitated the identification of a molecular marker. The efficacy of R-maintenance in clinical remission was confirmed for MRD-negative patients at the end of induction in terms of progression-free survival (PFS; hazard ratio [HR], 0.38 [95% CI, 0.21 to 0.63]) and overall survival (OS; HR, 0.37 [95% CI, 0.20 to 0.68]), particularly in R-CHOP–treated patients (PFS-HR, 0.23 [95% CI, 0.10 to 0.52]; OS-HR, 0.19 [95% CI, 0.07 to 0.52]). R-maintenance appeared less effective in MRD-positive patients (PFS-HR, 0.51 [95% CI, 0.26 to 1.02]) overall and after R-CHOP induction (PFS-HR, 0.59 [95% CI, 0.28 to 1.26]). R-FC achieved more frequent and faster MRD clearance compared with R-CHOP. MRD positivity in clinical remission after induction was associated with a short median time to clinical progression of approximately 1-1.7 years. CONCLUSION The results confirm the strong efficacy of R-maintenance in patients who are MRD-negative after induction. Treatment de-escalation for MRD-negative patients is discouraged by our results. More effective consolidation strategies should be explored in MRD-positive patients to improve their long-term prognosis.
Validation of the PEDiatric Behçet’s Disease classification criteria: an evidence-based approach
2023-11-22

Abstract Objectives To validate the PEDiatric Behçet’s Disease classification criteria (PEDBD) with an evidence-based approach. Methods A total of 210 pediatric patients [70 Behçet’s disease (BD), 40 periodic fever, aphthous stomatitis, pharyngitis, adenitis, 35 familial Mediterranean fever, 26 hyper-IgD syndrome, 22 TNF-receptor associated periodic fever syndrome, 17 undefined recurrent fevers] were randomly selected from the Eurofever Registry. A set of 11 experienced clinicians/researchers blinded to the original diagnosis evaluated the patients. Using the table consensus as gold standard (agreement ≥ 80%), the PEDBD, ISG and ICBD criteria were applied to BD patients and to confounding diseases with other autoinflammatory conditions in order to define their sensitivity, specificity and accuracy. Results At the end of the third round, a consensus was reached in 139/210 patients (66.2%). The patients with a consensus ≥80% were classified as confirmed BD (n = 24), and those with an agreement of 60–79% as probable BD (n = 10). When comparing these patients with the confounding diseases group, an older age at disease onset, the presence of oral and genital ulcers, skin papulo-pustular lesions, a positive pathergy test and posterior uveitis were BD distinctive elements. The ISG, ICBD and PEDBD criteria were applied to confirmed BD and to the confounding disease group, showing a sensitivity of 0.50, 0.79 and 0.58, a specificity of 1.00, 0.97 and 0.99, and an accuracy of 0.91, 0.94 and 0.92, respectively. Conclusions The PEDBD criteria were very specific, while the ICBD were more sensitive. The complexity of childhood BD suggests larger prospective international cohorts to further evaluate the performance of the criteria.
ThePgb1locus controls glycogen aggregation in astrocytes of the aged hippocampus without impacting cognitive function
2023-11-22

Abstract In aged humans and mice, aggregates of hypobranched glycogen molecules called polyglucosan bodies (PGBs) accumulate in hippocampal astrocytes. PGBs are known to drive cognitive decline in neurological diseases but remain largely unstudied in the context of typical brain aging. Here, we show that PGBs arise in autophagy-dysregulated astrocytes of the aged C57BL/6J mouse hippocampus. To map the genetic cause of age-related PGB accumulation, we quantified PGB burden in 32 fully sequenced BXD-recombinant inbred mouse strains, which display a 400-fold variation in hippocampal PGB burden at 16-18 months of age. A major modifier locus was mapped to chromosome 1 at 72–75 Mb, which we defined as the Pgb1 locus. To evaluate candidate genes and downstream mechanisms by which Pgb1 controls the aggregation of glycogen, extensive hippocampal transcriptomic and proteomic datasets were produced for aged mice of the BXD family. We utilized these datasets to identify Smarcal1 and Usp37 as potential regulators of PGB accumulation. To assess the effect of PGB burden on age-related cognitive decline, we performed phenome-wide association scans, transcriptomic analyses as well as conditioned fear memory and Y-maze testing. Importantly, we did not find any evidence suggesting a negative impact of PGBs on cognition. Taken together, our study demonstrates that the Pgb1 locus controls glycogen aggregation in astrocytes of the aged hippocampus without affecting age-related cognitive decline.
Diplomacy online: A case of mistaking broadcasting for dialogue
2023-11-22

Abstract Online discussions can fuel perceptions of misalignment, disagreement, conflict or even polarization. In this study, we look at everyday diplomatic expressions that could buffer this. We use automated and manual coding to analyze diplomatic behaviour in online discussions and its consequences for discussion sentiment. We analyze Reddit forums with differing norms: civil ( N = 4594 comments), incivil ( N = 2126) and social support subreddits ( N = 1401). The automated content analysis shows that diplomatic behaviour occurs but does not affect the subsequent discussion. The manual analysis reveals why: discussions consist of disjointed statements rather than dialogue, making diplomacy inconsequential. These results have consequences for the field. First, what appears to be an escalating dialogue might actually be a string of personal attitudes broadcasted in a shared space. Second, the usefulness of automated content analysis in studying interaction dynamics is limited because of difficulties distinguishing broadcasting from dialogue.
Researching far right extremism—a transdisciplinary, lifeworld, and political culture perspective
2023-11-22

Abstract Far right extremism, understood as both an ideology of inequality and exclusion that manifests itself in attitudes and behavior as well as a heterogeneous movement, partially with affinity to violence, challenges and even threatens democratic societies. We argue that social science research on far right extremism contributes to strengthen democracy and civil society against this threat. By adopting a transdisciplinary, lifeworld (Lebenswelt) and political culture perspective, social science can contribute to this task and also help to overcome the fragmentation of the research field. In this article, we first provide an overview of current developments in social science research on far right extremism with a focus on Germany. Second, we outline five premises for such a transdisciplinary research perspective on far right extremism. Thus, we argue for adopting both a theoretical perspective built around the lifeword’ concept and methodological pluralism. Third, we propose four interrelated thematic clusters as a taxonomy of transdisciplinary research perspectives on far right extremism: a) Far right ideologies and knowledge constructions; b) Far right actors, organizations, and networks; c) Far right extremist discourses, (digital) media, and strategies in the public sphere; and d) political education, transfer, and implementation research regarding projects against far right extremism. Fourth, we argue that further institutionalization research on far right extremism is indispensable to make research on far right extremism more sustainable, to connect research with societal actors, and to utilize research results to strengthen society’s democratic resilience.
Ein Konflikt in der Maxime. Kants Auffassung des moralischen Konflikts im Kontext seiner Zeit
2023-11-22

Abstract What does Kant mean when he claims that a moral conflict is only possible as a conflict between obligating reasons ( rationes obligandi )? How does this differ from a conflict of duties? And how does Kant’s idea relate to the understandings of moral conflict prevalent in his time? This paper distinguishes three influential traditional models (as represented by Wolff, Baumgarten, and Jesuit casuistry) for a comparison with Kant’s own conception of moral conflict. Before investigating these issues more deeply, the paper discusses a preliminary point regarding the liminal localization of the moral conflict between the domains of theory and practice. As a result, its solution depends both on the consistency of the moral theory and on the agent’s conscientiousness in the practice of moral judgment.
Eleven strategies for making reproducible research and open science training the norm at research institutions
2023-11-23

Reproducible research and open science practices have the potential to accelerate scientific progress by allowing others to reuse research outputs, and by promoting rigorous research that is more likely to yield trustworthy results. However, these practices are uncommon in many fields, so there is a clear need for training that helps and encourages researchers to integrate reproducible research and open science practices into their daily work. Here, we outline eleven strategies for making training in these practices the norm at research institutions. The strategies, which emerged from a virtual brainstorming event organized in collaboration with the German Reproducibility Network, are concentrated in three areas: (i) adapting research assessment criteria and program requirements; (ii) training; (iii) building communities. We provide a brief overview of each strategy, offer tips for implementation, and provide links to resources. We also highlight the importance of allocating resources and monitoring impact. Our goal is to encourage researchers – in their roles as scientists, supervisors, mentors, instructors, and members of curriculum, hiring or evaluation committees – to think creatively about the many ways they can promote reproducible research and open science practices in their institutions.
Accurate long-read sequencing identified GBA1 as major risk factor in the Luxembourgish Parkinson’s study
2023-11-23

Abstract Heterozygous variants in the glucocerebrosidase GBA1 gene are an increasingly recognized risk factor for Parkinson’s disease (PD). Due to the GBAP1 pseudogene, which shares 96% sequence homology with the GBA1 coding region, accurate variant calling by array-based or short-read sequencing methods remains a major challenge in understanding the genetic landscape of GBA1 -associated PD. We analyzed 660 patients with PD, 100 patients with Parkinsonism and 808 healthy controls from the Luxembourg Parkinson’s study, sequenced using amplicon-based long-read DNA sequencing technology. We found that 12.1% (77/637) of PD patients carried GBA1 variants, with 10.5% (67/637) of them carrying known pathogenic variants (including severe, mild, risk variants). In comparison, 5% (34/675) of the healthy controls carried GBA1 variants, and among them, 4.3% (29/675) were identified as pathogenic variant carriers. We found four GBA1 variants in patients with atypical parkinsonism. Pathogenic GBA1 variants were 2.6-fold more frequently observed in PD patients compared to controls (OR = 2.6; CI = [1.6,4.1]). Three novel variants of unknown significance (VUS) were identified. Using a structure-based approach, we defined a potential risk prediction method for VUS. This study describes the full landscape of GBA1 -related parkinsonism in Luxembourg, showing a high prevalence of GBA1 variants as the major genetic risk for PD. Although the long-read DNA sequencing technique used in our study may be limited in its effectiveness to detect potential structural variants, our approach provides an important advancement for highly accurate GBA1 variant calling, which is essential for providing access to emerging causative therapies for GBA1 carriers.
Parathyroid hormone stimulates bone regeneration in an atrophic non-union model in aged mice
2023-11-23

Abstract Background Non-union formation still represents a major burden in trauma and orthopedic surgery. Moreover, aged patients are at an increased risk for bone healing failure. Parathyroid hormone (PTH) has been shown to accelerate fracture healing in young adult animals. However, there is no information whether PTH also stimulates bone regeneration in atrophic non-unions in the aged. Therefore, the aim of the present study was to analyze the effect of PTH on bone regeneration in an atrophic non-union model in aged CD-1 mice. Methods After creation of a 1.8 mm segmental defect, mice femora were stabilized by pin-clip fixation. The animals were treated daily with either 200 μg/kg body weight PTH 1–34 (n = 17) or saline (control; n = 17) subcutaneously. Bone regeneration was analyzed by means of X-ray, biomechanics, micro-computed tomography (μCT) imaging as well as histological, immunohistochemical and Western blot analyses. Results In PTH-treated animals bone formation was markedly improved when compared to controls. This was associated with an increased bending stiffness as well as a higher number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts and CD31-positive microvessels within the callus tissue. Furthermore, PTH-treated aged animals showed a decreased inflammatory response, characterized by a lower number of MPO-positive granulocytes and CD68-positive macrophages within the bone defects when compared to controls. Additional Western blot analyses demonstrated a significantly higher expression of cyclooxygenase (COX)-2 and phosphoinositide 3-kinase (PI3K) in PTH-treated mice. Conclusion Taken together, these findings indicate that PTH is an effective pharmacological compound for the treatment of non-union formation in aged animals.