bluuebunny/crossref_metadata_2025_split huggingface dataset:
Revisiting the Proof-Structure of Kant’s Transcendental Deduction
Authors: Kim Hyoung Sung 
Published: November 2022

AbstractThere is no consensus concerning how to understand the ‘two-step proof structure’ (§§15–20, 21–7) of the Transcendental Deduction in the B-edition of the Critique of Pure Reason. This disagreement invites a closer examination of what Kant might have meant by a ‘transcendental deduction’. I argue that the transcendental deduction consists of three tasks that parallel Kant’s broader project of a ‘critique’ of pure reason; first, an origin task to justify reason’s authority to use them; second, an analytical task that determines the conditions under which this authority can be legitimately exercised; and third, a dialectical task to determine the conditions under which this authority cannot be legitimately exercised. So long as we continue to read the B-Deduction solely in terms of its two-step proof structure, we overlook how Kant’s notion of ‘critique’ constitutes the real grounds for his argumentative strategy there.
Metformin abrogates Fusobacterium nucleatum-induced chemoresistance in colorectal cancer by inhibiting miR-361-5p/sonic hedgehog signaling-regulated stemness
Authors: Hong Xia-Lu , Yu Ta-Chung , Huang Xiao-Wen , Wang Ji-Lin , Sun Tian-Tian , Yan Ting-Ting , Zhou Cheng-Bei , Chen Hui-Min , Su Wen-Yu , Du Wan , Xiong Hua 
Published: November 2022

Abstract
Background
Chemotherapy resistance is the major cause of recurrence in patients with colorectal cancer (CRC). A previous study found that Fusobacterium (F.) nucleatum promoted CRC chemoresistance. Additionally, metformin rescued F. nucleatum-induced tumorigenicity of CRC. Here, we aimed to investigate whether metformin could revert F. nucleatum-induced chemoresistance and explore the mechanism.

Methods
The role of metformin in F. nucleatum-infected CRC cells was confirmed using cell counting kit 8 assays and CRC xenograft mice. Stemness was identified by tumorsphere formation. Bioinformatic analyses were used to explore the regulatory molecules involved in metformin and F. nucleatum-mediated regulation of the sonic hedgehog pathway.

Results
We found that metformin abrogated F. nucleatum-promoted CRC resistance to chemotherapy. Furthermore, metformin attenuated F. nucleatum-stimulated stemness by inhibiting sonic hedgehog signaling. Mechanistically, metformin diminished sonic hedgehog signaling proteins by targeting the MYC/miR-361-5p cascade to reverse F. nucleatum-induced stemness, thereby rescuing F. nucleatum-triggered chemoresistance in CRC.

Conclusions
Metformin acts on F. nucleatum-infected CRC via the MYC/miR-361-5p/sonic hedgehog pathway cascade, subsequently reversing stemness and abolishing F. nucleatum-triggered chemoresistance. Our results identified metformin intervention as a potential clinical treatment for patients with chemoresistant CRC with high amounts of F. nucleatum.
Dietary long-chain omega 3 fatty acids modify sphingolipid metabolism to facilitate airway hyperreactivity
Authors: Heras Andrea , Gomi Rika , Young Madeline , Chang Chuchun L. , Wasserman Emily , Sharma Anurag , Wu Wenzhu , Gu Jinghua , Balaji Uthra , White Rachel , Permaul Perdita , Janahi Ibrahim , Worgall Tilla S. , Worgall Stefan 
Published: November 2022

AbstractOmega-3 polyunsaturated fatty acids (n-3 PUFAs) are essential nutrients that can affect inflammatory responses. While n-3 PUFAs are generally considered beneficial for cardiovascular disease and obesity, the effects on asthma, the most common inflammatory lung disease are unclear. While prenatal dietary n-3 PUFAs decrease the risk for childhood wheezing, postnatal dietary n-3 PUFAs can worsen allergic airway inflammation. Sphingolipid metabolism is also affected by dietary n-3 PUFAs. Decreased sphingolipid synthesis leads to airway hyperreactivity, besides inflammation, a cardinal feature of asthma, and common genetic asthma risk alleles lead to lower sphingolipid synthesis. We investigated the effect of dietary n-3 PUFAs on sphingolipid metabolism and airway reactivity. Comparing a fish-oil diet with a high n-3 PUFA content (FO) to an isocaloric coconut oil-enriched diet (CO), we found an n-3 PUFA-dependent effect on increased airway reactivity, that was not accompanied by inflammation. Lung and whole blood content of dihydroceramides, ceramides, sphingomyelins, and glucosylceramides were lower in mice fed the n-3 PUFA enriched diet consistent with lower sphingolipid synthesis. In contrast, phosphorylated long chain bases such as sphingosine 1-phosphate were increased. These findings suggest that dietary n-3 PUFAs affect pulmonary sphingolipid composition to favor innate airway hyperreactivity, independent of inflammation, and point to an important role of n-3 PUFAs in sphingolipid metabolism.
Nasal microbiome disruption and recovery after mupirocin treatment in Staphylococcus aureus carriers and noncarriers
Authors: Baede Valérie O. , Barray Anaïs , Tavakol Mehri , Lina Gérard , Vos Margreet C. , Rasigade Jean-Philippe 
Published: November 2022

AbstractNasal decolonization procedures against the opportunistic pathogen Staphylococcus aureus rely on topical antimicrobial drug usage, whose impact on the nasal microbiota is poorly understood. We examined this impact in healthy S. aureus carriers and noncarriers. This is a prospective interventional cohort study of 8 S. aureus carriers and 8 noncarriers treated with nasal mupirocin and chlorhexidine baths. Sequential nasal swabs were taken over 6 months. S. aureus was detected by quantitative culture and genotyped using spa typing. RNA-based 16S species-level metabarcoding was used to assess the living microbial diversity. The species Dolosigranulum pigrum, Moraxella nonliquefaciens and Corynebacterium propinquum correlated negatively with S. aureus carriage. Mupirocin treatment effectively eliminated S. aureus, D. pigrum and M. nonliquefaciens, but not corynebacteria. S. aureus recolonization in carriers occurred more rapidly than recolonization by the dominant species in noncarriers (median 3 vs. 6 months, respectively). Most recolonizing S. aureus isolates had the same spa type as the initial isolate. The impact of mupirocin-chlorhexidine treatment on the nasal microbiota was still detectable after 6 months. S. aureus recolonization predated microbiota recovery, emphasizing the strong adaptation of this pathogen to the nasal niche and the transient efficacy of the decolonization procedure.
Vitamin D status and severity of COVID-19
Authors: Nielsen Nete Munk , Junker Thor Grønborg , Boelt Sanne Grundvad , Cohen Arieh S. , Munger Kassandra L. , Stenager Egon , Ascherio Alberto , Boding Lasse , Hviid Anders 
Published: November 2022

AbstractWe explored the association between COVID-19 severity and vitamin D status using information from Danish nation-wide health registers, the COVID-19 surveillance database and stored blood samples from the national biobank. 25-hydroxyvitamin D (25(OH)D) was measured using tandem mass spectroscopy. The association between 25(OH)D levels and COVID-19 severity, classified hierarchical as non-hospitalized, hospitalized but not admitted to an intensive care unit (ICU), admitted to ICU, and death, was evaluated by proportional odds ratios (POR) assuming proportionality between the four degrees of severity. Among 447 adults tested SARS-CoV-2 positive in the spring of 2020, low levels of 25(OH)D were associated with a higher risk of severe COVID-19. Thus, odds of experiencing more severe COVID-19 among individuals with insufficient (25 to < 50 nmol/L) and sufficient (≥ 50 nmol/L) 25(OH)D levels were approximately 50% of that among individuals with deficient levels (< 25 nmol/L) (POR = 0.49 (95% CI 0.25–0.94), POR = 0.51 (95% CI 0.27–0.96), respectively). Dividing sufficient vitamin D levels into 50 to < 75 nmol/L and ≥ 75 nmol/L revealed no additional beneficial effect of higher 25(OH)D levels. In this observational study, low levels of 25(OH)D were associated with a higher risk of severe COVID-19. A possible therapeutic role of vitamin D should be evaluated in well-designed interventional studies.
Highly ordered laser imprinted plasmonic metasurfaces for polarization sensitive perfect absorption
Authors: Tasolamprou Anna C. , Skoulas Evangelos , Perrakis George , Vlahou Matina , Viskadourakis Zacharias , Economou Eleftherios N. , Kafesaki Maria , Kenanakis George , Stratakis Emmanuel 
Published: November 2022

AbstractWe present polarization-sensitive gap surface plasmon metasurfaces fabricated with direct material processing using pulsed laser light, an alternative and versatile approach. In particular we imprint laser induced periodic surface structures on nanometer-thick Ni films, which are back-plated by a grounded dielectric layer with TiO2 and ZnO deposition followed by Au evaporation. The procedure results in a metal-insulator-metal type plasmonic metasurface with a corrugated top layer consisting of highly-ordered, sinusoidal shaped, periodic, thin, metallic nanowires. The metasurface sustains sharp, resonant gap surface plasmons and provides various opportunities for polarization control in reflection, which is here switched by the size and infiltrating material of the insulating cavity. The polarization control is associated with the polarization sensitive perfect absorption and leads to high extinction ratios in the near-IR and mid-IR spectral areas. Corresponding Fourier-transform infrared spectroscopy measurements experimentally demonstrate that the fabrication approach produces metasurfaces with very well-defined, controllable, sharp resonances and polarization sensitive resonant absorption response which, depending on the insulating cavity size, impacts either the normal or the parallel to the nanowires polarization.
Serological fingerprints link antiviral activity of therapeutic antibodies to affinity and concentration
Authors: Fiedler Sebastian , Devenish Sean R. A. , Morgunov Alexey S. , Ilsley Alison , Ricci Francesco , Emmenegger Marc , Kosmoliaptsis Vasilis , Theel Elitza S. , Mills John R. , Sholukh Anton M. , Aguzzi Adriano , Iwasaki Akiko , Lynn Andrew K. , Knowles Tuomas P. J. 
Published: November 2022

AbstractThe effectiveness of therapeutic monoclonal antibodies (mAbs) against variants of the SARS-CoV-2 virus is highly variable. As target recognition of mAbs relies on tight binding affinity, we assessed the affinities of five therapeutic mAbs to the receptor binding domain (RBD) of wild type (A), Delta (B.1.617.2), and Omicron BA.1 SARS-CoV-2 (B.1.1.529.1) spike using microfluidic diffusional sizing (MDS). Four therapeutic mAbs showed strongly reduced affinity to Omicron BA.1 RBD, whereas one (sotrovimab) was less impacted. These affinity reductions correlate with reduced antiviral activities suggesting that affinity could serve as a rapid indicator for activity before time-consuming virus neutralization assays are performed. We also compared the same mAbs to serological fingerprints (affinity and concentration) obtained by MDS of antibodies in sera of 65 convalescent individuals. The affinities of the therapeutic mAbs to wild type and Delta RBD were similar to the serum antibody response, indicating high antiviral activities. For Omicron BA.1 RBD, only sotrovimab retained affinities within the range of the serum antibody response, in agreement with high antiviral activity. These results suggest that serological fingerprints provide a route to evaluating affinity and antiviral activity of mAb drugs and could guide the development of new therapeutics.
The role of individual variability on the predictive performance of machine learning applied to large bio-logging datasets
Authors: Chimienti Marianna , Kato Akiko , Hicks Olivia , Angelier Frédéric , Beaulieu Michaël , Ouled-Cheikh Jazel , Marciau Coline , Raclot Thierry , Tucker Meagan , Wisniewska Danuta Maria , Chiaradia André , Ropert-Coudert Yan 
Published: November 2022

AbstractAnimal-borne tagging (bio-logging) generates large and complex datasets. In particular, accelerometer tags, which provide information on behaviour and energy expenditure of wild animals, produce high-resolution multi-dimensional data, and can be challenging to analyse. We tested the performance of commonly used artificial intelligence tools on datasets of increasing volume and dimensionality. By collecting bio-logging data across several sampling seasons, datasets are inherently characterized by inter-individual variability. Such information should be considered when predicting behaviour. We integrated both unsupervised and supervised machine learning approaches to predict behaviours in two penguin species. The classified behaviours obtained from the unsupervised approach Expectation Maximisation were used to train the supervised approach Random Forest. We assessed agreement between the approaches, the performance of Random Forest on unknown data and the implications for the calculation of energy expenditure. Consideration of behavioural variability resulted in high agreement (> 80%) in behavioural classifications and minimal differences in energy expenditure estimates. However, some outliers with < 70% of agreement, highlighted how behaviours characterized by signal similarity are confused. We advise the broad bio-logging community, approaching these large datasets, to be cautious when upscaling predictions, as this might lead to less accurate estimates of behaviour and energy expenditure.
A gigantic bizarre marine turtle (Testudines: Chelonioidea) from the Middle Campanian (Late Cretaceous) of South-western Europe
Authors: Castillo-Visa Oscar , Luján Àngel H. , Galobart Àngel , Sellés Albert 
Published: November 2022

AbstractMarine turtles were common in the subtropical Upper Cretaceous epi-continental seas that once washed the coasts of the ancient European archipelago. But unlike its contemporaneous faunas from North America, in Europe no taxon surpassed the 1.5 m shell-length. Here, the remains of a new large marine turtle, Leviathanochelys aenigmatica gen. et sp. nov., from the Middle Campanian of the Southern Pyrenees are described. Anatomical and histological evidence concur in identifying the specimen as a basal chelonioid. The new taxon autapomorphically differs from other marine turtles by possessing an additional process on the anteromedial side of the pelvis, and an acetabulum directed strongly ventrally. Based on the pelvis size, it is likely that Leviathanochelys was as large as Archelon, thus becoming one of the largest marine turtles found to ever exist. The large body size of the new taxon could have evolved as a response to the unique habitat conditions of the European Cretaceous archipelago seas. The presence of the accessory pubic process further suggests the occurrence of an additional insertion point of the Musculus rectus abdominis, which together with the paleohistologic evidences support the hypothesis that the new taxon had an open marine pelagic lifestyle.
Influence of Dorper lamb development from birth to 120 days of age on clinical and echocardiographic parameters
Authors: Aleixo Amanda Sarita Cruz , Ferreira Danilo Otávio Laurenti , Tsunemi Miriam Harumi , Chiacchio Simone Biagio , Lourenço Maria Lucia Gomes 
Published: November 2022

AbstractThe expansion of the sheep model in research represents an attractive and economically beneficial academic reason for investigations in sheep echocardiography. The present study aimed to evaluate the clinical and echocardiographic parameters in Dorper lambs during the developmental period. Emphasis was placed on the use of the species in translational research for the echocardiographic diagnosis of congenital heart diseases, which can contribute to improvements in interventionist techniques. Ten Dorper lambs were evaluated at the following time points: 24 h after birth and 7, 14, 21, 30, 60, 90 and 120 days of age. Clinical parameters were compiled, and echocardiogram records were obtained without sedation. Rectal temperature was lower on the first day compared to the others. From 21 days of life, there was a reduction in HR, with differences between time points. Mean and systolic blood pressure differed, with the highest values at 90 and 120 days of age. The thickness of the interventricular septum in diastole (IVSd) increased as age progressed, with the highest value at 120 days of age, and the same occurred for LVIDd (left ventricle internal diameter in diastole), LVFWd (left ventricular free wall thickness in diastole), IVSs (interventricular septum thickness in systole), LVIDs (left ventricle internal diameter in systole) and LVFWs (left ventricular free wall thickness in systole). There were differences in the size of the LA, Ao and LA/Ao ratio, which were greater at 90 days and 120 days of age. Echocardiographic changes accompany the development of lambs, where changes in echocardiographic parameters are evident with advancing age. The echocardiographic measurements in lambs obtained in the present study are similar to those in newborns.
Tridimensional cell culture of dermal fibroblasts promotes exosome-mediated secretion of extracellular matrix proteins
Authors: Clément Vincent , Roy Vincent , Paré Bastien , Goulet Cassandra R. , Deschênes Lydia Touzel , Berthod François , Bolduc Stéphane , Gros-Louis François 
Published: November 2022

AbstractExtracellular matrix (ECM) secretion, deposition and assembly are part of a whole complex biological process influencing the microenvironment and other cellular behaviors. Emerging evidence is attributing a significant role to extracellular vesicles (EVs) and exosomes in a plethora of ECM-associated functions, but the role of dermal fibroblast-derived EVs in paracrine signalling is yet unclear. Herein, we investigated the effect of exosomes isolated from stimulated human dermal fibroblasts. We report that tridimensional (3D) cell culture of dermal fibroblasts promotes secretion of exosomes carrying a large quantity of proteins involved in the formation, organisation and remodelling of the ECM. In our 3D model, gene expression was highly modulated and linked to ECM, cellular migration and proliferation, as well as inflammatory response. Mass spectrometry analysis of exosomal proteins, isolated from 3D cultured fibroblast-conditioned media, revealed ECM protein enrichment, of which many were associated with the matrisome. We also show that the cytokine interleukin 6 (IL-6) is predicted to be central to the signalling pathways related to ECM formation and contributing to cell migration and proliferation. Overall, our data suggest that dermal fibroblast-derived EVs participate in many steps of the establishment of dermis’s ECM.
Uptake of Plasmodium chabaudi hemozoin drives Kupffer cell death and fuels superinfections
Authors: Hirako Isabella C. , Antunes Maísa Mota , Rezende Rafael Machado , Hojo-Souza Natália Satchiko , Figueiredo Maria Marta , Dias Thomaz , Nakaya Helder , Menezes Gustavo Batista , Gazzinelli Ricardo Tostes 
Published: November 2022

AbstractKupffer cells (KCs) are self-maintained tissue-resident macrophages that line liver sinusoids and play an important role on host defense. It has been demonstrated that upon infection or intense liver inflammation, KCs might be severely depleted and replaced by immature monocytic cells; however, the mechanisms of cell death and the alterations on liver immunity against infections deserves further investigation. We explored the impact of acute Plasmodium infection on KC biology and on the hepatic immune response against secondary infections. Similar to patients, infection with Plasmodium chabaudi induced acute liver damage as determined by serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevation. This was associated with accumulation of hemozoin, increased of proinflammatory response and impaired bacterial and viral clearance, which led to pathogen spread to other organs. In line with this, mice infected with Plasmodium had enhanced mortality during secondary infections, which was associated with increased production of mitochondrial superoxide, lipid peroxidation and increased free iron within KCs—hallmarks of cell death by ferroptosis. Therefore, we revealed that accumulation of iron with KCs, triggered by uptake of circulating hemozoin, is a novel mechanism of macrophage depletion and liver inflammation during malaria, providing novel insights on host susceptibility to secondary infections. Malaria can cause severe liver damage, along with depletion of liver macrophages, which can predispose individuals to secondary infections and enhance the chances of death.
Bioinformatics analysis of miRNAs in the neuroblastoma 11q-deleted region reveals a role of miR-548l in both 11q-deleted and MYCN amplified tumour cells
Authors: Jurcevic Sanja , Keane Simon , Borgmästars Emmy , Lubovac-Pilav Zelmina , Ejeskär Katarina 
Published: November 2022

AbstractNeuroblastoma is a childhood tumour that is responsible for approximately 15% of all childhood cancer deaths. Neuroblastoma tumours with amplification of the oncogene MYCN are aggressive, however, another aggressive subgroup without MYCN amplification also exists; rather, they have a deleted region at chromosome arm 11q. Twenty-six miRNAs are located within the breakpoint region of chromosome 11q and have been checked for a possible involvement in development of neuroblastoma due to the genomic alteration. Target genes of these miRNAs are involved in pathways associated with cancer, including proliferation, apoptosis and DNA repair. We could show that miR-548l found within the 11q region is downregulated in neuroblastoma cell lines with 11q deletion or MYCN amplification. In addition, we showed that the restoration of miR-548l level in a neuroblastoma cell line led to a decreased proliferation of these cells as well as a decrease in the percentage of cells in the S phase. We also found that miR-548l overexpression suppressed cell viability and promoted apoptosis, while miR-548l knockdown promoted cell viability and inhibited apoptosis in neuroblastoma cells. Our results indicate that 11q-deleted neuroblastoma and MYCN amplified neuroblastoma coalesce by downregulating miR-548l.
Aquaculture rearing systems induce no legacy effects in Atlantic cod larvae or their rearing water bacterial communities
Authors: Gundersen Madeleine S. , Vadstein Olav , De Schryver Peter , Attramadal Kari Johanne Kihle 
Published: November 2022

AbstractThe microbial rearing quality influences the survival of marine larvae. Microbially matured water treatment systems (MMS) provide a more favourable rearing water microbiome than flow-through systems (FTS). It has previously been hypothesised, but not investigated, that initial rearing in MMS leaves a protective legacy effect in Atlantic cod larvae (Gadus morhua). We tested this hypothesis through a crossover 2 × 2 factorial experiment varying the rearing water treatment system (MMS vs FTS) and the microbial carrying capacity (+ /− added organic matter). At 9 days post-hatching, we switched the rearing water treatment system. By comparing switched and unswitched rearing tanks, we evaluated if legacy effects had been established in the larvae or their surrounding rearing water bacterial community. We analysed the bacterial communities with flow cytometry and 16S rRNA gene sequencing. We found no evidence that the initial rearing condition left a legacy effect in the communities by evaluating the bacterial community diversity and structure. Instead, the present rearing condition was the most important driver for differences in the rearing water microbiota. Furthermore, we found that MMS with high microbial carrying capacity appeared to seed a stable bacterial community to the rearing tanks. This finding highlights the importance of keeping a similar carrying capacity between the inlet and rearing water. Moreover, we reject the hypothesis that the initial rearing condition leaves a protective legacy effect in larvae, as the larval survival and robustness were linked to the present rearing condition. In conclusion, our results highlight the importance of maintaining a beneficial microbial rearing environment from hatching and throughout the larval rearing period.