bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficient generative modeling of protein sequences using simple autoregressive models
Authors: Trinquier Jeanne , Uguzzoni Guido , Pagnani Andrea , Zamponi Francesco , Weigt Martin
Published: October 2021

Generative models emerge as promising candidates for novel sequence-data driven approaches to protein design, and for the extraction of structural and functional information about proteins deeply hidden in rapidly growing sequence databases. Here we propose simple autoregressive models as highly accurate but computationally efficient generative sequence models. We show that they perform similarly to existing approaches based on Boltzmann machines or deep generative models, but at a substantially lower computational cost (by a factor between 102 and 103). Furthermore, the simple structure of our models has distinctive mathematical advantages, which translate into an improved applicability in sequence generation and evaluation. Within these models, we can easily estimate both the probability of a given sequence, and, using the model’s entropy, the size of the functional sequence space related to a specific protein family. In the example of response regulators, we find a huge number of ca. 1068 possible sequences, which nevertheless constitute only the astronomically small fraction 10−80 of all amino-acid sequences of the same length. These findings illustrate the potential and the difficulty in exploring sequence space via generative sequence models.
Determinants of renal cell carcinoma invasion and metastatic competence
Authors: Kim Kangsan , Zhou Qinbo , Christie Alana , Stevens Christina , Ma Yuanqing , Onabolu Oreoluwa , Chintalapati Suneetha , Mckenzie Tiffani , Tcheuyap Vanina Toffessi , Woolford Layton , Zhang He , Singla Nirmish , Parida Pravat Kumar , Marquez-Palencia Mauricio , Pedrosa Ivan , Margulis Vitaly , Sagalowsky Arthur , Xie Zhiqun , Wang Tao , Durinck Steffen , Modrusan Zora , Seshagiri Somasekar , Kapur Payal , Brugarolas James , Malladi Srinivas
Published: October 2021

Metastasis is the principal cause of cancer related deaths. Tumor invasion is essential for metastatic spread. However, determinants of invasion are poorly understood. We addressed this knowledge gap by leveraging a unique attribute of kidney cancer. Renal tumors invade into large vessels forming tumor thrombi (TT) that migrate extending sometimes into the heart. Over a decade, we prospectively enrolled 83 ethnically-diverse patients undergoing surgical resection for grossly invasive tumors at UT Southwestern Kidney Cancer Program. In this study, we perform comprehensive histological analyses, integrate multi-region genomic studies, generate in vivo models, and execute functional studies to define tumor invasion and metastatic competence. We find that invasion is not always associated with the most aggressive clone. Driven by immediate early genes, invasion appears to be an opportunistic trait attained by subclones with diverse oncogenomic status in geospatial proximity to vasculature. We show that not all invasive tumors metastasize and identify determinants of metastatic competency. TT associated with metastases are characterized by higher grade, mTOR activation and a particular immune contexture. Moreover, TT grade is a better predictor of metastasis than overall tumor grade, which may have implications for clinical practice.
Unveiling unconventional magnetism at the surface of Sr2RuO4
Authors: Fittipaldi R. , Hartmann R. , Mercaldo M. T. , Komori S. , Bjørlig A. , Kyung W. , Yasui Y. , Miyoshi T. , Olde Olthof L. A. B. , Palomares Garcia C. M. , Granata V. , Keren I. , Higemoto W. , Suter A. , Prokscha T. , Romano A. , Noce C. , Kim C. , Maeno Y. , Scheer E. , Kalisky B. , Robinson J. W. A. , Cuoco M. , Salman Z. , Vecchione A. , Di Bernardo A.
Published: October 2021

Materials with strongly correlated electrons often exhibit interesting physical properties. An example of these materials is the layered oxide perovskite Sr2RuO4, which has been intensively investigated due to its unusual properties. Whilst the debate on the symmetry of the superconducting state in Sr2RuO4 is still ongoing, a deeper understanding of the Sr2RuO4 normal state appears crucial as this is the background in which electron pairing occurs. Here, by using low-energy muon spin spectroscopy we discover the existence of surface magnetism in Sr2RuO4 in its normal state. We detect static weak dipolar fields yet manifesting at an onset temperature higher than 50 K. We ascribe this unconventional magnetism to orbital loop currents forming at the reconstructed Sr2RuO4 surface. Our observations set a reference for the discovery of the same magnetic phase in other materials and unveil an electronic ordering mechanism that can influence electron pairing with broken time reversal symmetry.
Neural heterogeneity promotes robust learning
Authors: Perez-Nieves Nicolas , Leung Vincent C. H. , Dragotti Pier Luigi , Goodman Dan F. M.
Published: October 2021

The brain is a hugely diverse, heterogeneous structure. Whether or not heterogeneity at the neural level plays a functional role remains unclear, and has been relatively little explored in models which are often highly homogeneous. We compared the performance of spiking neural networks trained to carry out tasks of real-world difficulty, with varying degrees of heterogeneity, and found that heterogeneity substantially improved task performance. Learning with heterogeneity was more stable and robust, particularly for tasks with a rich temporal structure. In addition, the distribution of neuronal parameters in the trained networks is similar to those observed experimentally. We suggest that the heterogeneity observed in the brain may be more than just the byproduct of noisy processes, but rather may serve an active and important role in allowing animals to learn in changing environments.
Household cooking fuel estimates at global and country level for 1990 to 2030
Authors: Stoner Oliver , Lewis Jessica , Martínez Itzel Lucio , Gumy Sophie , Economou Theo , Adair-Rohani Heather
Published: October 2021

Household air pollution generated from the use of polluting cooking fuels and technologies is a major source of disease and environmental degradation in low- and middle-income countries. Using a novel modelling approach, we provide detailed global, regional and country estimates of the percentages and populations mainly using 6 fuel categories (electricity, gaseous fuels, kerosene, biomass, charcoal, coal) and overall polluting/clean fuel use – from 1990-2020 and with urban/rural disaggregation. Here we show that 53% of the global population mainly used polluting cooking fuels in 1990, dropping to 36% in 2020. In urban areas, gaseous fuels currently dominate, with a growing reliance on electricity; in rural populations, high levels of biomass use persist alongside increasing use of gaseous fuels. Future projections of observed trends suggest 31% will still mainly use polluting fuels in 2030, including over 1 billion people in Sub-Saharan African by 2025.
Enabling comprehensive optogenetic studies of mouse hearts by simultaneous opto-electrical panoramic mapping and stimulation
Authors: Rieger Michael , Dellenbach Christian , vom Berg Johannes , Beil-Wagner Jane , Maguy Ange , Rohr Stephan
Published: October 2021

During the last decade, cardiac optogenetics has turned into an essential tool for investigating cardiac function in general and for assessing functional interactions between different myocardial cell types in particular. To advance exploitation of the unique research opportunities offered by this method, we develop a panoramic opto-electrical measurement and stimulation (POEMS) system for mouse hearts. The core of the experimental platform is composed of 294 optical fibers and 64 electrodes that form a cup which embraces the entire ventricular surface of mouse hearts and enables straightforward ‘drop&go’ experimentation. The flexible assignment of fibers and electrodes to recording or stimulation tasks permits a precise tailoring of experiments to the specific requirements of individual optogenetic constructs thereby avoiding spectral congestion. Validation experiments with hearts from transgenic animals expressing the optogenetic voltage reporters ASAP1 and ArcLight-Q239 demonstrate concordance of simultaneously recorded panoramic optical and electrical activation maps. The feasibility of single fiber optical stimulation is proven with hearts expressing the optogenetic voltage actuator ReaChR. Adaptation of the POEMS system to larger hearts and incorporation of additional sensors can be achieved by redesigning the system-core accordingly.
Protein identification by nanopore peptide profiling
Authors: Lucas Florian Leonardus Rudolfus , Versloot Roderick Corstiaan Abraham , Yakovlieva Liubov , Walvoort Marthe T. C. , Maglia Giovanni
Published: October 2021

Nanopores are single-molecule sensors used in nucleic acid analysis, whereas their applicability towards full protein identification has yet to be demonstrated. Here, we show that an engineered Fragaceatoxin C nanopore is capable of identifying individual proteins by measuring peptide spectra that are produced from hydrolyzed proteins. Using model proteins, we show that the spectra resulting from nanopore experiments and mass spectrometry share similar profiles, hence allowing protein fingerprinting. The intensity of individual peaks provides information on the concentration of individual peptides, indicating that this approach is quantitative. Our work shows the potential of a low-cost, portable nanopore-based analyzer for protein identification.
Atomic level fluxional behavior and activity of CeO2-supported Pt catalysts for CO oxidation
Authors: Vincent Joshua L. , Crozier Peter A.
Published: October 2021

Reducible oxides are widely used catalyst supports that can increase oxidation reaction rates by transferring lattice oxygen at the metal-support interface. There are many outstanding questions regarding the atomic-scale dynamic meta-stability (i.e., fluxional behavior) of the interface during catalysis. Here, we employ aberration-corrected operando electron microscopy to visualize the structural dynamics occurring at and near Pt/CeO2 interfaces during CO oxidation. We show that the catalytic turnover frequency correlates with fluxional behavior that (a) destabilizes the supported Pt particle, (b) marks an enhanced rate of oxygen vacancy creation and annihilation, and (c) leads to increased strain and reduction in the CeO2 support surface. Overall, the results implicate the interfacial Pt-O-Ce bonds anchoring the Pt to the support as being involved also in the catalytically-driven oxygen transfer process, and they suggest that oxygen reduction takes place on the highly reduced CeO2 surface before migrating to the interfacial perimeter for reaction with CO.
Current and projected regional economic impacts of heatwaves in Europe
Authors: García-León David , Casanueva Ana , Standardi Gabriele , Burgstall Annkatrin , Flouris Andreas D. , Nybo Lars
Published: October 2021

Extreme heat undermines the working capacity of individuals, resulting in lower productivity, and thus economic output. Here we analyse the present and future economic damages due to reduced labour productivity caused by extreme heat in Europe. For the analysis of current impacts, we focused on heatwaves occurring in four recent anomalously hot years (2003, 2010, 2015, and 2018) and compared our findings to the historical period 1981–2010. In the selected years, the total estimated damages attributed to heatwaves amounted to 0.3–0.5% of European gross domestic product (GDP). However, the identified losses were largely heterogeneous across space, consistently showing GDP impacts beyond 1% in more vulnerable regions. Future projections indicate that by 2060 impacts might increase in Europe by a factor of almost five compared to the historical period 1981–2010 if no further mitigation or adaptation actions are taken, suggesting the presence of more pronounced effects in the regions where these damages are already acute.
Programmable nano-reactors for stochastic sensing
Authors: Jia Wendong , Hu Chengzhen , Wang Yuqin , Gu Yuming , Qian Guangrui , Du Xiaoyu , Wang Liying , Liu Yao , Cao Jiao , Zhang Shanyu , Yan Shuanghong , Zhang Panke , Ma Jing , Chen Hong-Yuan , Huang Shuo
Published: October 2021

Chemical reactions of single molecules, caused by rapid formation or breaking of chemical bonds, are difficult to observe even with state-of-the-art instruments. A biological nanopore can be engineered into a single molecule reactor, capable of detecting the binding of a monatomic ion or the transient appearance of chemical intermediates. Pore engineering of this type is however technically challenging, which has significantly restricted further development of this technique. We propose a versatile strategy, “programmable nano-reactors for stochastic sensing” (PNRSS), by which a variety of single molecule reactions of hydrogen peroxide, metal ions, ethylene glycol, glycerol, lactic acid, vitamins, catecholamines or nucleoside analogues can be observed directly. PNRSS presents a refined sensing resolution which can be further enhanced by an artificial intelligence algorithm. Remdesivir, a nucleoside analogue and an investigational anti-viral drug used to treat COVID-19, can be distinguished from its active triphosphate form by PNRSS, suggesting applications in pharmacokinetics or drug screening.
Wdr47, Camsaps, and Katanin cooperate to generate ciliary central microtubules
Authors: Liu Hao , Zheng Jianqun , Zhu Lei , Xie Lele , Chen Yawen , Zhang Yirong , Zhang Wei , Yin Yue , Peng Chao , Zhou Jun , Zhu Xueliang , Yan Xiumin
Published: October 2021

The axonemal central pair (CP) are non-centrosomal microtubules critical for planar ciliary beat. How they form, however, is poorly understood. Here, we show that mammalian CP formation requires Wdr47, Camsaps, and microtubule-severing activity of Katanin. Katanin severs peripheral microtubules to produce central microtubule seeds in nascent cilia. Camsaps stabilize minus ends of the seeds to facilitate microtubule outgrowth, whereas Wdr47 concentrates Camsaps into the axonemal central lumen to properly position central microtubules.Wdr47deficiency in mouse multicilia results in complete loss of CP, rotatory beat, and primary ciliary dyskinesia. Overexpression of Camsaps or their microtubule-binding regions induces central microtubules inWdr47−/−ependymal cells but at the expense of low efficiency, abnormal numbers, and wrong location. Katanin levels and activity also impact the central microtubule number. We propose that Wdr47, Camsaps, and Katanin function together for the generation of non-centrosomal microtubule arrays in polarized subcellular compartments.
Magnetic-field-controlled spin fluctuations and quantum criticality in Sr3Ru2O7
Authors: Lester C. , Ramos S. , Perry R. S. , Croft T. P. , Laver M. , Bewley R. I. , Guidi T. , Hiess A. , Wildes A. , Forgan E. M. , Hayden S. M.
Published: October 2021

When the transition temperature of a continuous phase transition is tuned to absolute zero, new ordered phases and physical behaviour emerge in the vicinity of the resulting quantum critical point. Sr3Ru2O7 can be tuned through quantum criticality with magnetic field at low temperature. Near its critical field Bc it displays the hallmark T-linear resistivity and a $$T\,{{{{{{\mathrm{log}}}}}}}\,(1/T)$$
T

log

(

1
/
T

)

electronic heat capacity behaviour of strange metals. However, these behaviours have not been related to any critical fluctuations. Here we use inelastic neutron scattering to reveal the presence of collective spin fluctuations whose relaxation time and strength show a nearly singular variation with magnetic field as Bc is approached. The large increase in the electronic heat capacity and entropy near Bc can be understood quantitatively in terms of the scattering of conduction electrons by these spin-fluctuations. On entering the spin-density-wave ordered phase present near Bc, the fluctuations become stronger suggesting that the order is stabilised through an “order-by-disorder” mechanism.
Chemical proteomic profiling reveals protein interactors of the alarmones diadenosine triphosphate and tetraphosphate
Authors: Krüger Lena , Albrecht Christoph J. , Schammann Hannah K. , Stumpf Florian M. , Niedermeier Marie L. , Yuan Yizhi , Stuber Katrin , Wimmer Josua , Stengel Florian , Scheffner Martin , Marx Andreas
Published: October 2021

The nucleotides diadenosine triphosphate (Ap3A) and diadenosine tetraphosphate (Ap4A) are formed in prokaryotic and eukaryotic cells. Since their concentrations increase significantly upon cellular stress, they are considered to be alarmones triggering stress adaptive processes. However, their cellular roles remain elusive. To elucidate the proteome-wide interactome of Ap3A and Ap4A and thereby gain insights into their cellular roles, we herein report the development of photoaffinity-labeling probes and their employment in chemical proteomics. We demonstrate that the identified ApnA interactors are involved in many fundamental cellular processes including carboxylic acid and nucleotide metabolism, gene expression, various regulatory processes and cellular response mechanisms and only around half of them are known nucleotide interactors. Our results highlight common functions of these ApnAs across the domains of life, but also identify those that are different for Ap3A or Ap4A. This study provides a rich source for further functional studies of these nucleotides and depicts useful tools for characterization of their regulatory mechanisms in cells.
Inhibiting endocytosis in CGRP+ nociceptors attenuates inflammatory pain-like behavior
Authors: Powell Rasheen , Young Violet A. , Pryce Kerri D. , Sheehan Garrett D. , Bonsu Kwaku , Ahmed Abdulelah , Bhattacharjee Arin
Published: October 2021

The advantage of locally applied anesthetics is that they are not associated with the many adverse effects, including addiction liability, of systemically administered analgesics. This therapeutic approach has two inherent pitfalls: specificity and a short duration of action. Here, we identified nociceptor endocytosis as a promising target for local, specific, and long-lasting treatment of inflammatory pain. We observed preferential expression of AP2α2, an α-subunit isoform of the AP2 complex, within CGRP+/IB4- nociceptors in rodents and in CGRP+ dorsal root ganglion neurons from a human donor. We utilized genetic and pharmacological approaches to inhibit nociceptor endocytosis demonstrating its role in the development and maintenance of acute and chronic inflammatory pain. One-time injection of an AP2 inhibitor peptide significantly reduced acute and chronic pain-like behaviors and provided prolonged analgesia. We evidenced sexually dimorphic recovery responses to this pharmacological approach highlighting the importance of sex differences in pain development and response to analgesics.
An ensemble reconstruction of global monthly sea surface temperature and sea ice concentration 1000–1849
Authors: Samakinwa Eric , Valler Veronika , Hand Ralf , Neukom Raphael , Gómez-Navarro Juan José , Kennedy John , Rayner Nick A. , Brönnimann Stefan
Published: October 2021

This paper describes a global monthly gridded Sea Surface Temperature (SST) and Sea Ice Concentration (SIC) dataset for the period 1000–1849, which can be used as boundary conditions for atmospheric model simulations. The reconstruction is based on existing coarse-resolution annual temperature ensemble reconstructions, which are then augmented with intra-annual and sub-grid scale variability. The intra-annual component of HadISST.2.0 and oceanic indices estimated from the reconstructed annual mean are used to develop grid-based linear regressions in a monthly stratified approach. Similarly, we reconstruct SIC using analog resampling of HadISST.2.0 SIC (1941–2000), for both hemispheres. Analogs are pooled in four seasons, comprising of 3-months each. The best analogs are selected based on the correlation between each member of the reconstructed SST and its target. For the period 1780 to 1849, We assimilate historical observations of SST and night-time marine air temperature from the ICOADS dataset into our reconstruction using an offline Ensemble Kalman Filter approach. The resulting dataset is physically consistent with information from models, proxies, and observations.
Antioxidant and antibacterial insights into the leaves, leaf tea and medicinal roots from Astragalus membranaceus (Fisch.) Bge.
Authors: Samuel Anim Okyere , Huang Bao-Ting , Chen Yuan , Guo Feng-Xia , Yang Dou-Dou , Jin Jian-Qin
Published: October 2021

Used as traditional Chinese medicine, Astragalus membranaceus (Fisch.) Bge. (A. membranaceus) roots are also used as tonic food material in a wide range of applications, while the leaves are left in the field, unused. Therefore, comprehensively exploring and utilizing the leaves will inevitably reduce the associated resource waste and environment pollution. In this study, the plant leaves were processed into tea using green tea processing technology. Bioactive components, antioxidant and antibacterial activities of the Leaf Tea (LT) and Dry Leaves (DL) were studied, and compared to that of the Dry Roots (DR). The results showed that the polysaccharides content (POL) in the DR (20.44%) was twice as high as the DL (10.18%) and LT (8.68%). However, the DL contained 36.85% more water-soluble extracts (WSE), 35.09% more ethanol-soluble extracts (ESE), 409.63% more total flavonoid content (TFC), 221.01% more total phenolic content (TPC) and 94.34% more proteins, and the LT contained 26.21% more WSE, 40.64% more ESE, 326.93% more TFC, 191.90% more TPC and 37.71% more proteins. The total amino acid (AA) content in the DR was 8.89%, while in that of the DL and LT were 24.18% and 28.96% respectively, nearly 3-times higher than that of the DR. The antioxidant activity of DR was much lower than those of DL and LT, both of which had antioxidant activity closer to that of Vitamin C (VC) and the antioxidant activities were even stronger when the optimal concentration was reached. Except for Aspergillus niger and Staphylococcus aureus, the DL and DR exhibited inhibition activities to Salmonella, Bacillus subtilis, Escherichia coli and yeast, while the LT had antimicrobial activities against all the strains except for A. niger. In summary, compared with the most commonly used DR, the DL and LT from A. membranaceus contained higher bioactive components, and stronger antioxidant and antimicrobial activities. Producing leaf tea may be an appropriate way to economically and reasonably utilize the plant leaves which are by-products.
Mass spectrometry imaging of mice brain lipid profile changes over time under high fat diet
Authors: Sighinolfi Gianluca , Clark Samantha , Blanc Landry , Cota Daniela , Rhourri-Frih Boutayna
Published: October 2021

Overweight and obesity have been shown to significantly affect brain structures and size. Obesity has been associated with cerebral atrophy, alteration of brain functions, including cognitive impairement, and psychiatric diseases such as depression. Given the importance of lipids in the structure of the brain, here, by using 47 mice fed a high fat diet (HFD) with 60% calories from fat (40% saturated fatty acids) and 20% calories from carbohydrates and age-matched control animals on a normal chow diet, we examined the effects of HFD and diet-induced obesity on the brain lipidome. Using a targeted liquid chromatography mass spectrometry analysis and a non-targeted mass spectrometry MALDI imaging approach, we show that the relative concentration of most lipids, in particular brain phospholipids, is modified by diet-induced obesity (+ 40%of body weight). Use of a non-targeted MALDI-MS imaging approach further allowed define cerebral regions of interest (ROI) involved in eating behavior and changes in their lipid profile. Principal component analysis (PCA) of the obese/chow lipidome revealed persistence of some of the changes in the brain lipidome of obese animals even after their switch to chow feeding and associated weight loss. Altogether, these data reveal that HFD feeding rapidly modifies the murine brain lipidome. Some of these HFD-induced changes persist even after weight loss, implying that some brain sequelae caused by diet-induced obesity are irreversible.
Japanese conservative messages propagate to moderate users better than their liberal counterparts on Twitter
Authors: Yoshida Mitsuo , Sakaki Takeshi , Kobayashi Tetsuro , Toriumi Fujio
Published: October 2021

To examine conservative–liberal differences in the extent to which partisan tweets reach less partisan moderate users in a nonwestern context, we analyzed a network of retweets about former Japanese Prime Minister Shinzo Abe. The analyses consistently demonstrated that partisan tweets originating from the conservative cluster reach a wider range of moderate users than those from the liberal cluster. Network analyses revealed that while the conservative and the liberal clusters’ internal structures were similar, the conservative cluster reciprocated the follows from moderate accounts at a higher rate than the liberal cluster. In addition, moderate accounts reciprocated the conservative cluster’s following at a higher rate than they did for the liberal cluster. The analysis of tweet content showed no difference in the frequency of hashtag use between conservatives and liberals, but there were differences in the use of emotion words and linguistic expressions. In particular, emotion words related to the propagation of messages, such as those expressing “dislike”, were used more frequently by conservatives, while the use of adjectives by conservatives was closer to that of moderate users, indicating that conservative tweets are more palatable for moderate users than liberal tweets.
Mauritia flexuosa palm trees airborne mapping with deep convolutional neural network
Authors: Arce Luciene Sales Dagher , Osco Lucas Prado , Arruda Mauro dos Santos de , Furuya Danielle Elis Garcia , Ramos Ana Paula Marques , Aoki Camila , Pott Arnildo , Fatholahi Sarah , Li Jonathan , Araújo Fábio Fernando de , Gonçalves Wesley Nunes , Marcato Junior José
Published: October 2021

Accurately mapping individual tree species in densely forested environments is crucial to forest inventory. When considering only RGB images, this is a challenging task for many automatic photogrammetry processes. The main reason for that is the spectral similarity between species in RGB scenes, which can be a hindrance for most automatic methods. This paper presents a deep learning-based approach to detect an important multi-use species of palm trees (Mauritia flexuosa; i.e., Buriti) on aerial RGB imagery. In South-America, this palm tree is essential for many indigenous and local communities because of its characteristics. The species is also a valuable indicator of water resources, which comes as a benefit for mapping its location. The method is based on a Convolutional Neural Network (CNN) to identify and geolocate singular tree species in a high-complexity forest environment. The results returned a mean absolute error (MAE) of 0.75 trees and an F1-measure of 86.9%. These results are better than Faster R-CNN and RetinaNet methods considering equal experiment conditions. In conclusion, the method presented is efficient to deal with a high-density forest scenario and can accurately map the location of single species like the M. flexuosa palm tree and may be useful for future frameworks.
The mannose receptor (CD206) identifies a population of colonic macrophages in health and inflammatory bowel disease
Authors: Wright Pamela B. , McDonald Elizabeth , Bravo-Blas Alberto , Baer Hannah M. , Heawood Anna , Bain Calum C. , Mowat Allan M. , Clay Slater L. , Robertson Elaine V. , Morton Fraser , Nijjar Jagtar Singh , Ijaz Umer Z. , Milling Simon W. F. , Gaya Daniel R.
Published: October 2021

To understand the contribution of mononuclear phagocytes (MNP), which include monocyte-derived intestinal macrophages, to the pathogenesis of inflammatory bowel disease (IBD), it is necessary to identify functionally-different MNP populations. We aimed to characterise intestinal macrophage populations in patients with IBD. We developed 12-parameter flow cytometry protocols to identify and human intestinal MNPs. We used these protocols to purify and characterize colonic macrophages from colonic tissue from patients with Crohn’s disease (CD), ulcerative colitis (UC), or non-inflamed controls, in a cross-sectional study. We identify macrophage populations (CD45+CD64+ HLA-DR+) and describe two distinct subsets, differentiated by their expression of the mannose receptor, CD206. CD206+ macrophages expressed markers consistent with a mature phenotype: high levels of CD68 and CD163, higher transcription of IL-10 and lower expression of TREM1. CD206− macrophages appear to be less mature, with features more similar to their monocytic precursors. We identified and purified macrophage populations from human colon. These appear to be derived from a monocytic precursor with high CCR2 and low CD206 expression. As these cells mature, they acquire expression of IL-10, CD206, CD63, and CD168. Targeting the newly recruited monocyte-derived cells may represent a fruitful avenue to ameliorate chronic inflammation in IBD.
Routing algorithms as tools for integrating social distancing with emergency evacuation
Authors: Tsai Yi-Lin , Rastogi Chetanya , Kitanidis Peter K. , Field Christopher B.
Published: October 2021

One of the lessons from the COVID-19 pandemic is the importance of social distancing, even in challenging circumstances such as pre-hurricane evacuation. To explore the implications of integrating social distancing with evacuation operations, we describe this evacuation process as a Capacitated Vehicle Routing Problem (CVRP) and solve it using a DNN (Deep Neural Network)-based solution (Deep Reinforcement Learning) and a non-DNN solution (Sweep Algorithm). A central question is whether Deep Reinforcement Learning provides sufficient extra routing efficiency to accommodate increased social distancing in a time-constrained evacuation operation. We found that, in comparison to the Sweep Algorithm, Deep Reinforcement Learning can provide decision-makers with more efficient routing. However, the evacuation time saved by Deep Reinforcement Learning does not come close to compensating for the extra time required for social distancing, and its advantage disappears as the emergency vehicle capacity approaches the number of people per household.
Mongolian pine forest decline by the combinatory effect of European woodwasp and plant pathogenic fungi
Authors: Wang Lixiang , Li Chunchun , Luo Youqing , Ren Lili , Lv Ning , Zhou Jing-Jiang , Wang Senshan
Published: October 2021

Interactions between the decline of Mongolian pine woodlands and fungal communities and invasive pests in northeastern China are poorly understood. In this study, we investigated the fungal communities occurring in three tree samples: the woodwaspSirex noctilioinfested, healthy uninfested and unhealthy uninfested Mongolian pine trees. We analyzed the relationships of the Mongolian pine decline with fungal infection and woodwasp infestation. Twenty-six fungal species were identified from the sampled trees. Each tree sample harbored a fungal endophyte community with a unique structure. Pathogenic fungi richness was four times higher in infested and unhealthy un-infested trees compared to that in healthy uninfested trees.Sphaeropsis sapineawas the most dominant pathogenic fungus in the sampled Mongolian pine trees. The number ofS. noctiliowas higher than native bark beetles in the declining Mongolian pine trees. The invasion of the woodwasp appeared to be promoted by the fungal infection in the Mongolian pine trees. The incidence ofS. noctilioinfestation was higher in the fungi infected trees (83.22%) than those without infection (38.72%).S. sapineapopulation exhibited positive associations with within-tree colonization ofS. noctilioand bark beetle. Collectively, these data indicate that the fungal disease may have caused as the initial reason the decline of the Mongolian pine trees, and also provided convenient conditions for the successful colonization of the woodwasp. The woodwasps attack the Mongolian pine trees infected by fungi and accelerated its decline.
A novel method for liquid-phase extraction of cell-free DNA for detection of circulating tumor DNA
Authors: Janku Filip , Huang Helen J. , Pereira David Y. , Kobayashi Masae , Chiu Chung Hei , Call S. Greg , Woodbury Kristen T. , Chao Felix , Marshak Daniel R. , Chiu Ricky Y. T.
Published: October 2021

Low yields of extracted cell-free DNA (cfDNA) from plasma limit continued development of liquid biopsy in cancer, especially in early-stage cancer diagnostics and cancer screening applications. We investigate a novel liquid-phase-based DNA isolation method that utilizes aqueous two-phase systems to purify and concentrate circulating cfDNA. The PHASIFY MAX and PHASIFY ENRICH kits were compared to a commonly employed solid-phase extraction method on their ability to extract cfDNA from a set of 91 frozen plasma samples from cancer patients. Droplet digital PCR (ddPCR) was used as the downstream diagnostic to detect mutant copies. Compared to the QIAamp Circulating Nucleic Acid (QCNA) kit, the PHASIFY MAX method demonstrated 60% increase in DNA yield and 171% increase in mutant copy recovery, and the PHASIFY ENRICH kit demonstrated a 35% decrease in DNA yield with a 153% increase in mutant copy recovery. A follow-up study with PHASIFY ENRICH resulted in the positive conversion of 9 out of 47 plasma samples previously determined negative with QCNA extraction (all with known positive tissue genotyping). Our results indicate that this novel extraction technique offers higher cfDNA recovery resulting in better sensitivity for detection of cfDNA mutations compared to a commonly used solid-phase extraction method.
The SARS-CoV-2 first wave impact in the acute inflammatory surgical pathologies
Authors: Guadalajara H. , Muñoz de Nova J. L. , Yiasemidou M. , Recarte Rico M. , Juez L. D. , García Septiem J. , Galindo Jara P. , García Virosta M. , Lobo Martínez E. , Martín-Pérez E. , Fernandez Gonzalez S. , Lopez-Fernandez O. , García-Olmo D. ,   PIACO Collaboration Group, Fernández-Cebrián J. M. , Jover J. M. , Acín-Gándara D. , Perea-del-Pozo E. , Dios-Barbeito S. , Martin-Antona E. , Durán-Poveda M. , Peinado Iribar B. , Pascual Migueláñez I. , Gortázar de las Casas S. , Fernández Luengas D. , Garcia Chiloeches A. , Puerta A. , Martín-Pérez E. , García del Álamo Hernández Y. , Maqueda González R. , Lathan R. , Gutiérrez Samaniego M. , Colao García L. , Núñez O’Sullivan S. , Vaquero M. A. , Picardo Nieto A. , Blazquez Martin A. , Vera-Mansilla C. , Soto Schüte S. , Gutiérrez Calvo A. , Sanchez Argüeso A. , Hernández-Villafranca S. , Qian Zhang S. , Mínguez García J. , Casalduero García L. , Iparraguirre M. A. , Florez Gamarra M. , Arguello Andres J. M. , Tallon Iglesias B. , Pereira Perez F. , Aparicio-Sanchez D. , Durán-Muñoz-Cruzado V. , Pareja-Ciuró F. , Cano-Valderrama O. , Torres-Garcia A. J. , Zarain Obrador L. , Moreno A. , Garcia Ureña M. A. , Paseiro G. , Fuenmayor-Valera M. L. , Pardo R.
Published: October 2021

Anecdotal evidence suggests that community infection control measures during the COVID-19 outbreak have modified the number and natural history of acute surgical inflammatory processes (ASIP—appendicitis, cholecystitis, diverticulitis and perianal abscesses) admissions. This study aims to evaluate the impact of the COVID-19 pandemic on the presentation and treatment ASIP and quantify the effect of COVID-19 infection on the outcomes of ASIP patients. This was a multicentre, comparative study, whereby ASIP cases from 2019, 2020 and 2021 (March 14th to May 2nd) were analyzed. Data regarding patient and disease characteristics as well as outcomes, were collected from sixteen centres in Madrid, and one in Seville (Spain). The number of patients treated for ASIP in 2019 was 822 compared to 521 in 2020 and 835 in 2021. This 1/3rd reduction occurs mainly in patients with mild cases, while the number of severe cases was similar. Surgical standards suffered a step back during the first wave: Lower laparoscopic approach and longer length of stay. We also found a more conservative approach to the patients this year, non-justified by clinical circumstances. Luckily these standards improved again in 2021. The positive COVID-19 status itself did not have a direct impact on mortality. Strikingly, none of the 33 surgically treated COVID positive patients during both years died postoperatively. This is an interesting finding which, if confirmed through future research with a larger sample size of COVID-19 positive patients, can expedite the recovery phase of acute surgical services.
Addressing hospitalisations with non-error-free data by generalised SEIR modelling of COVID-19 pandemic
Authors: Mendes Jorge M. , Coelho Pedro S.
Published: October 2021

Successive generalisations of the basic SEIR model have been proposed to accommodate the different needs of the organisations handling the SARS-CoV-2 epidemic. These generalisations have not been able until today to represent the potential of the epidemic to overwhelm hospital capacity until today. This work builds on previous generalisations, including a new compartment for hospital occupancy that allows accounting for the infected patients that need specialised medical attention. Consequently, a deeper understanding of the hospitalisations rate and probability as well as of the recovery rates for hospitalised and non-hospitalised individuals is achieved, offering new information and predictions of crucial importance for the planning of the health systems and global epidemic response. Additionally, a new methodology to calibrate epidemic flows between compartments is proposed. We conclude that the two-step calibration procedure is able to recalibrate non-error-free data and showed crucial to reconstruct the series in a specific situation characterised by significant errors over the official recovery cases. The performed modelling also allowed us to understand how effective the several interventions (lockdown or other mobility restriction measures) were, offering insight for helping public authorities to set the timing and intensity of the measures in order to avoid the implosion of the health systems.
Perinatal mortality and its association with antenatal care visit, maternal tetanus toxoid immunization and partograph utilization in Ethiopia: a meta-analysis
Authors: Desta Melaku , Akalu Tadesse Yirga , Alamneh Yoseph Merkeb , Talie Asmare , Alemu Addisu Alehegn , Tessema Zenaw , Yibeltal Desalegn , Alamneh Alehegn Aderaw , Ketema Daniel Bekele , Shiferaw Wondimeneh Shibabaw , Getaneh Temesgen
Published: October 2021

Despite remarkable progress in the reduction of under-five mortality; perinatal mortality is the major public health problem in Africa. In Ethiopia, the study findings on perinatal mortality and its predictors were inconsistent. Therefore, this systematic review and meta-analysis estimated the pooled perinatal mortality, and its association with antenatal care visit, maternal tetanus toxoid immunization, and partograph monitoring. International databases like PubMed, SCOPUS, Google Scholar and Science Direct were systematically searched. I squared statistics was used to determine the levels of heterogeneity across studies and the pooled estimate was computed using a random-effect model. The meta-analysis showed that a pooled prevalence of perinatal mortality in Ethiopia was 6.00% (95% CI 5.00%, 7.00%). The highest proportion of perinatal mortality was a stillbirth, 5.00% (95% CI 4.00%, 7.00%). Women who had antenatal care visit [OR = 0.20 (95% CI 0.12, 0.34)], maternal tetanus toxoid immunization [OR = 0.43 (95% CI 0.24, 0.77)] and partograph monitoring [POR = 0.22 (95% CI 0.06, 0.76)] reduced the risk of perinatal mortality. Whereas, previous history of perinatal mortality [POR = 7.95 (95% CI 5.59, 11.30)] and abortion history (POR = 2.02 (95% CI 1.18, 3.46)) significantly increased the risk of perinatal mortality. Therefore, antenatal care visit, maternal tetanus toxoid vaccination uptake, and partograph utilization should be an area of improvements to reduce perinatal mortality.
A unified constitutive model for pressure sensitive shear flow transitions in moderate dense granular materials
Authors: Cheng Xiaohui , Xiao Shize , Cao Alex Sixie , Hou Meiying
Published: October 2021

Granular shear flows exhibit complex transitional regimes that are dramatically affected by the pressure level and shear stress state. New advances in granular shear tests at low pressure have enlightened the understanding of the two granular shear flow transitions: between quasi-static and moderate shear flows, and between steady-state and transient shear flows. However, a unified constitutive model to describe these two transitions is yet to develop. In this work, a simplified and unified model is proposed based on innovative triaxial shear flow tests, using two dimensionless physical variables. Model results validated against experimental data suggest that the shear flow transition between a quasi-static to a moderate Isotach type flow state is highly pressure-dependent. At extremely low pressure, the granular viscosity becomes the primary mechanism, suppressing the quasi-static mechanism even under “quasi-static” shear rates. In transient to steady state granular flow transitions, a mobilized shear stress ratio or mobilized friction coefficient between zero and the critical state ratio for consolidated granular packings is taken into consideration. This is coupled with the mechanism of granular viscosity. These findings have not been discussed before and are of great relevance to granular mechanics as well as space and earthquake engineering.
Detection and analysis of COVID-19 in medical images using deep learning techniques
Authors: Yang Dandi , Martinez Cristhian , Visuña Lara , Khandhar Hardev , Bhatt Chintan , Carretero Jesus
Published: October 2021

The main purpose of this work is to investigate and compare several deep learning enhanced techniques applied to X-ray and CT-scan medical images for the detection of COVID-19. In this paper, we used four powerful pre-trained CNN models, VGG16, DenseNet121, ResNet50,and ResNet152, for the COVID-19 CT-scan binary classification task. The proposed Fast.AI ResNet framework was designed to find out the best architecture, pre-processing, and training parameters for the models largely automatically. The accuracy and F1-score were both above 96% in the diagnosis of COVID-19 using CT-scan images. In addition, we applied transfer learning techniques to overcome the insufficient data and to improve the training time. The binary and multi-class classification of X-ray images tasks were performed by utilizing enhanced VGG16 deep transfer learning architecture. High accuracy of 99% was achieved by enhanced VGG16 in the detection of X-ray images from COVID-19 and pneumonia. The accuracy and validity of the algorithms were assessed on X-ray and CT-scan well-known public datasets. The proposed methods have better results for COVID-19 diagnosis than other related in literature. In our opinion, our work can help virologists and radiologists to make a better and faster diagnosis in the struggle against the outbreak of COVID-19.
Iron homeostasis in the absence of ferricrocin and its consequences in fungal development and insect virulence in Beauveria bassiana
Authors: Jirakkakul Jiraporn , Wichienchote Nuchnudda , Likhitrattanapisal Somsak , Ingsriswang Supawadee , Yoocha Thippawan , Tangphatsornruang Sithichoke , Wasuwan Rudsamee , Cheevadhanarak Supapon , Tanticharoen Morakot , Amnuaykanjanasin Alongkorn
Published: October 2021

The putative ferricrocin synthetase gene ferS in the fungal entomopathogen Beauveria bassiana BCC 2660 was identified and characterized. The 14,445-bp ferS encodes a multimodular nonribosomal siderophore synthetase tightly clustered with Fusarium graminearum ferricrocin synthetase. Functional analysis of this gene was performed by disruption with the bar cassette. ΔferS mutants were verified by Southern and PCR analyses. HPLC and TLC analyses of crude extracts indicated that biosynthesis of ferricrocin was abolished in ΔferS. Insect bioassays surprisingly indicated that ΔferS killed the Spodoptera exigua larvae faster (LT50 59 h) than wild type (66 h). Growth and developmental assays of the mutant and wild type demonstrated that ΔferS had a significant increase in germination under iron depletion and radial growth and a decrease in conidiation. Mitotracker staining showed that the mitochondrial activity was enriched in ΔferS under both iron excess and iron depletion. Comparative transcriptomes between wild type and ΔferS indicated that the mutant was increased in the expression of eight cytochrome P450 genes and those in iron homeostasis, ferroptosis, oxidative stress response, ergosterol biosynthesis, and TCA cycle, compared to wild type. Our data suggested that ΔferS sensed the iron excess and the oxidative stress and, in turn, was up-regulated in the antioxidant-related genes and those in ergosterol biosynthesis and TCA cycle. These increased biological pathways help ΔferS grow and germinate faster than the wild type and caused higher insect mortality than the wild type in the early phase of infection.
The importance of three dimensional coronary artery reconstruction accuracy when computing virtual fractional flow reserve from invasive angiography
Authors: Solanki Roshni , Gosling Rebecca , Rammohan Vignesh , Pederzani Giulia , Garg Pankaj , Heppenstall James , Hose D. Rodney , Lawford Patricia V. , Narracott Andrew J. , Fenner John , Gunn Julian P. , Morris Paul D.
Published: October 2021

Three dimensional (3D) coronary anatomy, reconstructed from coronary angiography (CA), is now being used as the basis to compute ‘virtual’ fractional flow reserve (vFFR), and thereby guide treatment decisions in patients with coronary artery disease (CAD). Reconstruction accuracy is therefore important. Yet the methods required remain poorly validated. Furthermore, the magnitude of vFFR error arising from reconstruction is unkown. We aimed to validate a method for 3D CA reconstruction and determine the effect this had upon the accuracy of vFFR. Clinically realistic coronary phantom models were created comprosing seven standard stenoses in aluminium and 15 patient-based 3D-printed, imaged with CA, three times, according to standard clinical protocols, yielding 66 datasets. Each was reconstructed using epipolar line projection and intersection. All reconstructions were compared against the real phantom models in terms of minimal lumen diameter, centreline and surface similarity. 3D-printed reconstructions (n = 45) and the reference files from which they were printed underwent vFFR computation, and the results were compared. The average error in reconstructing minimum lumen diameter (MLD) was 0.05 (± 0.03 mm) which was < 1% (95% CI 0.13–1.61%) compared with caliper measurement. Overall surface similarity was excellent (Hausdorff distance 0.65 mm). Errors in 3D CA reconstruction accounted for an error in vFFR of ± 0.06 (Bland Altman 95% limits of agreement). Errors arising from the epipolar line projection method used to reconstruct 3D coronary anatomy from CA are small but contribute to clinically relevant errors when used to compute vFFR.