bluuebunny/crossref_metadata_2025 huggingface dataset:
Lipidomic profiling of human serum enables detection of pancreatic cancer
Authors: Wolrab Denise , Jirásko Robert , Cífková Eva , Höring Marcus , Mei Ding , Chocholoušková Michaela , Peterka Ondřej , Idkowiak Jakub , Hrnčiarová Tereza , Kuchař Ladislav , Ahrends Robert , Brumarová Radana , Friedecký David , Vivo-Truyols Gabriel , Škrha Pavel , Škrha Jan , Kučera Radek , Melichar Bohuslav , Liebisch Gerhard , Burkhardt Ralph , Wenk Markus R. , Cazenave-Gassiot Amaury , Karásek Petr , Novotný Ivo , Greplová Kristína , Hrstka Roman , Holčapek Michal
Published: January 2022

Pancreatic cancer has the worst prognosis among all cancers. Cancer screening of body fluids may improve the survival time prognosis of patients, who are often diagnosed too late at an incurable stage. Several studies report the dysregulation of lipid metabolism in tumor cells, suggesting that changes in the blood lipidome may accompany tumor growth. Here we show that the comprehensive mass spectrometric determination of a wide range of serum lipids reveals statistically significant differences between pancreatic cancer patients and healthy controls, as visualized by multivariate data analysis. Three phases of biomarker discovery research (discovery, qualification, and verification) are applied for 830 samples in total, which shows the dysregulation of some very long chain sphingomyelins, ceramides, and (lyso)phosphatidylcholines. The sensitivity and specificity to diagnose pancreatic cancer are over 90%, which outperforms CA 19-9, especially at an early stage, and is comparable to established diagnostic imaging methods. Furthermore, selected lipid species indicate a potential as prognostic biomarkers.
An optical neural network using less than 1 photon per multiplication
Authors: Wang Tianyu , Ma Shi-Yuan , Wright Logan G. , Onodera Tatsuhiro , Richard Brian C. , McMahon Peter L.
Published: January 2022

Deep learning has become a widespread tool in both science and industry. However, continued progress is hampered by the rapid growth in energy costs of ever-larger deep neural networks. Optical neural networks provide a potential means to solve the energy-cost problem faced by deep learning. Here, we experimentally demonstrate an optical neural network based on optical dot products that achieves 99% accuracy on handwritten-digit classification using ~3.1 detected photons per weight multiplication and ~90% accuracy using ~0.66 photons (~2.5 × 10−19 J of optical energy) per weight multiplication. The fundamental principle enabling our sub-photon-per-multiplication demonstration—noise reduction from the accumulation of scalar multiplications in dot-product sums—is applicable to many different optical-neural-network architectures. Our work shows that optical neural networks can achieve accurate results using extremely low optical energies.
Application of copper(II)-based chemicals induces CH3Br and CH3Cl emissions from soil and seawater
Authors: Jiao Yi , Zhang Wanying , Kim Jae Yun Robin , Deventer Malte Julian , Vollering Julien , Rhew Robert C.
Published: January 2022

Methyl bromide (CH3Br) and methyl chloride (CH3Cl) are major carriers of atmospheric bromine and chlorine, respectively, which can catalyze stratospheric ozone depletion. However, in our current understanding, there are missing sources associated with these two species. Here we investigate the effect of copper(II) on CH3Br and CH3Cl production from soil, seawater and model organic compounds: catechol (benzene-1,2-diol) and guaiacol (2-methoxyphenol). We show that copper sulfate (CuSO4) enhances CH3Br and CH3Cl production from soil and seawater, and it may be further amplified in conjunction with hydrogen peroxide (H2O2) or solar radiation. This represents an abiotic production pathway of CH3Br and CH3Cl perturbed by anthropogenic application of copper(II)-based chemicals. Hence, we suggest that the widespread application of copper(II) pesticides in agriculture and the discharge of anthropogenic copper(II) to the oceans may account for part of the missing sources of CH3Br and CH3Cl, and thereby contribute to stratospheric halogen load.
One-step synthesis of sequence-controlled multiblock polymers with up to 11 segments from monomer mixture
Authors: Xia Xiaochao , Suzuki Ryota , Gao Tianle , Isono Takuya , Satoh Toshifumi
Published: January 2022

Switchable polymerization holds considerable potential for the synthesis of highly sequence-controlled multiblock. To date, this method has been limited to three-component systems, which enables the straightforward synthesis of multiblock polymers with less than five blocks. Herein, we report a self-switchable polymerization enabled by simple alkali metal carboxylate catalysts that directly polymerize six-component mixtures into multiblock polymers consisting of up to 11 blocks. Without an external trigger, the catalyst polymerization spontaneously connects five catalytic cycles in an orderly manner, involving four anhydride/epoxide ring-opening copolymerizations and one L-lactide ring-opening polymerization, creating a one-step synthetic pathway. Following this autotandem catalysis, reasonable combinations of different catalytic cycles allow the direct preparation of diverse, sequence-controlled, multiblock copolymers even containing various hyperbranched architectures. This method shows considerable promise in the synthesis of sequentially and architecturally complex polymers, with high monomer sequence control that provides the potential for designing materials.
Harnessing protein folding neural networks for peptide–protein docking
Authors: Tsaban Tomer , Varga Julia K. , Avraham Orly , Ben-Aharon Ziv , Khramushin Alisa , Schueler-Furman Ora
Published: January 2022

Highly accurate protein structure predictions by deep neural networks such as AlphaFold2 and RoseTTAFold have tremendous impact on structural biology and beyond. Here, we show that, although these deep learning approaches have originally been developed for the in silico folding of protein monomers, AlphaFold2 also enables quick and accurate modeling of peptide–protein interactions. Our simple implementation of AlphaFold2 generates peptide–protein complex models without requiring multiple sequence alignment information for the peptide partner, and can handle binding-induced conformational changes of the receptor. We explore what AlphaFold2 has memorized and learned, and describe specific examples that highlight differences compared to state-of-the-art peptide docking protocol PIPER-FlexPepDock. These results show that AlphaFold2 holds great promise for providing structural insight into a wide range of peptide–protein complexes, serving as a starting point for the detailed characterization and manipulation of these interactions.
A smart and responsive crystalline porous organic cage membrane with switchable pore apertures for graded molecular sieving
Authors: He Ai , Jiang Zhiwei , Wu Yue , Hussain Hadeel , Rawle Jonathan , Briggs Michael E. , Little Marc A. , Livingston Andrew G. , Cooper Andrew I.
Published: January 2022

Membranes with high selectivity offer an attractive route to molecular separations, where technologies such as distillation and chromatography are energy intensive. However, it remains challenging to fine tune the structure and porosity in membranes, particularly to separate molecules of similar size. Here, we report a process for producing composite membranes that comprise crystalline porous organic cage films fabricated by interfacial synthesis on a polyacrylonitrile support. These membranes exhibit ultrafast solvent permeance and high rejection of organic dyes with molecular weights over 600 g mol−1. The crystalline cage film is dynamic, and its pore aperture can be switched in methanol to generate larger pores that provide increased methanol permeance and higher molecular weight cut-offs (1,400 g mol−1). By varying the water/methanol ratio, the film can be switched between two phases that have different selectivities, such that a single, ‘smart’ crystalline membrane can perform graded molecular sieving. We exemplify this by separating three organic dyes in a single-stage, single-membrane process.
Characteristics of ultrafine-ground potassium-bearing shale and the effects of roasting pre-cracking
Authors: Zhu Zaisheng , He Zhenquan , Gai Guosheng
Published: January 2022

Potassium-bearing shale is being developed as a potential alternative to potash for use in fertilisers. The first step in this process is to reduce its particle size by crushing. This paper explores whether roasting pre-cracked potassium-bearing shale can improve the quality of the resulting ultrafine product. Analysis of the particle size distribution of the ultrafine product and its fractal dimension found contradictory results: the minimum particle size distribution was obtained by roasting for 2.5 h, while the minimum fractal dimension was obtained by roasting for 1 h. Fuzzy comprehensive evaluation was conducted with three indicators—(1) the weight of the − 10 μm product, (2) the fractal dimension of the particle size distribution, and (3) d97—to obtain a unique combination of indicators that reflects the quality and quantity of the products. The weights of the three indicators were calculated by an analytic hierarchical process to be 0.69, 0.149 and 0.161, respectively. Roasting pre-cracked shale for 2–2.5 h was found to improve the mean values of the fuzzy comprehensive evaluation indicators by about 0.07. However, the cost increased from 2.82 RMB to ≥ 10.08 RMB, which is not feasible for widespread industrial implementation.
Consequences of quantum noise control for the relaxation resonance frequency and phase noise in heterogeneous Silicon/III–V lasers
Authors: Kim Dongwan , Harfouche Mark , Wang Huolei , Santis Christos T. , Vilenchik Yaakov , Satyan Naresh , Rakuljic George , Yariv Amnon
Published: January 2022

We have recently introduced a new semiconductor laser design which is based on an extreme, 99%, reduction of the laser mode absorption losses. In previous reports, we showed that this was achieved by a laser mode design which confines the great majority of the modal energy (> 99%) in a low-loss Silicon guiding layer rather than in highly-doped, thus lossy, III–V p$${}^+$$

+

and n$${}^+$$

+

layers, which is the case with traditional III–V lasers. The resulting reduced electron-field interaction was shown to lead to a commensurate reduction of the spontaneous emission rate by the excited conduction band electrons into the laser mode and thus to a reduction of the frequency noise spectral density of the laser field often characterized by the Schawlow–Townes linewidth. In this paper, we demonstrate theoretically and present experimental evidence of yet another major beneficial consequence of the new laser design: a near total elimination of the contribution of amplitude-phase coupling (the Henry $$\alpha $$
α
parameter) to the frequency noise at “high” frequencies. This is due to an order of magnitude lowering of the relaxation resonance frequency of the laser. Here, we show that the practical elimination of this coupling enables yet another order of magnitude reduction of the frequency noise at high frequencies, resulting in a quantum-limited frequency noise spectral density of 130 Hz$$^2$$

2

/Hz (linewidth of 0.4 kHz) for frequencies beyond the relaxation resonance frequency 680 MHz. This development is of key importance in the development of semiconductor lasers with higher coherence, particularly in the context of integrated photonics with a small laser footprint without requiring any sort of external cavity.
Sex differences in the 10-year survival of patients undergoing maintenance hemodialysis in the Q-Cohort Study
Authors: Tsujikawa Hiroaki , Yamada Shunsuke , Hiyamuta Hiroto , Taniguchi Masatomo , Tsuruya Kazuhiko , Torisu Kumiko , Nakano Toshiaki , Kitazono Takanari
Published: January 2022

Women have a longer life expectancy than men in the general population. However, it has remained unclear whether this advantage is maintained in patients undergoing maintenance hemodialysis. The aim of this study was to compare the risk of mortality, especially infection-related mortality, between male and female hemodialysis patients. A total of 3065 Japanese hemodialysis patients aged ≥ 18 years old were followed up for 10 years. The primary outcomes were all-cause and infection-related mortality. The associations between sex and these outcomes were examined using Cox proportional hazards models. During the median follow-up of 8.8 years, 1498 patients died of any cause, 387 of whom died of infection. Compared with men, the multivariable-adjusted hazard ratios (95% confidence interval) for all-cause and infection-related mortality in women were 0.51 (0.45–0.58, P < 0.05) and 0.36 (0.27–0.47, P < 0.05), respectively. These findings remained significant even when propensity score-matching or inverse probability of treatment weighting adjustment methods were employed. Furthermore, even when the non-infection-related mortality was considered a competing risk, the infection-related mortality rate in women was still significantly lower than that in men. Regarding all-cause and infection-related deaths, women have a survival advantage compared with men among Japanese patients undergoing maintenance hemodialysis.
Evaluation on the phenotypic diversity of Calamansi (Citrus microcarpa) germplasm in Hainan island
Authors: Xin Yong-Hui , Wu Yuan-Xin , Qiao Bin , Su Long , Xie Shang-Qian , Ling Peng
Published: January 2022

Calamansi or Philippine lime (Citrofortunella macrocarpa) is an important crop for local economic in Hainan Island. There is no study about Calamansi germplasm evaluation and cultivar development. In this study, Calamansi data were collected from 151 of Calamansi seedling trees, and 37 phenotypic traits were analyzed to investigate their genetic diversities. The cluster analysis and principal component analysis were conducted aiming to provide a theoretical basis for the Calamansi genetic improvement. The results of the diversity analysis revealed: (1) the diversity indexes for qualitative traits were ranged from 0.46–1.39, and the traits with the highest genetic diversity level were fruit shaped and pulp colored (H′ > 1.20); and the diversity indexes for quantitative traits ranged from 0.67–2.10, with the exception of a lower in fruit juice rate (1.08) and lower in number of petals (0.67). (2) The clustering analysis of phenotypic traits have arranged the samples into 4 categories: the first group characterized by fewer flesh Segment number per fruit (SNF) and more Oil cell number (OCN); the second group had 7 samples, all characterized with larger Crown breadth (CB), higher Yield per tree (YPT), the lager leaf, the higher Ascorbic acid (AA), and less Seed number per fruit (SNPF); the third group had 25 samples characterized by smaller Tree foot diameter (TFD),smaller Fruit shape index (FSI) and higher Total soluble solids (TSS) contain; the fourth group had 87 samples, they were characterized by shorter Petiole length (PEL), larger fruit, higher Juice ratio (JR), multiple Stamen number (SN) and longer Pistil length (PIL). (3) The principal component analysis showed the values of the first 9 major components characteristic vectors were all greater than 3, the cumulative contribution rate reach 72.20%, including the traits of single fruit weight, fruit diameter, tree height, tree canopy width etc. Finally, based on the comprehensive main component value of all samples, the Calamansi individuals with higher testing scores were selected for further observation. This study concludes that Calamansi seedling populations in the Hainan Island holds great genetic diversity in varies traits, and can be useful for the Calamansi variety improvements.
Predicting students’ performance in e-learning using learning process and behaviour data
Authors: Qiu Feiyue , Zhang Guodao , Sheng Xin , Jiang Lei , Zhu Lijia , Xiang Qifeng , Jiang Bo , Chen Ping-kuo
Published: January 2022

E-learning is achieved by the deep integration of modern education and information technology, and plays an important role in promoting educational equity. With the continuous expansion of user groups and application areas, it has become increasingly important to effectively ensure the quality of e-learning. Currently, one of the methods to ensure the quality of e-learning is to use mutually independent e-learning behaviour data to build a learning performance predictor to achieve real-time supervision and feedback during the learning process. However, this method ignores the inherent correlation between e-learning behaviours. Therefore, we propose the behaviour classification-based e-learning performance (BCEP) prediction framework, which selects the features of e-learning behaviours, uses feature fusion with behaviour data according to the behaviour classification model to obtain the category feature values of each type of behaviour, and finally builds a learning performance predictor based on machine learning. In addition, because existing e-learning behaviour classification methods do not fully consider the process of learning, we also propose an online behaviour classification model based on the e-learning process called the process-behaviour classification (PBC) model. Experimental results with the Open University Learning Analytics Dataset (OULAD) show that the learning performance predictor based on the BCEP prediction framework has a good prediction effect, and the performance of the PBC model in learning performance prediction is better than traditional classification methods. We construct an e-learning performance predictor from a new perspective and provide a new solution for the quantitative evaluation of e-learning classification methods.
The role of posterior pallial amygdala in mediating motor behaviors in pigeons
Authors: Tian Xinmao , Shi Yuhua , Zhang Yifeng , Wang Yijie , Li Mengke , Cheng Han , Wang Zhenlong
Published: January 2022

The posterior pallial amygdala (PoA) is located on the basolateral caudal telencephalon, including the basal division of PoA (PoAb) and the compact division of PoA (PoAc). PoA plays a vital role in emotion regulation and is considered a part of the amygdala in birds. However, the regulatory functions responsible for motor behaviors and emotions between PoAb and PoAc are poorly understood. Therefore, we studied the structure and function of PoA by tract-tracing methods, constant current electrical stimulation, and different dopamine receptor drug injections in pigeons (Columba livia domestica). PoAb connects reciprocally with two nuclear groups in the cerebrum: 1) a continuum comprising the temporo–parieto–occipitalis, corticoidea dorsolateralis, hippocampus, and parahippocampalis areas and 2) rostral areas of the hemisphere, including the nucleus septalis lateralis and nucleus taeniae amygdalae. Extratelencephalic projections of PoAb terminate in the lateral hypothalamic nucleus and are scattered in many limbic midbrain regions. PoAb and PoAc mainly mediated the turning movement. In the ‘open-field’ test, D1 agonist and D2 antagonist could significantly reduce the latency period for entering into the central area and increase the residence time in the central area, whereas D1 antagonist and D2 agonist had the opposite effect. PoAb and PoAc are important brain areas that mediate turning behavior.
Agr Quorum Sensing influences the Wood-Ljungdahl pathway in Clostridium autoethanogenum
Authors: Piatek Pawel , Humphreys Christopher , Raut Mahendra P. , Wright Phillip C. , Simpson Sean , Köpke Michael , Minton Nigel P. , Winzer Klaus
Published: January 2022

Acetogenic bacteria are capable of fermenting CO2 and carbon monoxide containing waste-gases into a range of platform chemicals and fuels. Despite major advances in genetic engineering and improving these biocatalysts, several important physiological functions remain elusive. Among these is quorum sensing, a bacterial communication mechanism known to coordinate gene expression in response to cell population density. Two putative agr systems have been identified in the genome of Clostridium autoethanogenum suggesting bacterial communication via autoinducing signal molecules. Signal molecule-encoding agrD1 and agrD2 genes were targeted for in-frame deletion. During heterotrophic growth on fructose as a carbon and energy source, single deletions of either gene did not produce an observable phenotype. However, when both genes were simultaneously inactivated, final product concentrations in the double mutant shifted to a 1.5:1 ratio of ethanol:acetate, compared to a 0.2:1 ratio observed in the wild type control, making ethanol the dominant fermentation product. Moreover, CO2 re-assimilation was also notably reduced in both hetero- and autotrophic growth conditions. These findings were supported through comparative proteomics, which showed lower expression of carbon monoxide dehydrogenase, formate dehydrogenase A and hydrogenases in the ∆agrD1∆agrD2 double mutant, but higher levels of putative alcohol and aldehyde dehydrogenases and bacterial micro-compartment proteins. These findings suggest that Agr quorum sensing, and by inference, cell density play a role in carbon resource management and use of the Wood-Ljungdahl pathway as an electron sink.
Cross-classification between self-rated health and health status: longitudinal analyses of all-cause mortality and leading causes of death in the UK
Authors: Mutz Julian , Lewis Cathryn M.
Published: January 2022

Risk stratification is an important public health priority that is central to clinical decision making and resource allocation. The aim of this study was to examine how different combinations of self-rated and objective health status predict all-cause mortality and leading causes of death in the UK. The UK Biobank study recruited > 500,000 participants between 2006 and 2010. Self-rated health was assessed using a single-item question and health status was derived from medical history, including data on 81 cancer and 443 non-cancer illnesses. Analyses included > 370,000 middle-aged and older adults with a median follow-up of 11.75 (IQR = 1.4) years, yielding 4,320,270 person-years of follow-up. Compared to individuals with excellent self-rated health and favourable health status, individuals with other combinations of self-rated and objective health status had a greater mortality risk, with hazard ratios ranging from HR = 1.22 (95% CI 1.15–1.29,PBonf. < 0.001) for individuals with good self-rated health and favourable health status to HR = 7.14 (95% CI 6.70–7.60,PBonf. < 0.001) for individuals with poor self-rated health and unfavourable health status. Our findings highlight that self-rated health captures additional health-related information and should be more widely assessed. The cross-classification between self-rated health and health status represents a straightforward metric for risk stratification, with applications to population health, clinical decision making and resource allocation.
In vitro antioxidant extracts evaluation from the residue of the Hevea brasiliensis seed
Authors: Oleinik Giovanna , Dario Priscila Paola , de Morais Gasperin Katiane , Benvegnú Dalila Moter , Lima Fernanda Oliveira , Soares Letiére Cabreira , Gallina André Lazarin
Published: January 2022

The antioxidants used in the food industry are essential to inhibit the formation of free radicals, preserving the existing properties in the different matrices. However, the insecurity of the synthetic antioxidants regarding human health propels search for natural substrates with potential antioxidant activity as an alternative to synthetic compounds. In this way, the work had as objective obtaining extracts from the seed pomace of the Hevea brasiliensis (rubber tree), relating the contents of flavonoids and total phenols in the application as an antioxidant. The methodology consisted of the extraction using four solvents, varying extractive methods, time, and seed concentrations. The antioxidant activity in vitro was evaluated by capturing the DPPH (2,2-diphenyl-1-picryl-hydrazil) radical. The optimized results demonstrate that the aqueous extracts produced in the Soxhlet in the concentrations of 85 g L−1 and retention time of 4 h reached 37.73 ± 1.69% in the antioxidant tests of the free radical DPPH capture, 1405.15 mg EAC 100 g−1 in the quantification of phenolic compounds and 223.34 mg 100 g−1 of total flavonoids. Thus, this work may contribute to the realization of studies and future research for characterization and identification concerning which phenolic compounds and flavonoids attribute the antioxidant characteristic to the extracts produced, enabling the discovery of products with high added value in the production chain. In addition, because the water used as a solvent showed greater antioxidant potential between the extracts, the non-toxic and environmentally friendly character is highlighted, allowing a wide variety of applications in the food industry.
Social norms in indirect reciprocity with ternary reputations
Authors: Murase Yohsuke , Kim Minjae , Baek Seung Ki
Published: January 2022

Indirect reciprocity is a key mechanism that promotes cooperation in social dilemmas by means of reputation. Although it has been a common practice to represent reputations by binary values, either ‘good’ or ‘bad’, such a dichotomy is a crude approximation considering the complexity of reality. In this work, we studied norms with three different reputations, i.e., ‘good’, ‘neutral’, and ‘bad’. Through massive supercomputing for handling more than thirty billion possibilities, we fully identified which norms achieve cooperation and possess evolutionary stability against behavioural mutants. By systematically categorizing all these norms according to their behaviours, we found similarities and dissimilarities to their binary-reputation counterpart, the leading eight. We obtained four rules that should be satisfied by the successful norms, and the behaviour of the leading eight can be understood as a special case of these rules. A couple of norms that show counter-intuitive behaviours are also presented. We believe the findings are also useful for designing successful norms with more general reputation systems.
Different sites of actions make different responses to thiazolidinediones between mouse and rat models of fatty liver
Authors: Ebihara Chihiro , Aizawa-Abe Megumi , Zhao Mingming , Gumbilai Valentino , Ebihara Ken
Published: January 2022

Therapeutic approach for NAFLD is limited and there are no approved drugs. Pioglitazone (PGZ), a thiazolidinedione (TZD) that acts via peroxisome proliferator activated receptor gamma (PPARγ) is the only agent that has shown consistent benefit and efficacy in clinical trials. However, the mechanism of its therapeutic effect on NAFLD remains unclear. The poor understanding may be due to problems with mouse, a species most used for animal experiments. TZDs exacerbate fatty liver in mouse models while they improve it in rat models like in human patients. Therefore, we compared the effects of TZDs including PGZ and rosiglitazone (RGZ) in ob/ob mice and Lepmkyo/Lepmkyo rats, models of leptin-deficient obesity, and A-ZIP/F-1 mice and seipin knockout (SKO) rats, models of generalized lipodystrophy. Pparg mRNA expression was markedly upregulated in fatty livers of mouse models while it was unchanged in rat models. TZDs exacerbated fatty liver in ob/ob and A-ZIP/F-1 mice, improved it in Lepmkyo/Lepmkyo rats and showed no effect in SKO rats. Gene expression analyses of Pparg and its target gene, Fsp27 revealed that PPARγ in the adipose tissue is the exclusive therapeutic target of TZDs in rats but PPARγ in the liver in addition to the adipose tissue is also a major site of actions for TZDs in mice. Although the response to TZDs in mice is the complete opposite of that in human patients, no report has pointed out the problem with TZD studies using mouse models so far. The present study might provide useful suggestions in research on TZDs.
Archaeometric perspective on the emergence of brass north of the Alps around the turn of the Era
Authors: Bursák Daniel , Danielisová Alžběta , Magna Tomáš , Pajdla Petr , Míková Jitka , Rodovská Zuzana , Strnad Ladislav , Trubač Jakub
Published: January 2022

Ancient brass (aurichalcum) was a valued commodity in the Antiquity, notably because of its gold-like appearance. After mastering brass fabrication using the cementation procedure in the first century BC in the Mediterranean, this material became widely used by the Romans for coins, jewellery and other artefacts. Because of its visual qualities, it is believed that since this period, brass played an important role in diplomatic and economic contacts with indigenous communities, notably Celtic and Germanic tribes north of Danube and west of Rhine. To test this hypothesis, we performed for the first time the advanced statistical multivariate analysis based on chemical composition and lead isotope systematics, coupled with informed typo-chronological categorisation, of a suite of late Iron Age and Early Roman period (first century BC – first century AD) brass and other copper-alloy artefacts from the territory of Bohemia. In order to to discuss their provenance, the results were compared to known contemporary sources of material. The new results for brass artefacts from this early phase of the massive occurrence of Romanaurichalcumin the Barbarian territories point to the ore deposits in the western Mediterranean or the Massif Central area in Gaul, consistent with historical events. These new findings underscore the great economic and political importance of the new and rich mineral resources in the Transalpine Gaul acquired due to Caesar's military campaigns.
Mapping silver eel migration routes in the North Sea
Authors: Verhelst Pieterjan , Reubens Jan , Coeck Johan , Moens Tom , Simon Janek , Van Wichelen Jeroen , Westerberg Håkan , Wysujack Klaus , Righton David
Published: January 2022

Recent developments in tracking technology resulted in the mapping of various marine spawning migration routes of the European eel (Anguilla anguilla). However, migration routes in the North Sea have rarely been studied, despite many large European rivers and hence potential eel growing habitat discharge into the North Sea. In this study, we present the most comprehensive map to date with migration routes by silver European eels in the North Sea and document for the first time successful eel migration through the English Channel. Migration tracks were reconstructed for 42 eels tagged in Belgium and 12 in Germany. Additionally, some eels moved up north to exit the North Sea over the British Isles, confirming the existence of two different routes, even for eels exiting from a single river catchment. Furthermore, we observed a wide range in migration speeds (6.8–45.2 km day−1). We hypothesize that these are likely attributed to water currents, with eels migrating through the English Channel being significantly faster than eels migrating northward.
CCR2 promotes monocyte recruitment and intestinal inflammation in mice lacking the interleukin-10 receptor
Authors: El Sayed Shorouk , Patik Izabel , Redhu Naresh S. , Glickman Jonathan N. , Karagiannis Konstantinos , El Naenaeey El Sayed Y. , Elmowalid Gamal A. , Abd El Wahab Ashraf M. , Snapper Scott B. , Horwitz Bruce H.
Published: January 2022

Macrophages are a heterogeneous population of mononuclear phagocytes abundantly distributed throughout the intestinal compartments that adapt to microenvironmental specific cues. In adult mice, the majority of intestinal macrophages exhibit a mature phenotype and are derived from blood monocytes. In the steady-state, replenishment of these cells is reduced in the absence of the chemokine receptor CCR2. Within the intestine of mice with colitis, there is a marked increase in the accumulation of immature macrophages that demonstrate an inflammatory phenotype. Here, we asked whether CCR2 is necessary for the development of colitis in mice lacking the receptor for IL10. We compared the development of intestinal inflammation in mice lacking IL10RA or both IL10RA and CCR2. The absence of CCR2 interfered with the accumulation of immature macrophages in IL10R-deficient mice, including a novel population of rounded submucosal Iba1+ cells, and reduced the severity of colitis in these mice. In contrast, the absence of CCR2 did not reduce the augmented inflammatory gene expression observed in mature intestinal macrophages isolated from mice lacking IL10RA. These data suggest that both newly recruited CCR2-dependent immature macrophages and CCR2-independent residual mature macrophages contribute to the development of intestinal inflammation observed in IL10R-deficient mice.
Blood meal analysis of Anopheles vectors of simian malaria based on laboratory and field studies
Authors: Jeyaprakasam Nantha Kumar , Low Van Lun , Liew Jonathan Wee Kent , Pramasivan Sandthya , Wan-Sulaiman Wan-Yusoff , Saeung Atiporn , Vythilingam Indra
Published: January 2022

Blood feeding and host-seeking behaviors of a mosquito play an imperative role in determining its vectorial capacity in transmitting pathogens. Unfortunately, limited information is available regarding blood feeding behavior of Anopheles species in Malaysia. Collection of resting Anopheles mosquitoes for blood meal analysis poses a great challenge especially for forest dwelling mosquitoes. Therefore, a laboratory-based study was conducted to evaluate the potential use of mosquitoes caught using human landing catch (HLC) for blood meal analysis, and subsequently to document blood feeding behavior of local Anopheles mosquitoes in Peninsular Malaysia. The laboratory-based experiment from this study revealed that mosquitoes caught using HLC had the potential to be used for blood meal analysis. Besides HLC, mosquitoes were also collected using manual aspirator and Mosquito Magnet. Overall, 47.4% of 321 field-caught Anopheles mosquitoes belonging to six species were positive for vertebrate host DNA in their blood meal. The most frequent blood meal source was human (45.9%) followed by wild boar (27.4%), dog (15.3%) and monkey (7.5%). Interestingly, only Anopheles cracens and Anopheles introlatus (Leucosphyrus Group) fed on monkey. This study further confirmed that members of the Leucosphyrus Group are the predominant vectors for knowlesi malaria transmission in Peninsular Malaysia mainly due to their simio-anthropophagic feeding behavior.
Prevalence, patterns and determinants of dyslipidaemia among South African adults with comorbidities
Authors: Masilela Charity , Adeniyi Oladele Vincent , Benjeddou Mongi
Published: January 2022

The present study assessed the prevalence, patterns and determinants of dyslipidaemia among South African adults with multi-morbidities. In this study, 614 individuals with DM and hypertension were recruited. Dyslipidaemia was defined as elevated levels of total cholesterol (TC) ≥ 5.2 mmol/L and/or low-density lipoprotein cholesterol (LDL-C) ≥ 2.6 mmol/L, triglycerides (TG) ≥ 1.8 mmol/L and low high-density lipoprotein cholesterol (HDL-C) < 1 mmol/L for men and < 1.2 mmol/L for women. Multivariate regression model (adjusted) analysis was used to identify the significant determinants of dyslipidaemia. The prevalence of dyslipidaemia was 76.7% (n = 471), with females showing the highest prevalence 357 (75.79%). Elevated TG (62.21%) was the most prevalent form of dyslipidemia. Only 103 (16.77%) participants were on statin therapy. The multivariate logistic regression model analysis (adjusted) showed that, the Zulu ethnicity (AOR = 2.45; 95%CI 1.48–4.05) was associated with high TC. DM (AOR = 2.00; 95%CI 1.30–3.06) and the female sex (AOR = 2.54; 95%CI 1.56–4.12) were associated with low HDL-C. Obesity (AOR = 1.57; 95%CI 1.12–2.21) and the Zulu ethnicity (AOR = 1.60; 95%CI 1.00–2.54) were associated with elevated LDL-C. DM (AOR = 2.32; 95%CI 1.61–3.34) was associated with elevated TG. We found a high prevalence of dyslipidaemia. The study further demonstrated that prevention and treatment of dyslipidaemia should be prioritised among individuals with multi-morbidities.
Relationship between maximum occlusal force and gastrointestinal cancer in community-dwelling older Japanese adults
Authors: Komiyama Takamasa , Ohi Takashi , Ito Wakana , Miyoshi Yoshitada , Hiratsuka Takako , Matsuyama Sanae , Tsuji Ichiro , Watanabe Makoto , Hattori Yoshinori
Published: January 2022

Globally, the cancer burden is expected to increase as populations are ageing. Therefore, cancer prevention among older age groups is important. This prospective cohort study examined the relationship between the number of remaining teeth, maximum occlusal force, and incidence of gastrointestinal cancer in community-dwelling older Japanese individuals using data from the Tsurugaya project; 847 participants were included. The exposure variables were the number of remaining teeth and the maximum occlusal force, with the outcome being the incidence of gastrointestinal cancer. Covariates were age, sex, medical history, smoking, alcohol consumption, educational attainment, and physical function. The Cox proportional hazard model was used to examine the relationship between the number of remaining teeth, maximum occlusal force, and incidence of gastrointestinal cancer. With a median follow-up of 7.6 years, 63 participants were confirmed to have gastrointestinal cancer. The risk of gastrointestinal cancer was significantly higher in those with an occlusal force lower than the median (hazard ratio, 2.80; 95% confidence interval, 1.54–5.10). No significant risk difference was found according to the number of remaining teeth. Low maximum occlusal force was associated with the incidence of gastrointestinal cancer in community-dwelling older Japanese adults.
A multi-center study evaluating the correlation between meibomian gland dysfunction and depressive symptoms
Authors: Wei Zhenyu , Liang Junqi , Cao Kai , Wang Leying , Baudouin Christophe , Labbé Antoine , Liang Qingfeng
Published: January 2022

Increased prevalence of depression has been found in patients with meibomian gland dysfunction (MGD); however, specific conditions of patients suffered from MGD and depression remains unclear. Our aim was to investigate the prevalence of depression in patients with MGD and analyze the risk factors of depression in MGD patients. In this multi-center cross-sectional study, we enrolled 830 MGD patients and 114 normal controls. Demographic information was collected by designed questionnaires about lifestyle habits, systemic and ocular medical history. Ophthalmic examinations were performed in a formal order. Depression symptoms were evaluated with a questionnaire survey using a modified self-rating depression scale (M-SDS). The correlations between the M-SDS score and demographic and clinical information were analyzed. The prevalence of hyperlipidemia and obstructive sleep apnea–hypopnea syndrome (OSAHS) was higher in the MGD group. There were 78 cases (9.4%) with depressive symptoms in the MGD group whereas there were 4 cases (3.5%) in controls. Similarly, M-SDS was higher in the MGD group. The characteristics of depression in the MGD group included: crying spells, sleep disturbance and depressed appetite. Some systemic diseases (OSAHS, allergy, skin disease) and the use of contact lenses was correlated with an increased risk of depressive symptoms in MGD patients.
Towards a metagenomics machine learning interpretable model for understanding the transition from adenoma to colorectal cancer
Authors: Casimiro-Soriguer Carlos S. , Loucera Carlos , Peña-Chilet María , Dopazo Joaquin
Published: January 2022

Gut microbiome is gaining interest because of its links with several diseases, including colorectal cancer (CRC), as well as the possibility of being used to obtain non-intrusive predictive disease biomarkers. Here we performed a meta-analysis of 1042 fecal metagenomic samples from seven publicly available studies. We used an interpretable machine learning approach based on functional profiles, instead of the conventional taxonomic profiles, to produce a highly accurate predictor of CRC with better precision than those of previous proposals. Moreover, this approach is also able to discriminate samples with adenoma, which makes this approach very promising for CRC prevention by detecting early stages in which intervention is easier and more effective. In addition, interpretable machine learning methods allow extracting features relevant for the classification, which reveals basic molecular mechanisms accounting for the changes undergone by the microbiome functional landscape in the transition from healthy gut to adenoma and CRC conditions. Functional profiles have demonstrated superior accuracy in predicting CRC and adenoma conditions than taxonomic profiles and additionally, in a context of explainable machine learning, provide useful hints on the molecular mechanisms operating in the microbiota behind these conditions.
The value of ventricular gradient for predicting pulmonary hypertension and mortality in hemodialysis patients
Authors: Jaroszyński A. , Schlegel T. T. , Zaborowski T. , Zapolski T. , Załuska W. , Janion-Sadowska A. , Kozieł D. , Głuszek S. , Dąbrowski W.
Published: January 2022

Pulmonary hypertension (PHT) is associated with increased mortality in hemodialysis (HD) patients. The ventricular gradient optimized for right ventricular pressure overload (VG-RVPO) is sensitive to early changes in right ventricular overload. The study aimed to assess the ability of the VG-RVPO to detect PHT and predict all-cause and cardiac mortality in HD patients. 265 selected HD patients were enrolled. Clinical, biochemical, electrocardiographic, and echocardiographic parameters were evaluated. Patients were divided into normal and abnormal VG-RVPO groups, and were followed-up for 3 years. Abnormal VG-RVPO patients were more likely to be at high or intermediate risk for PHT, were older, had longer HD vintage, higher prevalence of myocardial infarction, higher parathormone levels, shorter pulmonary flow acceleration time, lower left ventricular ejection fraction, higher values of left atrial volume index, left ventricular mass index, and peak tricuspid regurgitant velocity. Both all-cause and CV mortality were higher in abnormal VG-RVPO group. In multivariate Cox analysis, VG-RVPO remained an independent and strong predictor of all-cause and CV mortality. In HD patients, abnormal VG-RVPO not only predicts PHT, but also all-cause and CV mortality.
Thermodynamic surprises of Cu(II)–amylin analogue complexes in membrane mimicking solutions
Authors: Dzień Emilia , Dudek Dorota , Witkowska Danuta , Rowińska-Żyrek Magdalena
Published: January 2022

Membrane environment often has an important effect on the structure, and therefore also on the coordination mode of biologically relevant metal ions. This is also true in the case of Cu(II) coordination to amylin analogues—rat amylin, amylin1–19, pramlintide and Ac-pramlintide, which offer N-terminal amine groups and/or histidine imidazoles as copper(II) anchoring sites. Complex stabilities are comparable, with the exception of the very stable Cu(II)–amylin1–19, which proves that the presence of the amylin C-terminus lowers its affinity for copper(II); although not directly involved, its appropriate arrangement sterically prevents early metal binding. Most interestingly, in membrane-mimicking solution, the Cu(II) affinities of amylin analogues are lower than the ones in water, probably due to the crowding effect of the membrane solution and the fact that amide coordination occurs at higher pH, which happens most likely because the α-helical structure, imposed by the membrane-mimicking solvent, prevents the amides from binding at lower pH, requiring a local unwinding of the α-helix.
Manipulation of free-floating objects using Faraday flows and deep reinforcement learning
Authors: Hardman David , George Thuruthel Thomas , Iida Fumiya
Published: January 2022

The ability to remotely control a free-floating object through surface flows on a fluid medium can facilitate numerous applications. Current studies on this problem have been limited to uni-directional motion control due to the challenging nature of the control problem. Analytical modelling of the object dynamics is difficult due to the high-dimensionality and mixing of the surface flows while the control problem is hard due to the nonlinear slow dynamics of the fluid medium, underactuation, and chaotic regions. This study presents a methodology for manipulation of free-floating objects using large-scale physical experimentation and recent advances in deep reinforcement learning. We demonstrate our methodology through the open-loop control of a free-floating object in water using a robotic arm. Our learned control policy is relatively quick to obtain, highly data efficient, and easily scalable to a higher-dimensional parameter space and/or experimental scenarios. Our results show the potential of data-driven approaches for solving and analyzing highly complex nonlinear control problems.
Electrophysiological and behavioral indicators of musical knowledge about unfamiliar music
Authors: Cui Anja-Xiaoxing , Troje Nikolaus F. , Cuddy Lola L.
Published: January 2022

Most listeners possess sophisticated knowledge about the music around them without being aware of it or its intricacies. Previous research shows that we develop such knowledge through exposure. This knowledge can then be assessed using behavioral and neurophysiological measures. It remains unknown however, which neurophysiological measures accompany the development of musical long-term knowledge. In this series of experiments, we first identified a potential ERP marker of musical long-term knowledge by comparing EEG activity following musically unexpected and expected tones within the context of known music (n = 30). We then validated the marker by showing that it does not differentiate between such tones within the context of unknown music (n = 34). In a third experiment, we exposed participants to unknown music (n = 40) and compared EEG data before and after exposure to explore effects of time. Although listeners’ behavior indicated musical long-term knowledge, we did not find any effects of time on the ERP marker. Instead, the relationship between behavioral and EEG data suggests musical long-term knowledge may have formed before we could confirm its presence through behavioral measures. Listeners are thus not only knowledgeable about music but seem to also be incredibly fast music learners.
The impact of heat on kidney stone presentations in South Carolina under two climate change scenarios
Authors: Kaufman Jason , Vicedo-Cabrera Ana M. , Tam Vicky , Song Lihai , Coffel Ethan , Tasian Gregory
Published: January 2022

The risk of kidney stone presentations increases after hot days, likely due to greater insensible water losses resulting in more concentrated urine and altered urinary flow. It is thus expected that higher temperatures from climate change will increase the global prevalence of kidney stones if no adaptation measures are put in place. This study aims to quantify the impact of heat on kidney stone presentations through 2089, using South Carolina as a model state. We used a time series analysis of historical kidney stone presentations (1997–2014) and distributed lag non-linear models to estimate the temperature dependence of kidney stone presentations, and then quantified the projected impact of climate change on future heat-related kidney stone presentations using daily projections of wet-bulb temperatures to 2089, assuming no adaptation or demographic changes. Two climate change models were considered—one assuming aggressive reduction in greenhouse gas emissions (RCP 4.5) and one representing uninibited greenhouse gas emissions (RCP 8.5). The estimated total statewide kidney stone presentations attributable to heat are projected to increase by 2.2% in RCP 4.5 and 3.9% in RCP 8.5 by 2085–89 (vs. 2010–2014), with an associated total excess cost of ~ $57 million and ~ $99 million, respectively.