bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting SARS-CoV-2 Asymptomatic Infection Rate of Inpatients: A Time Series Analysis
Authors: Rivera Frida , Woo Ahn Kwang , Silvia Munoz-Price L.
Published: November 2021

Background: Asymptomatic SARS-CoV-2 infections play a crucial role in viral transmission. However, they are often difficult to identify given that widespread surveillance has not been the norm. We sought to determine whether COVID-19 rates reported at the county level could predict the positivity rates for SARS-CoV-2 among asymptomatic patients tested in a large academic health system. Methods: This observational study was conducted from April 23, 2020, to December 10, 2020, at Froedtert Health (FH) system, the largest academic health system in Wisconsin. On April 23, 2020, FH implemented SARS-CoV-2 surveillance among all consecutive admissions not suspected of COVID-19, all patients scheduled for elective procedures and deliveries, and all asymptomatic patients with known exposures. Samples were processed by the FH laboratory using molecular methods (RT-PCR). To obtain the daily number of newly confirmed COVID-19 cases in Milwaukee County, we accessed the Wisconsin Department of Health Services publicly available COVID-19 database. For the purpose of this study, COVID-19 rates were defined as the percentage of positive tests among all daily tests performed at the county level, while SARS-CoV-2 positivity rates were the percentage of positive tests among all daily surveillance tests performed at FH among asymptomatic patients. The association between COVID-19 rates in Milwaukee County and asymptomatic rates at FH were assessed using an autoregressive moving average time series analysis. To examine the association between these rates, we fitted a seventh-order autoregression for the residuals based on autocorrelation function and partial autocorrelation function plots of the residuals from linear regression. Results: From April 23, 2020, to December 10, 2020, there were 2,347 new asymptomatic infections detected at FH and 75,196 new COVID-19 cases reported in Milwaukee County. Figure 1 shows the time-series plot of asymptomatic SARS-CoV-2 positivity rates at FH and Figure 2 shows COVID-19 rates in Milwaukee County. As the COVID-19 rate in Milwaukee County increased by 1 unit, the asymptomatic infection rate in FH decreased by 0.024 unit (95% CI, −0.053 to 0.004; P = .095) after accounting for autocorrelation over time. Thus, there was no association between these rates. Conclusions: The positivity rates among asymptomatic patients at a large medical center were not predicted by the positivity rate at the county level. This finding suggests that the epidemiology at a county level may be determined by pockets in the population who may not interact, and thus not affect, the positivity rates among asymptomatic patients served by a hospital system within the county.

Funding: No

Disclosures: None
Compact and robust supercontinuum generation and post-compression using multiple thin plates
Authors: Xie Xinhua , Deng Yunpei , Johnson Steven L.
Published: November 2021

We report on compact and robust supercontinuum generation and post-compression using transmission of light through multiple thin solid plates at the SwissFEL X-ray free-electron laser facility. A single stage consisting of three thin plates followed by a chirped mirror compressor achieves compression of initially 30-fs pulses with 800-nm center wavelength to sub-10-fs duration. We also demonstrate a two-stage implementation to compress the pulses further to sub-5-fs duration. With the two-stage setup, the generated supercontinuum includes wavelengths ranging from 500 to 1100 nm. The multi-plate setup is compact, robust, and stable, which makes it ideal for applications at free-electron laser facilities such as pump-probe experiments and laser-arrival timing tools.
Law and Order, the Rule of Law, and the Legitimation of the Colonial Presence in Late British Burma
Authors: Brown Ian
Published: November 2021

In Britain's empire across Asia and Africa from the mid-nineteenth century, two political-legal principles were central to colonial modernity, law and order, and the rule of law. These two principles secured the legitimation of colonial rule, in the eyes of those who ruled. It is striking then to see that in late colonial Burma, in the 1920s and 1930s, the colonial government struggled to maintain law and order and to embed the rule of law. Violent crime soared while the criminal justice system failed hopelessly for serious offences. This article seeks to explore the ways in which senior British officials in Burma navigated the disjuncture between the imperial principles that were central to colonial justification and Burma's reality. Perhaps most notably, they did so by putting blame for the soaring crime rates and the failures of the criminal justice system firmly on the Burmese. In the early 1940s, however, with the end of colonial rule clearly imminent, the legitimation of the colonial presence became of less pressing importance, and the failure of colonial practice to live up to its ideological rhetoric could now be more openly faced.
Globalizing the History of the First World War: Economic Approaches
Authors: Martin Jamie
Published: November 2021

This historiographical review offers an overview of new approaches to the global history of the First World War. It first considers how, over the last decade, there has been a move to emphasize the war's imperial dimensions: in reconsiderations of the war in Africa, the experience of soldiers and workers from across Europe's colonial empires, and the German ‘global strategy’ of fomenting unrest within the Allied empires. It then suggests that new global histories of the First World War give further attention to its economic aspects, particularly in two ways: first, by recovering understudied global financial aspects of the war, including the effects of the 1914 financial crisis and wartime inflation on economies and societies far outside of Europe; and second, by investigating wartime histories of primary production, both in colonial territories and sovereign states in Latin America, Africa, and Southeast Asia. It argues that these approaches can offer an important corrective to common assumptions that the First World War led to a dramatic break with pre-war globalizing trends.
On physical investigation of ball lightnings
Authors: Oreshko A.G.
Published: November 2021

Explanations for the long lifetime of spherically symmetric objects in nature and the short lifetime of laboratory plasma are given. A qualitative description of the relativistic model of ball lightning is also given, which is a spherical electric region with strong electric and magnetic fields. The plasma temperature in the zone of the ball-lightning generation is measured by the spectroscopic method. A large ball lightning, the maximum diameter of which is equal to one meter and which stands in the region of its generation, is also registered after the formation and departure of a high-energy ball lightning. The reason for the low emissive power in the optical range characteristic for the atmospheric ball lightning is explained by the absence of electron transitions in the outer proton-containing shell. The absence of electrical breakdown at ultrahigh electric field between the core and the outer shell of the ball lightning and its destruction at the moment when the resulting force becomes nonzero are also explained.
Sustainable Tourism in Svalbard: Balancing economic growth, sustainability, and environmental governance
Authors: Hovelsrud Grete K. , Veland Siri , Kaltenborn Bjørn , Olsen Julia , Dannevig Halvor
Published: November 2021

This commentary introduces a methodology and theoretical framework for studying how the tourism industry might balance the competing demands of economic growth and environmental governance. We focus on the “balancing act” Svalbard tourism industry must play among sometimes competing demands of climate change mitigation and emissions from tourism, and of strict Norwegian environmental management policy and demands for increased tourism. While these are specific to Svalbard, the balancing act of competing needs is the core challenge of the UN Sustainability Goals giving this research global and pan-Arctic relevance. Through collaboration between two tourism organisations, the Association of Arctic Expedition Cruise Operators (AECO) and Visit Svalbard and an interdisciplinary team of scientists, we will co-produce knowledge about how to innovate new opportunities while protecting the wilderness, the very backbone of tourism. This collaboration considers how policy, climate change, and local attitudes together may affect the tourism industry and helps to define and develop sustainable tourism operations and products. For instance, tourists may participate in environmental and community-related activities or “micro safaris” rather than a sole focus on charismatic megafauna. Policy discussions about tourism growth need to consider how local and national governments anticipate and navigate rapid social, political, and environmental changes.
A synthesis of pathways linking diet, metabolic risk and cardiovascular disease: a framework to guide further research and approaches to evidence-based practice
Authors: Lima do Vale Marjorie Rafaela , Buckner Luke , Mitrofan Claudia Gabriela , Tramontt Claudia Raulino , Kargbo Sento Kai , Khalid Ali , Ashraf Sammyia , Mouti Saad , Dai Xiaowu , Unwin David , Bohn Jeffrey , Goldberg Lisa , Golubic Rajna , Ray Sumantra
Published: November 2021

Cardiovascular disease (CVD) is the most common non-communicable disease occurring globally. Although previous literature has provided useful insights into the important role that diet plays in CVD prevention and treatment, understanding the causal role of diets is a difficult task considering inherent and introduced weaknesses of observational (e.g. not properly addressing confounders and mediators) and experimental research designs (e.g. not appropriate or well designed). In this narrative review, we organised current evidence linking diet, as well as conventional and emerging physiological risk factors, with CVD risk, incidence and mortality in a series of diagrams. The diagrams presented can aid causal inference studies as they provide a visual representation of the types of studies underlying the associations between potential risk markers/factors for CVD. This may facilitate the selection of variables to be considered and the creation of analytical models. Evidence depicted in the diagrams was systematically collected from studies included in the British Nutrition Task Force report on diet and CVD and database searches, including Medline and Embase. Although several markers and disorders linked to conventional and emerging risk factors for CVD were identified, the causal link between many remains unknown. There is a need to address the multifactorial nature of CVD and the complex interplay between conventional and emerging risk factors with natural and built environments, while bringing the life course into the spotlight.
Not-negation revisited: variation betweenaandanyin verb complements in contemporary spoken American English
Authors: TOTTIE GUNNEL
Published: November 2021

Innot-negated English sentences with indefinite expressions following the verb, there is variation between the indefinite article andanyas determiners of nouns. The standard view is that singular count nouns take the indefinite article and singular non-count and plural nouns takeany.However, it is possible to encounter examples likeit isn'tany threat,there isn'tany lockorI don't haveany problem.

The article studies variation between the indefinite article andanyas post-verbal determiners of singular nouns in 21,084not-negated sentences in the spoken component ofThe Corpus of Contemporary American English, COCA SPOK. The indefinite article is dominant with 90 per cent of the tokens. Variation is extremely rare in sentences with copularbeand much more frequent in sentences with existentialbeandhave. Among the reasons for variation between verb types is the use ofdo-support withhave(but not withbe). Expressions such ashave a job/car/homeorthere's not a/anwith uncontractednotmay also prevent the use ofany.Variation occurs mostly with abstract nouns such asproblem,choice,way,place,reason. This finding is surprising as abstract nouns have rarely been discussed in the literature on varying countability of nouns.
Economic freedom improves income mobility: evidence from Canadian provinces, 1982–2018
Authors: Dean James , Geloso Vincent
Published: November 2021

Economic freedom is robustly associated with income growth, but does this association extend to the poorest in a society? In this paper, we employ Canada's longitudinal cohorts of income mobility between 1982 and 2018 to answer this question. We find that economic freedom, as measured by the Fraser Institute's Economic Freedom of North America (EFNA) index, is positively associated with multiple measures of income mobility for people in the lowest income deciles, including (a) absolute income gain; (b) the percentage of people with rising income; and (c) average decile mobility. For the overall population, economic freedom has weaker effects.
Regulation of MDM2 E3 ligase-dependent vascular calcification by MSX1/2
Authors: Kwon Duk-Hwa , Choe Nakwon , Shin Sera , Ryu Juhee , Kim Nacksung , Eom Gwang Hyeon , Nam Kwang-Il , Kim Hyung Seok , Ahn Youngkeun , Kim Young-Kook , Park Woo Jin , Mendrysa Susan M. , Kook Hyun
Published: November 2021

Vascular calcification increases morbidity and mortality in patients with cardiovascular and renal diseases. Previously, we reported that histone deacetylase 1 prevents vascular calcification, whereas its E3 ligase, mouse double minute 2 homolog (MDM2), induces vascular calcification. In the present study, we identified the upstream regulator of MDM2. By utilizing cellular models and transgenic mice, we confirmed that E3 ligase activity is required for vascular calcification. By promoter analysis, we found that both msh homeobox 1 (Msx1) and msh homeobox 2 (Msx2) bound to the MDM2 promoter region, which resulted in transcriptional activation of MDM2. The expression levels of both Msx1 and Msx2 were increased in mouse models of vascular calcification and in calcified human coronary arteries. Msx1 and Msx2 potentiated vascular calcification in cellular and mouse models in an MDM2-dependent manner. Our results establish a novel role for MSX1/MSX2 in the transcriptional activation of MDM2 and the resultant increase in MDM2 E3 ligase activity during vascular calcification.
The effects of altered BMP4 signaling in first branchial-arch-derived murine embryonic orofacial tissues
Authors: Xu Jue , Chen Meiling , Yan Yanan , Zhao Qiaoxue , Shao Meiying , Huang Zhen
Published: November 2021

The first branchial arch (BA1), which is derived from cranial neural crest (CNC) cells, gives rise to various orofacial tissues. Cre mice are widely used for the determination of CNC and exploration of gene functions in orofacial development. However, there is a lack of Cre mice specifically marked BA1’s cells. Pax2-Cre allele was previously generated and has been widely used in the field of inner ear development. Here, by compounding Pax2-Cre and R26R-mTmG mice, we found a specific expression pattern of Pax2+ cells that marked BA1’s mesenchymal cells and the BA1-derivatives. Compared to Pax2-Cre; R26R-mTmG allele, GFP+ cells were abundantly found both in BA1 and second branchial arch in Wnt1-Cre;R26R-mTmG mice. As BMP4 signaling is required for orofacial development, we over-activated Bmp4 by using Pax2-Cre; pMes-BMP4 strain. Interestingly, our results showed bilateral hyperplasia between the upper and lower teeth. We also compare the phenotypes of Wnt1-Cre; pMes-BMP4 and Pax2-Cre; pMes-BMP4 strains and found severe deformation of molar buds, palate, and maxilla-mandibular bony structures in Wnt1-Cre; pMes-BMP4 mice; however, the morphology of these orofacial organs were comparable between controls and Pax2-Cre; pMes-BMP4 mice except for bilateral hyperplastic tissues. We further explore the properties of the hyperplastic tissue and found it is not derived from Runx2+ cells but expresses Msx1, and probably caused by abnormal cell proliferation and altered expression pattern of p-Smad1/5/8. In sum, our findings suggest altering BMP4 signaling in BA1-specific cell lineage may lead to unique phenotypes in orofacial regions, further hinting that Pax2-Cre mice could be a new model for genetic manipulation of BA1-derived organogenesis in the orofacial region.
Is tumour volume an independent predictor of outcome after radical prostatectomy for high-risk prostate cancer?
Authors: Raison Nicholas , Servian Pol , Patel Amit , Santhirasekaram Ainkaran , Smith Andrew , Yeung Maidie , Lloyd Josephine , Mannion Ethna , Rockall Andrea , Ahmed Hashim , Winkler Mathias
Published: November 2021

Background

Preoperative PSA, ISUP grade group (GG), prostate examination and multiparametric MRI (mpMRI) form the basis of prostate cancer staging. Unlike other solid organ tumours, tumour volume (TV) is not routinely used aside from crude estimates such as maximum cancer core length. The aim of this study is to assess the role of TV as a marker for oncological outcomes in high-risk non-metastatic prostate cancer.

Methods

A prospectively maintained database of patients undergoing minimally invasive (laparoscopic or robot-assisted laparoscopic) radical prostatectomy at a UK centre between 2007 and 2019 were analysed. A total of 251 patients with NCCN high or very high-risk prostate cancer were identified. Primary outcome measure was time to biochemical recurrence (BCR) and the secondary outcome was time to treatment failure (TTF). TV was measured on the pathological specimen using the stacking method. Multivariable cox regression analysis was used to identify factors predicting BCR and TFF. TV as a predictor of BCR and TFF was further analysed through time-dependent receiver operating characteristic (ROC) curves. Kaplan–Meier survival estimates were used to evaluate TV cut-off scores.

Results

Median follow up was 4.50 years. Four factors were associated with BCR and TFF on multivariable analysis (TV, pathological GG, pathological T stage, positive margin >3 mm). Area under the Curve (AUC) for TV as a predictor of BCR and TTF at 5 years was 0.71 and 0.75, respectively. Including all 4 variables in the model increased AUC to 0.84 and 0.85 for BCR and TFF. A 2.50 cm TV cut off demonstrated a significance difference in time to BCR, p < 0.001.

Conclusions

Pathological tumour volume is an independent predictor of oncological outcomes in high risk prostate cancer but does not add significant prognostic value when combined with established variables. However, the option of accurate TV measurement on mpMRI raises the possibility of using TV as useful marker for preoperative risk stratification.
Nicotinamide promotes cardiomyocyte derivation and survival through kinase inhibition in human pluripotent stem cells
Authors: Meng Ya , Song Chengcheng , Ren Zhili , Li Xiaohong , Yang Xiangyu , Ai Nana , Yang Yang , Wang Dongjin , Zhan Meixiao , Wang Jiaxian , LEI Chon Lok , Liu Weiwei , Ge Wei , Lu Ligong , Chen Guokai
Published: November 2021

Nicotinamide, the amide form of Vitamin B3, is a common nutrient supplement that plays important role in human fetal development. Nicotinamide has been widely used in clinical treatments, including the treatment of diseases during pregnancy. However, its impacts during embryogenesis have not been fully understood. In this study, we show that nicotinamide plays multiplex roles in mesoderm differentiation of human embryonic stem cells (hESCs). Nicotinamide promotes cardiomyocyte fate from mesoderm progenitor cells, and suppresses the emergence of other cell types. Independent of its functions in PARP and Sirtuin pathways, nicotinamide modulates differentiation through kinase inhibition. A KINOMEscan assay identifies 14 novel nicotinamide targets among 468 kinase candidates. We demonstrate that nicotinamide promotes cardiomyocyte differentiation through p38 MAP kinase inhibition. Furthermore, we show that nicotinamide enhances cardiomyocyte survival as a Rho-associated protein kinase (ROCK) inhibitor. This study reveals nicotinamide as a pleiotropic molecule that promotes the derivation and survival of cardiomyocytes, and it could become a useful tool for cardiomyocyte production for regenerative medicine. It also provides a theoretical foundation for physicians when nicotinamide is considered for treatments for pregnant women.
MICU3 regulates mitochondrial Ca2+-dependent antioxidant response in skeletal muscle aging
Authors: Yang Yun-Fei , Yang Wu , Liao Zhi-Yin , Wu Yong-Xin , Fan Zhen , Guo Ai , Yu Jing , Chen Qiu-Nan , Wu Jiang-Hao , Zhou Jing , Xiao Qian
Published: November 2021

Age-related loss of skeletal muscle mass and function, termed sarcopenia, could impair the quality of life in the elderly. The mechanisms involved in skeletal muscle aging are intricate and largely unknown. However, more and more evidence demonstrated that mitochondrial dysfunction and apoptosis also play an important role in skeletal muscle aging. Recent studies have shown that mitochondrial calcium uniporter (MCU)-mediated mitochondrial calcium affects skeletal muscle mass and function by affecting mitochondrial function. During aging, we observed downregulated expression of mitochondrial calcium uptake family member3 (MICU3) in skeletal muscle, a regulator of MCU, which resulted in a significant reduction in mitochondrial calcium uptake. However, the role of MICU3 in skeletal muscle aging remains poorly understood. Therefore, we investigated the effect of MICU3 on the skeletal muscle of aged mice and senescent C2C12 cells induced by d-gal. Downregulation of MICU3 was associated with decreased myogenesis but increased oxidative stress and apoptosis. Reconstitution of MICU3 enhanced antioxidants, prevented the accumulation of mitochondrial ROS, decreased apoptosis, and increased myogenesis. These findings indicate that MICU3 might promote mitochondrial Ca2+ homeostasis and function, attenuate oxidative stress and apoptosis, and restore skeletal muscle mass and function. Therefore, MICU3 may be a potential therapeutic target in skeletal muscle aging.
Autophagy in Spinocerebellar ataxia type 2, a dysregulated pathway, and a target for therapy
Authors: Marcelo Adriana , Afonso Inês T. , Afonso-Reis Ricardo , Brito David V. C. , Costa Rafael G. , Rosa Ana , Alves-Cruzeiro João , Ferreira Benedita , Henriques Carina , Nobre Rui J. , Matos Carlos A. , de Almeida Luís Pereira , Nóbrega Clévio
Published: November 2021

Spinocerebellar ataxia type 2 (SCA2) is an incurable and genetic neurodegenerative disorder. The disease is characterized by progressive degeneration of several brain regions, resulting in severe motor and non-motor clinical manifestations. The mutation causing SCA2 disease is an abnormal expansion of CAG trinucleotide repeats in the ATXN2 gene, leading to a toxic expanded polyglutamine segment in the translated ataxin-2 protein. While the genetic cause is well established, the exact mechanisms behind neuronal death induced by mutant ataxin-2 are not yet completely understood. Thus, the goal of this study is to investigate the role of autophagy in SCA2 pathogenesis and investigate its suitability as a target for therapeutic intervention. For that, we developed and characterized a new striatal lentiviral mouse model that resembled several neuropathological hallmarks observed in SCA2 disease, including formation of aggregates, neuronal marker loss, cell death and neuroinflammation. In this new model, we analyzed autophagic markers, which were also analyzed in a SCA2 cellular model and in human post-mortem brain samples. Our results showed altered levels of SQSTM1 and LC3B in cells and tissues expressing mutant ataxin-2. Moreover, an abnormal accumulation of these markers was detected in SCA2 patients’ striatum and cerebellum. Importantly, the molecular activation of autophagy, using the compound cordycepin, mitigated the phenotypic alterations observed in disease models. Overall, our study suggests an important role for autophagy in the context of SCA2 pathology, proposing that targeting this pathway could be a potential target to treat SCA2 patients.
Phase segregation in mixed-halide perovskites affects charge-carrier dynamics while preserving mobility
Authors: Motti Silvia G. , Patel Jay B. , Oliver Robert D. J. , Snaith Henry J. , Johnston Michael B. , Herz Laura M.
Published: November 2021

Mixed halide perovskites can provide optimal bandgaps for tandem solar cells which are key to improved cost-efficiencies, but can still suffer from detrimental illumination-induced phase segregation. Here we employ optical-pump terahertz-probe spectroscopy to investigate the impact of halide segregation on the charge-carrier dynamics and transport properties of mixed halide perovskite films. We reveal that, surprisingly, halide segregation results in negligible impact to the THz charge-carrier mobilities, and that charge carriers within the I-rich phase are not strongly localised. We further demonstrate enhanced lattice anharmonicity in the segregated I-rich domains, which is likely to support ionic migration. These phonon anharmonicity effects also serve as evidence of a remarkably fast, picosecond charge funnelling into the narrow-bandgap I-rich domains. Our analysis demonstrates how minimal structural transformations during phase segregation have a dramatic effect on the charge-carrier dynamics as a result of charge funnelling. We suggest that because such enhanced recombination is radiative, performance losses may be mitigated by deployment of careful light management strategies in solar cells.
Subclone-specific microenvironmental impact and drug response in refractory multiple myeloma revealed by single‐cell transcriptomics
Authors: Tirier Stephan M. , Mallm Jan-Philipp , Steiger Simon , Poos Alexandra M. , Awwad Mohamed H. S. , Giesen Nicola , Casiraghi Nicola , Susak Hana , Bauer Katharina , Baumann Anja , John Lukas , Seckinger Anja , Hose Dirk , Müller-Tidow Carsten , Goldschmidt Hartmut , Stegle Oliver , Hundemer Michael , Weinhold Niels , Raab Marc S. , Rippe Karsten
Published: November 2021

Virtually all patients with multiple myeloma become unresponsive to treatment over time. Relapsed/refractory multiple myeloma (RRMM) is accompanied by the clonal evolution of myeloma cells with heterogeneous genomic aberrations and profound changes of the bone marrow microenvironment (BME). However, the molecular mechanisms that drive drug resistance remain elusive. Here, we analyze the heterogeneous tumor cell population and its complex interaction network with the BME of 20 RRMM patients by single cell RNA-sequencing before/after treatment. Subclones with chromosome 1q-gain express a specific transcriptomic signature and frequently expand during treatment. Furthermore, RRMM cells shape an immune suppressive BME by upregulation of inflammatory cytokines and close interaction with the myeloid compartment. It is characterized by the accumulation of PD1+γδ T-cells and tumor-associated macrophages as well as the depletion of hematopoietic progenitors. Thus, our study resolves transcriptional features of subclones in RRMM and mechanisms of microenvironmental reprogramming with implications for clinical decision-making.
Multi-species host range of staphylococcal phages isolated from wastewater
Authors: Göller Pauline C. , Elsener Tabea , Lorgé Dominic , Radulovic Natasa , Bernardi Viona , Naumann Annika , Amri Nesrine , Khatchatourova Ekaterina , Coutinho Felipe Hernandes , Loessner Martin J. , Gómez-Sanz Elena
Published: November 2021

The host range of bacteriophages defines their impact on bacterial communities and genome diversity. Here, we characterize 94 novel staphylococcal phages from wastewater and establish their host range on a diversified panel of 117 staphylococci from 29 species. Using this high-resolution phage-bacteria interaction matrix, we unveil a multi-species host range as a dominant trait of the isolated staphylococcal phages. Phage genome sequencing shows this pattern to prevail irrespective of taxonomy. Network analysis between phage-infected bacteria reveals that hosts from multiple species, ecosystems, and drug-resistance phenotypes share numerous phages. Lastly, we show that phages throughout this network can package foreign genetic material enclosing an antibiotic resistance marker at various frequencies. Our findings indicate a weak host specialism of the tested phages, and therefore their potential to promote horizontal gene transfer in this environment.
Thermochemical anomalies in the upper mantle control Gakkel Ridge accretion
Authors: O’Connor John M. , Jokat Wilfried , Michael Peter J. , Schmidt-Aursch Mechita C. , Miggins Daniel P. , Koppers Anthony A. P.
Published: November 2021

Despite progress in understanding seafloor accretion at ultraslow spreading ridges, the ultimate driving force is still unknown. Here we use40Ar/39Ar isotopic dating of mid-ocean ridge basalts recovered at variable distances from the axis of the Gakkel Ridge to provide new constraints on the spatial and temporal distribution of volcanic eruptions at various sections of an ultraslow spreading ridge. Our age data show that magmatic-dominated sections of the Gakkel Ridge spread at a steady rate of ~11.1 ± 0.9 mm/yr whereas amagmatic sections have a more widely distributed melt supply yielding ambiguous spreading rate information. These variations in spreading rate and crustal accretion correlate with locations of hotter thermochemical anomalies in the asthenosphere beneath the ridge. We conclude therefore that seafloor generation in ultra-slow spreading centres broadly reflects the distribution of thermochemical anomalies in the upper mantle.
A general strategy for C(sp3)–H functionalization with nucleophiles using methyl radical as a hydrogen atom abstractor
Authors: Leibler Isabelle Nathalie-Marie , Tekle-Smith Makeda A. , Doyle Abigail G.
Published: November 2021

Photoredox catalysis has provided many approaches to C(sp3)–H functionalization that enable selective oxidation and C(sp3)–C bond formation via the intermediacy of a carbon-centered radical. While highly enabling, functionalization of the carbon-centered radical is largely mediated by electrophilic reagents. Notably, nucleophilic reagents represent an abundant and practical reagent class, motivating the interest in developing a general C(sp3)–H functionalization strategy with nucleophiles. Here we describe a strategy that transforms C(sp3)–H bonds into carbocations via sequential hydrogen atom transfer (HAT) and oxidative radical-polar crossover. The resulting carbocation is functionalized by a variety of nucleophiles—including halides, water, alcohols, thiols, an electron-rich arene, and an azide—to effect diverse bond formations. Mechanistic studies indicate that HAT is mediated by methyl radical—a previously unexplored HAT agent with differing polarity to many of those used in photoredox catalysis—enabling new site-selectivity for late-stage C(sp3)–H functionalization.
Production of hydrogen from offshore wind in China and cost-competitive supply to Japan
Authors: Song Shaojie , Lin Haiyang , Sherman Peter , Yang Xi , Nielsen Chris P. , Chen Xinyu , McElroy Michael B.
Published: November 2021

The Japanese government has announced a commitment to net-zero greenhouse gas emissions by 2050. It envisages an important role for hydrogen in the nation’s future energy economy. This paper explores the possibility that a significant source for this hydrogen could be produced by electrolysis fueled by power generated from offshore wind in China. Hydrogen could be delivered to Japan either as liquid, or bound to a chemical carrier such as toluene, or as a component of ammonia. The paper presents an analysis of factors determining the ultimate cost for this hydrogen, including expenses for production, storage, conversion, transport, and treatment at the destination. It concludes that the Chinese source could be delivered at a volume and cost consistent with Japan’s idealized future projections.
Compressive stress-mediated p38 activation required for ERα + phenotype in breast cancer
Authors: Munne Pauliina M. , Martikainen Lahja , Räty Iiris , Bertula Kia , Nonappa  , Ruuska Janika , Ala-Hongisto Hanna , Peura Aino , Hollmann Babette , Euro Lilya , Yavuz Kerim , Patrikainen Linda , Salmela Maria , Pokki Juho , Kivento Mikko , Väänänen Juho , Suomi Tomi , Nevalaita Liina , Mutka Minna , Kovanen Panu , Leidenius Marjut , Meretoja Tuomo , Hukkinen Katja , Monni Outi , Pouwels Jeroen , Sahu Biswajyoti , Mattson Johanna , Joensuu Heikki , Heikkilä Päivi , Elo Laura L. , Metcalfe Ciara , Junttila Melissa R. , Ikkala Olli , Klefström Juha
Published: November 2021

Breast cancer is now globally the most frequent cancer and leading cause of women’s death. Two thirds of breast cancers express the luminal estrogen receptor-positive (ERα + ) phenotype that is initially responsive to antihormonal therapies, but drug resistance emerges. A major barrier to the understanding of the ERα-pathway biology and therapeutic discoveries is the restricted repertoire of luminal ERα + breast cancer models. The ERα + phenotype is not stable in cultured cells for reasons not fully understood. We examine 400 patient-derived breast epithelial and breast cancer explant cultures (PDECs) grown in various three-dimensional matrix scaffolds, finding that ERα is primarily regulated by the matrix stiffness. Matrix stiffness upregulates the ERα signaling via stress-mediated p38 activation and H3K27me3-mediated epigenetic regulation. The finding that the matrix stiffness is a central cue to the ERα phenotype reveals a mechanobiological component in breast tissue hormonal signaling and enables the development of novel therapeutic interventions. Subject terms: ER-positive (ER + ), breast cancer, ex vivo model, preclinical model, PDEC, stiffness, p38 SAPK.
Cerebrospinal fluid biomarkers in Parkinson’s disease with freezing of gait: an exploratory analysis
Authors: Hatcher-Martin J. M. , McKay J. L. , Pybus A. F. , Sommerfeld B. , Howell J. C. , Goldstein F. C. , Wood L. , Hu W. T. , Factor S. A.
Published: November 2021

We explore the association between three Alzheimer’s disease-related and ten inflammation-related CSF markers and freezing of gait (FOG) in patients with Parkinson’s disease (PD). The study population includes PD patients with FOG (PD-FOG,N = 12), without FOG (PD-NoFOG,N = 19), and healthy controls (HC,N = 12). Age and PD duration are not significantly different between groups. After adjusting for covariates and multiple comparisons, the anti-inflammatory marker, fractalkine, is significantly decreased in the PD groups compared to HC (P = 0.002), and further decreased in PD-FOG compared to PD-NoFOG (P = 0.007). The Alzheimer’s disease-related protein, Aβ42, is increased in PD-FOG compared to PD-NoFOG and HC (P = 0.001). Group differences obtained in individual biomarker analyses are confirmed with multivariate discriminant partial least squares regression (P < 0.001). High levels of Aβ42 in PD-FOG patients supports an increase over time from early to advanced state. Low levels of fractalkine might suggest anti-inflammatory effect. These findings warrant replication.
A real-world study of wearable sensors in Parkinson’s disease
Authors: Adams Jamie L. , Dinesh Karthik , Snyder Christopher W. , Xiong Mulin , Tarolli Christopher G. , Sharma Saloni , Dorsey E. Ray , Sharma Gaurav
Published: November 2021

Most wearable sensor studies in Parkinson’s disease have been conducted in the clinic and thus may not be a true representation of everyday symptoms and symptom variation. Our goal was to measure activity, gait, and tremor using wearable sensors inside and outside the clinic. In this observational study, we assessed motor features using wearable sensors developed by MC10, Inc. Participants wore five sensors, one on each limb and on the trunk, during an in-person clinic visit and for two days thereafter. Using the accelerometer data from the sensors, activity states (lying, sitting, standing, walking) were determined and steps per day were also computed by aggregating over 2 s walking intervals. For non-walking periods, tremor durations were identified that had a characteristic frequency between 3 and 10 Hz. We analyzed data from 17 individuals with Parkinson’s disease and 17 age-matched controls over an average 45.4 h of sensor wear. Individuals with Parkinson’s walked significantly less (median [inter-quartile range]: 4980 [2835–7163] steps/day) than controls (7367 [5106–8928] steps/day; P = 0.04). Tremor was present for 1.6 [0.4–5.9] hours (median [range]) per day in most-affected hands (MDS-UPDRS 3.17a or 3.17b = 1–4) of individuals with Parkinson’s, which was significantly higher than the 0.5 [0.3–2.3] hours per day in less-affected hands (MDS-UPDRS 3.17a or 3.17b = 0). These results, which require replication in larger cohorts, advance our understanding of the manifestations of Parkinson’s in real-world settings.
Mucosal vaccination induces protection against SARS-CoV-2 in the absence of detectable neutralizing antibodies
Authors: Zhong Chaojie , Xia Hongjie , Adam Awadalkareem , Wang Binbin , Hajnik Renee L. , Liang Yuejin , Rafael Grace H. , Zou Jing , Wang Xiaofang , Sun Jiaren , Soong Lynn , Barrett Alan D. T. , Weaver Scott C. , Shi Pei-Yong , Wang Tian , Hu Haitao
Published: November 2021

A candidate multigenic SARS-CoV-2 vaccine based on an MVA vector expressing both viral N and S proteins (MVA-S + N) was immunogenic, and induced T-cell responses and binding antibodies to both antigens but in the absence of detectable neutralizing antibodies. Intranasal immunization with the vaccine diminished viral loads and lung inflammation in mice after SARS-CoV-2 challenge, which correlated with the T-cell response induced by the vaccine in the lung, indicating that T-cell immunity is also likely critical for protection against SARS-CoV-2 infection in addition to neutralizing antibodies.
Epitope-coated polymer particles elicit neutralising antibodies against Plasmodium falciparum sporozoites
Authors: Evert Benjamin J. , Chen Shuxiong , McConville Robyn , Steel Ryan W. J. , Healer Julie , Boddey Justin A. , Huntimer Lucas , Rehm Bernd H. A.
Published: November 2021

The current Malaria RTS,S vaccine is based on virus-like particles (VLPs) comprising the NANP repetitive epitopes from the cicumsporozoite protein (CSP) of Plasmodium falciparum. This vaccine has limited efficacy, only preventing severe disease in about 30% of vaccinated individuals. A more efficacious vaccine is urgently needed to combat malaria. Here we developed a particulate malaria vaccine based on the same CSP epitopes but using biopolymer particles (BPs) as an antigen carrier system. Specific B- and T-cell epitope-coated BPs were assembled in vivo inside an engineered endotoxin-free mutant of Escherichia coli. A high-yield production process leading to ~27% BP vaccine weight over biomass was established. The epitope-coated BPs were purified and their composition, i.e., the polymer core and epitope identity, was confirmed. Epitope-coated BPs were used alongside soluble peptide epitopes and empty BPs to vaccinate sheep. Epitope-coated BPs showed enhanced immunogenicity by inducing anti-NANP antibody titre of EC50 > 150,000 that were at least 20 times higher than induced by the soluble peptides. We concluded that the additional T-cell epitope was not required as it did not enhance immunogenicity when compared with the B-cell epitope-coated BPs. Antibodies specifically bound to the surface of Plasmodium falciparum sporozoites and efficiently inhibited sporozoite motility and traversal of human hepatocytes. This study demonstrated the utility of biologically self-assembled epitope-coated BPs as an epitope carrier for inclusion in next-generation malaria vaccines.
Equilibrium in soil respiration across a climosequence indicates its resilience to climate change in a glaciated valley, western Himalaya
Authors: Tiwari Pankaj , Bhattacharya Pamela , Rawat Gopal Singh , Talukdar Gautam
Published: November 2021

Soil respiration (SR), a natural phenomenon, emits ten times more CO2 from land than anthropogenic sources. It is predicted that climate warming would increase SR in most ecosystems and give rise to positive feedback. However, there are uncertainties associated with this prediction primarily due to variability in the relationship of SR with its two significant drivers, soil temperature and moisture. Accounting for the variabilities, we use a climosequence in Himalaya with a temperature gradient of ~ 2.1 °C to understand the variations in the response of SR and its temperature sensitivity to climate change. Results indicate an equilibrium in SR ranging from 1.92 to 2.42 µmol m−2 s−1 across an elevation gradient (3300–3900 m) despite its increased sensitivity to temperature (Q10) from 0.47 to 4.97. Additionally, moisture reduction towards lower elevation weakens the temperature-SR relationship. Finally, soil organic carbon shows similarities at all the elevations, indicating a net-zero CO2 flux across the climosequence. The findings suggest that as the climate warms in this region, the temperature sensitivity of SR reduces drastically due to moisture reduction, limiting any change in SR and soil organic carbon to rising temperature. We introduce an equilibrium mechanism in this study which indicates the resilient nature of SR to climate change and will aid in enhancing the accuracy of climate change impact projections.
Prevalence of low muscle mass and associated factors in community-dwelling older adults in Singapore
Authors: Tey Siew Ling , Huynh Dieu Thi Thu , Berde Yatin , Baggs Geraldine , How Choon How , Low Yen Ling , Cheong Magdalin , Chow Wai Leng , Tan Ngiap Chuan , Chew Samuel Teong Huang
Published: November 2021

The population is rapidly aging worldwide, and there is an age-related decline in muscle mass. Therefore, it is important to examine the prevalence and associated factors of low appendicular skeletal muscle mass index (ASMI) in older adults. The objectives of this cross-sectional study were (i) to determine the prevalence of low ASMI (ASM/height2) and (ii) to identify factors associated with low ASMI. This study included 1211 community-dwelling adults aged ≥ 65 years. Low ASMI was defined as < 7.0 kg/m2 in males and < 5.7 kg/m2 in females (bioelectrical impedance analysis). Gender-specific cut-off values of calf circumference for low ASMI were determined. The prevalence of low ASMI in the overall cohort was 59.9%, i.e., 57.0% among males and 61.8% among females, with no significant difference between genders (P = 0.1068). The prevalence of low ASMI was 81.3% in individuals at risk of malnutrition compared to 20.6% in their counterparts with normal nutritional status (P < 0.0001). Participants with low ASMI were older, had lower physical activity scores, and greater likelihood of hospitalization in prior 6 months compared with normal ASMI (all P < 0.0001). Low ASMI was associated with risk of malnutrition (odds ratio: 3.58 for medium risk, odds ratio: 12.50 for high risk), older age, smoking, drinking, smaller calf circumference, and lower bone mass (all P ≤ 0.0328). Cut-off values of calf circumference for low ASMI for males was 33.4 cm and for females was 32.2 cm. In conclusion, we found that low ASMI was highly prevalent among community-dwelling older adults at risk of malnutrition. Other significant factors associated with low ASMI were age, smoking, drinking, calf circumference, and bone mass. Screening community-dwelling older adults for risk of malnutrition can prevent or delay onset of low ASMI.
Camera trap placement for evaluating species richness, abundance, and activity
Authors: Tanwar Kamakshi S. , Sadhu Ayan , Jhala Yadvendradev V.
Published: November 2021

Information from camera traps is used for inferences on species presence, richness, abundance, demography, and activity. Camera trap placement design is likely to influence these parameter estimates. Herein we simultaneously generate and compare estimates obtained from camera traps (a) placed to optimize large carnivore captures and (b) random placement, to infer accuracy and biases for parameter estimates. Both setups recorded 25 species when same number of trail and random cameras (n = 31) were compared. However, species accumulation rate was faster with trail cameras. Relative abundance indices (RAI) from random cameras surrogated abundance estimated from capture-mark-recapture and distance sampling, while RAI were biased higher for carnivores from trail cameras. Group size of wild-ungulates obtained from both camera setups were comparable. Random cameras detected nocturnal activities of wild ungulates in contrast to mostly diurnal activities observed from trail cameras. Our results show that trail and random camera setup give similar estimates of species richness and group size, but differ for estimates of relative abundance and activity patterns. Therefore, inferences made from each of these camera trap designs on the above parameters need to be viewed within this context.
Predicting the current and future global distribution of the invasive freshwater hydrozoan Craspedacusta sowerbii
Authors: Marchessaux Guillaume , Lüskow Florian , Sarà Gianluca , Pakhomov Evgeny A.
Published: November 2021

The freshwater jellyfish Craspedacusta sowerbii is one of the most widespread invasive species, but its global distribution remains uncertain due to ephemeral appearances and general lack of information in various aquatic environments. The aim of this study was to map current and future distributions (2050 and 2100) using Species Distribution Models allowing to visualize the habitat suitability and make projections of its changes under potential climate change scenarios. Except in Oceania where the range decreased, an expansion of C. sowerbii was projected during the next century under modeled future scenarios being most intensive during the first half of the century. The present study shows that the expansion of C. sowerbii worldwide would be facilitated mainly by precipitation, vapor pressure, and temperature. The predictions showed that this species over the eighty years will invade high-latitude regions in both hemispheres with ecological consequences in already threatened freshwater ecosystems.
Multisensory stimuli shift perceptual priors to facilitate rapid behavior
Authors: Plass John , Brang David
Published: November 2021

Multisensory stimuli speed behavioral responses, but the mechanisms subserving these effects remain disputed. Historically, the observation that multisensory reaction times (RTs) outpace models assuming independent sensory channels has been taken as evidence for multisensory integration (the “redundant target effect”; RTE). However, this interpretation has been challenged by alternative explanations based on stimulus sequence effects, RT variability, and/or negative correlations in unisensory processing. To clarify the mechanisms subserving the RTE, we collected RTs from 78 undergraduates in a multisensory simple RT task. Based on previous neurophysiological findings, we hypothesized that the RTE was unlikely to reflect these alternative mechanisms, and more likely reflected pre-potentiation of sensory responses through crossmodal phase-resetting. Contrary to accounts based on stimulus sequence effects, we found that preceding stimuli explained only 3–9% of the variance in apparent RTEs. Comparing three plausible evidence accumulator models, we found that multisensory RT distributions were best explained by increased sensory evidence at stimulus onset. Because crossmodal phase-resetting increases cortical excitability before sensory input arrives, these results are consistent with a mechanism based on pre-potentiation through phase-resetting. Mathematically, this model entails increasing the prior log-odds of stimulus presence, providing a potential link between neurophysiological, behavioral, and computational accounts of multisensory interactions.