bluuebunny/crossref_metadata_2025 huggingface dataset:
Summary of the 10th Conference on Magnetically Confined Fusion Theory and Simulation (CMCFTS)
Authors: WANG Zhibin , QIU Zhiyong , WANG Lu , CHEN Wei
Published: March 2023

This paper gives a summary of the organization and the presentations delivered at the 10th Conference on Magnetically Confined Fusion Theory and Simulation (CMCFTS) held in Zhuhai, China, from 28th to 31st October 2022. The conference focused on the latest progress in the research of the magnetic confined fusion plasma theory and simulations, as well as the large-scale numerical simulation techniques developed in recent years. This conference is held both online and offline, with about 110 domestic participants from 18 institutes participating in the live conference, and the statistical data from the live broadcast platform indicated that the online conference attracted over 20 000 views per day. A summary of the conference is given, and the history of the CMCFTS is presented. A brief introduction to the poster section is also included in this paper.
Status and outlook for lithium-ion battery cathode material synthesis and the application of mechanistic modeling
Authors: Pardikar Kunal , Entwistle Jake , Ge Ruihuan , Cumming Denis , Smith Rachel
Published: March 2023

This work reviews different techniques available for the synthesis and modification of cathode active material (CAM) particles used in Li-ion batteries. The synthesis techniques are analyzed in terms of processes involved and product particle structure. The knowledge gap in the process-particle structure relationship is identified. Many of these processes are employed in other similar industries; hence, parallel insights and knowledge transfer can be applied to battery materials. Here, we discuss examples of applications of different mechanistic models outside the battery literature and identify similar potential applications for the synthesis of CAMs. We propose that the widespread implementation of such mechanistic models will increase the understanding of the process-particle structure relationship. Such understanding will provide better control over the CAM synthesis technique and open doors to the precise tailoring of product particle morphologies favorable for enhanced electrochemical performance.
On reflexive and 𝐼-Ulrich modules over curve singularities
Authors: Dao Hailong , Maitra Sarasij , Sridhar Prashanth
Published: March 2023

We study reflexive modules over one dimensional Cohen-Macaulay rings. Our key technique exploits the concept of

I
I

-Ulrich modules.
Genetic risk, muscle strength and risk of incident major depressive disorder: results from the UK Biobank
Authors: Gu Yeqing , Zhang Tingjing , Wang Jinhan , Song Yanqi , Meng Ge , Wu Hongmei , Zhang Shunming , Wang Xuena , Zhang Juanjuan , Lu Xinran , Liu Qiang , Huang Tao , Yang Jian , Niu Kaijun
Published: March 2023

Background

Genetic factors and muscle strength both contribute to the risk of major depressive disorder (MDD), but whether high muscle strength can offset the risk of MDD with different genetic risk is unknown. This study aims to examine whether a higher muscle strength is associated with lower risk of MDD regardless of genetic risk among middle-aged and older adults.

Methods

This cohort study obtained data from the UK Biobank, which includes 345,621 individuals aged 40–69 years (mean (standard deviation): 56.7 (7.99) years) without baseline MDD. Polygenic risk score for MDD was categorised as low, intermediate or high. The mean of the right- and left-hand grip strength values was used in the analysis and was divided into three categories.

Results

9,753 individuals developed MDD within 2,752,461 person-years of follow-up. The multivariable adjusted hazard ratios (HRs) (95% confidence intervals (CIs)) of MDD across increased grip strength categories were 1.00, 0.72 (0.68–0.75) and 0.56 (0.53–0.59) (P for trend <0.0001). The HRs (95% CIs) of incident MDD across the genetic risk categories were 1.00, 1.11 (1.05–1.17) and 1.20 (1.13–1.28) (P for trend <0.0001); 4.07% of individuals with a high genetic risk and low grip strength developed MDD, and 1.72% of individuals with a low genetic risk and high grip strength developed MDD, with an HR (95% CI) of 0.44 (0.39–0.50).

Conclusions

Both muscle strength and genetic risk were significantly associated with incident MDD. A higher muscle strength was associated with a lower MDD risk among individuals with a high genetic risk. Improving muscle strength should be encouraged for all individuals, including individuals with high genetic risk for MDD.
linemodels: clustering effects based on linear relationships
Authors: Pirinen Matti
Published: March 2023

Estimation of effects of multiple explanatory variables on multiple outcome measures has become routine across life sciences with high-throughput molecular technologies. The linemodels R-package allows a probabilistic clustering of variables based on their observed effect sizes on two outcomes.

Availability and implementation

An open source implementation in R available at github.com/mjpirinen/linemodels.
Measuring What We Don't Know: Biodiversity Catalogs Reveal Bias in Taxonomic Effort
Authors: Gorneau Jacob A , Kulkarni Siddharth , Cala-Riquelme Franklyn , Esposito Lauren A
Published: March 2023

Biodiversity catalogs are an invaluable resource for biological research. Efforts to scientifically document biodiversity have not been evenly applied, either because of charisma or because of ease of study. Spiders are among the most precisely cataloged and diverse invertebrates, having surpassed 50,000 described species globally. The World Spider Catalog presents a unique opportunity to assess the disproportionate documentation of spider diversity. In the present article, we develop a taxonomic ratio relating new species descriptions to other taxonomic activity as a proxy for taxonomic effort, using spiders as a case study. We use this taxonomic effort metric to examine biases along multiple axes: phylogeny, zoogeography, and socioeconomics. We also use this metric to estimate the number of species that remain to be described. This work informs arachnologists in identifying high-priority taxa and regions for species discovery and highlights the benefits of maintaining open-access taxonomic databases—a necessary step in overcoming bias and documenting the world's biodiversity.
Statin use and risk of cutaneous melanoma: a nationwide nested case–control study
Authors: Ghiasvand Reza , Berge Leon A M , Andreassen Bettina K , Green Adele C , Al Rahmoun Marie , Fournier Agnès , Kvaskoff Marina , Veierød Marit B , Robsahm Trude E  
Published: March 2023

This nationwide nested case–control study examined the association between statin use and risk of cutaneous melanoma. We included 12 048 adult patients with melanoma and 117 895 randomly selected cancer-free controls, matched on age and sex. Cancer data were obtained from the Cancer Registry of Norway and data on drug use was retrieved from the Norwegian Prescription Database. We estimated rate ratios with 95% confidence intervals and conducted sensitivity analyses. We observed an inverse dose–response association between statin use and melanoma risk, stronger in women. The highest statin intake was associated with a reduced risk of melanoma, particularly on the head/neck and lower limbs. Our finding may have implications for melanoma prevention in high-risk groups.
Pathological combinations in neurodegenerative disease are heterogeneous and disease-associated
Authors: Robinson John L , Xie Sharon X , Baer Daniel R , Suh EunRan , Van Deerlin Vivianna M , Loh Nicholas J , Irwin David J , McMillan Corey T , Wolk David A , Chen-Plotkin Alice , Weintraub Daniel , Schuck Theresa , Lee Virginia M Y , Trojanowski John Q , Lee Edward B
Published: March 2023

Pathologies that are causative for neurodegenerative disease (ND) are also frequently present in unimpaired, older individuals. In this retrospective study of 1647 autopsied individuals, we report the incidence of 10 pathologies across ND and normal ageing in attempt to clarify which pathological combinations are disease-associated and which are ageing-related. Eight clinically defined groups were examined including unimpaired individuals and those with clinical Alzheimer’s disease, mixed dementia, amyotrophic lateral sclerosis, frontotemporal degeneration, multiple system atrophy, probable Lewy body disease or probable tauopathies. Up to seven pathologies were observed concurrently resulting in a heterogeneous mix of 161 pathological combinations. The presence of multiple additive pathologies associated with older age, increasing disease duration, APOE e4 allele and presence of dementia across the clinical groups. Fifteen to 67 combinations occurred in each group, with the unimpaired group defined by 35 combinations. Most combinations occurred at a <5% prevalence including 86 that were present in only one or two individuals. To better understand this heterogeneity, we organized the pathological combinations into five broad categories based on their age-related frequency: (i) ‘Ageing only’ for the unimpaired group combinations; (ii) ‘ND only’ if only the expected pathology for that individual’s clinical phenotype was present; (iii) ‘Other ND’ if the expected pathology was not present; (iv) ‘ND + ageing’ if the expected pathology was present together with ageing-related pathologies at a similar prevalence as the unimpaired group; and (v) ‘ND + associated’ if the expected pathology was present together with other pathologies either not observed in the unimpaired group or observed at a greater frequency. ND only cases comprised a minority of cases (19–45%) except in the amyotrophic lateral sclerosis (56%) and multiple system atrophy (65%) groups. The ND + ageing category represented 9–28% of each group, but was rare in Alzheimer’s disease (1%). ND + associated combinations were common in Alzheimer’s disease (58%) and Lewy body disease (37%) and were observed in all groups. The Ageing only and Other ND categories accounted for a minority of individuals in each group. This observed heterogeneity indicates that the total pathological burden in ND is frequently more than a primary expected clinicopathological correlation with a high frequency of additional disease- or age-associated pathologies.
Familial hypotrichosis simplex of the scalp associated with a novel heterozygous nonsense variant in CDSN
Authors: Rayinda Tuntas , McSweeney Sheila M , Lalagianni Nikolina , Liu Lu , Guy Alyson , Fenton David , Stefanato Catherine M , Dand Nick , McGrath John A , Tziotzios Christos
Published: March 2023

This report describes a case of an 18-year-old white British woman with HTSS1, whose phenotype was characterized by the inability to grow long scalp hair. Whole exome sequencing identified a novel pathogenic heterozygous nonsense variant (NM_001264.4: c.484C>T, NP_001255.3: p.Gln162Ter) in CDSN, which encodes corneodesmosin. HTSS1, described in this patient’s case, showed distinct clinical and histopathological features, thereby expanding the genotype–phenotype paradigm of HTSS1.
Harnessing the power of memory-like NK cells to fight cancer
Authors: Foo Yun Yan , Tiah Angelina , Aung Shuh Wen
Published: March 2023

Natural killer (NK) cells possess the innate ability to eliminate cancerous cells effectively.

Their crucial role in immunosurveillance has been widely recognized and exploited for therapeutic intervention. Despite the fast-acting nature of NK cells, NK adoptive cell transfer lacks favorable response in some patients. Patient NK cells often display diminished phenotype in preventing cancer progression resulting in poor prognosis. Tumor microenvironment plays a significant role in causing the downfall of NK cells in patients. The release of inhibitory factors by tumor microenvironment hinders normal function of NK cells against tumor. To overcome this challenge, therapeutic strategies such as cytokine stimulation and genetic manipulation are being investigated to improve NK tumor-killing capacity. One of the promising approaches includes generation of more competent NK cells via ex vivo cytokines activation and proliferation. Cytokine-induced ML-NK demonstrated phenotypic alterations such as enhanced expression of activating receptors which help elevate their antitumor response. Previous preclinical studies showed enhanced cytotoxicity and IFNγ production in ML-NK cells compared to normal NK cells against malignant cells. Similar effects are shown in clinical studies in which MK–NK demonstrated encouraging results in treating hematological cancer. However, there is still a lack of in-depth studies using ML-NK in treating different types of tumors and cancers. With convincing preliminary response, this cell-based approach could be used to complement other therapeutic modalities to achieve better clinical outcomes.
Heterogeneous effects of S100 proteins during cell interactions between immune cells and stromal cells from synovium or skin
Authors: Noack Mélissa , Miossec Pierre
Published: March 2023

Cell interactions represent an important mechanism involved in the pathogenesis of chronic inflammation. The key S100 proteins A8 and A9 have been studied in several models of chronic inflammatory diseases with highly heterogeneous conclusions. In this context, the aim of this study was to determine the role of cell interactions on S100 protein production and their effect on cytokine production during cell interactions, between immune and stromal cells from synovium or skin. Peripheral blood mononuclear cells (PBMC) were cultured alone or with synoviocytes or skin fibroblasts, with or without phytohemagglutinin, exogenous A8, A9, A8/A9 proteins or anti-A8/A9 antibody. Production of IL-6, IL-1β, IL-17, TNF, A8, A9, and A8/A9 was measured by ELISA. Cell interactions with synoviocytes had no effect on A8, A9, or A8/A9 secretion, while cell interactions with skin fibroblasts decreased A8 production. This highlights the importance of stromal cell origin. The addition of S100 proteins in co-cultures with synoviocytes did not increase the production of IL-6, IL-17, or IL-1β, except for an increase of IL-6 secretion with A8. The presence of anti-S100A8/A9 antibody did not show obvious effects. Low concentration or absence of serum in the culture medium decreased the production of IL-17, IL-6, and IL-1β but despite these conditions, the addition of S100 proteins did not increase cytokine secretion. In conclusion, the role of A8/A9 in cell interactions during chronic inflammation appears complex and heterogeneous, depending on multiple factors, notably the origin of stromal cells that can affect their secretion.
Secure and Efficient Masking of Lightweight Ciphers in Software and Hardware
Authors: Zhao Xuefeng
Published: March 2023

Masking is a well used and widely deployed countermeasure against side channel attacks, both in software and hardware. With masking comes at a great cost, search has focused on how to lower a performance penalty or find efficient masking implementation. In particular, our contribution is 2-fold: for software masking, we first find bitsliced implementations of Sbox with Multiplicative Complexity 4 and Multiplicative Depth 2, then adapt the common shares approach introduced by Coron et al. at CHES 2016 to make many cross-products $a_{i}\cdot b_{j}$ can be reuse for parallel ISW-based 32-bit nonlinear operations. Therefore, we improve the efficiency of 2$\times b/4/32$ parallel high-order masking of ISW scheme for RECTANGLE, TANGRAM and KNOT on 32-bit ARM embedded microprocessor, with roughly a 13%-34% speed-up, at cost of $(1+d) \times 32$-bit randomness. For hardware masking, 4 bit cubic Sboxes with quadratic decomposition length 2, including RECTANGLE, TANGRAM, KNOT and LWC third-round candidates, can be implemented with a 3-share and 4-share threshold implementation (TI) by decomposing cubic permutations $S$ as a composition of sub-permutations having lower algebraic degrees. We use two decomposition form: one composition of two quadratic permutations $G$ and $F$, $S = F\circ G$, is for efficiency; the other composition of some linear permutations $A_i$ and one quadratic permutation $G$, $S=A_3 \circ G \circ A_2 \circ G \circ A_1 $, is for reducing the area requirements. For $S = F\circ G$, we introduce a new approach of searching through all possible quadratic permutations $G$ with 2$^{25.71}$, which is effcient than 2$^{26.23}$ in Poschmann et al. at J. Cryptol 2011. For $S=A_3 \circ G \circ A_2 \circ G \circ A_1 $, our approach of finding $A_i$ with complexity 2$^{27.71} $, which is effcient than the method introduced by Moradi et al. at ASIACRYPT 2016. In addition, we proposes a new decomposition that $S=G \circ A_2 \circ G \circ A_1 $. We can find the fastest and the smallest hard-ware decomposition implementation of 4-bit permutations for TI with 3 and 4 shares.
Neuroprognostication after cardiac arrest: what the cardiologist should know
Authors: Kondziella Daniel
Published: March 2023

Two aspects are a key to mastering prognostication of comatose cardiac arrest survivors: a detailed knowledge about the clinical trajectories of consciousness recovery (or lack thereof) and the ability to correctly interpret the results of multimodal investigations, which include clinical examination, electroencephalography, neuroimaging, evoked potentials, and blood biomarkers. While the very good and the very poor ends of the clinical spectrum typically do not pose diagnostic challenges, the intermediate ‘grey zone’ of post-cardiac arrest encephalopathy requires cautious interpretation of the available information and sufficiently long clinical observation. Late recovery of coma patients with initially ambiguous diagnostic results is increasingly reported, as are unresponsive patients with various forms of residual consciousness, including so-called cognitive motor dissociation, rendering prognostication of post-anoxic coma highly complex. The aim of this paper is to provide busy clinicians with a high-yield, concise overview of neuroprognostication after cardiac arrest, emphasizing notable developments in the field since 2020.
Support for evidence-based alcohol policy in Ireland: results from a representative household survey
Authors: Calnan Susan , Millar Seán R , Mongan Deirdre
Published: March 2023

Background

Alcohol use is a leading risk factor for death and disability and there is a need for evidence-based policy measures to tackle excess alcohol consumption and related harms. The aim of this study was to examine attitudes towards alcohol control measures among the general public in the context of significant reforms undertaken in the Irish alcohol policymaking landscape.

Methods

A representative household survey was conducted among individuals aged 18+ years in Ireland. Descriptive and univariate analyses were used.

Results

A total of 1069 participants took part (48% male) and there was broad support (>50%) for evidence-based alcohol policies. Support was strongest for a ban on alcohol advertising near schools and creches (85.1%) and for warning labels (81.9%). Women were more likely than men to support alcohol control policy measures while participants with harmful alcohol use patterns were significantly less likely to support these measures. Respondents with a greater awareness of the health risks of alcohol showed higher levels of support, while those who had experienced harms due to other people’s drinking showed lower support compared with those who had not experienced such harms.

Conclusions

This study provides evidence of support for alcohol control policies in Ireland. However, notable differences were found in levels of support according to sociodemographic characteristics, alcohol consumption patterns, knowledge of health risks and harms experienced. Further research on reasons behind public support towards alcohol control measures would be worthwhile, given the importance of public opinion in the development of alcohol policy.
Contact With Older Adults Is Related to Positive Age Stereotypes and Self-Views of Aging: The Older You Are the More You Profit
Authors: Cohn-Schwartz Ella , de Paula Couto M Clara , Fung Helene H , Graf Sylvie , Hess Thomas M , Liou Shyhnan , Nikitin Jana , Rothermund Klaus
Published: March 2023

Objectives

Past studies showed that intergenerational contact is beneficial in improving attitudes toward older people. To date, however, research on the benefits of contact with older adults focused on younger adults (intergenerational contact), overlooking the effects for older adults (contact with same-age peers). In this study, we investigated the association between contact with older adults and views of the self in old age in a domain-specific way among younger and older adults.

Methods

The sample (n = 2,356) comprised younger (39–55 years) and older (65–90 years) adults who participated in the aging as future study and were from China (Hong Kong and Taiwan), the Czech Republic, Germany, and the United States. We used moderated mediation models for data analysis.

Results

Contact with older adults was related to more positive views of the self in old age and this effect was mediated by more positive stereotypes of older people. These relations were stronger for older adults. Beneficial effects of contact with older adults emerged mostly in the domains of friends and leisure, but less in the family domain.

Discussion

Having interactions with other older adults may help favorably shape how younger adults and particularly older adults view their own aging, especially in relation to friends and leisure activities. From the perspective of older adults, having regular contacts with other older adults may increase the heterogeneity of exposure to different aging experiences, thus encouraging the formation of more differentiated stereotypes of older people and of their views of themselves in old age.
Spatiotemporal variation of crustal deformation in northeastern Tibet following the 2008Mw 7.9 Wenchuan earthquake and its impact on fault activity
Authors: Wei Congmin , Meng Guojie , Wu Weiwei , Liu Tai , Ge Weipeng , Chen Xueliang , Zhao Guoqiang , He Tian
Published: March 2023

The 2008 Wenchuan earthquake, which occurred on the eastern edge of the Tibetan Plateau, produced significant time-dependent post-seismic deformation in the northeastern Tibetan Plateau. To explore the spatio-temporal evolution of crustal deformation and its impact on nearby active faults due to the Wenchuan earthquake, we first solve the velocity fields, strain rates and slip rates of the major faults at different stages of the earthquake cycle, based on GPS observations spanning approximately 10 yr before and after the Wenchuan earthquake. The results show that: (a) during the late interseismic phase, the GPS velocity fields relative to the Sichuan basin and strain rates near the Longmenshan fault (the seismogenic fault of the Wenchuan earthquake) are insignificant in magnitude, and the geodetic slip rates of the major faults are in good agreement with geological investigations; (b) After the Wenchuan earthquake, post-seismic deformation on both flanks of the causative Longmenshan fault is asymmetrically distributed, with significant deformation distributed between the Longmenshan fault and the Longriba fault. The post-seismic deformation decreases with increasing distance away from the Longmenshan fault. Furthermore, geodetic slip rates for the major active faults at the early post-seismic stage differ significantly from those at the late interseismic stage; (c) The crustal deformation in the northeastern Tibetan Plateau is generally small during the late interseismic phase, but it increases significantly during the early post-seismic stage and begins to decrease again as it progresses to the second post-seismic stage. We speculate that this kinematic evolution of crustal deformation is ascribed to that the Longmenshan fault was in a locking state during the late interseismic period, whereas the Longmenshan fault is no longer locked after the Wenchuan earthquake, and thus the marked post-seismic deformation occurred in the epicentral and its surrounding area. Then, the post-seismic deformation becomes weaker with time lapse, and generally the crustal deformation begins to slowly recover to the pre-seismic level. Using a forward model, we test whether post-seismic deformation caused by viscoelastic relaxation of the lower crust 4 yr after the Wenchuan earthquake can explain the observed spatio-temporal pattern of the crustal deformation. We find that this mechanism can account for the evolutionary pattern of crustal motion in the Songpan-Ganzi block east of the Longriba fault in central-east Tibet and central-eastern and southern regions of the West Qinling-Songpan Tectonic Syntaxis in east Tibet 4 yr after the Wenchuan earthquake. Moreover, the post-seismic viscoelastic relaxation of the Wenchuan earthquake is the main cause of loading rate variations of primary faults in the early post-seismic stage in the northeastern Tibetan Plateau.
Superposition of induced polarization signals measured on pyrite–sand mixtures
Authors: Martin Tina , Weller Andreas
Published: March 2023

Induced polarization (IP) is a common method in ore exploration. IP spectra measured over a wide frequency range can be used to characterize material properties of ores, slags and other residual material from mines and processing facilities. Previous studies have shown that IP parameters are sensitive to type, content or grain size of electronically conductive or semi-conductive minerals. Up to now, a variety of experiments has been performed on sand mixtures with fractions of ore minerals. Most experiments consider only a single fraction with a fixed grain size. We continue a series of experiments that have been done with sand–pyrite mixtures. The presented study compares IP spectra recorded for samples either with a single grain radius fraction (E-samples) or with two different grain radii fractions (Z-samples). The spectra are fitted to Pelton models. A Debye decomposition that provides a relaxation time distribution (RTD) is applied to the complex conductivity spectra. The RTD indicates separated maxima only if the ratio of mean grain radii is larger than a factor five. The resolution of the phase spectra and the spectra of imaginary part of conductivity is lower. Even though the volumetric pyrite content is equal in each fraction, the phase spectra and RTD of the Z-samples indicate much higher signals for the pyrite fraction with smaller grain radius. The same observation is made for the chargeability that shows larger values for decreasing grain radii. This finding contradicts existing theories that consider the chargeability as a suitable proxy of the volumetric content of ore minerals. We explain the observed effect by an interaction between neighbouring pyrite particles. The conductivity of the mixtures of the E-samples increases with decreasing grain radius of the pyrite fraction. This effect is attributed to dissolution effects on the surface of the pyrite particles during the sample preparation. We find that the additive superposition of the phase spectra of two E-samples is in good agreement with the measured phase spectra of the Z-samples (measured superposition) containing the two corresponding pyrite fractions. The agreement is slightly worse for the spectra of imaginary part of conductivity, where the measured superposition overestimates the mathematical superposition. The experimental results of our study motivate a further improvement of existing mechanistic models.
Observations and simulations of the meteotsunami generated by the Tonga eruption on 15 January 2022 in the Mediterranean Sea
Authors: Heinrich P , Gailler A , Dupont A , Rey V , Hébert H , Listowski C
Published: March 2023

The 15 January 2022 eruption of the Hunga–Tunga volcano generated a Lamb pressure wave propagating all over the globe and triggering a tsunami throughout the planet. A first atmospheric wave arrived 16 hr after the eruption on the French Mediterranean coasts and propagated southward. A second one originating from Africa was observed 4 hr later with an attenuated amplitude. The first wave can be roughly defined either by a N wave or a sinusoid signal with a period close to 50 min and an amplitude of 130 Pa. In the Mediterranean Sea, the tsunami was recorded by almost all standard coastal tide gauges or pressure gauges. The French tide gauge stations recorded water waves with amplitudes ranging from a few centimetres to 10 cm and with periods ranging from 10 min to 1 hr. Numerical simulation of the tsunami is performed by the operational code Taitoko for different atmospheric sources. Non-linear shallow water equations are solved by a finite-difference method, using the nested multigrid approach. The tsunami is generated by calculating analytically the atmospheric pressure gradient in the momentum equations. Comparisons of time-series between numerical solutions and records are satisfactory for most tide-gauges along the French Mediterranean coast. Sensitivity analysis on the atmospheric source and on the resolution is performed. For most tide-gauge stations, numerical results show that the wave forms depend first on local resonance phenomena.
A Fast And Versatile Method for Simultaneous HCR, Immunohistochemistry And Edu Labeling (SHInE)
Authors: Ćorić Aida , Stockinger Alexander W , Schaffer Petra , Rokvić Dunja , Tessmar-Raible Kristin , Raible Florian
Published: March 2023

Access to newer, fast, and cheap sequencing techniques, particularly on the single-cell level, have made transcriptomic data of tissues or single cells accessible to many researchers. As a consequence, there is an increased need for in situ visualization of gene expression or encoded proteins to validate, localize, or help interpret such sequencing data, as well as put them in context with cellular proliferation. A particular challenge for labeling and imaging transcripts are complex tissues that are often opaque and/or pigmented, preventing easy visual inspection. Here, we introduce a versatile protocol that combines in situ hybridization chain reaction, immunohistochemistry, and proliferative cell labeling using 5-ethynyl-2′-deoxyuridine, and demonstrate its compatibility with tissue clearing. As a proof-of-concept, we show that our protocol allows for the parallel analysis of cell proliferation, gene expression, and protein localization in bristleworm heads and trunks.
In vitroactivity of eravacycline and comparator agents against bacterial pathogens isolated from patients with cancer
Authors: Rolston Kenneth , Gerges Bahgat , Nesher Lior , Shelburne Samuel A , Prince Randall , Raad Issam
Published: March 2023

Background

Bacterial infections are common in patients with cancer, and many bacteria have developed resistance to currently used antibiotics.

Objectives

We evaluated the in vitro activity of eravacycline (a recently developed fluorocycline) and comparators against bacterial pathogens isolated from patients with cancer.

Methods

Antimicrobial susceptibility testing was performed using CLSI-approved methodology and interpretive criteria for 255 Gram-positive and 310 Gram-negative bacteria. MIC and susceptibility percentage were calculated according to CLSI and FDA breakpoints when available.

Results

Eravacycline had potent activity against most Gram-positive bacteria, including MRSA. Of 80 Gram-positive isolates with available breakpoints, 74 (92.5%) were susceptible to eravacycline. Eravacycline had potent activity against most Enterobacterales, including ESBL-producing organisms. Of 230 Gram-negative isolates with available breakpoints, 201 (87.4%) were susceptible to eravacycline. Eravacycline had the best activity among comparators against carbapenem-resistant Enterobacterales, with 83% susceptibility. Eravacycline was also active against many non-fermenting Gram-negative bacteria, with the lowest MIC90 value among comparators.

Conclusions

Eravacycline was active against many clinically significant bacteria isolated from patients with cancer, including MRSA, carbapenem-resistant Enterobacterales, and non-fermenting Gram-negative bacilli. Eravacycline might play an important role in the treatment of bacterial infections in patients with cancer, and additional clinical evaluation is warranted.
Cyclical Time Is Greener: The Impact of Temporal Perspective on Pro-Environmental Behavior
Authors: Xu Lan , Zhao Shuangshuang , Cotte June , Cui Nan
Published: March 2023

The natural environment is deteriorating. However, humans have not slowed down their pace of resource depletion and environmental destruction. This research takes a particular path to understanding environmental consumption—through a focus on temporal perspective. Evidence from six studies demonstrates the positive effect of a cyclical temporal perspective, versus a linear temporal perspective, on consumers’ pro-environmental behavior. The research shows that individuals with a cyclical perspective are more likely to include the environment in the self, which leads to higher pro-environmental behavioral intentions and more pro-environmental behavior. This temporal perspective effect is attenuated for consumers already high on green values. The authors also examine a marketer-controlled moderator and show that consumers are more likely to purchase a pro-environmental product when they see a temporal-perspective-congruent promotional appeal. The research contributes to both the time perception and the environmental consumption literature and offers several practical implications for organizations to promote sustainable consumer behavior.
Investigating spatial scan statistics for multivariate functional data
Authors: Frévent Camille , Ahmed Mohamed-Salem , Dabo-Niang Sophie , Genin Michaël
Published: March 2023

In environmental surveillance, cluster detection of environmental black spots is of major interest due to the adverse health effects of pollutants, as well as their known synergistic effect. Thus, this paper introduces three new spatial scan statistics for multivariate functional data, applicable for detecting clusters of abnormal air pollutants concentrations measured spatially at a very fine scale in northern France in October 2021 taking into account their correlations. Mathematically, our methodology is derived from a functional multivariate analysis of variance, an adaptation of the Hotelling T2-test statistic, and a multivariate extension of the Wilcoxon test statistic. The approaches were evaluated in a simulation study and then applied to the air pollution dataset.
Alterations in faecal microbiome and resistome in Chinese international travellers: a metagenomic analysis
Authors: Cheung Man Kit , Ng Rita W Y , Lai Christopher K C , Zhu Chendi , Au Eva T K , Yau Jennifer W K , Li Carmen , Wong Ho Cheong , Wong Bonnie C K , Kwok Kin On , Chen Zigui , Chan Paul K S , Lui Grace C Y , Ip Margaret
Published: March 2023

Background

International travel increases the risk of acquisition of antibiotic-resistant bacteria and antibiotic resistance genes (ARGs). Previous studies have characterized the changes in the gut microbiome and resistome of Western travellers; however, information on non-Western populations and the effects of travel-related risk factors on the gut microbiome and resistome remains limited.

Methods

We conducted a prospective observational study on a cohort of 90 healthy Chinese adult residents of Hong Kong. We characterized the microbiome and resistome in stools collected from the subjects before and after travelling to diverse international locations using shotgun metagenomic sequencing and examined their associations with travel-related variables.

Results

Our results showed that travel neither significantly changed the taxonomic composition of the faecal microbiota nor altered the alpha (Shannon) or beta diversity of the faecal microbiome or resistome. However, travel significantly increased the number of ARGs. Ten ARGs, including aadA, TEM, mgrB, mphA, qnrS9 and tetR, were significantly enriched in relative abundance after travel, eight of which were detected in metagenomic bins belonging to Escherichia/Shigella flexneri in the post-trip samples. In sum, 30 ARGs significantly increased in prevalence after travel, with the largest changes observed in tetD and a few qnrS variants (qnrS9, qnrS and qnrS8). We found that travel to low- or middle-income countries, or Africa or Southeast Asia, increased the number of ARG subtypes, whereas travel to low- or middle-income countries and the use of alcohol-based hand sanitizer (ABHS) or doxycycline as antimalarial prophylaxis during travel resulted in increased changes in the beta diversity of the faecal resistome.

Conclusions

Our study highlights travel to low- or middle-income countries, Africa or Southeast Asia, a long travel duration, or the use of ABHS or doxycycline as antimalarial prophylaxis as important risk factors for the acquisition/enrichment of ARGs during international travel.
Development of a prediction model for the acquisition of extended spectrum beta-lactam-resistant organisms in U.S. international travellers
Authors: Brown David Garrett , Worby Colin J , Pender Melissa A , Brintz Ben J , Ryan Edward T , Sridhar Sushmita , Oliver Elizabeth , Harris Jason B , Turbett Sarah E , Rao Sowmya R , Earl Ashlee M , LaRocque Regina C , Leung Daniel T
Published: March 2023

Background

Extended spectrum beta-lactamase producing Enterobacterales (ESBL-PE) present a risk to public health by limiting the efficacy of multiple classes of beta-lactam antibiotics against infection. International travellers may acquire these organisms and identifying individuals at high risk of acquisition could help inform clinical treatment or prevention strategies.

Methods

We used data collected from a cohort of 528 international travellers enrolled in a multicentre US-based study to derive a clinical prediction rule (CPR) to identify travellers who developed ESBL-PE colonization, defined as those with new ESBL positivity in stool upon return to the United States. To select candidate features, we used data collected from pre-travel and post-travel questionnaires, alongside destination-specific data from external sources. We utilized LASSO regression for feature selection, followed by random forest or logistic regression modelling, to derive a CPR for ESBL acquisition.

Results

A CPR using machine learning and logistic regression on 10 features has an internally cross-validated area under the receiver operating characteristic curve (cvAUC) of 0.70 (95% confidence interval 0.69–0.71). We also demonstrate that a four-feature model performs similarly to the 10-feature model, with a cvAUC of 0.68 (95% confidence interval 0.67–0.69). This model uses traveller’s diarrhoea, and antibiotics as treatment, destination country waste management rankings and destination regional probabilities as predictors.

Conclusions

We demonstrate that by integrating traveller characteristics with destination-specific data, we could derive a CPR to identify those at highest risk of acquiring ESBL-PE during international travel.
Possible evidence for a large-scale enhancement in the Lyman-α forest power spectrum at redshiftz≥ 4
Authors: Molaro Margherita , Iršič Vid , Bolton James S , Lieu Maggie , Keating Laura C , Puchwein Ewald , Haehnelt Martin G , Viel Matteo
Published: March 2023

Inhomogeneous reionization enhances the 1D Ly α forest power spectrum on large scales at redshifts z ≥ 4. This is due to coherent fluctuations in the ionized hydrogen fraction that arise from large-scale variations in the post-reionization gas temperature, which fade as the gas cools. It is therefore possible to use these relic fluctuations to constrain inhomogeneous reionization with the power spectrum at wavenumbers $\log _{10}(k/{\rm km^{-1}\, s})\lesssim -1.5$. We use the Sherwood-Relics suite of hybrid radiation hydrodynamical simulations to perform a first analysis of new Ly α forest power spectrum measurements at 4.0 ≤ z ≤ 4.6. These data extend to wavenumbers $\log _{10}(k/{\rm km^{-1}\, s})\simeq -3$, with a relative uncertainty of 10–20 per cent in each wavenumber bin. Our analysis returns a 2.7σ preference for an enhancement in the Ly α forest power spectrum at large scales, in excess of that expected for a spatially uniform ultraviolet background. This large-scale enhancement could be a signature of inhomogeneous reionization, although the statistical precision of these data is not yet sufficient for obtaining a robust detection of the relic post-reionization fluctuations. We show that future power spectrum measurements with relative uncertainties of ≲ 2.5 per cent should provide unambiguous evidence for an enhancement in the power spectrum on large scales.
Initial flash and spectral formation of Type Ia supernovae with an envelope: applications to overluminous SNe Ia
Authors: Maeda Keiichi , Jiang Ji-an , Doi Mamoru , Kawabata Miho , Shigeyama Toshikazu
Published: March 2023

Overluminous Type Ia supernovae (SNe Ia) show peculiar observational features, for which an explosion of a super-massive white dwarf (WD) beyond the classical Chandrasekhar-limiting mass has been suggested, largely based on their high luminosities and slow light-curve evolution. However, their observational features are diverse, with a few extremely peculiar features whose origins have not been clarified; strong and persisting C II lines, late-time accelerated luminosity decline and red spectra, and a sub-day time-scale initial flash clearly identified so far at least for three overluminous SNe Ia. In the present work, we suggest a scenario that provides a unified solution to these peculiarities, through hydrodynamic and radiation transfer simulations together with analytical considerations; a C+O-rich envelope (∼0.01−0.1M⊙) attached to an exploding WD. Strong C II lines are created within the shocked envelope. Dust formation is possible in the late phase, providing a sufficient optical depth thereafter. The range of the envelope mass considered here predicts an initial flash with time-scale of ∼0.5−3 days. The scenario thus can explain some of the key diverse observational properties by a different amount of the envelope, but additional factors are also required; we argue that the envelope is distributed in a disc-like structure, and also the ejecta properties, e.g. the mass of the WD, play a key role. Within the context of the hypothesized super-Chandrasekhar-mass WD scenario, we speculatively suggest a progenitor WD evolution including a spin-up accretion phase followed by a spin-down mass-ejection phase.
Accretion within the innermost stable circular orbit: analytical thermodynamic solutions in the adiabatic limit
Authors: Mummery Andrew , Balbus Steven
Published: March 2023

We present analytical solutions for the thermodynamic (temperature, pressure, density, etc.) properties of thin accretion flows in the region within the innermost stable circular orbit (ISCO) of a Kerr black hole, the first analytical solutions of their kind. These solutions are constructed in the adiabatic limit and neglect radiative losses, an idealization valid for a restricted region of parameter space. We highlight a number of remarkable properties of these solutions, including that these solutions cool for radii rI/2 < r < rI, before increasing in temperature for 0 < r < rI/2, independent of black hole spin and assumptions regarding the equation of state of the accretion flow. The radiative temperature of these solutions can, for some values of the free parameters of the theory, peak within the ISCO and not in the main body of the disc. These solutions represent a fundamentally new class of analytical accretion solutions, which are both non-circular and non-radial in character.
Accurate analytic mass–scale relations for dark matter haloes of all masses and redshifts
Authors: Salvador-Solé Eduard , Manrique Alberto , Canales David , Botella Ignacio
Published: March 2023

CUSP is a powerful formalism that recovers, from first principles and with no free parameter, all the macroscopic properties of dark matter haloes found in cosmological N-body simulations and unveils the origin of their characteristic features. Since it is not restricted by the limitations of simulations, it covers the whole mass and redshift ranges. In the present Paper we use CUSP to calculate the mass–scale relations holding for halo density profiles fitted to the usual NFW and Einasto functions in the most relevant cosmologies and for the most usual mass definitions. We clarify the origin of these relations and provide accurate analytic expressions holding for all masses and redshifts. The performance of those expressions is compared to that of previous models and to the mass–concentration relation spanning more than 20 orders of magnitude in mass at z = 0 obtained in recent simulations of a 100 GeV WIMP universe.
Human senataxin is a bona fide R-loop resolving enzyme and transcription termination factor
Authors: Hasanova Zdenka , Klapstova Veronika , Porrua Odil , Stefl Richard , Sebesta Marek
Published: March 2023

Prolonged pausing of the transcription machinery may lead to the formation of three-stranded nucleic acid structures, called R-loops, typically resulting from the annealing of the nascent RNA with the template DNA. Unscheduled persistence of R-loops and RNA polymerases may interfere with transcription itself and other essential processes such as DNA replication and repair. Senataxin (SETX) is a putative helicase, mutated in two neurodegenerative disorders, which has been implicated in the control of R-loop accumulation and in transcription termination. However, understanding the precise role of SETX in these processes has been precluded by the absence of a direct characterisation of SETX biochemical activities. Here, we purify and characterise the helicase domain of SETX in parallel with its yeast orthologue, Sen1. Importantly, we show that SETX is a bona fide helicase with the ability to resolve R-loops. Furthermore, SETX has retained the transcription termination activity of Sen1 but functions in a species-specific manner. Finally, subsequent characterisation of two SETX variants harbouring disease-associated mutations shed light into the effect of such mutations on SETX folding and biochemical properties. Altogether, these results broaden our understanding of SETX function in gene expression and the maintenance of genome integrity and provide clues to elucidate the molecular basis of SETX-associated neurodegenerative diseases.
HPV integration generates a cellular super-enhancer which functions as ecDNA to regulate genome-wide transcription
Authors: Tian Rui , Huang Zheying , Li Lifang , Yuan Jingping , Zhang Qinghua , Meng Lirong , Lang Bin , Hong Yongfeng , Zhong Chaoyue , Tian Xun , Cui Zifeng , Jin Zhuang , Liu Jiashuo , Huang Zhaoyue , Wang Yuyan , Chen Ye , Hu Zheng
Published: March 2023

Human papillomavirus (HPV) integration is a critical step in cervical cancer development; however, the oncogenic mechanism at the genome-wide transcriptional level is still poorly understood. In this study, we employed integrative analysis on multi-omics data of six HPV-positive and three HPV-negative cell lines. Through HPV integration detection, super-enhancer (SE) identification, SE-associated gene expression and extrachromosomal DNA (ecDNA) investigation, we aimed to explore the genome-wide transcriptional influence of HPV integration. We identified seven high-ranking cellular SEs generated by HPV integration in total (the HPV breakpoint-induced cellular SEs, BP-cSEs), leading to intra-chromosomal and inter-chromosomal regulation of chromosomal genes. The pathway analysis revealed that the dysregulated chromosomal genes were correlated to cancer-related pathways. Importantly, we demonstrated that BP-cSEs existed in the HPV–human hybrid ecDNAs, explaining the above transcriptional alterations. Our results suggest that HPV integration generates cellular SEs that function as ecDNA to regulate unconstrained transcription, expanding the tumorigenic mechanism of HPV integration and providing insights for developing new diagnostic and therapeutic strategies.