bluuebunny/crossref_metadata_2025 huggingface dataset:
Under threat: emotional and behavioral responses to occupational identity threat
Authors: Yang Na , Zhang Ruoyong
Published: October 2021

Research on identity threat has predominantly focused on the consequences of threat to some ascribed or involuntary identities, while overlooking individuals' responses to occupational identity threat. Integrating identity theory with identity threat literature, we argue that encountering occupational identity threat promotes negative emotion and feedback-seeking behavior, and negative emotion further mediates the relationship between occupational identity threat and feedback-seeking behavior. Moreover, individuals' performance self-esteem strengthens both the direct effect of occupational identity threat on negative emotion, and the indirect effect of occupational identity threat on feedback-seeking behavior through negative emotion. The results from two experimental studies and one field study provide support for these predictions. We discuss the theoretical and practical implications of our findings.
Milk intake and incident stroke and CHD in populations of European descent: a Mendelian randomisation study
Authors: Vissers L. E. T. , Sluijs I. , Burgess S. , Forouhi N. G. , Freisling H. , Imamura F. , Nilsson T. K. , Renström F. , Weiderpass E. , Aleksandrova K. , Dahm C. C. , Perez-Cornago A. , Schulze M. B. , Tong T. Y. N. , Aune D. , Bonet C. , Boer J. M. A. , Boeing H. , Chirlaque M. D. , Conchi M. I. , Imaz L. , Jäger S. , Krogh V. , Kyrø C. , Masala G. , Melander O. , Overvad K. , Panico S. , Sánches M. J. , Sonestedt E. , Tjønneland A. , Tzoulaki I. , Verschuren W. M. M. , Riboli E. , Wareham N. J. , Danesh J. , Butterworth A. S. , van der Schouw Y. T.
Published: October 2021

Higher milk intake has been associated with a lower stroke risk, but not with risk of CHD. Residual confounding or reverse causation cannot be excluded. Therefore, we estimated the causal association of milk consumption with stroke and CHD risk through instrumental variable (IV) and gene-outcome analyses. IV analysis included 29 328 participants (4611 stroke; 9828 CHD) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD (eight European countries) and European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) case-cohort studies. rs4988235, a lactase persistence (LP) SNP which enables digestion of lactose in adulthood was used as genetic instrument. Intake of milk was first regressed on rs4988235 in a linear regression model. Next, associations of genetically predicted milk consumption with stroke and CHD were estimated using Prentice-weighted Cox regression. Gene-outcome analysis included 777 024 participants (50 804 cases) from MEGASTROKE (including EPIC-CVD), UK Biobank and EPIC-NL for stroke, and 483 966 participants (61 612 cases) from CARDIoGRAM, UK Biobank, EPIC-CVD and EPIC-NL for CHD. In IV analyses, each additional LP allele was associated with a higher intake of milk in EPIC-CVD (β = 13·7 g/d; 95 % CI 8·4, 19·1) and EPIC-NL (36·8 g/d; 95 % CI 20·0, 53·5). Genetically predicted milk intake was not associated with stroke (HR per 25 g/d 1·05; 95 % CI 0·94, 1·16) or CHD (1·02; 95 % CI 0·96, 1·08). In gene-outcome analyses, there was no association of rs4988235 with risk of stroke (OR 1·02; 95 % CI 0·99, 1·05) or CHD (OR 0·99; 95 % CI 0·95, 1·03). Current Mendelian randomisation analysis does not provide evidence for a causal inverse relationship between milk consumption and stroke or CHD risk.
Introduction: Is a Military Really Worth Having?
Authors: Balint Peter
Published: October 2021

Just war theory has traditionally focused onjus ad bellum(the justiceofwar) andjus in bello(justiceinwar). What has been neglected is the question ofjus ante bellum, or justicebeforewar. In particular: Under what circumstances is it justifiable for a polity topreparefor war by militarizing? When (if ever) and why (if at all) is it morally permissible or even obligatory to create and maintain the potential to wage war? What are the alternatives to the military? And if we do have militaries, how should they be arranged, trained, and equipped? These considerations are not about whether warmakingis justified, but about whether warbuildingis justified.InEthics, Security, and the War-Machine, Ned Dobos argues that we have not sufficiently calculated the true (noneconomic) costs of the military, and that if we did, having a standing defense force would not seem like as good an idea. Dobos pushes us to reflect on something we have taken for granted: that one of the biggest institutions in our society, which is supposed to keep us safe and allow us to lead our own lives, may in fact pose great dangers and risks to us physically, morally, and culturally. The essays in this symposium take Dobos's work as a starting point and show the importance, complexity, and richness of this new strand of ethical inquiry.
Reduced Legal Equality of Combatants in War
Authors: Gisbertz-Astolfi Philipp
Published: October 2021

The focus on the moral rights of combatants in the ethics of war ignores a very important point: although morally unjust combatants cannot be considered moral equals to just combatants, especially with regard to the right to kill, there are sound moral reasons why the laws of war should accept a kind of equality between them, a concept referred to as “reduced legal equality.” Reduced legal equality is not about equal moral rights but about granting legal immunity to combatants for their conduct in accordance with the laws of war. This article shows that reduced legal equality of combatants is not only the morally best legal regulation in our nonideal international world but also the correct interpretation of international law.
Discriminatory Immigration Bans Elicit Anti-Americanism in Targeted Communities: Evidence from Nigerian Expatriates
Authors: Erlich Aaron , Soehl Thomas , Chen Annie Y.
Published: October 2021

Do discriminatory US immigration policies affect foreign public opinion about Americans? When examining negative reactions to US actions perceived as bullying on the world stage, existing research has focused either on US policies that involve direct foreign military intervention or seek to influence foreign countries’ domestic economic policy or policies advocating minority representation. We argue that US immigration policies – especially when they are perceived as discriminatory – can similarly generate anti-American sentiment. We use a conjoint experiment embedded in a unique survey of Nigerian expatriates in Ghana. Comparing respondents before and after President Trump surpisingly announced a ban on Nigerian immigration to the United States, we find a large drop (13 percentage points) in Nigerian’s favorability towards Americans.
Flows, Transport, and Effective Drag in Intertidal Salt Marsh Creeks
Authors: Ortals Collin , Cordero Orlando , Valle‐Levinson Arnoldo , Angelini Christine
Published: October 2021

Intertidal creeks (channel width <5 m) weave through salt marshes, delivering water, nutrients, and sediments into the marsh interior and affecting spatial heterogeneity in plant and animal distributions. Despite their global prevalence, creek connectivity, and the mechanisms controlling cross‐marsh hydrodynamics, remain poorly resolved. In this study, we measured flow and total suspended solids transport in three intertidal creeks within a confined drainage basin in a Georgia, USA salt marsh. We discovered that the effective drag is 3–12 times greater than bed drag, reaching levels similar to those observed in coral reefs. Furthermore, the drag between tidal flood and ebb phases differs, indicating an asymmetric drag. Analyses of along‐channel momentum reveal that pressure gradient m/s2 and friction m/s2 dominate creek momentum balance. Divergence in tidal and suspended solids transport between adjacent creeks revealed contrasting tidal transport asymmetries (i.e., flood or ebb dominated) within this confined basin. We discuss how these differences may alter the eco‐geospatial evolution of salt marshes and their response to sea‐level rise.
Fronto-limbic neural variability as a transdiagnostic correlate of emotion dysregulation
Authors: Kebets Valeria , Favre Pauline , Houenou Josselin , Polosan Mircea , Perroud Nader , Aubry Jean-Michel , Van De Ville Dimitri , Piguet Camille
Published: October 2021

Emotion dysregulation is central to the development and maintenance of psychopathology, and is common across many psychiatric disorders. Neurobiological models of emotion dysregulation involve the fronto-limbic brain network, including in particular the amygdala and prefrontal cortex (PFC). Neural variability has recently been suggested as an index of cognitive flexibility. We hypothesized that within-subject neural variability in the fronto-limbic network would be related to inter-individual variation in emotion dysregulation in the context of low affective control. In a multi-site cohort (N = 166, 93 females) of healthy individuals and individuals with emotional dysregulation (attention deficit/hyperactivity disorder (ADHD), bipolar disorder (BD), and borderline personality disorder (BPD)), we applied partial least squares (PLS), a multivariate data-driven technique, to derive latent components yielding maximal covariance between blood-oxygen level-dependent (BOLD) signal variability at rest and emotion dysregulation, as expressed by affective lability, depression and mania scores. PLS revealed one significant latent component (r = 0.62, p = 0.044), whereby greater emotion dysregulation was associated with increased neural variability in the amygdala, hippocampus, ventromedial, dorsomedial and dorsolateral PFC, insula and motor cortex, and decreased neural variability in occipital regions. This spatial pattern bears a striking resemblance to the fronto-limbic network, which is thought to subserve emotion regulation, and is impaired in individuals with ADHD, BD, and BPD. Our work supports emotion dysregulation as a transdiagnostic dimension with neurobiological underpinnings that transcend diagnostic boundaries, and adds evidence to neural variability being a relevant proxy of neural efficiency.
SIRT3 protects bovine mammary epithelial cells from heat stress damage by activating the AMPK signaling pathway
Authors: Sun Xiao-Chun , Wang Yue , Zeng Han-Fang , Xi Yu-Meng , Lin Hong , Han Zhao-Yu , Chen Kun-Lin
Published: October 2021

With global warming, heat stress has become an important challenge for the global dairy industry. Sirtuin 3 (SIRT3), an important mitochondrial NAD+dependent decarboxylase and a major regulator of cellular energy metabolism and antioxidant defense, is integral to maintaining normal mitochondrial function. The aim of this study was to assess the protective effect of SIRT3 on damage to bovine mammary epithelial cells (BMECs) induced by heat stress and to explore its potential mechanism. Our results indicate that SIRT3 is significantly downregulated in heat-stressed mammary tissue and high-temperature-treated BMECs. SIRT3 knockdown significantly increased the expression of HSP70, Bax, and cleaved-caspase 3 and inhibited the production of antioxidases, thus promoting ROS production and cell apoptosis in BMECs. In addition, SIRT3 knockdown can aggravate mitochondrial damage by mediating the expression of genes related to mitochondrial fission and fusion, including dynamin-related protein 1, mitochondrial fission 1 protein, and mitochondrial fusion proteins 1and 2. In addition, SIRT3 knockdown substantially decreased AMPK phosphorylation in BMECs. In contrast, SIRT3 overexpression in high-temperature treatment had the opposite effect to SIRT3 knockdown in BMECs. SIRT3 overexpression reduced mitochondrial damage and weakened the oxidative stress response of BMECs induced by heat stress and promoted the phosphorylation of AMPK. Taken together, our results indicate that SIRT3 can protect BMECs from heat stress damage through the AMPK signaling pathway. Therefore, the reduction of oxidative stress by SIRT3 may be the primary molecular mechanism underlying resistance to heat stress in summer cows.
Next-generation ensemble projections reveal higher climate risks for marine ecosystems
Authors: Tittensor Derek P. , Novaglio Camilla , Harrison Cheryl S. , Heneghan Ryan F. , Barrier Nicolas , Bianchi Daniele , Bopp Laurent , Bryndum-Buchholz Andrea , Britten Gregory L. , Büchner Matthias , Cheung William W. L. , Christensen Villy , Coll Marta , Dunne John P. , Eddy Tyler D. , Everett Jason D. , Fernandes-Salvador Jose A. , Fulton Elizabeth A. , Galbraith Eric D. , Gascuel Didier , Guiet Jerome , John Jasmin G. , Link Jason S. , Lotze Heike K. , Maury Olivier , Ortega-Cisneros Kelly , Palacios-Abrantes Juliano , Petrik Colleen M. , du Pontavice Hubert , Rault Jonathan , Richardson Anthony J. , Shannon Lynne , Shin Yunne-Jai , Steenbeek Jeroen , Stock Charles A. , Blanchard Julia L.
Published: October 2021

Projections of climate change impacts on marine ecosystems have revealed long-term declines in global marine animal biomass and unevenly distributed impacts on fisheries. Here we apply an enhanced suite of global marine ecosystem models from the Fisheries and Marine Ecosystem Model Intercomparison Project (Fish-MIP), forced by new-generation Earth system model outputs from Phase 6 of the Coupled Model Intercomparison Project (CMIP6), to provide insights into how projected climate change will affect future ocean ecosystems. Compared with the previous generation CMIP5-forced Fish-MIP ensemble, the new ensemble ecosystem simulations show a greater decline in mean global ocean animal biomass under both strong-mitigation and high-emissions scenarios due to elevated warming, despite greater uncertainty in net primary production in the high-emissions scenario. Regional shifts in the direction of biomass changes highlight the continued and urgent need to reduce uncertainty in the projected responses of marine ecosystems to climate change to help support adaptation planning.
Novel HLA-B7-restricted human metapneumovirus epitopes enhance viral clearance in mice and are recognized by human CD8+ T cells
Authors: Miranda-Katz Margot , Erickson John J. , Lan Jie , Ecker Alwyn , Zhang Yu , Joyce Sebastian , Williams John V.
Published: October 2021

Human metapneumovirus (HMPV) is a leading cause of acute lower respiratory tract illness in children and adults. Repeated infections are common and can be severe in young, elderly, and immunocompromised persons due to short-lived protective humoral immunity. In turn, few protective T cell epitopes have been identified in humans. Thus, we infected transgenic mice expressing the common human HLA MHC-I allele B*07:02 (HLA-B7) with HMPV and screened a robust library of overlapping and computationally predicted HLA-B7 binding peptides. Six HLA-B7-restricted CD8+ T cell epitopes were identified using ELISPOT screening in the F, M, and N proteins, with M195–203 (M195) eliciting the strongest responses. MHC-tetramer flow cytometric staining confirmed HLA-B7 epitope-specific CD8+ T cells migrated to lungs and spleen of HMPV-immune mice. Immunization with pooled HLA-B7-restricted peptides reduced viral titer and protected mice from virulent infection. Finally, we confirmed that CD8+ T cells from HLA-B7 positive humans also recognize the identified epitopes. These results enable identification of HMPV-specific CD8+ T cells in humans and help to inform future HMPV vaccine design.
An ALE meta-analytic review of top-down and bottom-up processing of music in the brain
Authors: Pando-Naude Victor , Patyczek Agata , Bonetti Leonardo , Vuust Peter
Published: October 2021

A remarkable feature of the human brain is its ability to integrate information from the environment with internally generated content. The integration of top-down and bottom-up processes during complex multi-modal human activities, however, is yet to be fully understood. Music provides an excellent model for understanding this since music listening leads to the urge to move, and music making entails both playing and listening at the same time (i.e., audio-motor coupling). Here, we conducted activation likelihood estimation (ALE) meta-analyses of 130 neuroimaging studies of music perception, production and imagery, with 2660 foci, 139 experiments, and 2516 participants. We found that music perception and production rely on auditory cortices and sensorimotor cortices, while music imagery recruits distinct parietal regions. This indicates that the brain requires different structures to process similar information which is made available either by an interaction with the environment (i.e., bottom-up) or by internally generated content (i.e., top-down).
The early maternal environment shapes the parental response to offspring UV ornamentation
Authors: García-Campa Jorge , Müller Wendt , Hernández-Correas Ester , Morales Judith
Published: October 2021

Parents allocate resources to offspring to increase their survival and to maximize their own fitness, while this investment implies costs to their condition and future reproduction. Parents are hence expected to optimally allocate their resources. They should invest equally in all their offspring under good conditions, but when parental capacity is limited, parents should invest in the offspring with the highest probability of survival. Such parental favouritism is facilitated by the fact that offspring have evolved condition-dependent traits to signal their quality to parents. In this study we explore whether the parental response to an offspring quality signal depends on the intrinsic capacity of the parents, here the female. We first manipulated the intrinsic capacity of blue tit (Cyanistes caeruleus) females through lutein-supplementation during egg laying, and we subsequently blocked the UV/yellow reflectance of breast feathers on half of the nestlings in each brood. We did not find evidence that the female intrinsic capacity shaped parental feeding or sibling competition according to offspring UV/yellow colouration. However, nestling UV/yellow colour affected costly behavioural interactions in the form of prey-testings (when a parent places a prey item into a nestling’s gape but removes it again). In lutein-supplemented nests, fathers but not mothers favoured UV-blocked chicks by testing them less often, supporting previous results. Accordingly, in lutein-supplemented nests, UV-blocked nestlings gained more mass than their siblings, while in control nests we found the opposite effect and UV-blocked nestlings gained less. Our results emphasize that the prenatal environment shaped the role of offspring UV/yellow colour during certain family interactions and are indicative for sex-specific parental care strategies.
High canopy cover of invasive Acer negundo L. affects ground vegetation taxonomic richness
Authors: Veselkin D. V. , Dubrovin D. I. , Pustovalova L. A.
Published: October 2021

We assessed the link between canopy cover degree and ground vegetation taxonomic richness under alien ash-leaved maple (Acer negundo) and other (native or alien) tree species. We investigated urban and suburban forests in the large city of Yekaterinburg, Russia. Forests were evaluated on two spatial scales. Through an inter-habitat comparison we recorded canopy cover and plant taxonomic richness among 13 sample plots of 20 × 20 m where A.negundo dominated and 13 plots where other tree species dominated. In an intra-habitat comparison, we recorded canopy cover and ground vegetation taxonomic richness among 800 sample plots measuring 1 m2in the extended urbanised forest, which featured abundant alien (308 plots) and native trees (492 plots). We observed decreased taxonomic richness among vascular ground plant species by 40% (inter-habitat) and 20% (intra-habitat) in areas dominated byA. negundocompared to areas dominated by native tree and shrub species. An abundance of A. negundo was accompanied by increased canopy cover. We found a negative relationship between canopy cover and the number of understory herbaceous species. Thus, the interception of light and the restriction of its amount for other species is a main factor supporting the negative influence of A.negundo on native plant communities.
Interspecific variation in evaporative water loss and temperature response, but not metabolic rate, among hibernating bats
Authors: McGuire Liam P. , Fuller Nathan W. , Dzal Yvonne A. , Haase Catherine G. , Klüg-Baerwald Brandon J. , Silas Kirk A. , Plowright Raina K. , Lausen Cori L. , Willis Craig K. R. , Olson Sarah H.
Published: October 2021

Hibernation is widespread among mammals in a variety of environmental contexts. However, few experimental studies consider interspecific comparisons, which may provide insight into general patterns of hibernation strategies. We studied 13 species of free-living bats, including populations spread over thousands of kilometers and diverse habitats. We measured torpid metabolic rate (TMR) and evaporative water loss (two key parameters for understanding hibernation energetics) across a range of temperatures. There was no difference in minimum TMR among species (i.e., all species achieved similarly low torpid metabolic rate) but the temperature associated with minimum TMR varied among species. The minimum defended temperature (temperature below which TMR increased) varied from 8 °C to < 2 °C among species. Conversely, evaporative water loss varied among species, with species clustered in two groups representing high and low evaporative water loss. Notably, species that have suffered population declines due to white-nose syndrome fall in the high evaporative water loss group and less affected species in the low evaporative water loss group. Documenting general patterns of physiological diversity, and associated ecological implications, contributes to broader understanding of biodiversity, and may help predict which species are at greater risk of environmental and anthropogenic stressors.
Simple urine storage protocol for extracellular vesicle proteomics compatible with at-home self-sampling
Authors: Erozenci L. A. , Pham T. V. , Piersma S. R. , Dits N. F. J. , Jenster G. W. , van Royen M. E. , Moorselaar R. J. A. , Jimenez C. R. , Bijnsdorp I. V.
Published: October 2021

Urinary extracellular vesicles (EVs) have gained increased interest as a biomarker source. Clinical implementation on a daily basis requires protocols that inevitably includes short-term storage of the clinical samples, especially when collected at home. However, little is known about the effect of delayed processing on the urinary EVs concentration and proteome. We evaluated two storage protocols. First, urine stored at 4 °C. Secondly a protocol compatible with at-home collection, in which urine was stored with the preservative EDTA at room temperature (RT). EVs were isolated using the ME-kit (VN96-peptide). For both conditions we explored the effect of storage duration (0, 2, 4 and 8 days) on EV concentration and proteome using EVQuant and data-independent acquisition mass spectrometry, respectively. The urinary EV concentration and proteome was highly stable using both protocols, in terms of protein number and quantitative changes. Furthermore, EDTA does not affect the urinary EV concentration or global proteome. In conclusion, urine can be stored either at 4 °C or with EDTA at RT for up to 8 days without any significant decay in EV concentration or a notable effect on the EV-proteome. These findings open up biomarker studies in urine collected via self-sampling at home.
De novo electrocardiographic abnormalities in persons living with HIV
Authors: Knudsen Andreas D. , Graff Claus , Nielsen Jonas Bille , Thomsen Magda Teresa , Høgh Julie , Benfield Thomas , Gerstoft Jan , Køber Lars , Kofoed Klaus F. , Nielsen Susanne D.
Published: October 2021

Persons living with HIV (PLWH) may have increased incidence of cardiovascular events and longer QTc intervals than uninfected persons. We aimed to investigate the incidence and risk factors of de novo major electrocardiogram (ECG) abnormalities and QTc prolongation in well-treated PLWH. We included virologically suppressed PLWH without major ECG abnormalities, who attended the 2-year follow-up in the Copenhagen comorbidity in HIV infection (COCOMO) study. ECGs were categorized according to Minnesota Code Manual. We defined de novo major ECG abnormalities as new major Minnesota Code Manual abnormalities. Prolonged QTc was defined as QTc > 460 ms in females and QTc > 450 ms in males. Of 667 PLWH without major ECG abnormalities at baseline, 34 (5%) developed de novo major ECG abnormalities after a median of 2.3 years. After adjustment, age (RR: 1.57 [1.08–2.28] per decade older), being underweight (RR: 5.79 [1.70–19.71]), current smoking (RR: 2.34 [1.06–5.16]), diabetes (RR: 3.89 [1.72–8.80]) and protease inhibitor use (RR: 2.45 [1.27–4.74) were associated with higher risk of getting de novo major ECG abnormalities. Of PLWH without prolonged QTc at baseline, only 11 (1.6%) participants developed de novo prolonged QTc. Five percent of well-treated PLWH acquired de novo major ECG abnormalities and protease inhibitor use was associated with more than twice the risk of de novo major ECG abnormalities. De novo prolonged QTc was rare and did not seem to constitute a problem in well-treated PLWH.
Quantum chemical insight into the effects of the local electron environment on T2*-based MRI
Authors: Petronek M. S. , St-Aubin J. J. , Lee C. Y. , Spitz D. R. , Gillan E. G. , Allen B. G. , Magnotta V. A.
Published: October 2021

T2* relaxation is an intrinsic magnetic resonance imaging (MRI) parameter that is sensitive to local magnetic field inhomogeneities created by the deposition of endogenous paramagnetic material (e.g. iron). Recent studies suggest that T2* mapping is sensitive to iron oxidation state. In this study, we evaluate the spin state-dependence of T2* relaxation using T2* mapping. We experimentally tested this physical principle using a series of phantom experiments showing that T2* relaxation times are directly proportional to the spin magnetic moment of different transition metals along with their associated magnetic susceptibility. We previously showed that T2* relaxation time can detect the oxidation of Fe2+. In this paper, we demonstrate that T2* relaxation times are significantly longer for the diamagnetic, d10 metal Ga3+, compared to the paramagnetic, d5 metal Fe3+. We also show in a cell culture model that cells supplemented with Ga3+ (S = 0) have a significantly longer relaxation time compared to cells supplemented with Fe3+ (S = 5/2). These data support the hypothesis that dipole–dipole interactions between protons and electrons are driven by the strength of the electron spin magnetic moment in the surrounding environment giving rise to T2* relaxation.
Expectations of objective threats and aversive feelings in specific fears
Authors: Elsey James W. B. , Kindt Merel
Published: October 2021

Mistaken beliefs about danger posed by feared stimuli are considered a key factor causing and maintaining fears. Such beliefs are intriguing because many fearful people express them, but acknowledge they are untrue in reality. While previous research indicates fearful individuals may not wholly endorse their beliefs about objective threats (e.g., the spider will bite), expectations of negative subjective consequences (e.g., I will feel terrible) are also likely to be important. We investigated the extent to which participants’ expectations of objective and subjective threats were sensitive to manipulations that encouraged them to consider whether their expectations were likely to happen in reality. Across five online experiments (N = 560, or 727 with more liberal inclusion criteria), such manipulations produced lower expectancy ratings for objective but not subjective threats (versus participants who gave ratings without the manipulation). Most participants reported that anticipation of negative feelings was more concerning than actual danger. Hence, numerous fear-relevant expectations about objective threat—considered central in understanding why people are irrationally afraid—respond to small cognitive manipulations. Additionally, expectations of negative subjective experiences during fear-provoking encounters appear to be more consistently endorsed, and feature prominently in fearful individuals’ concerns about what will happen in a fear-relevant situation.
The nomogram based on the 6-lncRNA model can promote the prognosis prediction of patients with breast invasive carcinoma
Authors: Luo Dankun , Yao Wenchao , Wang Qiang , Yang Qiu , Liu Xuxu , Yang Yang , Zhang Weihui , Xue Dongbo , Ma Biao
Published: October 2021

Long non-coding RNA (lncRNA) is a prognostic biomarker for many types of cancer. Here, we aimed to study the prognostic value of lncRNA in Breast Invasive Carcinoma (BRCA). We downloaded expression profiles from The Cancer Genome Atlas (TCGA) datasets. Subsequently, we screened the differentially expressed genes between normal tissues and tumor tissues. Univariate Cox, LASSO regression, and multivariate Cox regression analysis were used to construct a lncRNA prognostic model. Finally, a nomogram based on the lncRNAs model was developed, and weighted gene co-expression network analysis (WGCNA) was used to predict mRNAs related to the model, and to perform function and pathway enrichment. We constructed a 6-lncRNA prognostic model. Univariate and multivariate Cox regression analysis showed that the 6-lncRNA model could be used as an independent prognostic factor for BRCA patients. We developed a nomogram based on the lncRNAs model and age, and showed good performance in predicting the survival rates of BRCA patients. Also, functional pathway enrichment analysis showed that genes related to the model were enriched in cell cycle-related pathways. Tumor immune infiltration analysis showed that the types of immune cells and their expression levels in the high-risk group were significantly different from those in the low-risk group. In general, the 6-lncRNA prognostic model and nomogram could be used as a practical and reliable prognostic tool for invasive breast cancer.
Shotgun-metagenomics based prediction of antibiotic resistance and virulence determinants in Staphylococcus aureus from periprosthetic tissue on blood culture bottles
Authors: Sanabria Adriana Maria , Janice Jessin , Hjerde Erik , Simonsen Gunnar Skov , Hanssen Anne-Merethe
Published: October 2021

Shotgun-metagenomics may give valuable clinical information beyond the detection of potential pathogen(s). Identification of antimicrobial resistance (AMR), virulence genes and typing directly from clinical samples has been limited due to challenges arising from incomplete genome coverage. We assessed the performance of shotgun-metagenomics on positive blood culture bottles (n = 19) with periprosthetic tissue for typing and prediction of AMR and virulence profiles in Staphylococcus aureus. We used different approaches to determine if sequence data from reads provides more information than from assembled contigs. Only 0.18% of total reads was derived from human DNA. Shotgun-metagenomics results and conventional method results were consistent in detecting S. aureus in all samples. AMR and known periprosthetic joint infection virulence genes were predicted from S. aureus. Mean coverage depth, when predicting AMR genes was 209 ×. Resistance phenotypes could be explained by genes predicted in the sample in most of the cases. The choice of bioinformatic data analysis approach clearly influenced the results, i.e. read-based analysis was more accurate for pathogen identification, while contigs seemed better for AMR profiling. Our study demonstrates high genome coverage and potential for typing and prediction of AMR and virulence profiles in S. aureus from shotgun-metagenomics data.
The technology of artificial pneumoperitoneum CT and its application in diagnosis of abdominal adhesion
Authors: Wang Gui-sheng , Zhang Zhi-yi , Qi Xue-ting , Liu Jin , Liu Ting , Zhao Jing-wei , Chen Xiao-xia , Chen Yi
Published: October 2021

To retrospectively analyze the use of artificial pneumoperitoneum in CT scans, to explore its operation methods and technical points, and to lay the foundation for the widespread application of artificial pneumoperitoneum in CT. A total of 331 patients who underwent artificial pneumoperitoneum with CT angiography from January 1, 2013, to November 1, 2019, were recruited. All patients underwent standardized artificial pneumoperitoneum in the horizontal, left and right lateral, and prone positions during CT thin-layer scans of the abdomen and 3D reconstruction. Taking the surgical results as the gold standard, and using kappa test to verify the consistency of surgical results and imaging results. In all 331 patients, 43 patients had a normal peritoneal space, and 288 patients had an abnormal peritoneal space. And only 22 patients developed complications of subcutaneous emphysema, accounting for 6.6% of all 331 patients. In terms of the postoperative results, 28 were normal, and 303 were abnormal. The sensitivity, specificity and accuracy of CT diagnosis of abdominal adhesions using artificial pneumoperitoneum were 100%, 95.04%, and 95.46%, respectively. According to the Kappa consistency test, the imaging diagnosis from the CT scan with artificial pneumoperitoneum had a high consistency with the surgical results (kappa = 0.796, P < 0.05). The technique of artificial pneumoperitoneum CT is safe, reliable, highly practical, and proficient for obtaining good imaging results. It provides a good imaging basis for the diagnosis of intra-abdominal diseases, especially intra-abdominal adhesions.
Expression of p53, p63, podoplanin and Ki-67 in recurring versus non-recurring oral leukoplakia
Authors: Sundberg Jonas , Pandey Sushma , Giglio Daniel , Holmberg Erik , Kjeller Göran , Kovács Anikó , Sand Lars Peter , Tokozlu Burcu , Öhman Jenny , Sapkota Dipak , Hasséus Bengt
Published: October 2021

Oral leukoplakia (OL), a potentially malignant disorder, recurs in 40% of cases after surgical removal. Recurrence is a risk factor for malignant transformation. We aimed to examine the prognostic significance of four biomarkers related to cell proliferation: p53, p63, podoplanin (PDPN) and Ki-67 in predicting recurrence. Formalin-fixed-paraffin-embedded specimens from excised OL (n = 73, 33 recurrent; 40 non-recurrent) were collected in a prospective study. Immunohistochemistry was used to visualise expression of p53, p63, PDPN and Ki-67. Image analysis software was used for quantification of p53-, p63- and Ki-67-expressing cells, while PDPN was analysed visually. The expression of all four proteins were higher in recurrent compared with non-recurrent OL, only expression of p53 was statistically significant. In uni- and multivariable Cox regression analyses of individual markers, expression of p63 was significantly associated with higher recurrence risk (p = 0.047). OL with a combined high expression of both p53 and p63 had a significantly higher risk to recur [Log Rank,p = 0.036; multivariate Cox, HR: 2.48 (1.13–5.44;p = 0.024)]. Combination of p53 and p63 expression may be used as a prognostic biomarker for recurrence of OL.
Short-term and long-term mate preference in men and women in an Iranian population
Authors: Mirfazeli Fatemeh Sadat , Lai Meng-Chuan , Memari Amirhossein , Rajab Armin , Shafizadeh Milad , Zarei Sahar , Shariat Seyed Vahid , Fashi Maryam Haghighi , Barzegary Ebrahim , Vahabie Abdol-Hossein
Published: October 2021

Mate preference in short-term relationships and long-term ones may depend on many physical, psychological, and socio-cultural factors. In this study, 178 students (81 females) in sports and 153 engineering students (64 females) answered the systemizing quotient (SQ) and empathizing quotient (EQ) questionnaires and had their digit ratio measured. They rated their preferred mate on 12 black-line drawing body figures varying in body mass index (BMI) and waist to hip ratio (WHR) for short-term and long-term relationships. Men relative to women preferred lower WHR and BMI for mate selection for both short-term and long-term relationships. BMI and WHR preference in men is independent of each other, but has a negative correlation in women. For men, digit ratio was inversely associated with BMI (p = 0.039, B = − 0.154) preference in a short-term relationship, and EQ was inversely associated with WHR preference in a long-term relationship (p = 0.045, B = − 0.164). Furthermore, men and women in sports, compared to engineering students, preferred higher (p = 0.009, B = 0.201) and lower BMI (p = 0.034, B = − 0.182) for short-term relationships, respectively. Women were more consistent in their preferences for short-term and long-term relationships relative to men. Both biological factors and social/experiential factors contribute to mate preferences in men while in women, mostly social/experiential factors contribute to them.
The associations between maternal BMI and gestational weight gain and health outcomes in offspring at age 1 and 7 years
Authors: Chiavaroli Valentina , Hopkins Sarah A. , Biggs Janene B. , Rodrigues Raquel O. , Seneviratne Sumudu N. , Baldi James C. , McCowan Lesley M. E. , Cutfield Wayne S. , Hofman Paul L. , Derraik José G. B.
Published: October 2021

In secondary analyses of a randomised controlled trial of exercise during pregnancy, we examined associations between mid-pregnancy maternal body mass index (BMI) and excessive gestational weight gain (GWG) with offspring health. Follow-up data were available on 57 mother–child pairs at 1-year and 52 pairs at 7-year follow-ups. Clinical assessments included body composition and fasting blood tests. At age 1 year, increased maternal BMI in mid-gestation was associated with greater weight standard deviation scores (SDS) in the offspring (p = 0.035), with no observed associations for excessive GWG. At age 7 years, greater maternal BMI was associated with increased weight SDS (p < 0.001), BMI SDS (p = 0.005), and total body fat percentage (p = 0.037) in their children. Irrespective of maternal BMI, children born to mothers with excessive GWG had greater abdominal adiposity (p = 0.043) and less favourable lipid profile (lower HDL-C and higher triglycerides). At 7 years, maternal BMI and excessive GWG had compounded adverse associations with offspring adiposity. Compared to offspring of mothers with overweight/obesity plus excessive GWG, children of normal-weight mothers with adequate and excessive GWG were 0.97 and 0.64 SDS lighter (p = 0.002 and p = 0.014, respectively), and 0.98 and 0.63 SDS leaner (p = 0.001 and p = 0.014, respectively). Both greater maternal BMI in mid-pregnancy and excessive GWG were independently associated with increased adiposity in offspring at 7 years.
Systematic characterization of human response to H1N1 influenza vaccination through the construction and integration of personalized transcriptome response profiles
Authors: De Intinis Carlo , Bodini Margherita , Maffione Denise , De Mot Laurane , Coccia Margherita , Medini Duccio , Siena Emilio
Published: October 2021

Gene expression data is commonly used in vaccine studies to characterize differences between treatment groups or sampling time points. Group-wise comparisons of the transcriptional perturbations induced by vaccination have been applied extensively for investigating the mechanisms of action of vaccines. Such approaches, however, may not be sensitive enough for detecting changes occurring within a minority of the population under investigation or in single individuals. In this study, we developed a data analysis framework to characterize individual subject response profiles in the context of repeated measure experiments, which are typical of vaccine mode of action studies. Following the definition of the methodology, this was applied to the analysis of human transcriptome responses induced by vaccination with a subunit influenza vaccine. Results highlighted a substantial heterogeneity in how different subjects respond to vaccination. Moreover, the extent of transcriptional modulation experienced by each individual subject was found to be associated with the magnitude of vaccine-specific functional antibody response, pointing to a mechanistic link between genes involved in protein production and innate antiviral response. Overall, we propose that the improved characterization of the intersubject heterogeneity, enabled by our approach, can help driving the improvement and optimization of current and next-generation vaccines.
Comparison of bacteria disintegration methods and their influence on data analysis in metabolomics
Authors: Mielko Karolina Anna , Jabłoński Sławomir Jan , Łukaszewicz Marcin , Młynarz Piotr
Published: October 2021

Metabolomic experiments usually contain many different steps, each of which can strongly influence the obtained results. In this work, metabolic analyses of six bacterial strains were performed in light of three different bacterial cell disintegration methods. Three strains were gram-negative (Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae), and three were gram-positive (Corynebacterium glutamicum, Bacillus cereus, and Enterococcus faecalis). For extraction, the methanol–water extraction method (1:1) was chosen. To compare the efficiency of different cell disintegration methods, sonication, sand mill, and tissue lyser were used. For bacterial extract metabolite analysis, 1H NMR together with univariate and multivariate analyses were applied. The obtained results showed that metabolite concentrations are strongly dependent on the cell lysing methodology used and are different for various bacterial strains. The results clearly show that one of the disruption methods gives the highest concentration for most identified compounds (e. g. sand mill for E. faecalis and tissue lyser for B. cereus). This study indicated that the comparison of samples prepared by different procedures can lead to false or imprecise results, leaving an imprint of the disintegration method. Furthermore, the presented results showed that NMR might be a useful bacterial strain identification and differentiation method. In addition to disintegration method comparison, the metabolic profiles of each elaborated strain were analyzed, and each exhibited its metabolic profile. Some metabolites were identified by the 1H NMR method in only one strain. The results of multivariate data analyses (PCA) show that regardless of the disintegration method used, the strain group can be identified. Presented results can be significant for all types of microbial studies containing the metabolomic targeted and non-targeted analysis.
Two-level modeling approach to identify the regulatory dynamics capturing drug response heterogeneity in single-cells
Authors: Chaves Madalena , Gomes-Pereira Luis C. , Roux Jérémie
Published: October 2021

Single-cell multimodal technologies reveal the scales of cellular heterogeneity impairing cancer treatment, yet cell response dynamics remain largely underused to decipher the mechanisms of drug resistance they take part in. As the phenotypic heterogeneity of a clonal cell population informs on the capacity of each single-cell to recapitulate the whole range of observed behaviors, we developed a modeling approach utilizing single-cell response data to identify regulatory reactions driving population heterogeneity in drug response. Dynamic data of hundreds of HeLa cells treated with TNF-related apoptosis-inducing ligand (TRAIL) were used to characterize the fate-determining kinetic parameters of an apoptosis receptor reaction model. Selected reactions sets were augmented to incorporate a mechanism that leads to the separation of the opposing response phenotypes. Using a positive feedback loop motif to identify the reaction set, we show that caspase-8 is able to encapsulate high levels of heterogeneity by introducing a response delay and amplifying the initial differences arising from natural protein expression variability. Our approach enables the identification of fate-determining reactions that drive the population response heterogeneity, providing regulatory targets to curb the cell dynamics of drug resistance.
Chemical hybridization of sulfasalazine and dihydroartemisinin promotes brain tumor cell death
Authors: Ackermann Annemarie , Çapcı Aysun , Buchfelder Michael , Tsogoeva Svetlana B. , Savaskan Nicolai
Published: October 2021

Gliomas are primary brain tumors with still poor prognosis for the patients despite a combination of cytoreduction via surgery followed by a radio-chemotherapy. One strategy to find effective treatment is to combine two different compounds in one hybrid molecule via linker to add to or at best potentiate their impact on malignant cells. Here, we report on the effects of a newly synthesized hybrid of sulfasalazine (SAS) and dihydroartemisinin (DHA), called AC254. In previous studies, both SAS and DHA have already proved to have anti-tumor properties themselves and to have sensitizing respectively potentiating effects on other treatments against malignant tumors. We investigated the impact of individual drugs SAS and DHA, their 1:1 combination and a novel SAS-DHA hybrid compound (AC254) on rodent and human glioma cells. In our study SAS alone showed no or only a mild effect on glioma, whereas DHA led to a significant reduction of cell viability in a dose-dependent manner. Next we compared the efficacy of the hybrid AC254 to the combinational treatment of its parent compounds SAS and DHA. The hybrid was highly efficient in combating glioma cells compared to single treatment strategies regarding cell viability and cell death. Interestingly, AC254 showed a remarkable advantage over the combinational treatment with both parent compounds in most used concentrations. In addition to its reduction of tumor cell viability and induction of cell death, the hybrid AC254 displayed changes in cell cycle and reduction of cell migration. Taken together, these results demonstrate that clinically established compounds such as SAS and DHA can be potentiated in their anti-cancer effects by chemical hybridization. Thus, this concept provides the opportunity to devise new effective chemotherapeutic agents.
Electrocorticography reveals thalamic control of cortical dynamics following traumatic brain injury
Authors: Mofakham Sima , Fry Adam , Adachi Joseph , Stefancin Patricia L. , Duong Tim Q. , Saadon Jordan R. , Winans Nathan J. , Sharma Himanshu , Feng Guanchao , Djuric Petar M. , Mikell Charles B.
Published: October 2021

The return of consciousness after traumatic brain injury (TBI) is associated with restoring complex cortical dynamics; however, it is unclear what interactions govern these complex dynamics. Here, we set out to uncover the mechanism underlying the return of consciousness by measuring local field potentials (LFP) using invasive electrophysiological recordings in patients recovering from TBI. We found that injury to the thalamus, and its efferent projections, on MRI were associated with repetitive and low complexity LFP signals from a highly structured phase space, resembling a low-dimensional ring attractor. But why do thalamic injuries in TBI patients result in a cortical attractor? We built a simplified thalamocortical model, which connotes that thalamic input facilitates the formation of cortical ensembles required for the return of cognitive function and the content of consciousness. These observations collectively support the view that thalamic input to the cortex enables rich cortical dynamics associated with consciousness.