bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex steroids receptors, hypertension, and vascular ageing
Authors: Connelly Paul J. , Casey Helen , Montezano Augusto C. , Touyz Rhian M. , Delles Christian 
Published: July 2021

AbstractSex hormone receptors are expressed throughout the vasculature and play an important role in the modulation of blood pressure in health and disease. The functions of these receptors may be important in the understanding of sexual dimorphism observed in the pathophysiology of both hypertension and vascular ageing. The interconnectivity of these factors can be exemplified in postmenopausal females, who with age and estrogen deprivation, surpass males with regard to hypertension prevalence, despite experiencing significantly less disease burden in their estrogen replete youth. Estrogen and androgen receptors mediate their actions via direct genomic effects or rapid non-genomic signaling, involving a host of mediators. The expression and subtype composition of these receptors changes through the lifespan in response to age, disease and hormonal exposure. These factors may promote sex steroid receptor-mediated alterations to the Renin–Angiotensin–Aldosterone System (RAAS), and increases in oxidative stress and inflammation, thereby contributing to the development of hypertension and vascular injury with age.
Effects of single family room architecture on parent–infant closeness and family centered care in neonatal environments—a single-center pre–post study
Authors: Kainiemi Emma , Hongisto Pilvi , Lehtonen Liisa , Pape Bernd , Axelin Anna 
Published: July 2021

AbstractObjectiveThe aim of this study was to evaluate the effects of a single family room architecture in a neonatal intensive care unit (SFR-NICU) on parents’ presence, parent–infant skin-to-skin contact (SSC) and the quality of family centered care.Study designTwo cohorts of parents of preterm infants were compared: those in the unit before and after the move to SFR-NICU. The parents used daily diaries to report their presence and SSC, and they responded to daily text message questions about the quality of family centered care.ResultsParents spent more time in the SFR-NICU, but no significant change was found in SSC. Parents rated the quality of family centered care highly in both unit architectures, without a change in rating after the move.ConclusionThe SFR-NICU increased parents’ presence but not SSC. The change in architecture did not affect parents’ evaluations of the quality of family centered care, which was already highly rated before the move.
Integration of genome-level data to allow identification of subtype-specific vulnerability genes as novel therapeutic targets
Authors: Schwalbe Edward C. , H Lalchungnunga , Lafta Fadhel , Barrow Timothy M. , Strathdee Gordon 
Published: July 2021

AbstractThe identification of cancer-specific vulnerability genes is one of the most promising approaches for developing more effective and less toxic cancer treatments. Cancer genomes exhibit thousands of changes in DNA methylation and gene expression, with the vast majority likely to be passenger changes. We hypothesised that, through integration of genome-wide DNA methylation/expression data, we could exploit this inherent variability to identify cancer subtype-specific vulnerability genes that would represent novel therapeutic targets that could allow cancer-specific cell killing. We developed a bioinformatics pipeline integrating genome-wide DNA methylation/gene expression data to identify candidate subtype-specific vulnerability partner genes for the genetic drivers of individual genetic/molecular subtypes. Using acute lymphoblastic leukaemia as an initial model, 21 candidate subtype-specific vulnerability genes were identified across the five common genetic subtypes, with at least one per subtype. To confirm the approach was applicable across cancer types, we also assessed medulloblastoma, identifying 15 candidate subtype-specific vulnerability genes across three of four established subtypes. Almost all identified genes had not previously been implicated in these diseases. Functional analysis of seven candidate subtype-specific vulnerability genes across the two tumour types confirmed that siRNA-mediated knockdown induced significant inhibition of proliferation/induction of apoptosis, which was specific to the cancer subtype in which the gene was predicted to be specifically lethal. Thus, we present a novel approach that integrates genome-wide DNA methylation/expression data to identify cancer subtype-specific vulnerability genes as novel therapeutic targets. We demonstrate this approach is applicable to multiple cancer types and identifies true functional subtype-specific vulnerability genes with high efficiency.
Applicability of liquid biopsies to represent the mutational profile of tumor tissue from different cancer entities
Authors: Liebs Sandra , Eder Theresa , Klauschen Frederick , Schütte Moritz , Yaspo Marie-Laure , Keilholz Ulrich , Tinhofer Ingeborg , Kidess-Sigal Evelyn , Braunholz Diana 
Published: July 2021

AbstractGenetic investigation of tumor heterogeneity and clonal evolution in solid cancers could be assisted by the analysis of liquid biopsies. However, tumors of various entities might release different quantities of circulating tumor cells (CTCs) and cell-free DNA (cfDNA) into the bloodstream, potentially limiting the diagnostic potential of liquid biopsy in distinct tumor histologies. Patients with advanced colorectal cancer (CRC), head and neck squamous cell carcinoma (HNSCC), and melanoma (MEL) were enrolled in the study, representing tumors with different metastatic patterns. Mutation profiles of cfDNA, CTCs, and tumor tissue were assessed by panel sequencing, targeting 327 cancer-related genes. In total, 30 tissue, 18 cfDNA, and 7 CTC samples from 18 patients were sequenced. Best concordance between the mutation profile of tissue and cfDNA was achieved in CRC and MEL, possibly due to the remarkable heterogeneity of HNSCC (63%, 55% and 11%, respectively). Concordance especially depended on the amount of cfDNA used for library preparation. While 21 of 27 (78%) tissue mutations were retrieved in high-input cfDNA samples (30–100 ng, N = 8), only 4 of 65 (6%) could be detected in low-input samples (<30 ng, N = 10). CTCs were detected in 13 of 18 patients (72%). However, downstream analysis was limited by poor DNA quality, allowing targeted sequencing of only seven CTC samples isolated from four patients. Only one CTC sample reflected the mutation profile of the respective tumor. Private mutations, which were detected in CTCs but not in tissue, suggested the presence of rare subclones. Our pilot study demonstrated superiority of cfDNA- compared to CTC-based mutation profiling. It was further shown that CTCs may serve as additional means to detect rare subclones possibly involved in treatment resistance. Both findings require validation in a larger patient cohort.
Cancer detection rates of the PI-RADSv2.1 assessment categories: systematic review and meta-analysis on lesion level and patient level
Authors: Oerther Benedict , Engel Hannes , Bamberg Fabian , Sigle August , Gratzke Christian , Benndorf Matthias 
Published: July 2021

Abstract
Background
The Prostate Imaging Reporting and Data System, version 2.1 (PI-RADSv2.1) standardizes reporting of multiparametric MRI of the prostate. Assigned assessment categories are a risk stratification algorithm, higher categories indicate a higher probability of clinically significant cancer compared to lower categories. PI-RADSv2.1 does not define these probabilities numerically. We conduct a systematic review and meta-analysis to determine the cancer detection rates (CDR) of the PI-RADSv2.1 assessment categories on lesion level and patient level.

Methods
Two independent reviewers screen a systematic PubMed and Cochrane CENTRAL search for relevant articles (primary outcome: clinically significant cancer, index test: prostate MRI reading according to PI-RADSv2.1, reference standard: histopathology). We perform meta-analyses of proportions with random-effects models for the CDR of the PI-RADSv2.1 assessment categories for clinically significant cancer. We perform subgroup analysis according to lesion localization to test for differences of CDR between peripheral zone lesions and transition zone lesions.

Results
A total of 17 articles meet the inclusion criteria and data is independently extracted by two reviewers. Lesion level analysis includes 1946 lesions, patient level analysis includes 1268 patients. On lesion level analysis, CDR are 2% (95% confidence interval: 0–8%) for PI-RADS 1, 4% (1–9%) for PI-RADS 2, 20% (13–27%) for PI-RADS 3, 52% (43–61%) for PI-RADS 4, 89% (76–97%) for PI-RADS 5. On patient level analysis, CDR are 6% (0–20%) for PI-RADS 1, 9% (5–13%) for PI-RADS 2, 16% (7–27%) for PI-RADS 3, 59% (39–78%) for PI-RADS 4, 85% (73–94%) for PI-RADS 5. Higher categories are significantly associated with higher CDR (P < 0.001, univariate meta-regression), no systematic difference of CDR between peripheral zone lesions and transition zone lesions is identified in subgroup analysis.

Conclusions
Our estimates of CDR demonstrate that PI-RADSv2.1 stratifies lesions and patients as intended. Our results might serve as an initial evidence base to discuss management strategies linked to assessment categories.
Resistance to immune checkpoint inhibitors in advanced gastro-oesophageal cancers
Authors: Baxter Mark A. , Middleton Fearghas , Cagney Hannah P. , Petty Russell D. 
Published: July 2021

AbstractImmune checkpoint inhibitors (ICIs) have altered the treatment paradigm across a range of tumour types, including gastro-oesophageal cancers. For patients with any cancer type who respond, ICIs can confer long-term disease control and significantly improve survival and quality of life, but for patients with gastro-oesophageal cancer, ICIs can be transformative, as durable responses in advanced disease have hitherto been rare, especially in those patients who are resistant to first-line cytotoxic therapies. Results from trials in patients with advanced-stage gastro-oesophageal cancer have raised hopes that ICIs will be successful as adjuvant and neoadjuvant treatments in early-stage disease, when the majority of patients relapse after potential curative treatments, and several trials are ongoing. Unfortunately, however, ICI-responding patients appear to constitute a minority subgroup within gastro-oesophageal cancer, and resistance to ICI therapy (whether primary or acquired) is common. Understanding the biological mechanisms of ICI resistance is a current major research challenge and involves investigation of both tumour and patient-specific factors. In this review, we discuss the mechanisms underlying ICI resistance and their potential specific applications of this knowledge towards precision medicine strategies in the management of gastro-oesophageal cancers in clinical practice.
Prolonged SARS-CoV-2 RNA virus shedding and lymphopenia are hallmarks of COVID-19 in cancer patients with poor prognosis
Authors: Goubet Anne-Gaëlle , Dubuisson Agathe , Geraud Arthur , Danlos François-Xavier , Terrisse Safae , Silva Carolina Alves Costa , Drubay Damien , Touri Lea , Picard Marion , Mazzenga Marine , Silvin Aymeric , Dunsmore Garett , Haddad Yacine , Pizzato Eugenie , Ly Pierre , Flament Caroline , Melenotte Cléa , Solary Eric , Fontenay Michaela , Garcia Gabriel , Balleyguier Corinne , Lassau Nathalie , Maeurer Markus , Grajeda-Iglesias Claudia , Nirmalathasan Nitharsshini , Aprahamian Fanny , Durand Sylvère , Kepp Oliver , Ferrere Gladys , Thelemaque Cassandra , Lahmar Imran , Fahrner Jean-Eudes , Meziani Lydia , Ahmed-Belkacem Abdelhakim , Saïdani Nadia , La Scola Bernard , Raoult Didier , Gentile Stéphanie , Cortaredona Sébastien , Ippolito Giuseppe , Lelouvier Benjamin , Roulet Alain , Andre Fabrice , Barlesi Fabrice , Soria Jean-Charles , Pradon Caroline , Gallois Emmanuelle , Pommeret Fanny , Colomba Emeline , Ginhoux Florent , Kazandjian Suzanne , Elkrief Arielle , Routy Bertrand , Miyara Makoto , Gorochov Guy , Deutsch Eric , Albiges Laurence , Stoclin Annabelle , Gachot Bertrand , Florin Anne , Merad Mansouria , Scotte Florian , Assaad Souad , Kroemer Guido , Blay Jean-Yves , Marabelle Aurélien , Griscelli Frank , Zitvogel Laurence , Derosa Lisa 
Published: July 2021

AbstractPatients with cancer are at higher risk of severe coronavirus infectious disease 2019 (COVID-19), but the mechanisms underlying virus–host interactions during cancer therapies remain elusive. When comparing nasopharyngeal swabs from cancer and noncancer patients for RT-qPCR cycle thresholds measuring acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in 1063 patients (58% with cancer), we found that malignant disease favors the magnitude and duration of viral RNA shedding concomitant with prolonged serum elevations of type 1 IFN that anticorrelated with anti-RBD IgG antibodies. Cancer patients with a prolonged SARS-CoV-2 RNA detection exhibited the typical immunopathology of severe COVID-19 at the early phase of infection including circulation of immature neutrophils, depletion of nonconventional monocytes, and a general lymphopenia that, however, was accompanied by a rise in plasmablasts, activated follicular T-helper cells, and non-naive Granzyme B+FasL+, EomeshighTCF-1high, PD-1+CD8+ Tc1 cells. Virus-induced lymphopenia worsened cancer-associated lymphocyte loss, and low lymphocyte counts correlated with chronic SARS-CoV-2 RNA shedding, COVID-19 severity, and a higher risk of cancer-related death in the first and second surge of the pandemic. Lymphocyte loss correlated with significant changes in metabolites from the polyamine and biliary salt pathways as well as increased blood DNA from Enterobacteriaceae and Micrococcaceae gut family members in long-term viral carriers. We surmise that cancer therapies may exacerbate the paradoxical association between lymphopenia and COVID-19-related immunopathology, and that the prevention of COVID-19-induced lymphocyte loss may reduce cancer-associated death.
Ten-year panel data confirm generation gap but climate beliefs increase at similar rates across ages
Authors: Milfont Taciano L. , Zubielevitch Elena , Milojev Petar , Sibley Chris G. 
Published: July 2021

AbstractAccumulating evidence indicates that climate change awareness and concern has increased globally, but commentators suggest a climate change generation gap whereby younger people care more about climate change than older people. Here we use a decade of panel data from 56,513 New Zealanders to test whether belief that “Climate change is real” and “Climate change is caused by humans” increased over the 2009-2018 period; and whether changes are uniform across 12 five-year birth cohorts spanning those born from 1936 to 1995. Results confirm a generation gap in mean (intercept) climate change beliefs but not in over-time increase (slope). The generation gap occurs because older cohorts started from a lower initial belief level (circa 2009), but all age cohorts increased their belief level at a similar rate over the last decade; and these results were not qualified by respondents’ gender. The findings offer hope for collective action that bridges efforts across generations.
Global distribution patterns of marine nitrogen-fixers by imaging and molecular methods
Authors: Pierella Karlusich Juan José , Pelletier Eric , Lombard Fabien , Carsique Madeline , Dvorak Etienne , Colin Sébastien , Picheral Marc , Cornejo-Castillo Francisco M. , Acinas Silvia G. , Pepperkok Rainer , Karsenti Eric , de Vargas Colomban , Wincker Patrick , Bowler Chris , Foster Rachel A. 
Published: July 2021

AbstractNitrogen fixation has a critical role in marine primary production, yet our understanding of marine nitrogen-fixers (diazotrophs) is hindered by limited observations. Here, we report a quantitative image analysis pipeline combined with mapping of molecular markers for mining >2,000,000 images and >1300 metagenomes from surface, deep chlorophyll maximum and mesopelagic seawater samples across 6 size fractions (<0.2–2000 μm). We use this approach to characterise the diversity, abundance, biovolume and distribution of symbiotic, colony-forming and particle-associated diazotrophs at a global scale. We show that imaging and PCR-free molecular data are congruent. Sequence reads indicate diazotrophs are detected from the ultrasmall bacterioplankton (<0.2 μm) to mesoplankton (180–2000 μm) communities, while images predict numerous symbiotic and colony-forming diazotrophs (>20 µm). Using imaging and molecular data, we estimate that polyploidy can substantially affect gene abundances of symbiotic versus colony-forming diazotrophs. Our results support the canonical view that larger diazotrophs (>10 μm) dominate the tropical belts, while unicellular cyanobacterial and non-cyanobacterial diazotrophs are globally distributed in surface and mesopelagic layers. We describe co-occurring diazotrophic lineages of different lifestyles and identify high-density regions of diazotrophs in the global ocean. Overall, we provide an update of marine diazotroph biogeographical diversity and present a new bioimaging-bioinformatic workflow.
Majorana zero modes in impurity-assisted vortex of LiFeAs superconductor
Authors: Kong Lingyuan , Cao Lu , Zhu Shiyu , Papaj Michał , Dai Guangyang , Li Geng , Fan Peng , Liu Wenyao , Yang Fazhi , Wang Xiancheng , Du Shixuan , Jin Changqing , Fu Liang , Gao Hong-Jun , Ding Hong 
Published: July 2021

AbstractThe iron-based superconductor is emerging as a promising platform for Majorana zero mode, which can be used to implement topological quantum computation. One of the most significant advances of this platform is the appearance of large vortex level spacing that strongly protects Majorana zero mode from other low-lying quasiparticles. Despite the advantages in the context of physics research, the inhomogeneity of various aspects hampers the practical construction of topological qubits in the compounds studied so far. Here we show that the stoichiometric superconductor LiFeAs is a good candidate to overcome this obstacle. By using scanning tunneling microscopy, we discover that the Majorana zero modes, which are absent on the natural clean surface, can appear in vortices influenced by native impurities. Our detailed analysis reveals a new mechanism for the emergence of those Majorana zero modes, i.e. native tuning of bulk Dirac fermions. The discovery of Majorana zero modes in this homogeneous material, with a promise of tunability, offers an ideal material platform for manipulating and braiding Majorana zero modes, pushing one step forward towards topological quantum computation.
EZH2-induced lysine K362 methylation enhances TMPRSS2-ERG oncogenic activity in prostate cancer
Authors: Zoma Marita , Curti Laura , Shinde Dheeraj , Albino Domenico , Mitra Abhishek , Sgrignani Jacopo , Mapelli Sarah N. , Sandrini Giada , Civenni Gianluca , Merulla Jessica , Chiorino Giovanna , Kunderfranco Paolo , Cacciatore Alessia , Kokanovic Aleksandra , Rinaldi Andrea , Cavalli Andrea , Catapano Carlo V. , Carbone Giuseppina M. 
Published: July 2021

AbstractThe TMPRSS2-ERG gene fusion is the most frequent alteration observed in human prostate cancer. However, its role in disease progression is still unclear. In this study, we uncover an important mechanism promoting ERG oncogenic activity. We show that ERG is methylated by Enhancer of zest homolog 2 (EZH2) at a specific lysine residue (K362) located within the internal auto-inhibitory domain. Mechanistically, K362 methylation modifies intra-domain interactions, favors DNA binding and enhances ERG transcriptional activity. In a genetically engineered mouse model of ERG fusion-positive prostate cancer (Pb-Cre4 Ptenflox/floxRosa26-ERG, ERG/PTEN), ERG K362 methylation is associated with PTEN loss and progression to invasive adenocarcinomas. In both ERG positive VCaP cells and ERG/PTEN mice, PTEN loss results in AKT activation and EZH2 phosphorylation at serine 21 that favors ERG methylation. We find that ERG and EZH2 interact and co-occupy several sites in the genome forming trans-activating complexes. Consistently, ERG/EZH2 co-regulated target genes are deregulated preferentially in tumors with concomitant ERG gain and PTEN loss and in castration-resistant prostate cancers. Collectively, these findings identify ERG methylation as a post-translational modification sustaining disease progression in ERG-positive prostate cancers.
High spatiotemporal resolution optoacoustic sensing with photothermally induced acoustic vibrations in optical fibres
Authors: Liang Yizhi , Sun Huojiao , Cheng Linghao , Jin Long , Guan Bai-Ou 
Published: July 2021

AbstractOptoacoustic vibrations in optical fibres have enabled spatially resolved sensing, but the weak electrostrictive force hinders their application. Here, we introduce photothermally induced acoustic vibrations (PTAVs) to realize high-performance fibre-based optoacoustic sensing. Strong acoustic vibrations with a wide range of axial wavenumbers kz are photothermally actuated by using a focused pulsed laser. The local transverse resonant frequency and loss coefficient can be optically measured by an intra-core acoustic sensor via spectral analysis. Spatially resolved sensing is further achieved by mechanically scanning the laser spot. The experimental results show that the PTAVs can be used to resolve the acoustic impedance of the surrounding fluid at a spatial resolution of approximately 10 μm and a frame rate of 50 Hz. As a result, PTAV-based optoacoustic sensing can provide label-free visualization of the diffusion dynamics in microfluidics at a higher spatiotemporal resolution.
Coordination of endothelial cell positioning and fate specification by the epicardium
Authors: Quijada Pearl , Trembley Michael A. , Misra Adwiteeya , Myers Jacquelyn A. , Baker Cameron D. , Pérez-Hernández Marta , Myers Jason R. , Dirkx Ronald A. , Cohen Ethan David , Delmar Mario , Ashton John M. , Small Eric M. 
Published: July 2021

AbstractThe organization of an integrated coronary vasculature requires the specification of immature endothelial cells (ECs) into arterial and venous fates based on their localization within the heart. It remains unclear how spatial information controls EC identity and behavior. Here we use single-cell RNA sequencing at key developmental timepoints to interrogate cellular contributions to coronary vessel patterning and maturation. We perform transcriptional profiling to define a heterogenous population of epicardium-derived cells (EPDCs) that express unique chemokine signatures. We identify a population of Slit2+ EPDCs that emerge following epithelial-to-mesenchymal transition (EMT), which we term vascular guidepost cells. We show that the expression of guidepost-derived chemokines such as Slit2 are induced in epicardial cells undergoing EMT, while mesothelium-derived chemokines are silenced. We demonstrate that epicardium-specific deletion of myocardin-related transcription factors in mouse embryos disrupts the expression of key guidance cues and alters EPDC-EC signaling, leading to the persistence of an immature angiogenic EC identity and inappropriate accumulation of ECs on the epicardial surface. Our study suggests that EC pathfinding and fate specification is controlled by a common mechanism and guided by paracrine signaling from EPDCs linking epicardial EMT to EC localization and fate specification in the developing heart.