bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive analysis of the 21-gene recurrence score in invasive ductal breast carcinoma with or without ductal carcinoma in situ component
Authors: Zeng Yufei , Gao Weiqi , Chen Xiaosong , Shen Kunwei 
Published: December 2020

Abstract
Background
Invasive ductal carcinoma (IDC) is often accompanied by ductal carcinoma in situ (DCIS). Whether the DCIS component affects the 21-gene recurrence score (RS) is unclear.

Methods
Consecutive ER-positive, HER2-negative, N0–1 patients with RS results were included. Patients were divided into pure IDC and IDC with DCIS (IDC/DCIS) groups. The RS, the expression of its 16 cancer genes and prognosis were compared between IDC and IDC/DCIS patients.

Results
A total of 1458 patients were enrolled, 320 of whom had concomitant DCIS. DCIS component was independently associated with lower RS (P = 0.038). IDC/DCIS patients more often had a low-risk RS (P = 0.018) or intermediate-risk RS (P = 0.024). Regarding individual genes in the RS panel, Ki67, CCNB1 and MYBL2 in the proliferation group and MMP11 and CTSL2 in the invasion group were significantly lower among IDC/DCIS patients than pure IDC patients. Among IDC/DCIS patients, lower RS was independently correlated with a higher DCIS proportion and lower DCIS grade. Within a median follow-up of 31 months, the DCIS component in IDC did not significantly influence prognosis.

Conclusions
IDC with DCIS component is associated with a lower 21-gene RS, possibly due to lower expression of proliferation and invasion genes. DCIS proportion and grade independently influenced the 21-gene RS in IDC/DCIS patients. Due to the relatively short follow-up period and low recurrence rate, the impact of the DCIS component in IDC on prognosis needs further evaluation.
Ferroptotic pores induce Ca2+ fluxes and ESCRT-III activation to modulate cell death kinetics
Authors: Pedrera Lohans , Espiritu Rafael A. , Ros Uris , Weber Josephine , Schmitt Anja , Stroh Jenny , Hailfinger Stephan , von Karstedt Silvia , García-Sáez Ana J. 
Published: December 2020

AbstractFerroptosis is an iron-dependent form of regulated necrosis associated with lipid peroxidation. Despite its key role in the inflammatory outcome of ferroptosis, little is known about the molecular events leading to the disruption of the plasma membrane during this type of cell death. Here we show that a sustained increase in cytosolic Ca2+ is a hallmark of ferroptosis that precedes complete bursting of the cell. We report that plasma membrane damage leading to ferroptosis is associated with membrane nanopores of a few nanometers in radius and that ferroptosis, but not lipid peroxidation, can be delayed by osmoprotectants. Importantly, Ca2+ fluxes during ferroptosis induce the activation of the ESCRT-III-dependent membrane repair machinery, which counterbalances the kinetics of cell death and modulates the immunological signature of ferroptosis. Our findings with ferroptosis provide a unifying concept that sustained increase of cytosolic Ca2+ prior to plasma membrane rupture is a common feature of regulated types of necrosis and position ESCRT-III activation as a general protective mechanism in these lytic cell death pathways.
ER-mitochondria contact sites in neurodegeneration: genetic screening approaches to investigate novel disease mechanisms
Authors: Wilson Emma Louise , Metzakopian Emmanouil 
Published: December 2020

AbstractMitochondria-ER contact sites (MERCS) are known to underpin many important cellular homoeostatic functions, including mitochondrial quality control, lipid metabolism, calcium homoeostasis, the unfolded protein response and ER stress. These functions are known to be dysregulated in neurodegenerative diseases, including Parkinson’s disease (PD), Alzheimer’s disease (AD) and amyloid lateral sclerosis (ALS), and the number of disease-related proteins and genes being associated with MERCS is increasing. However, many details regarding MERCS and their role in neurodegenerative diseases remain unknown. In this review, we aim to summarise the current knowledge regarding the structure and function of MERCS, and to update the field on current research in PD, AD and ALS. Furthermore, we will evaluate high-throughput screening techniques, including RNAi vs CRISPR/Cas9, pooled vs arrayed formats and how these could be combined with current techniques to visualise MERCS. We will consider the advantages and disadvantages of each technique and how it can be utilised to uncover novel protein pathways involved in MERCS dysfunction in neurodegenerative diseases.
Reviving lower body negative pressure as a countermeasure to prevent pathological vascular and ocular changes in microgravity
Authors: Harris Katie M. , Petersen Lonnie G. , Weber Tobias 
Published: December 2020

AbstractMitigation of spaceflight-related pathologies such as spaceflight-associated neuro-ocular syndrome (SANS) and the recently discovered risk of venous thrombosis must happen before deep space exploration can occur. Lower body negative pressure (LBNP) can simulate gravitational stress during spaceflight that is likely to counteract SANS and venous thrombosis, but the ideal dose and method of delivery have yet to be determined. We undertook a review of current LBNP literature and conducted a gap analysis to determine the steps needed to adapt LBNP for in-flight use. We found that to use LBNP in flight, it must be adapted to long time duration/low pressure use that should be compatible with crew activities. A lack of understanding of the etiology of the pathologies that LBNP can counteract hinders the application of LBNP as a countermeasure during spaceflight. Future research should aim at filling the knowledge gaps outlined in this review.
CREAM, a component level coffeemaker electrical activity measurement dataset
Authors: Jorde Daniel , Kriechbaumer Thomas , Berger Tim , Zitzlsperger Stefan , Jacobsen Hans-Arno 
Published: December 2020

AbstractMonitoring the internal conditions of a machine is essential to increase its production efficiency and to reduce energy waste. Non-intrusive condition monitoring techniques, such as analysing electrical signals, provide insights by disaggregating a composite signal of a machine as a whole into the individual components to determine their states. Developing and evaluating new algorithms for condition monitoring and maintenance-related analysis tasks require a fully-labelled dataset for a machine, which comprises standard industrial components that are triggered following a typical manufacturing process to produce goods. For this purpose, we introduce CREAM, a component level electrical measurement dataset for two industrial-grade coffeemakers, simulating industrial processes. The dataset contains continuous voltage and current measurements provided at 6400 samples per second, as well as the product and maintenance-related event labels, such as 370600 expert-labelled component-level electrical events, 1734 product ones and 3646 maintenance ones. CREAM provides fully-labelled ground-truth to establish a benchmark and comparative studies of manufacturing-related analysis in a controlled and transparent environment.
New glacier evidence for ice-free summits during the life of the Tyrolean Iceman
Authors: Bohleber Pascal , Schwikowski Margit , Stocker-Waldhuber Martin , Fang Ling , Fischer Andrea 
Published: December 2020

AbstractDetailed knowledge of Holocene climate and glaciers dynamics is essential for sustainable development in warming mountain regions. Yet information about Holocene glacier coverage in the Alps before the Little Ice Age stems mostly from studying advances of glacier tongues at lower elevations. Here we present a new approach to reconstructing past glacier low stands and ice-free conditions by assessing and dating the oldest ice preserved at high elevations. A previously unexplored ice dome at Weißseespitze summit (3500 m), near where the “Tyrolean Iceman” was found, offers almost ideal conditions for preserving the original ice formed at the site. The glaciological settings and state-of-the-art micro-radiocarbon age constraints indicate that the summit has been glaciated for about 5900 years. In combination with known maximum ages of other high Alpine glaciers, we present evidence for an elevation gradient of neoglaciation onset. It reveals that in the Alps only the highest elevation sites remained ice-covered throughout the Holocene. Just before the life of the Iceman, high Alpine summits were emerging from nearly ice-free conditions, during the start of a Mid-Holocene neoglaciation. We demonstrate that, under specific circumstances, the old ice at the base of high Alpine glaciers is a sensitive archive of glacier change. However, under current melt rates the archive at Weißseespitze and at similar locations will be lost within the next two decades.
A systematic review and meta-analysis on chloroquine and hydroxychloroquine as monotherapy or combined with azithromycin in COVID-19 treatment
Authors: Ghazy Ramy Mohamed , Almaghraby Abdallah , Shaaban Ramy , Kamal Ahmed , Beshir Hatem , Moursi Amr , Ramadan Ahmed , Taha Sarah Hamed N. 
Published: December 2020

AbstractMany recent studies have investigated the role of either Chloroquine (CQ) or Hydroxychloroquine (HCQ) alone or in combination with azithromycin (AZM) in the management of the emerging coronavirus. This systematic review and meta-analysis of either published or preprint observational studies or randomized control trials (RCT) aimed to assess mortality rate, duration of hospital stay, need for mechanical ventilation (MV), virologic cure rate (VQR), time to a negative viral polymerase chain reaction (PCR), radiological progression, experiencing drug side effects, and clinical worsening. A search of the online database through June 2020 was performed and examined the reference lists of pertinent articles for in-vivo studies only. Pooled relative risks (RRs), standard mean differences of 95% confidence intervals (CIs) were calculated with the random-effects model. Mortality was not different between the standard care (SC) and HCQ groups (RR = 0.99, 95% CI 0.61–1.59, I2 = 82%), meta-regression analysis proved that mortality was significantly different across the studies from different countries. However, mortality among the HCQ + AZM was significantly higher than among the SC (RR = 1.8, 95% CI 1.19–2.27, I2 = 70%). The duration of hospital stay in days was shorter in the SC in comparison with the HCQ group (standard mean difference = 0.57, 95% CI 0.20–0.94, I2 = 92%), or the HCQ + AZM (standard mean difference = 0.77, 95% CI 0.46–1.08, I2 = 81). Overall VQR, and that at days 4, 10, and 14 among patients exposed to HCQ did not differ significantly from the SC [(RR = 0.92, 95% CI 0.69–1.23, I2 = 67%), (RR = 1.11, 95% CI 0.26–4.69, I2 = 85%), (RR = 1.21, 95% CI 0.70–2.01, I2 = 95%), and (RR = 0.98, 95% CI 0.76–1.27, I2 = 85% )] respectively. Exposure to HCQ + AZM did not improve the VQR as well (RR = 3.23, 95% CI 0.70–14.97, I2 = 58%). The need for MV was not significantly different between the SC and HCQ (RR = 1.5, 95% CI 0.78–2.89, I2 = 81%), or HCQ + AZM (RR = 1.27, 95% CI 0.7–2.13, I2 = 88%). Side effects were more reported in the HCQ group than in the SC (RR = 3.14, 95% CI 1.58–6.24, I2 = 0). Radiological improvement and clinical worsening were not statistically different between HCQ and SC [(RR = 1.11, 95% CI 0.74–1.65, I2 = 45%) and (RR = 1.28, 95% CI 0.33–4.99), I2 = 54%] respectively. Despite the scarcity of published data of good quality, the effectiveness and safety of either HCQ alone or in combination with AZM in treating COVID-19 cannot be assured. Future high-quality RCTs need to be carried out.PROSPERO registration: CRD42020192084.
Biological and physical approaches on the role of piplartine (piperlongumine) in cancer
Authors: Henrique Tiago , Zanon Caroline de F. , Girol Ana P. , Stefanini Ana Carolina Buzzo , Contessoto Nayara S. de A. , da Silveira Nelson J. F. , Bezerra Daniel P. , Silveira Edilberto R. , Barbosa-Filho José M. , Cornélio Marinonio L. , Oliani Sonia M. , Tajara Eloiza H. 
Published: December 2020

AbstractChronic inflammation provides a favorable microenvironment for tumorigenesis, which opens opportunities for targeting cancer development and progression. Piplartine (PL) is a biologically active alkaloid from long peppers that exhibits anti-inflammatory and antitumor activity. In the present study, we investigated the physical and chemical interactions of PL with anti-inflammatory compounds and their effects on cell proliferation and migration and on the gene expression of inflammatory mediators. Molecular docking data and physicochemical analysis suggested that PL shows potential interactions with a peptide of annexin A1 (ANXA1), an endogenous anti-inflammatory mediator with therapeutic potential in cancer. Treatment of neoplastic cells with PL alone or with annexin A1 mimic peptide reduced cell proliferation and viability and modulated the expression of MCP-1 chemokine, IL-8 cytokine and genes involved in inflammatory processes. The results also suggested an inhibitory effect of PL on tubulin expression. In addition, PL apparently had no influence on cell migration and invasion at the concentration tested. Considering the role of inflammation in the context of promoting tumor initiation, the present study shows the potential of piplartine as a therapeutic immunomodulator for cancer prevention and progression.
A 10-year follow-up of infliximab monotherapy for refractory uveitis in Behçet’s syndrome
Authors: Horiguchi Noe , Kamoi Koju , Horie Shintaro , Iwasaki Yuko , Kurozumi-Karube Hisako , Takase Hiroshi , Ohno-Matsui Kyoko 
Published: December 2020

AbstractInfliximab (IFX) was the first biologic introduced for refractory uveitis treatment in Behçet’s syndrome (BS). However, there have been few reports on the safety and efficacy of IFX monotherapy over follow-up periods of more than 10 years. This retrospective study evaluated the 10-year safety and efficacy of IFX monotherapy compared to IFX combination therapies with colchicine or corticosteroid for refractory uveitis in BS patients. Monotherapy was performed in 30 eyes of 16 patients while combination therapies were performed in 20 eyes of 11 patients. Continuation of IFX occurred in 70.3% of enrolled patients for 10 years without any significant difference noted in the retention rate between the monotherapy and combination therapies (p = 0.86). Reduction of ocular inflammatory attacks and improvement of best corrected visual acuity occurred in the monotherapy group after 10 years, which was equivalent to that for the combination therapies. Although adverse events (AEs) or therapy discontinuation occurred during the initial 5 years in both therapies, no AEs were observed for either therapy after 6 years. Our results suggested that IFX monotherapy proved to be effective and not inferior to combination therapies over a 10-year follow-up. Although loss of response and AEs may be noticed during the initial 5-year period, a safe and effective continuation can be expected thereafter.
Oral health and functional capacity of centenarians
Authors: Sekundo Caroline , Langowski Eva , Kilian Samuel , Frese Cornelia 
Published: December 2020

AbstractThe number of very old individuals, namely centenarians, is growing fast. In dentistry, the increasing number of older adults retaining natural teeth present new challenges for preventive and restorative dental care. However, there is a considerable lack of knowledge on the oral health status and needs in this exceptional age group. The aim of this population-based study was to identify the prevalence of oral diseases, therapeutic needs and functional capacity (evaluating centenarians’ autonomy and their capabilities regarding treatment and oral hygiene) in centenarians. Subjects born before 1920 were recruited from population registries in South-Western Germany, providing information on dental health experiences, oral health behaviors and undergoing dental examination. 55 centenarians participated in the study (mean age ± SD = 101.2 ± 1.6, 83.6% females). Results were compared to epidemiological data on adults aged 75–100 years examined in the Fifth German Oral Health Study. Adherence to recommended dental behaviors and dental check-ups was lower in the centenarian population. Moreover, with the exception of a lower Root Caries Index, centenarians showed a higher caries experience, and presented with a mean DMFT of 25.2 ± 3.9, a DMFS of 111.0 ± 21.8, a root caries prevalence of 34.5% and a Restorative Index of 54.0%. Centenarians’ functional capacity was also considerably lower. Non-existent or greatly reduced treatment capabilities and oral hygiene capabilities were registered in 63.7% and 43.6% of cases, respectively. Centenarians with a lower educational level (p = 0.018), in a care facility (p = 0.045) or in need of nursing care (p = 0.001) were more likely to have a low functional capacity. 98.2% of centenarians received help in their daily activities but only 12.7% in their oral hygiene. In conclusion, although most still have natural teeth, a decline of oral health can be perceived. As compliance with recommended behaviors is limited and most centenarians can no longer undergo dental treatment, the lack of assistance in daily oral health care is problematic.
Universal atom interferometer simulation of elastic scattering processes
Authors: Fitzek Florian , Siemß Jan-Niclas , Seckmeyer Stefan , Ahlers Holger , Rasel Ernst M. , Hammerer Klemens , Gaaloul Naceur 
Published: December 2020

AbstractIn this article, we introduce a universal simulation framework covering all regimes of matter-wave light-pulse elastic scattering. Applied to atom interferometry as a study case, this simulator solves the atom-light diffraction problem in the elastic case, i.e., when the internal state of the atoms remains unchanged. Taking this perspective, the light-pulse beam splitting is interpreted as a space and time-dependent external potential. In a shift from the usual approach based on a system of momentum-space ordinary differential equations, our position-space treatment is flexible and scales favourably for realistic cases where the light fields have an arbitrary complex spatial behaviour rather than being mere plane waves. Moreover, the solver architecture we developed is effortlessly extended to the problem class of trapped and interacting geometries, which has no simple formulation in the usual framework of momentum-space ordinary differential equations. We check the validity of our model by revisiting several case studies relevant to the precision atom interferometry community. We retrieve analytical solutions when they exist and extend the analysis to more complex parameter ranges in a cross-regime fashion. The flexibility of the approach, the insight it gives, its numerical scalability and accuracy make it an exquisite tool to design, understand and quantitatively analyse metrology-oriented matter-wave interferometry experiments.
Phylogenomic analysis of Clostridioides difficile ribotype 106 strains reveals novel genetic islands and emergent phenotypes
Authors: Roxas Bryan Angelo P. , Roxas Jennifer Lising , Claus-Walker Rachel , Harishankar Anusha , Mansoor Asad , Anwar Farhan , Jillella Shobitha , Williams Alison , Lindsey Jason , Elliott Sean P. , Shehab Kareem W. , Viswanathan V. K. , Vedantam Gayatri 
Published: December 2020

AbstractClostridioides difficile infection (CDI) is a major healthcare-associated diarrheal disease. Consistent with trends across the United States, C. difficile RT106 was the second-most prevalent molecular type in our surveillance in Arizona from 2015 to 2018. A representative RT106 strain displayed robust virulence and 100% lethality in the hamster model of acute CDI. We identified a unique 46 KB genomic island (GI1) in all RT106 strains sequenced to date, including those in public databases. GI1 was not found in its entirety in any other C. difficile clade, or indeed, in any other microbial genome; however, smaller segments were detected in Enterococcus faecium strains. Molecular clock analyses suggested that GI1 was horizontally acquired and sequentially assembled over time. GI1 encodes homologs of VanZ and a SrtB-anchored collagen-binding adhesin, and correspondingly, all tested RT106 strains had increased teicoplanin resistance, and a majority displayed collagen-dependent biofilm formation. Two additional genomic islands (GI2 and GI3) were also present in a subset of RT106 strains. All three islands are predicted to encode mobile genetic elements as well as virulence factors. Emergent phenotypes associated with these genetic islands may have contributed to the relatively rapid expansion of RT106 in US healthcare and community settings.
MEK reduces cancer-specific PpIX accumulation through the RSK-ABCB1 and HIF-1α-FECH axes
Authors: Chelakkot Vipin Shankar , Liu Kaiwen , Yoshioka Ema , Saha Shaykat , Xu Danyang , Licursi Maria , Dorward Ann , Hirasawa Kensuke 
Published: December 2020

AbstractThe efficacy of aminolevulinic acid (5-ALA)-based photodynamic diagnosis (5-ALA-PDD) and photodynamic therapy (5-ALA-PDT) is dependent on 5-ALA-induced cancer-specific accumulation of protoporphyrin IX (PpIX). We previously reported that inhibition of oncogenic Ras/MEK increases PpIX accumulation in cancer cells by reducing PpIX efflux through ATP-binding cassette sub-family B member 1 (ABCB1) and ferrochelatase (FECH)-catalysed PpIX conversion to haem. Here, we sought to identify the downstream pathways of Ras/MEK involved in the regulation of PpIX accumulation via ABCB1 and FECH. First, we demonstrated that Ras/MEK activation reduced PpIX accumulation in RasV12-transformed NIH3T3 cells and HRAS transgenic mice. Knockdown of p90 ribosomal S6 kinases (RSK) 2, 3, or 4 increased PpIX accumulation in RasV12-transformed NIH3T3 cells. Further, treatment with an RSK inhibitor reduced ABCB1 expression and increased PpIX accumulation. Moreover, HIF-1α expression was reduced when RasV12-transformed NIH3T3 cells were treated with a MEK inhibitor, demonstrating that HIF-1α is a downstream element of MEK. HIF-1α inhibition decreased FECH activity and increased PpIX accumulation. Finally, we demonstrated the involvement of RSKs and HIF-1α in the regulation of PpIX accumulation in human cancer cell lines. These results demonstrate that the RSK-ABCB1 and HIF-1α-FECH axes are the downstream pathways of Ras/MEK involved in the regulation of PpIX accumulation.
Development of β-Ga2O3 layers growth on sapphire substrates employing modeling of precursors ratio in halide vapor phase epitaxy reactor
Authors: Pozina Galia , Hsu Chih-Wei , Abrikossova Natalia , Kaliteevski Mikhail A. , Hemmingsson Carl 
Published: December 2020

AbstractGallium oxide is a promising semiconductor with great potential for efficient power electronics due to its ultra-wide band gap and high breakdown electric field. Optimization of halide vapor phase epitaxy growth of heteroepitaxial $$\upbeta$$
β
-Ga2O3 layers is demonstrated using a simulation model to predict the distribution of the ratio of gallium to oxygen precursors inside the reactor chamber. The best structural quality is obtained for layers grown at 825–850 °C and with a III/VI precursor ratio of 0.2. Although the structural and optical properties are similar, the surface morphology is more deteriorated for the $$\upbeta$$
β
-Ga2O3 layers grown on 5 degree off-axis sapphire substrates compared to on-axis samples even for optimized process parameters. Cathodoluminescence with a peak at 3.3 eV is typical for unintentionally doped n-type $$\upbeta$$
β
-Ga2O3 and shows the appearance of additional emissions in blue and green region at ~ 3.0, ~ 2.8, ~ 2.6 and ~ 2.4 eV, especially when the growth temperatures is lowered to 800–825 °C. Estimation of the band gap energy to ~ 4.65 eV from absorption indicates a high density of vacancy defects.