bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patterns of care and clinical outcomes in stage IVA cervical cancer: 14-year experience from a tertiary care centre in South India
Authors: John Neenu Oliver , Sathyamurthy Arvind , Prasoona Shanthi , Ramireddy Jeba Karunya , Rebekah Grace , Das Saikat , George Reena Mary , John Subhashini , Ram Thomas Samuel 
Published: December 2021

Abstract

Aim:
To analyse the patterns of care and clinical outcomes of patients diagnosed with cervical cancer International Federation of Gynecology and Obstetrics (FIGO) stage IVA treated at a tertiary care centre in South India.

Materials and methods:
The electronic medical records of 2,476 patients diagnosed with cervical cancer at a tertiary care institution between January 2005 and December 2018 were reviewed. Among them, 96 patients diagnosed with histologically proven carcinoma cervix stage IVA established by either cystoscopy or proctoscopy were included. Four patients who did not receive treatment at the study centre were excluded and 92 patients were available for final analysis.

Results:
The median follow-up period was 12 months (2–131 months). Of the 92 patients, 59 patients (64·13%) received radiation therapy (RT) alone, 22 patients (23·9%) received chemoradiation (CRT), three patients (3·26%) received neoadjuvant chemotherapy (NACT) followed by RT, one (1·08%) received NACT followed by CRT, four patients (4·35%) received chemotherapy alone, while three (3·26%) were offered best supportive care. The median progression-free survival (PFS) was 12 months (95% CI: 9·6–14·4 months) and median overall survival (OS) was 25 months (95% CI: 16·6–33·4 months). The 2-year and 3-year PFS was 30 and 20%, respectively, and the OS was 50 and 32%, respectively.

Conclusion:
The management of stage IVA cervical cancer needs to be individualised to achieve a fine balance between local control, toxicity, and quality of life. RT is the mainstay of treatment with concurrent chemotherapy in carefully selected patients. Involvement of palliative care team early in the course of treatment adds a holistic approach to the continuum of oncological care.
Adaptives Testen von Textverständnis in der Grundschule
Authors: Ludewig Ulrich , Trendtel Matthias , Schlitter Theresa , McElvany Nele 
Published: December 2021

Zusammenfassung. Die vorliegende Studie befasst sich mit Entwicklung eines Itempools für einen computeradaptiver Test (CAT) zur Erfassung von Textverständnis in der Grundschule. Der Effizienzgewinn von CATs im Vergleich zu Tests mit festgelegter Itemabfolge (FITs) wird untersucht. Für die Kalibrierung eines Textverständnisitempools wurden Stichproben von N = 1 975 Schülerinnen und Schülern aus der 3. und 4. Klassenstufe erhoben. Der finale Itempool umfasst 132 auf Messgüte geprüfte Items. Eine CAT Simulation mit 25 Items zeigte, dass ein CAT das Textverständnis mit sehr guter Reliabilität ( Releap ≈ .92) erfassen kann. Ein CAT mit 8 Items erreichte eine gute Reliabilität ( Releap ≈ .80). Analysen zur Konstruktvalidierung werden berichtet. Ein CAT basierend auf dem Itempool misst bis zu 19 % effizienter als ein vergleichbarer FIT und wäre besonders für die Erfassung von Textverständnis bei Schülerinnen und Schülern eines breiten Leistungsspektrums und für die Lernverlaufsdiagnostik geeignet.
Some Lava Flows May Not Have Been as Thick as They Appear
Authors: Katona Jonas , Fu Xiaojing , Mittal Tushar , Manga Michael , Self Stephen 
Published: December 2021

AbstractIndividual lava flows in flood basalt provinces are composed of sheet pāhoehoe lobes and the 10–100 m thick lobes are thought to form by inflation. Quantifying the emplacement history of these lobes can help infer the magnitude and temporal dynamics of prehistoric eruptions. Here we use a phase‐field model to describe solidification and remelting of sequentially emplaced lava lobes to explore additional processes that may lead to thick flows and lobes. We calibrate parameters using field measurements at Makaopuhi lava lake. We vary the lobe thicknesses and the time interval between eruptions to study the interplay between these factors and their impact on the thermal evolution of flows. Our analysis shows that if the time between emplacements is sufficiently short, remelting may merge sequentially emplaced lobes—making lava flows appear thicker than they actually were—which suggests that fused lobes could be another mechanism that creates apparently thick lava flows.
Nitrous Oxide Emissions From Drying Streams and Rivers
Authors: Tonina D. , Marzadri A. , Bellin A. , Dee M. M. , Bernal S. , Tank J. L. 
Published: December 2021

AbstractStreams and rivers are suffering more extreme and prolonged low flows than those naturally occurring without human intervention with potential relevant worldwide effects on the production of nitrous oxide (N2O), a greenhouse gas 300 times more potent than carbon dioxide. Here, we address the question of whether droughts and management‐induced low flows increase riverine N2O emissions causing positive feedback in response to climate change. Supported by field data, we model riverine N2O emissions for decreasing mean summer flows in a forested and agricultural watershed under chemostatic and chemodynamic dissolved inorganic reactive nitrogen (DIN) concentrations. Our results demonstrate that total N2O emissions decrease with increasing low flow severity in both watersheds regardless of DIN scenario; which imparts a form of climate resilience.
Biased Estimates of Equilibrium Climate Sensitivity and Transient Climate Response Derived From Historical CMIP6 Simulations
Authors: Dong Yue , Armour Kyle C. , Proistosescu Cristian , Andrews Timothy , Battisti David S. , Forster Piers M. , Paynter David , Smith Christopher J. , Shiogama Hideo 
Published: December 2021

AbstractThis study assesses the effective climate sensitivity (EffCS) and transient climate response (TCR) derived from global energy budget constraints within historical simulations of eight CMIP6 global climate models (GCMs). These calculations are enabled by use of the Radiative Forcing Model Intercomparison Project (RFMIP) simulations, which permit accurate quantification of the radiative forcing. Long‐term historical energy budget constraints generally underestimate EffCS from CO2 quadrupling and TCR from CO2 ramping, owing to changes in radiative feedbacks and changes in ocean heat uptake efficiency. Atmospheric GCMs forced by observed warming patterns produce lower values of EffCS that are more in line with those inferred from observed historical energy budget changes. The differences in the EffCS estimates from historical energy budget constraints of models and observations are traced to discrepancies between modeled and observed historical surface warming patterns.
Hysteresis of the Glacial Atlantic Meridional Overturning Circulation Controlled by Thermal Feedbacks
Authors: Ando Taigo , Oka Akira 
Published: December 2021

AbstractThe multiple equilibrium behavior of the Atlantic meridional overturning circulation (AMOC) is related to the mode transition of the AMOC, which played an important role in abrupt glacial climate changes. However, the difference between modern and glacial climates is not well understood. Here, we examined the structure of the multiple equilibria of the AMOC under the modern and glacial climates through hysteresis experiments using an earth system model of intermediate complexity. The glacial AMOC exhibited a shallower AMOC mode but not the off mode, and a narrower range of multiple equilibria than the modern AMOC. This glacial hysteresis behavior occurred associated with a shift of deep water formation due to changes in surface air temperature and sea ice, whereas that of the modern AMOC is attributed to the basin‐scale salinity feedback. These features were commonly found in two glacial simulations with different strengths of the AMOC at the Last Glacial Maximum.
Event‐Based Training in Label‐Limited Regimes
Authors: Linville Lisa M. 
Published: December 2021

AbstractThe distribution of attributes assigned using data on independent sensors for a specific source, for example, magnitude, can be richly descriptive for final event characterization and associated uncertainty. Attribute distributions can also provide powerful context for event characterization in the absence of comprehensive annotation. This work develops a way to leverage distributional information across a set of sensors in the absence of comprehensive annotation as a domain‐informed regularization term applied during gradient‐based learning. The regularization term is the basis of event‐based training which I show can be a powerful semi‐supervised learning (SSL) approach. I first use a simple feed forward neural network and a toy data set to outline how data set structure interacts with the assumptions inherent to many semi‐supervised learning approaches. I then demonstrate the effectiveness of event‐based training using a deep convolutional neural network for seismic event classification in Utah, which increases SSL accuracy from 92% to 97% on event classification with a limited number of training labels.
Mesoscale Convective Systems in a Superparameterized E3SM Simulation at High Resolution
Authors: Lin Guangxing , Jones Christopher R. , Leung L. Ruby , Feng Zhe , Ovchinnikov Mikhail 
Published: December 2021

AbstractAccurately representing mesoscale convective systems (MCSs) is crucial to simulating the energy and water cycles in global climate models. Using a novel MCS identification and tracking algorithm applied to observations and model simulations, we evaluate how well the Energy Exascale Earth System Model (E3SM) simulates MCSs over the central US. Simulations performed by E3SM at 25 km grid spacing with and without superparameterization (SP) are compared and evaluated against observations using multiple metrics highlighting important MCS characteristics. Compared to E3SM, the superparameterized model (SP‐E3SM) better simulates MCS number and MCS precipitation amount, diurnal cycle, propagation, and the probability distribution of precipitation rate in both spring and summer. The improvement from SP is partly contributed by improvement in simulating the large‐scale environments, featuring enhanced atmospheric low‐level moisture and larger moisture transport to the central US relative to E3SM. However, SP‐E3SM still underestimates MCS precipitation amount, particularly in summer. This underestimation is closely related to the negative bias in MCS precipitation intensity, although the drier environments simulated during summer also contributes to underestimation of MCS frequency. Without SP, the larger bias in MCS precipitation amount is closely related to the negative bias in MCS frequency, while the substantial dry bias in the large‐scale environments also contributes to underestimation of MCS intensity. Our results suggest that SP improves MCS simulation by improving modeling of the large‐scale environments and convection initiation, which are both major limiting factors in E3SM even at 25 km grid spacing where deep convection is represented by a cumulus parameterization.
Circular RNA circCCNT2 is upregulated in the anterior cingulate cortex of individuals with bipolar disorder
Authors: Lin Rixing , Lopez Juan Pablo , Cruceanu Cristiana , Pierotti Caroline , Fiori Laura M. , Squassina Alessio , Chillotti Caterina , Dieterich Christoph , Mellios Nikolaos , Turecki Gustavo 
Published: December 2021

AbstractGene expression dysregulation in the brain has been associated with bipolar disorder, but little is known about the role of non-coding RNAs. Circular RNAs are a novel class of long noncoding RNAs that have recently been shown to be important in brain development and function. However, their potential role in psychiatric disorders, including bipolar disorder, has not been well investigated. In this study, we profiled circular RNAs in the brain tissue of individuals with bipolar disorder. Total RNA sequencing was initially performed in samples from the anterior cingulate cortex of a cohort comprised of individuals with bipolar disorder (N = 13) and neurotypical controls (N = 13) and circular RNAs were identified and analyzed using “circtools”. Significant circular RNAs were validated by RT-qPCR and replicated in the anterior cingulate cortex in an independent cohort (24 bipolar disorder cases and 27 controls). In addition, we conducted in vitro studies using B-lymphoblastoid cells collected from bipolar cases (N = 19) and healthy controls (N = 12) to investigate how circular RNAs respond following lithium treatment. In the discovery RNA sequencing analysis, 26 circular RNAs were significantly differentially expressed between bipolar disorder cases and controls (FDR < 0.1). Of these, circCCNT2 was RT-qPCR validated showing significant upregulation in bipolar disorder (p = 0.03). This upregulation in bipolar disorder was replicated in an independent post-mortem human anterior cingulate cortex cohort and in B-lymphoblastoid cell culture. Furthermore, circCCNT2 expression was reduced in response to lithium treatment in vitro. Together, our study is the first to associate circCCNT2 to bipolar disorder and lithium treatment.
Brain network coupling associated with cognitive performance varies as a function of a child’s environment in the ABCD study
Authors: Ellwood-Lowe Monica E. , Whitfield-Gabrieli Susan , Bunge Silvia A. 
Published: December 2021

AbstractPrior research indicates that lower resting-state functional coupling between two brain networks, lateral frontoparietal network (LFPN) and default mode network (DMN), relates to cognitive test performance, for children and adults. However, most of the research that led to this conclusion has been conducted with non-representative samples of individuals from higher-income backgrounds, and so further studies including participants from a broader range of socioeconomic backgrounds are required. Here, in a pre-registered study, we analyzed resting-state fMRI from 6839 children ages 9–10 years from the ABCD dataset. For children from households defined as being above poverty (family of 4 with income > $25,000, or family of 5+ with income > $35,000), we replicated prior findings; that is, we found that better performance on cognitive tests correlated with weaker LFPN-DMN coupling. For children from households defined as being in poverty, the direction of association was reversed, on average: better performance was instead directionally related to stronger LFPN-DMN connectivity, though there was considerable variability. Among children in households below poverty, the direction of this association was predicted in part by features of their environments, such as school type and parent-reported neighborhood safety. These results highlight the importance of including representative samples in studies of child cognitive development.
Influence of the chirality of carbon nanodots on their interaction with proteins and cells
Authors: Yan Huijie , Cacioppo Michele , Megahed Saad , Arcudi Francesca , Đorđević Luka , Zhu Dingcheng , Schulz Florian , Prato Maurizio , Parak Wolfgang J. , Feliu Neus 
Published: December 2021

AbstractCarbon nanodots with opposite chirality possess the same major physicochemical properties such as optical features, hydrodynamic diameter, and colloidal stability. Here, a detailed analysis about the comparison of the concentration of both carbon nanodots is carried out, putting a threshold to when differences in biological behavior may be related to chirality and may exclude effects based merely on differences in exposure concentrations due to uncertainties in concentration determination. The present study approaches this comparative analysis evaluating two basic biological phenomena, the protein adsorption and cell internalization. We find how a meticulous concentration error estimation enables the evaluation of the differences in biological effects related to chirality.
Computational mechanisms of distributed value representations and mixed learning strategies
Authors: Farashahi Shiva , Soltani Alireza 
Published: December 2021

AbstractLearning appropriate representations of the reward environment is challenging in the real world where there are many options, each with multiple attributes or features. Despite existence of alternative solutions for this challenge, neural mechanisms underlying emergence and adoption of value representations and learning strategies remain unknown. To address this, we measure learning and choice during a multi-dimensional probabilistic learning task in humans and trained recurrent neural networks (RNNs) to capture our experimental observations. We find that human participants estimate stimulus-outcome associations by learning and combining estimates of reward probabilities associated with the informative feature followed by those of informative conjunctions. Through analyzing representations, connectivity, and lesioning of the RNNs, we demonstrate this mixed learning strategy relies on a distributed neural code and opponency between excitatory and inhibitory neurons through value-dependent disinhibition. Together, our results suggest computational and neural mechanisms underlying emergence of complex learning strategies in naturalistic settings.
Dynamic regulation of N6,2′-O-dimethyladenosine (m6Am) in obesity
Authors: Ben-Haim Moshe Shay , Pinto Yishay , Moshitch-Moshkovitz Sharon , Hershkovitz Vera , Kol Nitzan , Diamant-Levi Tammy , Beeri Michal Schnaider , Amariglio Ninette , Cohen Haim Y. , Rechavi Gideon 
Published: December 2021

AbstractThe prevalent m6Am mRNA cap modification was recently identified as a valid target for removal by the human obesity gene FTO along with the previously established m6A mRNA modification. However, the deposition and dynamics of m6Am in regulating obesity are unknown. Here, we investigate the liver m6A/m methylomes in mice fed on a high fat Western-diet and in ob/ob mice. We find that FTO levels are elevated in fat mice, and that genes which lost m6Am marking under obesity are overly downregulated, including the two fatty-acid-binding proteins FABP2, and FABP5. Furthermore, the cellular perturbation of FTO correspondingly affect protein levels of its targets. Notably, generally m6Am- but not m6A-methylated genes, are found to be highly enriched in metabolic processes. Finally, we deplete all m6A background via Mettl3 knockout, and unequivocally uncover the association of m6Am methylation with increased mRNA stability, translation efficiency, and higher protein expression. Together, these results strongly implicate a dynamic role for m6Am in obesity-related translation regulation.
Tribo-electrochemistry induced artificial solid electrolyte interface by self-catalysis
Authors: Qin Chichu , Wang Dong , Liu Yumin , Yang Pengkun , Xie Tian , Huang Lu , Zou Haiyan , Li Guanwu , Wu Yingpeng 
Published: December 2021

AbstractPotassium (K) metal is a promising alkali metal anode for its high abundance. However, dendrite on K anode is a serious problem which is even worse than Li. Artificial SEI (ASEI) is one of effective routes for suppressing dendrite. However, there are still some issues of the ASEI made by the traditional methods, e.g. weak adhesion, insufficient/uneven reaction, which deeply affects the ionic diffusion kinetics and the effect of inhibiting dendrites. Herein, through a unique self-catalysis tribo-electrochemistry reaction, a continuous and compact protective layer is successfully constructed on K metal anode in seconds. Such a continuous and compact protective layer can not only improve the K+ diffusion kinetics, but also strongly suppress K dendrite formation by its hard mechanical properties derived from rigid carbon system, as well as the improved K+ conductivity and lowered electronic conductivity from the amorphous KF. As a result, the potassium symmetric cells exhibit stable cycles last more than 1000 h, which is almost 500 times that of pristine K.
KDM6B promotes activation of the oncogenic CDK4/6-pRB-E2F pathway by maintaining enhancer activity in MYCN-amplified neuroblastoma
Authors: D’Oto Alexandra , Fang Jie , Jin Hongjian , Xu Beisi , Singh Shivendra , Mullasseril Anoushka , Jones Victoria , Abu-Zaid Ahmed , von Buttlar Xinyu , Cooke Bailey , Hu Dongli , Shohet Jason , Murphy Andrew J. , Davidoff Andrew M. , Yang Jun 
Published: December 2021

AbstractThe H3K27me2/me3 histone demethylase KDM6B is essential to neuroblastoma cell survival. However, the mechanism of KDM6B action remains poorly defined. We demonstrate that inhibition of KDM6B activity 1) reduces the chromatin accessibility of E2F target genes and MYCN, 2) selectively leads to an increase of H3K27me3 but a decrease of the enhancer mark H3K4me1 at the CTCF and BORIS binding sites, which may, consequently, disrupt the long-range chromatin interaction of MYCN and E2F target genes, and 3) phenocopies the transcriptome induced by the specific CDK4/6 inhibitor palbociclib. Overexpression of CDK4/6 or Rb1 knockout confers neuroblastoma cell resistance to both palbociclib and the KDM6 inhibitor GSK-J4. These data indicate that KDM6B promotes an oncogenic CDK4/6-pRB-E2F pathway in neuroblastoma cells via H3K27me3-dependent enhancer-promoter interactions, providing a rationale to target KDM6B for high-risk neuroblastoma.
KRas-transformed epithelia cells invade and partially dedifferentiate by basal cell extrusion
Authors: Fadul John , Zulueta-Coarasa Teresa , Slattum Gloria M. , Redd Nadja M. , Jin Mauricio Franco , Redd Michael J. , Daetwyler Stephan , Hedeen Danielle , Huisken Jan , Rosenblatt Jody 
Published: December 2021

AbstractMetastasis is the main cause of carcinoma-related death, yet we know little about how it initiates due to our inability to visualize stochastic invasion events. Classical models suggest that cells accumulate mutations that first drive formation of a primary mass, and then downregulate epithelia-specific genes to cause invasion and metastasis. Here, using transparent zebrafish epidermis to model simple epithelia, we can directly image invasion. We find that KRas-transformation, implicated in early carcinogenesis steps, directly drives cell invasion by hijacking a process epithelia normally use to promote death—cell extrusion. Cells invading by basal cell extrusion simultaneously pinch off their apical epithelial determinants, endowing new plasticity. Following invasion, cells divide, enter the bloodstream, and differentiate into stromal, neuronal-like, and other cell types. Yet, only invading KRasV12 cells deficient in p53 survive and form internal masses. Together, we demonstrate that KRas-transformation alone causes cell invasion and partial dedifferentiation, independently of mass formation.
Molecular basis of enzymatic nitrogen-nitrogen formation by a family of zinc-binding cupin enzymes
Authors: Zhao Guiyun , Peng Wei , Song Kaihui , Shi Jingkun , Lu Xingyu , Wang Binju , Du Yi-Ling 
Published: December 2021

AbstractMolecules with a nitrogen-nitrogen (N-N) bond in their structures exhibit various biological activities and other unique properties. A few microbial proteins are recently emerging as dedicated N-N bond forming enzymes in natural product biosynthesis. However, the details of these biochemical processes remain largely unknown. Here, through in vitro biochemical characterization and computational studies, we report the molecular basis of hydrazine bond formation by a family of di-domain enzymes. These enzymes are widespread in bacteria and sometimes naturally exist as two standalone enzymes. We reveal that the methionyl-tRNA synthase-like domain/protein catalyzes ATP-dependent condensation of two amino acids substrates to form a highly unstable ester intermediate, which is subsequently captured by the zinc-binding cupin domain/protein and undergoes redox-neutral intramolecular rearrangement to give the N-N bond containing product. These results provide important mechanistic insights into enzymatic N-N bond formation and should facilitate future development of novel N-N forming biocatalyst.