bluuebunny/crossref_metadata_2025_split huggingface dataset:
Joint modeling under competing risks: Application to survival prediction in patients admitted in Intensive Care Unit for sepsis with daily Sequential Organ Failure Assessment score assessments
Authors: Lavalley‐Morelle Alexandra , Timsit Jean‐François , Mentré France , Mullaert Jimmy ,   The OUTCOMEREA network
Published: October 2022

AbstractJoint models of longitudinal process and time‐to‐event data have recently gained attention, notably to provide individualized dynamic predictions. In the presence of competing risks, models published mostly involve cause‐specific hazard functions jointly estimated with a linear or generalized linear model. Here we propose to extend the modeling to full parametric joint estimation of a nonlinear mixed‐effects model and a subdistribution hazard model. We apply this approach on 6046 patients admitted in intensive care unit (ICU) for sepsis with daily Sequential Organ Failure Assessment (SOFA) score measurements. The joint model is built on a randomly selected training set of two thirds of patients and links the current predicted SOFA measurement to the instantaneous risks of ICU death and discharge from ICU, both adjusted on the patient age. Stochastic Approximation Expectation Maximization algorithm in Monolix is used for estimation. SOFA evolution is significantly associated with both risks: 0.37, 95% confidence interval (CI) = [0.35, 0.39] for the risk of death and −0.38, 95% CI = [−0.39, −0.36] for the risk of discharge. A simulation study, inspired from the real data, shows the good estimation properties of the parameters. We assess on the validation set the added value of modeling the longitudinal SOFA follow‐up for the prediction of death compared with a model that includes only SOFA at baseline. Time‐dependent receiver operating characteristic area under the curve and Brier scores show that when enough longitudinal individual information is available, joint modeling provides better predictions. The methodology can easily be applied to other clinical applications because of the general form of the model.
Atractylodin targets GLA to regulate D‐mannose metabolism to inhibit osteogenic differentiation of human valve interstitial cells and ameliorate aortic valve calcification
Authors: Qu Linghang , Wang Chunli , Xu Haiying , Li Lanqing , Liu Yanju , Wan Qianyun , Xu Kang 
Published: October 2022

AbstractAtractylodin (ATL) has been reported to exert anti‐inflammatory effects. Osteogenic changes induced by inflammation in valve interstitial cells (VICs) play a key role in the development of calcified aortic valve disease (CAVD). This study aimed to investigate the anti‐calcification effects of ATL on aortic valves. Human VICs (hVICs) were exposed to osteogenic induction medium (OM) containing ATL to investigate cell viability, osteogenic gene and protein expression, and anti‐calcification effects. Gas chromatography–mass spectroscopy (GC–MS) metabolomics analysis was used to detect changes in the metabolites of hVICs stimulated with OM before and after ATL administration. The compound‐reaction‐enzyme‐gene network was used to identify drug targets. Gene interference was used to verify the targets. ApoE−/− mice fed a high‐fat (HF) diet were used to evaluate the inhibition of aortic valve calcification by ATL. Treatment with 20 μM ATL in OM prevented calcified nodule accumulation and decreases in the gene and protein expression levels of ALP, RUNX2, and IL‐1β. Differential metabolite analysis showed that D‐mannose was highly associated with the anti‐calcification effect of ATL. The addition of D‐mannose prevented calcified nodule accumulation and inhibited succinate‐mediated HIF‐1α activation and IL‐1β production. The target of ATL was identified as GLA. Silencing of the GLA gene (si‐GLA) reversed the anti‐osteogenic differentiation of ATL. In vivo, ATL ameliorated aortic valve calcification by preventing decreases in GLA expression and the up‐regulation of IL‐1β expression synchronously. In conclusion, ATL is a potential drug for the treatment of CAVD by targeting GLA to regulate D‐mannose metabolism, thereby inhibiting succinate‐mediated HIF‐1α activation and IL‐1β production.
Two Asymptomatic Facial Erythematous Macules in an Adult Male
Authors: Balighi Kamran , Kamyab-hesari Kambiz , Hatami Parvaneh , Aryanian Zeinab 
Published: October 2022

Abstract
Pemphigus is a group of autoimmune bullous disorders with different types. Pemphigus foliaceous (PF) is a difficult-to-diagnosis disorder which shares clinical features with many dermatoses. We hereby, present an interesting case of PF which serves as a reminder for clinicians that pemphigus is not always a serious condition with rapid extension of lesions and it could have a very limited and benign form.
Indomethacin Synthesis, Historical Overview of Their Structural Modifications
Authors: Torres‐Carbajal Karina R. , Segura‐Quezada Luis A. , Ortíz‐Alvarado Rafael , Chávez‐Rivera Rubén , Tapia‐Juárez Melissa , González‐Domínguez Martha I. , Ruiz‐Padilla Alan J. , Zapata‐Morales Juan R. , de León‐Solís Claudia , Solorio Alvarado César R. 
Published: October 2022

AbstractOne of the most important (NSAID) non‐steroidal anti‐inflammatory drug‐containing the indol core is represented by the indomethacin. This highly relevant compound has been used for the last 50 years with excellent pharmacological results. Due to its relevant efficacy as an anti‐inflammatory treatment, several syntheses have been developed during this half of century. Herein is summarized and discussed the most representative strategies which successfully addressed the total syntheses of indomethacin as well as some of its derivatives generated by carrying out strategic modifications at the nitrogen atom, the carboxylic acid at C‐3, the methoxy group at C‐5 and the methyl group at C‐2.
Docking and Molecular Dynamics Simulations of Flavonoids as Inhibitors of Infectious Agents: Rutin as a Coronavirus Protease Inhibitor
Authors: Salarizadeh Navvabeh , Aallaei Mohammad Reza , Zarei Ali , Malekshah Rahime Eshaghi , Molaakbari Elaheh , Farajnezhadi Amirreza 
Published: October 2022

Abstract3CL protease as the main protease (Mpro) of coronavirus is investigated as a potential target in medicine. Flavonoid compounds with polyphenolic structures exhibited anti‐viral, anti‐bacterial, immunomodulatory and anti‐inflammatory effects against infectious agents. In this study, the inhibitory effect of flavonoid‐based compounds was evaluated against coronavirus Mpro using molecular docking and dynamic simulations. Molegro Virtual Docker 6.0 (MVD) software was used to ensure the accuracy of the docking analysis. Eventually, four compounds including two herbal‐based (Rutin and Quercetin) and two chemical‐based (2‐Iodoadenosine‐5’‐O‐[(phosphonomethyl)phosphonic Acid] and Camostat) are selected based on the interaction energies and docking scores of the investigated structures. The values of MolDock Score for Rutin was −174.355 docked to Mpro enzyme. The molecular dynamics was performed by using GROMACS in 100 ns to refine the docking simulation results and evaluated the binding stability of Rutin. Potential energy of Rutin/Mpro complex stabilization was measured approximately −1.11×106 kcal/mol for 100 ns. As a result, Rutin is suggested as a potent inhibitor for Mpro and can be used as an effective drug in the treatment and prevention of covid.
Enhancement of Emission and Negative Thermal Quenching Effect of Na2TiF6:Mn4+,TEAH+ by Antenna Effect of TEAH+
Authors: Deng Daishu , Wang Lin , Yu Yan , Wang Tianman , Zhong Xue , Lei Jun , Liao Sen , Huang Yingheng 
Published: October 2022

AbstractIn order to develop new red‐emitting phosphors, in this work, a series of organic‐inorganic hybrid Na2TiF6 : Mn4+, (CH3CH2)3NH+ (NTF : Mn4+, TEAH+) red‐emitting phosphors have been prepared. Due to the antenna effect of TEAH+, double improvement in emission intensity and luminous thermal stability of the optimal sample are obtained: (a) The integrated emission intensity of the hybrid NTF : Mn4+,TEAH+ sample is 150 % of the un‐doping one (NTF : Mn4+), (b) The luminescent thermal stability of the hybrid NTF : Mn4+,TEAH+ sample is obviously increased because of strong negative thermal quenching (NTQ) effect. The integrated emission intensity at 150 °C is 176.2 % of the initial value at 30 °C, and the intensity at 178 °C is still 100 % of the initial one. The strong NTQ effect is attributed to the driving of the antenna effect of TEAH+. The above double improvements make the optimal sample has extensive application prospects for daily lighting white light‐emitting diodes (WLEDs).
New CuSO4‐related high‐temperature polymorph of AgIISO4**
Authors: Domański Mateusz , Mazej Zoran , Grochala Wojciech 
Published: October 2022

AbstractSilver(II) compounds exhibit powerful oxidizing properties and strong magnetic superexchange, but most of them comprise fluoride ligands. AgSO4 is a rare fluorine‐free salt of Ag(II) which found some application in organic chemistry. Here, we report a discovery of a new AgSO4 polymorph (β). The distinct nature of the two polytypes of AgSO4 is established using powder X‐ray diffraction, vibrational spectroscopy and theoretical calculations. The β polymorph crystallizes in the monoclinic system (P21/n) and shows structural similarities with CuSO4. DFT calculations indicate very small differences in the energy of the two AgSO4 polymorphs and that the relative stability of the β polymorph should increase with temperature. The monoclinic distortion of the orthorhombic CuSO4 prototype originates from an unprecedented strong antiferromagnetic interaction between Ag sites along the unit cell diagonal.
New instabilities for non-supersymmetric AdS4 orientifold vacua
Authors: Marchesano Fernando , Quirant Joan , Zatti Matteo 
Published: October 2022

Abstract
We consider massive type IIA orientifold compactifications of the form AdS4× X6, where X6 admits a Calabi-Yau metric and is threaded by background fluxes. From a 4d viewpoint, fluxes generate a potential whose vacua have been classified, including one $$ \mathcal{N} $$
N
= 1 and three perturbatively stable $$ \mathcal{N} $$
N
= 0 branches. We reproduce this result from a 10d viewpoint, by solving the type IIA equations at the same level of detail as previously done for the $$ \mathcal{N} $$
N
= 1 branch. All solutions exhibit localised sources and parametric scale separation. We then analyse the non-perturbative stability of the $$ \mathcal{N} $$
N
= 0 branches. We consider new 4d membranes, obtained from wrapping D8-branes on X6 or D6-branes on its divisors, threaded by non-diluted worldvolume fluxes. Using them we show that all branches are compatible with the Weak Gravity Conjecture for membranes. In fact, most vacua satisfy the sharpened conjecture that predicts superextremal membranes in $$ \mathcal{N} $$
N
= 0 settings, except for a subset whose non-perturbative stability remains an open problem.
Resolving black-hole microstructure with new momentum carriers
Authors: Bena Iosif , Čeplak Nejc , Hampton Shaun , Li Yixuan , Toulikas Dimitrios , Warner Nicholas P. 
Published: October 2022

Abstract
All known horizonless black-hole microstate geometries correspond to brane sources that acquire a finite size, and hence break the spherical symmetry of the black hole. We construct, for the first time, solutions with zero horizon area that have the same charges as a three-charge F1-NS5-P Type-IIA black hole and preserve this spherical symmetry. The momentum of these solutions is carried by longitudinal D0-D4 density fluctuations inside the NS5-branes. We argue that these solutions should be interpreted as the long-throat limit of a family of smooth, horizonless microstate geometries, called superstrata, where such geometries degenerate. The existence of these geometries indicates that a finite-size horizon does not appear even in the singular corners of the moduli space of three-charge microstate geometries.
Phagocytosing differentiated cell-fragments is a novel mechanism for controlling somatic stem cell differentiation within a short time frame
Authors: Wakao Shohei , Oguma Yo , Kushida Yoshihiro , Kuroda Yasumasa , Tatsumi Kazuki , Dezawa Mari 
Published: October 2022

AbstractStem cells undergo cytokine-driven differentiation, but this process often takes longer than several weeks to complete. A novel mechanism for somatic stem cell differentiation via phagocytosing ‘model cells’ (apoptotic differentiated cells) was found to require only a short time frame. Pluripotent-like Muse cells, multipotent mesenchymal stem cells (MSCs), and neural stem cells (NSCs) phagocytosed apoptotic differentiated cells via different phagocytic receptor subsets than macrophages. The phagocytosed-differentiated cell-derived contents (e.g., transcription factors) were quickly released into the cytoplasm, translocated into the nucleus, and bound to promoter regions of the stem cell genomes. Within 24 ~ 36 h, the cells expressed lineage-specific markers corresponding to the phagocytosed-differentiated cells, both in vitro and in vivo. At 1 week, the gene expression profiles were similar to those of the authentic differentiated cells and expressed functional markers. Differentiation was limited to the inherent potential of each cell line: triploblastic-, adipogenic-/chondrogenic-, and neural-lineages in Muse cells, MSCs, and NSCs, respectively. Disruption of phagocytosis, either by phagocytic receptor inhibition via small interfering RNA or annexin V treatment, impeded differentiation in vitro and in vivo. Together, our findings uncovered a simple mechanism by which differentiation-directing factors are directly transferred to somatic stem cells by phagocytosing apoptotic differentiated cells to trigger their rapid differentiation into the target cell lineage.
Two decades of climate change alters seed longevity in an alpine herb: implications for ex situ seed conservation
Authors: White F. J. , Hay F. R. , Abeli T. , Mondoni A. 
Published: October 2022

AbstractClimate warming in mountain areas is increasing faster than the global average, threatening alpine plants. Climate affects many traits including seeds, the longevity of which is important for conservation, facilitating genebank storage. Seeds of alpine species are considered short-lived in storage, but their longevity increases when produced under a warmer parental environment. Consequently, with climate warming, seeds of alpine species may have increased fitness and be longer-lived in genebank storage. We assessed seed longevity under artificial ageing in 10 accessions of the arctic-alpine species Viscaria alpina stored under genebank conditions for different time periods over the last 20 years. The seed collection site was in the northern Apennines, where above average warming and variable precipitation has been recorded. The time taken for viability to fall to 50% (p50) was estimated using probit analysis; correlation and general linear regression were used to investigate the effects of length of time in storage, seed mass and climate under which seeds were produced on seed longevity. p50 varied between 7.77 and 18.49 days. There was no relationship between length of time in storage or seed mass on seed longevity. p50 was higher in years with increased temperature and lower precipitation during the growing season, with precipitation having more impact than temperature. The results suggest that seeds of alpine species are suitable for genebank storage, and inter-annual variation in precipitation induces a plastic response in seed longevity. Using genebank stored seeds provides insights into how alpine species may respond to future climate changes and could have implications for genebank storage.
Inverse design in nanoscale heat transport via interpolating interfacial phonon transmission
Authors: Romano Giuseppe , Johnson Steven G. 
Published: October 2022

AbstractWe introduce a methodology for density-based topology optimization of non-Fourier thermal transport in nanostructures, based upon adjoint-based sensitivity analysis of the phonon Boltzmann transport equation (BTE) and a novel material interpolation technique, the “transmission interpolation model” (TIM). The key challenge in BTE optimization is handling the interplay between real- and momentum-resolved material properties. By parameterizing the material density with aninterfacialtransmission coefficient, TIM is able to recover the hard-wall and no-interface limits, while guaranteeing a smooth transition between void and solid regions. We first use our approach to tailor the effective thermal conductivity tensor of a periodic nanomaterial; then, we maximize classical phonon size effects under constrained diffusive transport, identifying a promising new thermoelectric material design. Our method enables the systematic optimization of materials for heat management and conversion and, more broadly, the design of devices where diffusive transport is not valid.
Quicksort leave-pair-out cross-validation for ROC curve analysis
Authors: Numminen Riikka , Montoya Perez Ileana , Jambor Ivan , Pahikkala Tapio , Airola Antti 
Published: October 2022

AbstractReceiver Operating Characteristic (ROC) curve analysis and area under the ROC curve (AUC) are commonly used performance measures in diagnostic systems. In this work, we assume a setting, where a classifier is inferred from multivariate data to predict the diagnostic outcome for new cases. Cross-validation is a resampling method for estimating the prediction performance of a classifier on data not used for inferring it. Tournament leave-pair-out (TLPO) cross-validation has been shown to be better than other resampling methods at producing a ranking of data that can be used for estimating the ROC curves and areas under them. However, the time complexity of TLPOCV,$$O\left( n^2\right)$$On2, means that it is impractical in many applications. In this article, a method called quicksort leave-pair-out cross-validation (QLPOCV) is presented in order to decrease the time complexity of obtaining a reliable ranking of data to$$O\left( n\log n\right)$$Onlogn. The proposed method is compared with existing ones in an experimental study, demonstrating that in terms of ROC curves and AUC values QLPOCV produces as accurate performance estimation as TLPOCV, outperforming bothk-fold and leave-one-out cross-validation.
Influence of the lunar cycle and spatial gradients on size-dependent male and female reproductive investment decisions of a protogynous reef fish
Authors: Mitterwallner Pauline , Shima Jeffrey S. 
Published: October 2022

AbstractCoral reef fish species experience variable environments and may employ a range of reproductive strategies to help them maximize fitness. Here, we explore patterns of variation in size- and sex-dependent spawning strategies (pair spawning, group spawning, and streaking tactics) of a sex-changing, highly iteroparous fish (the sixbar wrasseThalassoma hardwicke) across the lunar month, and in relation to proximity to the reef edge. We test the hypothesis that adults vary their investment strategies as a function of body size. We evaluated reproductive behaviour patterns at 2–3 days intervals over 5 consecutive months, and found that frequencies of pair spawning, group spawning, and streaking attempts all significantly increased around the new moon and were greatest in the most exposed territories (i.e., those located closest to the reef edge). Smaller females and IP males largely curtailed reproductive activities during the full moon and third quarter moon, while larger individuals reproduced more consistently across the lunar month. Size-dependent reproductive decisions appeared to mediate frequencies of specific reproductive tactics (e.g., prevalence of pair spawning, group spawning, and streaking strategies). We speculate that (1) optimal tactics are shaped by size- and sex-dependent trade-offs between reproduction and growth in relation to environmental conditions, and that (2) individual investment decisions determine the prevailing reproductive mode at a spawning site. Variation in female choice might thereby act as a mechanism for maintaining these two reproductive modes (pair spawning and group spawning) in a population.
Natural history of familial cerebral cavernous malformation syndrome in children: a multicenter cohort study
Authors: Geraldo Ana Filipa , Alves Cesar Augusto P. F. , Luis Aysha , Tortora Domenico , Guimarães Joana , Abreu Daisy , Reimão Sofia , Pavanello Marco , de Marco Patrizia , Scala Marcello , Capra Valeria , Vaz Rui , Rossi Andrea , Schwartz Erin Simon , Mankad Kshitij , Severino Mariasavina 
Published: October 2022

Abstract

Purpose

There is limited data concerning neuroimaging findings and longitudinal evaluation of familial cerebral cavernous malformations (FCCM) in children. Our aim was to study the natural history of pediatric FCCM, with an emphasis on symptomatic hemorrhagic events and associated clinical and imaging risk factors.

Methods
We retrospectively reviewed all children diagnosed with FCCM in four tertiary pediatric hospitals between January 2010 and March 2022. Subjects with first available brain MRI and $$\ge$$
≥
3 months of clinical follow-up were included. Neuroimaging studies were reviewed, and clinical data collected. Annual symptomatic hemorrhage risk rates and cumulative risks were calculated using survival analysis and predictors of symptomatic hemorrhagic identified using regression analysis.

Results
Forty-one children (53.7% males) were included, of whom 15 (36.3%) presenting with symptomatic hemorrhage. Seven symptomatic hemorrhages occurred during 140.5 person-years of follow-up, yielding a 5-year annual hemorrhage rate of 5.0% per person-year. The 1-, 2-, and 5-year cumulative risks of symptomatic hemorrhage were 7.3%, 14.6%, and 17.1%, respectively. The latter was higher in children with prior symptomatic hemorrhage (33.3%), CCM2 genotype (33.3%), and positive family history (20.7%). Number of brainstem (adjusted hazard ratio [HR] = 1.37, P = 0.005) and posterior fossa (adjusted HR = 1.64, P = 0.004) CCM at first brain MRI were significant independent predictors of prospective symptomatic hemorrhage.

Conclusion
The 5-year annual and cumulative symptomatic hemorrhagic risk in our pediatric FCCM cohort equals the overall risk described in children and adults with all types of CCM. Imaging features at first brain MRI may help to predict potential symptomatic hemorrhage at 5-year follow-up.