bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictive monitoring using machine learning algorithms and a real‐life example on schizophrenia
Authors: Huberts Leo C. E. , Does Ronald J. M. M. , Ravesteijn Bastian , Lokkerbol Joran 
Published: July 2021

AbstractPredictive process monitoring aims to produce early warnings of unwanted events. We consider the use of the machine learning method extreme gradient boosting as the forecasting model in predictive monitoring. A tuning algorithm is proposed as the signaling method to produce a required false alarm rate. We demonstrate the procedure using a unique data set on mental health in the Netherlands. The goal of this application is to support healthcare workers in identifying the risk of a mental health crisis in people diagnosed with schizophrenia. The procedure we outline offers promising results and a novel approach to predictive monitoring.
Inflammation protein quantification by multiple reaction monitoring mass spectrometry in lipopolysaccharide‐stimulated THP‐1 cells
Authors: Illiano Anna , Pinto Gabriella , Gaglione Rosa , Arciello Angela , Amoresano Angela 
Published: July 2021

RationaleInflammation is a cascade of events mediated by a cytokine network triggering the cellular response. In order to monitor the modulation of the crucial inflammatory proteins, e.g., Tumour Necrosis Factor‐α (TNF‐α), Interferon‐γ (INF‐γ), Interleukin‐8 (IL‐8) and Interleukin‐10 (IL‐10), upon stimulation with endotoxins, differentiated and undifferentiated THP‐1 cells were treated with lipopolysaccharides (LPSs) from E. coli, key cell wall components of Gram‐negative bacteria.MethodsThe multiple reaction monitoring mass spectrometry (MRM‐MS) method was optimized by using the standard proteins to be quantified, in order to construct external calibration curves and define the analytical parameters. The developed method was used to quantify the above‐mentioned inflammatory proteins in THP‐1 differentiated cells upon stimulation with LPSs with high accuracy, sensitivity, and robustness.ResultsThe analysis of such proteins in MRM mode allowed the kinetics of stimulation along the time up to 24 h to be followed and the MS results were found to be comparable with those obtained by Western‐blotting. A significant increase in TNF‐α release triggered a cascade mechanism leading to the production of INF‐γ and IL‐8. IL‐10, instead, was found to be constant throughout the process.ConclusionsThe developed MRM‐MS method allowed the quantification of TNF‐α, INF‐γ, IL‐8 and IL‐10 along a time‐course from 2 to 24 h. Hence, a trace of the kinetics of the inflammatory response in THP‐1 cells upon stimulation with E. coli LPSs was obtained. Finally, the extensibility of the developed MRM method to serum samples and other matrices demonstrated the versatility of the approach and the possibility to quantify multiple target proteins in different biological samples by using a few microliters in a single analysis.
Controlled CRISPR‐Cas9 Ribonucleoprotein Delivery for Sensitized Photothermal Therapy
Authors: Chen Chao , Ma Yupei , Du Shiyu , Wu Yueyao , Shen Peiliang , Yan Tao , Li Xueqing , Song Yujun , Zha Zhengbao , Han Xin 
Published: July 2021

AbstractManipulation of CRISPR delivery for stimuli‐responsive gene editing is crucial for cancer therapeutics through maximizing efficacy and minimizing side‐effects. However, realizing controlled gene editing for synergistic combination therapy remains a key challenge. Here, a near‐infrared (NIR) light‐triggered thermo‐responsive copper sulfide (CuS) multifunctional nanotherapeutic platform is constructed to achieve controlled release of CRISPR‐Cas9 ribonucleoprotein (RNP) and doxorubicin for tumor synergistic combination therapy involving in gene therapy, mild‐photothermal therapy (PTT), and chemotherapy. The semiconductor CuS serves as a “photothermal converter” and can stably convert NIR light (808 nm) into local thermal effect to provide photothermal stimulation. The double‐strand formed between CuS nanoparticle‐linked DNA fragments and single‐guide RNA is employed as a controlled element in response to photothermal stimulation for controlled gene editing and drug release. Hsp90α, one subunit of heat shock protein 90 (Hsp90), is targeted by Cas9 RNP to reduce tumor heat tolerance for enhanced mild‐PTT effects (≈43 °C). Significant synergistic therapy efficacy can be observed by twice NIR light irradiation both in vitro and in vivo, compared to PTT alone. Overall, this exogenously controlled method provides a versatile strategy for controlled gene editing and drug release with potentially synergistic combination therapy.
Long‐Residence Pneumonia Vaccine Developed Using PEG‐Grafted Hybrid Nanovesicles from Cell Membrane Fusion of Mycoplasma and IFN‐γ‐Primed Macrophages
Authors: Zhang Zhenzhen , Wang Haiyan , Xie Xing , Chen Rong , Li Jun , Ni Bo , Yu Pei , Liu Zunfeng , Shao Guoqing , Xiong Qiyan , Wei Yanna , Liu Beibei , Feng Zhixin , Zhou Xiang , Zhang Chao 
Published: July 2021

AbstractCD8+ T cell responses play a critical regulatory role in protection against mycoplasma infection‐related respiratory diseases. Nanovesicles derived from cell membranes have been shown to induce CD8+ T cell responses. Moreover, the short residence time of mycoplasma membrane‐related vaccines in local lymph nodes limits the efficacy of current mycoplasma vaccines. Here, a long‐residence pneumonia vaccine is developed using nanovesicles prepared by cell membrane fusion of Mycoplasma hyopneumoniae and interferon‐γ (IFN‐γ   )‐primed macrophages, which are grafted with polyethylene glycol to increase residence time in the lymph nodes. Upregulation of intercellular adhesion molecule‐1 (ICAM‐1) on the membrane of IFN‐γ‐primed macrophages increases the targeting of the hybrid nanovesicle vaccine to the local lymph nodes, with increased CD8+ T cell activation. A mechanistic study reveals that CD8+ T cell activation is achieved via a pathway involving upregulation of C‐C motif chemokine ligand 2/3 expression by E26 transformation‐specific sequences, followed by increased immune‐stimulatory activity of dendritic cells. In vivo, prophylactic testing reveals that the hybrid nanovesicle vaccine triggers a long‐term immune response, as evidenced by a memory CD8+ T cell response against mycoplasma infection. The current study provides a new design strategy for mycoplasma vaccines that involves a hybrid method using biological sources and artificial modification.
Electric Field Induced Biomimetic Transmembrane Electron Transport Using Carbon Nanotube Porins
Authors: Hicks Jacqueline M. , Yao Yun‐Chiao , Barber Sydney , Neate Nigel , Watts Julie A. , Noy Aleksandr , Rawson Frankie J. 
Published: July 2021

AbstractCells modulate their homeostasis through the control of redox reactions via transmembrane electron transport systems. These are largely mediated via oxidoreductase enzymes. Their use in biology has been linked to a host of systems including reprogramming for energy requirements in cancer. Consequently, the ability to modulate membrane redox systems may give rise to opportunities to modulate underlying biology. The current work aims to develop a wireless bipolar electrochemical approach to form on‐demand electron transfer across biological membranes. To achieve this goal, it is shown that by using membrane inserted carbon nanotube porins (CNTPs) that can act as bipolar nanoelectrodes, one can control electron flow with externally applied electric fields across membranes. Before this work, bipolar electrochemistry has been thought to require high applied voltages not compatible with biological systems. It is shown that bipolar electrochemical reaction via gold reduction at the nanotubes can be modulated at low cell‐friendly voltages, providing an opportunity to use bipolar electrodes to control electron flux across membranes. The authors provide new mechanistic insight into this newly describe phenomena at the nanoscale. The results presented give rise to a new method using CNTPs to modulate cell behavior via wireless control of membrane electron transfer.
Diseases and histopathological findings from lesional pinnae of 10 bats
Authors: Boone Johann M. , Fountain Kay , Williams Jonathan , Lloyd David H. , Killick Rowena , Rodriguez Barbón Alberto , Stidworthy Mark F. , Loeffler Anette 
Published: July 2021

AbstractPinnae are vital structures for echolocation and survival in many species of bats. Pinnal lesions have been described as common in captive bats, but information on specific diseases affecting the pinnae is scarce. A collection of histological sections of lesional pinnae from 10 bats, archived by bat conservation centers worldwide, was examined to identify potential aetiologies of disease. No neoplastic changes were seen but all pinnae showed inflammation, most commonly intraepidermal pustular dermatitis, deep perivascular dermatitis, nodular and/or diffuse dermatitis, and panniculitis. All bats with deep inflammation had concurrent pinnal perichondritis and cartilage necrosis. Microbial overgrowth was frequent, and pyoderma was confirmed in two bats based on histopathological and culture findings. Although no single aetiological agent was identified, deep inflammation was common and severe, highlighting the potential detriment to affected bats and the need for future study of these delicate structures.
New Aspects of Uranium Ore Concentration by using Acidic Media Solutions
Authors: Aly Hanan A. S. , El‐Taher Atef , Tork Hossam S. , Abdel‐Rahman Mohamed A. E. 
Published: July 2021

AbstractThe present investigation aims to compare the leaching characteristics of uranium isotopes in acidic and alkaline dissolving solutions with different concentrations. The leachate of uranium is prepared from sedimentary rocks collected from SW Sinai, Egypt. The uranium isotope activity concentration was measured using gamma counting recorded by the HPGe detector. Additionally, activity ratios as well as the leaching efficiency of different uranium isotopes were calculated. Results have shown that sulfuric acid at 40 % has been able to outpace other concentrations in dissolving a higher ratio of uranium isotopes with a 1 : 4 solid to acid ratio and 2 days as soaking time.234Th contributes to the 234U activity causes a significant efficiency difference as opposed to 235U & 238U in prepared bearing solutions. The recorded pH values in a bearing solution of different samples at investigated leaching conditions were oscillated from −1.2 to 4 due to lead impurities diffusion to bearing solutions.
EFT compatible PBHs: effective spawning of the seeds for primordial black holes during inflation
Authors: Ashoorioon Amjad , Rostami Abasalt , Firouzjaee Javad T. 
Published: July 2021

Abstract
Most of the inflationary scenarios that try to explain the origin of Primordial Black Holes (PBHs) from the enhancements of the power spectrum to values of order one, at the relevant scales, run into clashes with the Effective Field Theory (EFT) criteria or fail to enhance the power spectrum to such large amplitudes. In this paper, we unravel a mechanism for enhancing the power spectrum during inflation that does not use the flattening of the potential or reduction of the sound speed of scalar perturbations. The mechanism is based on this observation in the formalism of Extended EFT of inflation (EEFToI) with the sixth order polynomial dispersion relation for scalar perturbations that if the quartic coefficient in the dispersion relation is negative and smaller than a certain threshold, the amplitude of the power spectrum is enhanced substantially. The instability mechanism must arrange to kick in at the scales of interest related to the mass of the PBHs one would like to produce, which can be ten(s) of solar mass PBHs, suitable for LIGO events, or 10−17− 10−13 solar mass PBHs, which can comprise the whole dark matter energy density. We argue that the strong coupling is avoided for the range of parameters that the mechanisms enhance the power spectrum to the required amount.
Sharp boundaries for the swampland
Authors: Caron-Huot Simon , Mazáč Dalimil , Rastelli Leonardo , Simmons-Duffin David 
Published: July 2021

Abstract
We reconsider the problem of bounding higher derivative couplings in consistent weakly coupled gravitational theories, starting from general assumptions about analyticity and Regge growth of the S-matrix. Higher derivative couplings are expected to be of order one in the units of the UV cutoff. Our approach justifies this expectation and allows to prove precise bounds on the order one coefficients. Our main tool are dispersive sum rules for the S-matrix. We overcome the difficulties presented by the graviton pole by measuring couplings at small impact parameter, rather than in the forward limit. We illustrate the method in theories containing a massless scalar coupled to gravity, and in theories with maximal supersymmetry.
Interior product, Lie derivative and Wilson line in the KBc subsector of open string field theory
Authors: Hata Hiroyuki , Takeda Daichi 
Published: July 2021

Abstract
The open string field theory of Witten (SFT) has a close formal similarity with Chern-Simons theory in three dimensions. This similarity is due to the fact that the former theory has concepts corresponding to forms, exterior derivative, wedge product and integration over the manifold. In this paper, we introduce the interior product and the Lie derivative in the KBc subsector of SFT. The interior product in SFT is specified by a two-component “tangent vector” and lowers the ghost number by one (like the ordinary interior product maps a p-form to (p − 1)-form). The Lie derivative in SFT is defined as the anti-commutator of the interior product and the BRST operator. The important property of these two operations is that they respect the KBc algebra.Deforming the original (K, B, c) by using the Lie derivative, we can consider an infinite copies of the KBc algebra, which we call the KBc manifold. As an application, we construct the Wilson line on the manifold, which could play a role in reproducing degenerate fluctuation modes around a multi-brane solution.
Primary metabolic processes as drivers of leaf ageing
Authors: Kanojia Aakansha , Shrestha Deny K. , Dijkwel Paul P. 
Published: July 2021

AbstractAgeing in plants is a highly coordinated and complex process that starts with the birth of the plant or plant organ and ends with its death. A vivid manifestation of the final stage of leaf ageing is exemplified by the autumn colours of deciduous trees. Over the past decades, technological advances have allowed plant ageing to be studied on a systems biology level, by means of multi-omics approaches. Here, we review some of these studies and argue that these provide strong support for basic metabolic processes as drivers for ageing. In particular, core cellular processes that control the metabolism of chlorophyll, amino acids, sugars, DNA and reactive oxygen species correlate with leaf ageing. However, while multi-omics studies excel at identifying correlative processes and pathways, molecular genetic approaches can provide proof that such processes and pathways control ageing, by means of knock-out and ectopic expression of predicted regulatory genes. Therefore, we also review historic and current molecular evidence to directly test the hypotheses unveiled by the systems biology approaches. We found that the molecular genetic approaches, by and large, confirm the multi-omics-derived hypotheses with notable exceptions, where there is scant evidence that chlorophyll and DNA metabolism are important drivers of leaf ageing. We present a model that summarises the core cellular processes that drive leaf ageing and propose that developmental processes are tightly linked to primary metabolism to inevitably lead to ageing and death.
Total body irradiation as part of conditioning regimens in childhood leukemia—long-term outcome, toxicity, and secondary malignancies
Authors: Gruen Arne , Exner Sebastian , Kühl Jörn-Sven , von Stackelberg Arend , Budach Volker , Stromberger Carmen , Boehmer Dirk 
Published: July 2021

Abstract
Background
Total body irradiation (TBI) is an established part of conditioning regimens prior to stem cell transplantation in childhood leukemia but is associated with long-term toxicity. We retrospectively analyzed survival, long-term toxicity, and secondary malignancies in a pooled cohort of pediatric patients (pts.) treated with the same TBI regimen.

Methods
Analyzed were 109 pts. treated between September 1996 and November 2015. Conditioning treatment according to EBMT guidelines and the ALL SCTped 2012 FORUM trial consisted of chemotherapy (CT) and TBI with 2 Gy b.i.d. on 3 consecutive days to a total dose of 12 Gy. Median follow-up was 97.9 months (2–228 months).

Results
Overall survival (OS) in our cohort at 2, 5, and 10 years was 86.1, 75.5, and 63.0%, respectively. Median survival was not reached. Long-term toxicity developed in 47 pts. After chronically abnormal liver and kidney parameters in 31 and 7 pts., respectively, growth retardation was the most frequent finding as seen in 13 pts. Secondary malignancies were rare (n = 3).

Conclusion
TBI-containing conditioning regimens in pediatric stem cell transplantation (SCT) are highly effective. Efforts to replace TBI- with CT-containing regimens have only been successful in subgroups of pts. Although we could show long-term toxicity in 43% of pts., overall survival was 63% at 10 years. Still, long-term effects such as growth retardation can permanently impact the pts.’ quality of life and functioning. Along with new substances, efforts should be undertaken to optimize TBI techniques and accompany the treatment by systematic follow-up programs beyond 5 years to improve detection of rare events.
Development of B. carinata with super-high erucic acid content through interspecific hybridization
Authors: Roslinsky Vicky , Falk Kevin C. , Gaebelein Roman , Mason Annaliese S. , Eynck Christina 
Published: July 2021

Abstract
Key message
Disomic alien chromosome addition Brassica carinata lines with super-high erucic acid content were developed through interspecific hybridization with B. juncea and characterized using molecular, cytological and biochemical techniques.

Abstract
Brassica carinata [A.] Braun (BBCC, 2n = 34) is a climate-resilient oilseed. Its seed oil is high in erucic acid (> 40%), rendering it well suited for the production of biofuel and other bio-based applications. To enhance the competitiveness of B. carinata with high erucic B. napus (HEAR), lines with super-high erucic acid content were developed through interspecific hybridization. To this end, a fad2B null allele from Brassica juncea (AABB, 2n = 36) was introgressed into B. carinata, resulting in a B. carinata fad2B mutant with erucic acid levels of over 50%. Subsequently, the FAE allele from B. rapa spp. yellow sarson (AA, 2n = 20) was transferred to the fad2B B. carinata line, yielding lines with erucic acid contents of up to 57.9%. Molecular analysis using the Brassica 90 K Illumina Infinium™ SNP genotyping array identified these lines as disomic alien chromosome addition lines, with two extra A08 chromosomes containing the BrFAE gene. The alien chromosomes from B. rapa were clearly distinguished by molecular cytogenetics in one of the addition lines. Analysis of microspore-derived offspring and hybrids from crosses with a CMS B. carinata line showed that the transfer rate of the A08 chromosome into male gametes was over 98%, resulting in almost completely stable transmission of an A08 chromosome copy into the progeny. The increase in erucic acid levels was accompanied by changes in the proportions of other fatty acids depending on the genetic changes that were introduced in the interspecific hybrids, providing valuable insights into erucic acid metabolism in Brassica.
DR15-DQ6 remains dominantly protective against type 1 diabetes throughout the first five decades of life
Authors: Thomas Nicholas J. , Dennis John M. , Sharp Seth A. , Kaur Akaal , Misra Shivani , Walkey Helen C. , Johnston Desmond G. , Oliver Nick S. , Hagopian William A. , Weedon Michael N. , Patel Kashyap A. , Oram Richard A. 
Published: July 2021

AbstractAims/hypothesisAmong white European children developing type 1 diabetes, the otherwise common HLA haplotype DR15-DQ6 is rare, and highly protective. Adult-onset type 1 diabetes is now known to represent more overall cases than childhood onset, but it is not known whether DR15-DQ6 is protective in older-adult-onset type 1 diabetes. We sought to quantify DR15-DQ6 protection against type 1 diabetes as age of onset increased.MethodsIn two independent cohorts we assessed the proportion of type 1 diabetes cases presenting through the first 50 years of life with DR15-DQ6, compared with population controls. In the After Diabetes Diagnosis Research Support System-2 (ADDRESS-2) cohort (n = 1458) clinician-diagnosed type 1 diabetes was confirmed by positivity for one or more islet-specific autoantibodies. In UK Biobank (n = 2502), we estimated type 1 diabetes incidence rates relative to baseline HLA risk for each HLA group using Poisson regression. Analyses were restricted to white Europeans and were performed in three groups according to age at type 1 diabetes onset: 0–18 years, 19–30 years and 31–50 years.ResultsDR15-DQ6 was protective against type 1 diabetes through to age 50 years (OR < 1 for each age group, allp < 0.001). The following ORs for type 1 diabetes, relative to a neutral HLA genotype, were observed in ADDRESS-2: age 5–18 years OR 0.16 (95% CI 0.08, 0.31); age 19–30 years OR 0.10 (0.04, 0.23); and age 31–50 years OR 0.37 (0.21, 0.68). DR15-DQ6 also remained highly protective at all ages in UK Biobank. Without DR15-DQ6, the presence of major type 1 diabetes high-risk haplotype (either DR3-DQ2 or DR4-DQ8) was associated with increased risk of type 1 diabetes.Conclusions/interpretationHLA DR15-DQ6 confers dominant protection from type 1 diabetes across the first five decades of life.Graphical abstract
A continuum theory for mineral solid solutions undergoing chemo-mechanical processes
Authors: Clavijo Santiago P. , Espath Luis , Sarmiento Adel , Calo Victor M. 
Published: July 2021

AbstractRecent studies on metamorphic petrology as well as microstructural observations suggest the influence of mechanical effects upon chemically active metamorphic minerals. Thus, the understanding of such a coupling is crucial to describe the dynamics of geomaterials. In this effort, we derive a thermodynamically consistent framework to characterize the evolution of chemically active minerals. We model the metamorphic mineral assemblages as a solid-species solution where the species mass transport and chemical reaction drive the stress generation process. The theoretical foundations of the framework rely on modern continuum mechanics, thermodynamics far from equilibrium, and the phase-field model. We treat the mineral solid solution as a continuum body, and following the Larché and Cahn network model, we define displacement and strain fields. Consequently, we obtain a set of coupled chemo-mechanical equations. We use the aforementioned framework to study single minerals as solid solutions during metamorphism. Furthermore, we emphasise the use of the phase-field framework as a promising tool to model complex multi-physics processes in geoscience. Without loss of generality, we use common physical and chemical parameters found in the geoscience literature to portrait a comprehensive view of the underlying physics. Thereby, we carry out 2D and 3D numerical simulations using material parameters for mineral solid solutions to showcase and verify the chemo-mechanical interactions of mineral solid solutions that undergo spinodal decomposition, chemical reactions, and deformation.