bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel deep intronic variant strongly associates with Alkaptonuria
Authors: Lai Chien-Yi , Tsai I-Jung , Chiu Pao-Chin , Ascher David B. , Chien Yin-Hsiu , Huang Yu-Hsuan , Lin Yi-Lin , Hwu Wuh-Liang , Lee Ni-Chung 
Published: October 2021

AbstractAlkaptonuria is a rare autosomal recessive inherited disorder of tyrosine metabolism, which causes ochronosis, arthropathy, cardiac valvular calcification, and urolithiasis. The epidemiology of alkaptonuria in East Asia is not clear. In this study, patients diagnosed with alkaptonuria from January 2010 to June 2020 were reviewed. Their clinical and molecular features were further compared with those of patients from other countries. Three patients were found to have alkaptonuria. Mutation analyses of the homogentisate 1,2-dioxygenase gene (HGD) showed four novel variants c.16-2063 A > C, p.(Thr196Ile), p.(Gly344AspfsTer25), and p.(Gly362Arg) in six mutated alleles (83.3%). RNA sequencing revealed that c.16-2063 A > C activates a cryptic exon, causing protein truncation p.(Tyr5_Ile6insValTer17). A literature search identified another 6 patients with alkaptonuria in East Asia; including our cases, 13 of the 18 mutated alleles have not been reported elsewhere in the world. Alkaptonuria is rare in Taiwan and East Asia, with HGD variants being mostly novel and private.
A robust multiple-objective decision-making paradigm based on the water–energy–food security nexus under changing climate uncertainties
Authors: Enayati Maedeh , Bozorg-Haddad Omid , Fallah-Mehdipour Elahe , Zolghadr-Asli Babak , Chu Xuefeng 
Published: October 2021

AbstractFrom the perspective of the water–energy–food (WEF) security nexus, sustainable water-related infrastructure may hinge on multi-dimensional decision-making, which is subject to some level of uncertainties imposed by internal or external sources such as climate change. It is important to note that the impact of this phenomenon is not solely limited to the changing behavior patterns of hydro-climatic variables since it can also affect the other pillars of the WEF nexus both directly and indirectly. Failing to address these issues can be costly, especially for those projects with long-lasting economic lifetimes such as hydropower systems. Ideally, a robust plan can tolerate these projected changes in climatic behavior and their associated impacts on other sectors, while maintaining an acceptable performance concerning environmental, socio-economic, and technical factors. This study, thus, aims to develop a robust multiple-objective decision-support framework to address these concerns. In principle, while this framework is sensitive to the uncertainties associated with the climate change projections, it can account for the intricacies that are commonly associated with the WEF security network. To demonstrate the applicability of this new framework, the Karkheh River basin in Iran was selected as a case study due to its critical role in ensuring water, energy, and food security of the region. In addition to the status quo, a series of climate change projections (i.e., RCP 2.6, RCP 4.5, and RCP 8.5) were integrated into the proposed decision support framework as well. Resultantly, the mega decision matrix for this problem was composed of 56 evaluation criteria and 27 feasible alternatives. A TOPSIS/Entropy method was used to select the most robust renovation plan for a hydropower system in the basin by creating a robust and objective weighting mechanism to quantify the role of each sector in the decision-making process. Accordingly, in this case, the energy, food, and environment sectors are objectively more involved in the decision-making process. The results revealed that the role of the social aspect is practically negligible. The results also unveiled that while increasing the power plant capacity or the plant factor would be, seemingly, in favor of the energy sector, if all relevant factors are to be considered, the overall performance of the system might resultantly become sub-optimal, jeopardizing the security of other aspects of the water–energy–food nexus.
Prokaryotic responses to a warm temperature anomaly in northeast subarctic Pacific waters
Authors: Traving Sachia J. , Kellogg Colleen T. E. , Ross Tetjana , McLaughlin Ryan , Kieft Brandon , Ho Grace Y. , Peña Angelica , Krzywinski Martin , Robert Marie , Hallam Steven J. 
Published: October 2021

AbstractRecent studies on marine heat waves describe water temperature anomalies causing changes in food web structure, bloom dynamics, biodiversity loss, and increased plant and animal mortality. However, little information is available on how water temperature anomalies impact prokaryotes (bacteria and archaea) inhabiting ocean waters. This is a nontrivial omission given their integral roles in driving major biogeochemical fluxes that influence ocean productivity and the climate system. Here we present a time-resolved study on the impact of a large-scale warm water surface anomaly in the northeast subarctic Pacific Ocean, colloquially known as the Blob, on prokaryotic community compositions. Multivariate statistical analyses identified significant depth- and season-dependent trends that were accentuated during the Blob. Moreover, network and indicator analyses identified shifts in specific prokaryotic assemblages from typically particle-associated before the Blob to taxa considered free-living and chemoautotrophic during the Blob, with potential implications for primary production and organic carbon conversion and export.
Accurate detection and quantification of SARS-CoV-2 genomic and subgenomic mRNAs by ddPCR and meta-transcriptomics analysis
Authors: Oranger Annarita , Manzari Caterina , Chiara Matteo , Notario Elisabetta , Fosso Bruno , Parisi Antonio , Bianco Angelica , Iacobellis Michela , d’Avenia Morena , D’Erchia Anna Maria , Pesole Graziano 
Published: October 2021

AbstractSARS-CoV-2 replication requires the synthesis of a set of structural proteins expressed through discontinuous transcription of ten subgenomic mRNAs (sgmRNAs). Here, we have fine-tuned droplet digital PCR (ddPCR) assays to accurately detect and quantify SARS-CoV-2 genomic ORF1ab and sgmRNAs for the nucleocapsid (N) and spike (S) proteins. We analyzed 166 RNA samples from anonymized SARS-CoV-2 positive subjects and we observed a recurrent and characteristic pattern of sgmRNAs expression in relation to the total viral RNA content. Additionally, expression profiles of sgmRNAs, as determined by meta-transcriptomics sequencing of a subset of 110 RNA samples, were highly correlated with those obtained by ddPCR. By providing a comprehensive and dynamic snapshot of the levels of SARS-CoV-2 sgmRNAs in infected individuals, our results may contribute a better understanding of the dynamics of transcription and expression of the genome of SARS-CoV-2 and facilitate the development of more accurate molecular diagnostic tools for the stratification of COVID-19 patients.
Accelerating charge transfer via nonconjugated polyelectrolyte interlayers toward efficient versatile photoredox catalysis
Authors: Li Tao , Feng Chuang , Yap Boon Kar , Zhu Xuhui , Xiong Biquan , He Zhicai , Wong Wai-Yeung 
Published: October 2021

AbstractOne of the challenges for high-efficiency single-component-based photoredox catalysts is the low charge transfer and extraction due to the high recombination rate. Here, we demonstrate a strategy to precisely control the charge separation and transport efficiency of the catalytic host by introducing electron or hole extraction interlayers to improve the catalytic efficiency. We use simple and easily available non-conjugated polyelectrolytes (NCPs) (i.e., polyethyleneimine, PEI; poly(allylamine hydrochloride), PAH) to form interlayers, wherein such NCPs consist of the nonconjugated backbone with charge transporting functional groups. Taking CdS as examples, it is shown that although PEI and PAH are insulators and therefore do not have the ability to conduct electricity, they can form good electron or hole transport extraction layers due to the higher charge-transfer kinetics of pendant groups along the backbones, thereby greatly improving the charge transfer capability of CdS. Consequently, the resultant PEI-/PAH-functionalized nanocomposites exhibit significantly enhanced and versatile photoredox catalysis.
The Development of Cognate Awareness in Child Second/Third Language Learners of French in French Immersion: The Effects of Orthographic Overlap and Cognate Status
Authors: Hipfner-Boucher Kathleen , Pasquarella Adrian , Prasad Sonal , Chen Xi 
Published: October 2021

Purpose
Our 1-year longitudinal study tracked the development of cognate awareness among second (L2) and third language (L3) learners of French in French immersion in Grades 1 and 2 to explore the impact of orthographic overlap and cognate status (true vs. false) on children's ability to recognize cognate relationships. We also assessed the impact of French L2/L3 status on performance.

Method

We compared performance on three conditions (true cognates with same and similar spellings, false cognates with same spellings) within and across grades. We used a direct measure of cognate awareness that required children (
n
= 81) to distinguish true from false cognates presented orally and in print.

Results
Overall, Grade 1 children failed to recognize cognate relationships between true cognates with similar spellings, but successfully recognized true cognates with same spellings. Performance on all conditions increased significantly between Grades 1 and 2. The greatest improvement was seen on true cognates with similar spellings. Performance on false cognates was inferior to performance on true cognates with same spellings in Grade 1, and inferior to performance on both same and similar spelled true cognates in Grade 2. No differences were found due to L2/L3 status.

Conclusions
Among sequential learners of L2/L3 French in the early stages of additional language learning, cognate awareness is impacted by the degree of orthographic overlap, as well as by cognate status. Children's ability to recognize cross-language orthographic and semantic relationships improves substantially across the early elementary grades.

Supplemental Material

https://doi.org/10.23641/asha.16821106
Application of an Ageing Model to a Hydrogen-Fuelled PEM Fuel Cell
Authors: Riccardi Matteo , Romagnoli Marcello , Corda Giuseppe 
Published: October 2021

Hydrogen is one of the most promising energy vectors for achieving the decarbonization of the propulsion systems market. Polymer Electrolyte Membrane Fuel Cell system (PEMFCs) stand out in this panorama, thanks to reduced activation times and low temperatures of use, easily adapting to the needs of the sector. In this paper, a multi-phase, multi-component and non-isothermal 3D-CFD model is proposed to simulate the effects of PEMFC ageing, limiting the system durability due to slow membrane corrosion and loss of material performance and properties degradation, resulting in a reduced current density under equal voltage.
The model is applied both in 1D and 3D frameworks implementing a validated model from literature, allowing to estimate the useful life of the cell as a function of parameters such as the degradation rate and the crossover rate. Simulations are carried out at different membrane thicknesses and for different membrane conductivities, using a hydrogen-fuelled serpentine-type PEM fuel cell. The study relevance lies in the possibility to investigate the critical aspects limiting PEMFC system durability, as well as the optimal conditions of use, and it allows to identify corrective design actions.
The estimates of the ill-posedness index of the (deformed-) continuous Heisenberg spin equation
Authors: Zhong Penghong , Chen Ye , Yang Ganshan 
Published: October 2021

Although the exact treatment of the continuous Heisenberg spin is already known, the exact solution of the deformed system is not found in the literature. In this paper, some traveling wave solutions of the deformed (indicated by the coefficient α) continuous Heisenberg spin equation are obtained. Based on the exact solution being constructed here, the ill-posedness results are proved by the estimation of the Fourier integral in Ḣs. If α ≠ 0, the range of the mild ill-posedness index s is (1,32), which is consistent with the result of the formal analysis of the solution. Moreover, the upper bound of the strong ill-posedness index s jumps at α = 0: if α ≠ 0, the upper bound is 2; if α = 0, then the upper bound jumps to 32.
Advanced x-ray spectroscopy of actinide trichlorides
Authors: Butorin Sergei M. 
Published: October 2021

The application of core-to-core (3d-to-4f) resonant inelastic x-ray scattering (RIXS) and high-energy-resolution fluorescence-detected x-ray absorption (HERFD-XAS) at actinide M4,5 edges, as techniques with the enhanced sensitivity to changes in the chemical state, was analyzed for trivalent actinide compounds. As an example, a series of actinide chlorides AnCl3 (An = U, Np, Pu, Am, Cm, Bk, and Cf) was used. The crystal-field multiplet formalism was applied to calculate the 3d-4f RIXS maps, and the HERFD-XAS spectra were extracted as cuts of these RIXS maps along the incident energy axis at the constant emitted energy, corresponding to the maximum of the RIXS intensity. A relation between HERFD and conventional XAS methods was also examined. Despite some differences between profiles of the An M5 HERFD and conventional XAS spectra of trivalent actinides, the results of calculations indicate that the HERFD method can be used at the An M5 edge for monitoring even small variations in the An chemical state. As a whole, better agreement between the HERFD and XAS spectra was found for the An M4 edges as compared to the An M5 edges. By using the point charge electrostatic model, the dependence of the An M4,5 HERFD-XAS spectra on the An coordination number was studied, which indicates the significant sensitivity of the distribution of the An 5f states to the ligand structural arrangement around the An sites.
Soft hydraulics: from Newtonian to complex fluid flows through compliant conduits
Authors: Christov Ivan C 
Published: October 2021

Abstract
Microfluidic devices manufactured from soft polymeric materials have emerged as a paradigm for cheap, disposable and easy-to-prototype fluidic platforms for integrating chemical and biological assays and analyses. The interplay between the flow forces and the inherently compliant conduits of such microfluidic devices requires careful consideration. While mechanical compliance was initially a side-effect of the manufacturing process and materials used, compliance has now become a paradigm, enabling new approaches to microrheological measurements, new modalities of micromixing, and improved sieving of micro- and nano-particles, to name a few applications. This topical review provides an introduction to the physics of these systems. Specifically, the goal of this review is to summarize the recent progress towards a mechanistic understanding of the interaction between non-Newtonian (complex) fluid flows and their deformable confining boundaries. In this context, key experimental results and relevant applications are also explored, hand-in-hand with the fundamental principles for their physics-based modeling. The key topics covered include shear-dependent viscosity of non-Newtonian fluids, hydrodynamic pressure gradients during flow, the elastic response (deformation and bulging) of soft conduits due to flow within, the effect of cross-sectional conduit geometry on the resulting fluid–structure interaction, and key dimensionless groups describing the coupled physics. Open problems and future directions in this nascent field of soft hydraulics, at the intersection of non-Newtonian fluid mechanics, soft matter physics, and microfluidics, are noted.
Smart personal protective equipment (PPE): current PPE needs, opportunities for nanotechnology and e-textiles
Authors: Basodan Rayan A M , Park Byoungyoul , Chung Hyun-Joong 
Published: October 2021

Abstract
Smart personal protective equipment (PPE) is the future of improved occupational health and safety, and nanotechnology facilitates the development of critical smart PPE components such as smart textiles, wearable/flexible electronics, and augmented reality among others. Smart PPE utilizes sensing and communication technology in a way that is non-intrusive to either improve workplace safety or enhance occupational capabilities. The development of such smart PPE requires a multidisciplinary approach. This paper investigates the current state of PPE technologies for firefighters, healthcare workers, police/military, and construction workers. The modern PPE needs are identified from both end user surveys as well as expert third-party studies. There are already some smart PPE solutions for the challenges identified. Recent advances in stretchable and textile-based electronics, enabled by nanotechnology, demonstrate almost all imaginable solutions to the unmet needs that PPE users and expert advisor groups have identified. However, integration into smart PPE requires attention to the unique harsh conditions of hazardous workplaces. This review aims to inspire researchers in the field of flexible and printed electronics to develop and improve future smart PPE.
Biological activity validation of a computationally designed Rituximab/CD3 T cell engager targeting CD20+ cancers with multiple mechanisms of action
Authors: Cai Wenyan , Dong Jianbo , Gallolu Kankanamalage Sachith , Titong Allison , Shi Jiadong , Jia Zhejun , Wang Bo , Huang Cai , Zhang Jing , Lin Jun , Kan Steven Z , Han Shuhua , Zhou Joe , Liu Yue 
Published: October 2021

Abstract

Background
Bispecific T cell engaging antibodies (TEAs) with one arm targeting a cancer antigen and another arm binding to CD3 have demonstrated impressive efficacy in multiple clinical studies. However, establishing a safety/efficacy balance remains challenging. For instance, some TEAs have severe safety issues. Additionally, not all patients or all cancer cells of one patient respond equally to TEAs.

Methods
Here, we developed a next-generation bispecific TEA with better safety/efficacy balance and expanded mechanisms of action. Using the computer-aided antibody design strategy, we replaced heavy chain complementarity-determining regions (HCDRs) in one Rituximab arm with HCDRs from a CD3 antibody and generated a novel CD20/CD3 bispecific antibody.

Results
After series of computer-aided sequence optimization, the lead molecule, GB261, showed great safety/efficacy balance both in vitro and in animal studies. GB261 exhibited high affinity to CD20 and ultra-low affinity to CD3. It showed comparable T cell activation and reduced cytokine secretion compared with a benchmark antibody (BM). ADCC and CDC caused by GB261 only killed CD20+ cells but not CD3+ cells. It exhibited better RRCL cell killing than the BM in a PBMC-engrafted, therapeutic treatment mouse model and good safety in cynomolgus monkeys.

Conclusions
Thus, GB261 is a promising novel TEA against CD20+ cancers.
Case report: Stepwise transition from subcutaneous treprostinil to epoprostenol in high-risk pulmonary arterial hypertension
Authors: Mori Ana Laura , Rodríguez Andrea , Gagliardi Juan Alberto , Stewart Harris Alejandro 
Published: October 2021

Abstract

Background
Idiopathic pulmonary arterial hypertension is associated with high morbidity and mortality. In recent years, the use of targeted therapies has led to an improvement in prognosis. Prostacyclin analogues treprostinil and epoprostenol require continuous subcutaneous or intravenous infusion and are generally administered in a stepwise approach. However, there are no clear recommendations for transition in high-risk patients requiring high doses of prostacyclin analogues.

Case summary
In this report, we describe the case of a 20-year-old woman under combined treatment with sildenafil, macitentan, and treprostinil who required transition from subcutaneous treprostinil therapy to intravenous epoprostenol due to erratic drug absorption and functional class progression. The transition was performed over 48 h in a stepwise approach reducing treprostinil dose 4 ng/kg/min every 3 h while increasing epoprostenol infusion 2 ng/kg/min until achieving a maintenance dose of 32 ng/kg/min. There were no side effects requiring changes in the infusion rate.

Discussion
Patients with advanced pulmonary arterial hypertension may necessitate switching from subcutaneous treprostinil to epoprostenol. Although many protocols have been used to date, there are no guidelines to direct this process safely. This 48-h scheme based on the pharmacokinetic properties of each drug was successful and well-tolerated.
Myocardial infarction versus COVID-19 blood secretome
Authors: Sadykov V F , Bogdanova A A , Sergeev A A , Konovalova M V , Konstantinova E , Pyregov A V , Poltavtseva R A , Gilyarov M Y , Svirshchevskaya E V 
Published: October 2021

Abstract

Background
Both myocardial infarction (MI) and COVID-19 are characterized by cytokine storm in blood.

Purpose
The objective of this study was to compare the concentration of 39 cytokines, chemokines, and growth factors in blood sera of patients with MI, COVID-19 (COV), and healthy donors.

Methods
Patients' blood was collected within 1–2 days after hospitalization in the cardiovascular or COVID intensive care units. All COV patients were in a severe condition; all had increased C reactive protein, 86 and 95% had increased ferritin and D-dimers levels accordingly, 8–10 times decreased lymphocyte numbers. The analysis of the humoral factors in blood serum of MI (n=22), COV (n=23) and donors (n=27) was performed using a 39-plex cytometric analysis.

Results
Among all factors analyzed TGFa, IL-1b, 2, 3, 5, 9, 13, 17A were almost not detectable both in patient and donor sera. The concentrations of the other 31 humoral factors in normal sera differed significantly from 0 to 22000 pg/mL. We divided them into house-keeping factors HKF ranged from 1000 to 22000 pg/mL; sentinel innate immunity factors SIF (30–200 pg/mL), and acute phase factors APF (0–30 pg/mL). HKF were detected in all samples. Among SIF and APF IL-1a, G-CSF, IFNa2, IL-7, MIP-1a, IL-12, and IFNg were detected in 56–80% donor blood while IL-1RA, MCP-3, IL-2, 6, 10, 12, 15, FLT-3F, GM-CSF, TNF-b – only in 10–55%. At the same time all MI patients were 100% positive in all these factors showing extensive activation of blood secretome. Among low incidence APF cytokines in COV patients, percentage of IL-1RA, MCP-3, IFNa2, IL-6, 10, 15, FLT-3L negative sera decreased 3–5 times; and all sera were positive for MIP-1a and IL-12. At the same time TNF-a level decreased significantly from 0 in control to 85% of negative sera in COV patients. Summarized results are shown as the ratios of factor concentrations in MI or COV sera to normal control (Fig). Blood secretome of MI changed more significantly than of COV patients. The major factors (shown in red) in MI were IL-6, IL-12, IFNg, FLT-3L, GM-CSF, and IL-15, which increased 12, 9, 6, 6, 6, and 5 times accordingly. In COV sera IL-6, IL-10, IP-10, and MCP-3 increased by 28, 12, 10, and 9 times accordingly. Less expressed however significant increases are marked with asterisks.

Conclusions
Acute MI is characterized by severe disturbances in blood secretome with an increased level of 25 out of 39 factors studied. Contrary to it, in COV patients the levels of IL-6, 10, IP-10, and MCP-3 were more enhanced while only 15 out of 31 exceeded normal levels.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): Public Institution