bluuebunny/crossref_metadata_2025 huggingface dataset:
A Physically Based Model of a Two‐Pass Digital Filter for Separating Groundwater Runoff From Streamflow Time Series
Authors: Pozdniakov Sergey P. , Wang Ping , Grinevsky Sergey O. , Frolova Natalia L.
Published: March 2022

Groundwater runoff is an important component of river runoff and is sensitive to climate change. However, it is difficult to differentiate groundwater runoff from total river runoff by current base flow separation methods. Here, we propose a physically based model with a two‐pass digital filter for separating groundwater runoff from streamflow time series. The proposed method is based on the fundamental theory of surface–groundwater interactions under a variable groundwater recharge process that is highly associated with river stages. Our results show that the groundwater flow recession constant and the base flow recession constant can be determined separately by performing variogram analysis on long‐term streamflow time series data. For watersheds with areas of 103–104 km2, the groundwater flow recession constant differs from the typical values of the base flow recession constant by an order of magnitude or more. Therefore, the developed method can be used to quantify groundwater runoff dynamics on a temporal scale spanning tens of years. Unlike other approaches to base flow separation, our proposed method can reveal the effects of climate change on groundwater runoff.
At-Home Astronomers Help Discover a New, Unique Exoplanet
Authors: Besl J.
Published: March 2022

Amateur astronomers sifting through NASA’s public data uncovered a long-orbit gas giant that could help scientists understand how these planets form.
Adverse childhood experiences and severity levels of inflammation and depression from childhood to young adulthood: a longitudinal cohort study
Authors: Iob Eleonora , Lacey Rebecca , Giunchiglia Valentina , Steptoe Andrew
Published: March 2022

Adverse childhood experiences (ACEs) are associated with depression and systemic inflammation in adults. However, limited longitudinal research has tested these relationships in children and young people, and it is unclear whether inflammation is an underlying mechanism through which ACEs influence depression. We examined the longitudinal associations of several ACEs across different early-life periods with longitudinal patterns of early-life inflammation and depression in young adulthood and assessed the mediating role of inflammation. The data came from the Avon Longitudinal Study of Parents and Children (N = 3931). ACEs from the prenatal period through to adolescence were operationalised using cumulative scores, single adversities, and dimensions derived through factor analysis. Inflammation (C-reactive protein) was measured on three occasions (9–18 years) and depressive symptoms were ascertained on four occasions (18–23 years). Latent class growth analysis was employed to delineate group-based trajectories of inflammation and depression. The associations between ACEs and the inflammation/depression trajectories were tested using multinomial logistic regression analysis. Most types of ACEs across all early-life periods were associated with elevated depression trajectories, with larger associations for threat-related adversities compared with other ACEs. Bullying victimisation and sexual abuse in late childhood/adolescence were associated with elevated CRP trajectories, while other ACEs were unrelated to inflammation. Inflammation was also unrelated to depression and did not mediate the associations with ACEs. These results suggest that ACEs are consistently associated with depression, whereas the associations of inflammation with ACEs and depression are weak in young people. Interventions targeting inflammation in this population might not offer protection against depression.
Seasonal variability of ocean circulation near the Dotson Ice Shelf, Antarctica
Authors: Yang H. W. , Kim T.-W. , Dutrieux Pierre , Wåhlin A. K. , Jenkins Adrian , Ha H. K. , Kim C. S. , Cho K.-H. , Park T. , Lee S. H. , Cho Y.-K.
Published: March 2022

Recent rapid thinning of West Antarctic ice shelves are believed to be caused by intrusions of warm deep water that induce basal melting and seaward meltwater export. This study uses data from three bottom-mounted mooring arrays to show seasonal variability and local forcing for the currents moving into and out of the Dotson ice shelf cavity. A southward flow of warm, salty water had maximum current velocities along the eastern channel slope, while northward outflows of freshened ice shelf meltwater spread at intermediate depth above the western slope. The inflow correlated with the local ocean surface stress curl. At the western slope, meltwater outflows followed the warm influx along the eastern slope with a ~2–3 month delay. Ocean circulation near Dotson Ice Shelf, affected by sea ice distribution and wind, appears to significantly control the inflow of warm water and subsequent ice shelf melting on seasonal time-scales.
A multi-factor trafficking site on the spliceosome remodeling enzyme BRR2 recruits C9ORF78 to regulate alternative splicing
Authors: Bergfort Alexandra , Preußner Marco , Kuropka Benno , Ilik İbrahim Avşar , Hilal Tarek , Weber Gert , Freund Christian , Aktaş Tuğçe , Heyd Florian , Wahl Markus C.
Published: March 2022

The intrinsically unstructured C9ORF78 protein was detected in spliceosomes but its role in splicing is presently unclear. We find that C9ORF78 tightly interacts with the spliceosome remodeling factor, BRR2, in vitro. Affinity purification/mass spectrometry and RNA UV-crosslinking analyses identify additional C9ORF78 interactors in spliceosomes. Cryogenic electron microscopy structures reveal how C9ORF78 and the spliceosomal B complex protein, FBP21, wrap around the C-terminal helicase cassette of BRR2 in a mutually exclusive manner. Knock-down of C9ORF78 leads to alternative NAGNAG 3′-splice site usage and exon skipping, the latter dependent on BRR2. Inspection of spliceosome structures shows that C9ORF78 could contact several detected spliceosome interactors when bound to BRR2, including the suggested 3′-splice site regulating helicase, PRPF22. Together, our data establish C9ORF78 as a late-stage splicing regulatory protein that takes advantage of a multi-factor trafficking site on BRR2, providing one explanation for suggested roles of BRR2 during splicing catalysis and alternative splicing.
Single-cell transcriptomics links malignant T cells to the tumor immune landscape in cutaneous T cell lymphoma
Authors: Liu Xiangjun , Jin Shanzhao , Hu Simeng , Li Ruoyan , Pan Haihao , Liu Yi , Lai Pan , Xu Deshu , Sun Jingru , Liu Ziyang , Gao Yumei , Zhao Yifan , Liu Fengjie , Xiao Yu , Li Yingyi , Wen Yujie , Chen Zhuojing , Xu Bufang , Lin Yuchieh , Ran Menglong , Li Qianxi , Yang Shuxia , Li Hang , Tu Ping , Haniffa Muzlifah , Teichmann Sarah A. , Bai Fan , Wang Yang
Published: March 2022

Cutaneous T cell lymphoma (CTCL) represents a heterogeneous group of non-Hodgkin lymphoma distinguished by the presence of clonal malignant T cells. The heterogeneity of malignant T cells and the complex tumor microenvironment remain poorly characterized. With single-cell RNA analysis and bulk whole-exome sequencing on 19 skin lesions from 15 CTCL patients, we decipher the intra-tumor and inter-lesion diversity of CTCL patients and propose a multi-step tumor evolution model. We further establish a subtyping scheme based on the molecular features of malignant T cells and their pro-tumorigenic microenvironments: the TCyEM group, demonstrating a cytotoxic effector memory T cell phenotype, shows more M2 macrophages infiltration, while the TCM group, featured by a central memory T cell phenotype and adverse patient outcome, is infiltrated by highly exhausted CD8+ reactive T cells, B cells and Tregs with suppressive activities. Our results establish a solid basis for understanding the nature of CTCL and pave the way for future precision medicine for CTCL patients.
Precision of morphogen gradients in neural tube development
Authors: Vetter Roman , Iber Dagmar
Published: March 2022

Morphogen gradients encode positional information during development. How high patterning precision is achieved despite natural variation in both the morphogen gradients and in the readout process, is still largely elusive. Here, we show that the positional error of gradients in the mouse neural tube has previously been overestimated, and that the reported accuracy of the central progenitor domain boundaries in the mouse neural tube can be achieved with a single gradient, rather than requiring the simultaneous readout of opposing gradients. Consistently and independently, numerical simulations based on measured molecular noise levels likewise result in lower gradient variabilities than reported. Finally, we show that the patterning mechanism yields progenitor cell numbers with even greater precision than boundary positions, as gradient amplitude changes do not affect interior progenitor domain sizes. We conclude that single gradients can yield the observed developmental precision, which provides prospects for tissue engineering.
Cryo-EM structure of a SARS-CoV-2 omicron spike protein ectodomain
Authors: Ye Gang , Liu Bin , Li Fang
Published: March 2022

The omicron variant of SARS-CoV-2 has been spreading rapidly across the globe. The virus-surface spike protein plays a critical role in the cell entry and immune evasion of SARS-CoV-2. Here we determined the 3.0 Å cryo-EM structure of the omicron spike protein ectodomain. In contrast to the original strain of SARS-CoV-2 where the receptor-binding domain (RBD) of the spike protein takes a mixture of open (“standing up”) and closed (“lying down”) conformations, the omicron spike molecules are predominantly in the open conformation, with one upright RBD ready for receptor binding. The open conformation of the omicron spike is stabilized by enhanced inter-domain and inter-subunit packing, which involves new mutations in the omicron strain. Moreover, the omicron spike has undergone extensive mutations in RBD regions where known neutralizing antibodies target, allowing the omicron variant to escape immune surveillance aimed at the original viral strain. The stable open conformation of the omicron spike sheds light on the cell entry and immune evasion mechanisms of the omicron variant.
Distinct metabolic profiles associated with autism spectrum disorder versus cancer in individuals with germline PTEN mutations
Authors: Yehia Lamis , Ni Ying , Sadler Tammy , Frazier Thomas W. , Eng Charis
Published: March 2022

PTEN hamartoma tumor syndrome (PHTS), caused by germline PTEN mutations, has been associated with organ-specific cancers and autism spectrum disorder (ASD) and/or developmental delay (DD). Predicting precise clinical phenotypes in any one PHTS individual remains impossible. We conducted an untargeted metabolomics study on an age- and sex-matched series of PHTS individuals with ASD/DD, cancer, or both phenotypes. Using agnostic metabolomic-analyses from patient-derived lymphoblastoid cells and their spent media, we found 52 differentially abundant individual metabolites, 69 cell/media metabolite ratios, and 327 pair-wise metabotype (shared metabolic phenotype) ratios clearly distinguishing PHTS individuals based on phenotype. Network analysis based on significant metabolites pointed to hubs converging on PTEN-related insulin, MAPK, AMPK, and mTOR signaling cascades. Internal cross-validation of significant metabolites showed optimal overall accuracy in distinguishing PHTS individuals with ASD/DD versus those with cancer. Such metabolomic markers may enable more accurate risk predictions and prevention in individual PHTS patients at highest risk.
Green flexible electronics based on starch
Authors: Xiang Huacui , Li Zhijian , Liu Hanbin , Chen Tao , Zhou Hongwei , Huang Wei
Published: March 2022

Flexible electronics (FEs) with excellent flexibility or foldability may find widespread applications in the wearable devices, artificial intelligence (AI), Internet of Things (IoT), and other areas. However, the widely utilization may also bring the concerning for the fast accumulation of electronic waste. Green FEs with good degradability might supply a way to overcome this problem. Starch, as one of the most abundant natural polymers, has been exhibiting great potentials in the development of environmental-friendly FEs due to its inexpensiveness, good processability, and biodegradability. Lots of remarks were made this field but no summary was found. In this review, we discussed the preparation and applications of starch-based FEs, highlighting the role played by the starch in such FEs and the impacts on the properties. Finally, the challenge was discussed and the outlook for the further development was also presented.
Haemagglutinin antigen selectively targeted to chicken CD83 overcomes interference from maternally derived antibodies in chickens
Authors: Shrestha Angita , Meeuws Rick , Sadeyen Jean-Remy , Chang Pengxiang , Van Hulten Marielle , Iqbal Munir
Published: March 2022

Maternally derived antibodies (MDAs) are important for protecting chickens against pathogens in the neonatal stage however, they often interfere with vaccine performance. Here, we investigated the effects of MDAs on a targeted antigen delivery vaccine (TADV), which is developed by conjugating H9 subtype avian influenza virus haemagglutinin (HA) antigen to single chain fragment variable (scFv) antibodies specific for the chicken antigen presenting cell receptor CD83. Groups of 1-day-old chickens carrying high levels of MDAs (MDA++) and 14-day old chickens carrying medium levels of MDAs (MDA+) were immunised with TADV (rH9HA-CD83 scFv), untargeted rH9HA or inactivated H9N2 vaccines. Immunogenicity in these vaccinated chickens was compared using haemagglutination inhibition (HI) and enzyme-linked immunosorbent assays (ELISA). The results showed that the TADV (rH9HA-CD83 scFv) induced significantly higher levels of H9HA-specific antibody titres compared to the untargeted rH9HA and inactivated H9N2 vaccines in MDA++ and MDA+ chickens. Overall, the data demonstrates immune responses induced by TADV are not affected by the MDA in chickens.
Antibody evasion properties of SARS-CoV-2 Omicron sublineages
Authors: Iketani Sho , Liu Lihong , Guo Yicheng , Liu Liyuan , Chan Jasper F.-W. , Huang Yiming , Wang Maple , Luo Yang , Yu Jian , Chu Hin , Chik Kenn K.-H. , Yuen Terrence T.-T. , Yin Michael T. , Sobieszczyk Magdalena E. , Huang Yaoxing , Yuen Kwok-Yung , Wang Harris H. , Sheng Zizhang , Ho David D.
Published: March 2022

The identification of the Omicron (B.1.1.529.1 or BA.1) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Botswana in November 20211 immediately caused concern owing to the number of alterations in the spike glycoprotein that could lead to antibody evasion. We2 and others3–6 recently reported results confirming such a concern. Continuing surveillance of the evolution of Omicron has since revealed the rise in prevalence of two sublineages, BA.1 with an R346K alteration (BA.1+R346K, also known as BA.1.1) and B.1.1.529.2 (BA.2), with the latter containing 8 unique spike alterations and lacking 13 spike alterations found in BA.1. Here we extended our studies to include antigenic characterization of these new sublineages. Polyclonal sera from patients infected by wild-type SARS-CoV-2 or recipients of current mRNA vaccines showed a substantial loss in neutralizing activity against both BA.1+R346K and BA.2, with drops comparable to that already reported for BA.1 (refs. 2,3,5,6). These findings indicate that these three sublineages of Omicron are antigenically equidistant from the wild-type SARS-CoV-2 and thus similarly threaten the efficacies of current vaccines. BA.2 also exhibited marked resistance to 17 of 19 neutralizing monoclonal antibodies tested, including S309 (sotrovimab)7, which had retained appreciable activity against BA.1 and BA.1+R346K (refs. 2–4,6). This finding shows that no authorized monoclonal antibody therapy could adequately cover all sublineages of the Omicron variant, except for the recently authorized LY-CoV1404 (bebtelovimab).
Designing sensitive viral diagnostics with machine learning
Authors: Metsky Hayden C. , Welch Nicole L. , Pillai Priya P. , Haradhvala Nicholas J. , Rumker Laurie , Mantena Sreekar , Zhang Yibin B. , Yang David K. , Ackerman Cheri M. , Weller Juliane , Blainey Paul C. , Myhrvold Cameron , Mitzenmacher Michael , Sabeti Pardis C.
Published: March 2022

Design of nucleic acid-based viral diagnostics typically follows heuristic rules and, to contend with viral variation, focuses on a genome’s conserved regions. A design process could, instead, directly optimize diagnostic effectiveness using a learned model of sensitivity for targets and their variants. Toward that goal, we screen 19,209 diagnostic–target pairs, concentrated on CRISPR-based diagnostics, and train a deep neural network to accurately predict diagnostic readout. We join this model with combinatorial optimization to maximize sensitivity over the full spectrum of a virus’s genomic variation. We introduce Activity-informed Design with All-inclusive Patrolling of Targets (ADAPT), a system for automated design, and use it to design diagnostics for 1,933 vertebrate-infecting viral species within 2 hours for most species and within 24 hours for all but three. We experimentally show that ADAPT’s designs are sensitive and specific to the lineage level and permit lower limits of detection, across a virus’s variation, than the outputs of standard design techniques. Our strategy could facilitate a proactive resource of assays for detecting pathogens.
Functional, metabolic and transcriptional maturation of human pancreatic islets derived from stem cells
Authors: Balboa Diego , Barsby Tom , Lithovius Väinö , Saarimäki-Vire Jonna , Omar-Hmeadi Muhmmad , Dyachok Oleg , Montaser Hossam , Lund Per-Eric , Yang Mingyu , Ibrahim Hazem , Näätänen Anna , Chandra Vikash , Vihinen Helena , Jokitalo Eija , Kvist Jouni , Ustinov Jarkko , Nieminen Anni I. , Kuuluvainen Emilia , Hietakangas Ville , Katajisto Pekka , Lau Joey , Carlsson Per-Ola , Barg Sebastian , Tengholm Anders , Otonkoski Timo
Published: March 2022

Transplantation of pancreatic islet cells derived from human pluripotent stem cells is a promising treatment for diabetes. Despite progress in the generation of stem-cell-derived islets (SC-islets), no detailed characterization of their functional properties has been conducted. Here, we generated functionally mature SC-islets using an optimized protocol and benchmarked them comprehensively against primary adult islets. Biphasic glucose-stimulated insulin secretion developed during in vitro maturation, associated with cytoarchitectural reorganization and the increasing presence of alpha cells. Electrophysiology, signaling and exocytosis of SC-islets were similar to those of adult islets. Glucose-responsive insulin secretion was achieved despite differences in glycolytic and mitochondrial glucose metabolism. Single-cell transcriptomics of SC-islets in vitro and throughout 6 months of engraftment in mice revealed a continuous maturation trajectory culminating in a transcriptional landscape closely resembling that of primary islets. Our thorough evaluation of SC-islet maturation highlights their advanced degree of functionality and supports their use in further efforts to understand and combat diabetes.
Transcriptional kinetics and molecular functions of long noncoding RNAs
Authors: Johnsson Per , Ziegenhain Christoph , Hartmanis Leonard , Hendriks Gert-Jan , Hagemann-Jensen Michael , Reinius Björn , Sandberg Rickard
Published: March 2022

An increasing number of long noncoding RNAs (lncRNAs) have experimentally confirmed functions, yet little is known about their transcriptional dynamics and it is challenging to determine their regulatory effects. Here, we used allele-sensitive single-cell RNA sequencing to demonstrate that, compared to messenger RNAs, lncRNAs have twice as long duration between two transcriptional bursts. Additionally, we observed increased cell-to-cell variability in lncRNA expression due to lower frequency bursting producing larger numbers of RNA molecules. Exploiting heterogeneity in asynchronously growing cells, we identified and experimentally validated lncRNAs with cell state-specific functions involved in cell cycle progression and apoptosis. Finally, we identified cis-functioning lncRNAs and showed that knockdown of these lncRNAs modulated the nearby protein-coding gene’s transcriptional burst frequency or size. In summary, we identified distinct transcriptional regulation of lncRNAs and demonstrated a role for lncRNAs in the regulation of mRNA transcriptional bursting.
Immune response to SARS-CoV-2 after a booster of mRNA-1273: an open-label phase 2 trial
Authors: Chu Laurence , Vrbicky Keith , Montefiori David , Huang Wenmei , Nestorova Biliana , Chang Ying , Carfi Andrea , Edwards Darin K. , Oestreicher Judy , Legault Holly , Dutko Frank J. , Girard Bethany , Pajon Rolando , Miller Jacqueline M. , Das Rituparna , Leav Brett , McPhee Roderick
Published: March 2022

Rising breakthrough infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in previously immunized individuals have raised concerns for the need for a booster vaccine dose to combat waning antibody levels and new variants. Here we report the results of the open-label, non-randomized part B of a phase 2 trial in which we evaluated the safety and immunogenicity of a booster injection of 50 µg of the coronavirus disease 2019 (COVID-19) vaccine mRNA-1273 in 344 adult participants immunized 6–8 months earlier with a primary series of two doses of 50 µg or 100 µg of mRNA-1273 (NCT04405076). Neutralizing antibody (nAb) titers against wild-type SARS-CoV-2 at 1 month after the booster were 1.7-fold (95% confidence interval (CI): 1.5, 1.9) higher than those at 28 days after the second injection of the primary series, which met the pre-specified non-inferiority criterion (primary immunogenicity objective) and might indicate a memory B cell response. The nAb titers against the Delta variant (B.1.617.2) (exploratory objective) at 1 month after the booster were 2.1-fold (95% CI: 1.8, 2.4) higher than those at 28 days after the second injection of the primary series. The seroresponse rate (95% CI (four-fold rise from baseline)) was 100% (98.7, 100.0) at 28 days after the booster compared to 98.3% (96.0, 99.4) after the primary series. The higher antibody titers at 28 days after the booster dose compared to 28 days after the second dose in the phase 3 COVE study were also observed in two assays for anti-spike IgG antibody measured by ELISA and by Meso Scale Discovery (MSD) Multiplex. The frequency of solicited local and systemic adverse reactions after the booster dose was similar to that after the second dose in the primary two-dose series of mRNA-1273 (50 µg or 100 µg); no new signals were observed in the unsolicited adverse events; and no serious adverse events were reported in the 1-month follow-up period. These results show that a booster injection of mRNA-1273 more than 6 months after completing the primary two-dose series is safe and elicited nAb titers that were statistically significantly higher than the peak titers detected after the primary vaccination series, suggesting that a booster dose of mRNA-1273 might result in increased vaccine effectiveness against infection and disease caused by SARS-CoV-2.
Modeling energy depletion in rat livers using Nash equilibrium metabolic pathway analysis
Authors: Lucia Angelo , Ferrarese Emily , Uygun Korkut
Published: March 2022

The current gold standard of Static Cold Storage (SCS), which is static cold storage on ice (about + 4 °C) in a specialized media such as the University of Wisconsin solution (UW), limits storage to few hours for vascular and metabolically active tissues such as the liver and the heart. The liver is arguably the pinnacle of metabolism in human body and therefore metabolic pathway analysis immediately becomes very relevant. In this article, a Nash Equilibrium (NE) approach, which is a first principles approach, is used to model and simulate the static cold storage and warm ischemia of a proposed model of liver cells. Simulations of energy depletion in the liver in static cold storage measured by ATP content and energy charge are presented along with comparisons to experimental data. In addition, conversion of Nash Equilibrium iterations to time are described along with an uncertainty analysis for the parameters in the model. Results in this work show that the Nash Equilibrium approach provides a good match to experimental data for energy depletion and that the uncertainty in model parameters is very small with percent variances less than 0.1%.
Federated learning for multi-center imaging diagnostics: a simulation study in cardiovascular disease
Authors: Linardos Akis , Kushibar Kaisar , Walsh Sean , Gkontra Polyxeni , Lekadir Karim
Published: March 2022

Deep learning models can enable accurate and efficient disease diagnosis, but have thus far been hampered by the data scarcity present in the medical world. Automated diagnosis studies have been constrained by underpowered single-center datasets, and although some results have shown promise, their generalizability to other institutions remains questionable as the data heterogeneity between institutions is not taken into account. By allowing models to be trained in a distributed manner that preserves patients’ privacy, federated learning promises to alleviate these issues, by enabling diligent multi-center studies. We present the first simulated federated learning study on the modality of cardiovascular magnetic resonance and use four centers derived from subsets of the M&M and ACDC datasets, focusing on the diagnosis of hypertrophic cardiomyopathy. We adapt a 3D-CNN network pretrained on action recognition and explore two different ways of incorporating shape prior information to the model, and four different data augmentation set-ups, systematically analyzing their impact on the different collaborative learning choices. We show that despite the small size of data (180 subjects derived from four centers), the privacy preserving federated learning achieves promising results that are competitive with traditional centralized learning. We further find that federatively trained models exhibit increased robustness and are more sensitive to domain shift effects.
High-speed imaging of light-induced photoreceptor microsaccades in compound eyes
Authors: Kemppainen Joni , Mansour Neveen , Takalo Jouni , Juusola Mikko
Published: March 2022

Inside compound eyes, photoreceptors contract to light changes, sharpening retinal images of the moving world in time. Current methods to measure these so-called photoreceptor microsaccades in living insects are spatially limited and technically challenging. Here, we present goniometric high-speed deep pseudopupil (GHS-DPP) microscopy to assess how the rhabdomeric insect photoreceptors and their microsaccades are organised across the compound eyes. This method enables non-invasive rhabdomere orientation mapping, whilst their microsaccades can be locally light-activated, revealing the eyes’ underlying active sampling motifs. By comparing the microsaccades in wild-type Drosophila’s open rhabdom eyes to spam-mutant eyes, reverted to an ancestral fused rhabdom state, and honeybee’s fused rhabdom eyes, we show how different eye types sample light information. These results show different ways compound eyes initiate the conversion of spatial light patterns in the environment into temporal neural signals and highlight how this active sampling can evolve with insects’ visual needs.
A hydrazine-directed Rh(iii) catalyzed (4+2) annulation with sulfoxonium ylides: synthesis and photophysical properties of dihydrocinnolines
Authors: Prabhakar Ganesh Pothapragada S. K. , Muthuraja Perumal , Gopinath Purushothaman
Published: March 2022

Hydrazine-directed, Rh(iii) catalyzed (4+2) annulation with sulfoxonium ylides.
Bifunctional Pt/Au Janus electrocatalysts for simultaneous oxidation/reduction of furfural with bipolar electrochemistry
Authors: Ketkaew Marisa , Assavapanumat Sunpet , Klinyod Sorasak , Kuhn Alexander , Wattanakit Chularat
Published: March 2022

We report the simultaneous electro-oxidation/-reduction of biomass-derived furfural in a one-pot approach, using bipolar electrochemistry with bifunctional Pt/Au Janus electrocatalysts, selectively into both, furfuryl alcohol and furoic acid.
Fabrication, thermal analysis, and heavy ion irradiation resistance of epoxy matrix nanocomposites loaded with silane-functionalized ceria nanoparticles
Authors: Chin Clare Davis-Wheeler , Ringgold Marissa A. , Redline Erica M. , Bregman Avi G. , Hattar Khalid , Peretti Amanda S. , Treadwell LaRico J.
Published: March 2022

This paper describes a detailed understanding of how nanofillers function as radiation barriers within the polymer matrix, and how their effectiveness is impacted by factors such as composition, size, loading, surface chemistry, and dispersion.
Interaction of chiral l-dialanine with Cu(100)
Authors: Martín Romano Juan Carlos , Casado Aguilar Pablo , Vázquez de Parga Amadeo L. , Garnica Manuela , Rodríguez de la Fuente Oscar , Rojo Juan M. , Niño Miguel Angel
Published: March 2022

l-Dialanine adsorbs on Cu(100) in the submonolayer regime as an entire, non-zwitterionic and strongly bound molecule. In subsequent layers the molecule is, instead, zwitterionic and loosely bound.
Universal shape of graphene nanobubbles on metallic substrate
Authors: Aslyamov Timur , Zahra Khadisha M. , Zhilyaev Petr , Walton Alex S.
Published: March 2022

Graphene nanobubbles on metallic substrate exhibit the universal shape.
Quantification of C, H, N and O in polymers using WDXRF scattering spectra and PLS regression depending on the spectral resolution
Authors: Breuckmann Michael , Wacker Georg , Hanning Stephanie , Otto Matthias , Kreyenschmidt Martin
Published: March 2022

The C, H, N and O composition of polymers, sometimes called “dark matrix”, is determined by wavelength dispersive X-ray fluorescence (WDXRF). The recovery was best for the lowest spectral resolution and highest recorded intensity.
An all-in-one nanomaterial derived from rGO-MoS2 for photo/chemotherapy of tuberculosis
Authors: Mehnath Sivaraj , Chitra Karuppannan , Jeyaraj Murugaraj
Published: March 2022

A combination of therapeutic modalities has recently emerged as an alternative technique for combating Mycobacterium tuberculosis.
Sulfonated carbons from agro-industrial residues: simple and efficient catalysts for the Biginelli reaction
Authors: do Nascimento Letícia Gomes , Dias Isabela Milhomem , de Souza Guilherme Botelho Meireles , Mourão Lucas Clementino , Pereira Mariana Bisinotto , Viana Júlio Cezár Vieira , Lião Luciano Morais , de Oliveira Guilherme Roberto , Alonso Christian Gonçalves
Published: March 2022

An eco-friendly catalyst prepared from rice husk was used to synthesize dihydropyrimidinones (DHPMs) and achieved a yield of 92%.
Electroconductive and photoactive poly(phenylenediamine)s with antioxidant and antimicrobial activities for potential photothermal therapy
Authors: Ghahremanloo Atefe , Zare Ehsan Nazarzadeh , Salimi Fatemeh , Makvandi Pooyan
Published: March 2022

Poly(ortho-phenylenediamine), poly(meta-phenylenediamine) and poly(para-phenylenediamine) with biological activities as good candidates for biomedical applications.
DNA/RNA sequencing using germanene nanoribbons via two dimensional molecular electronic spectroscopy: an ab initio study
Authors: Reza Rezapour M. , Biel Blanca
Published: March 2022

Germanene nanoribbons, compatible with the current technology of fabricating electronic devices, exhibit promising potential as a feasible nano-biosensor for DNA/RNA sequencing and molecular sensing provided the 2DMES technique is applied.
Reflective leaky waveguide gratings (LWGs) with internal referencing for sensing
Authors: Gupta Ruchi , Goddard Nicholas J.
Published: March 2022

Current transmission grating sensors are unsuitable for use in typical samples that absorb and scatter light.
Multiple annulations of inert C(sp2)–H bonds with alkynes
Authors: Saha Arijit , Shankar Majji , Sau Somratan , Sahoo Akhila K.
Published: March 2022

This feature article uncovers a tactical blueprint for the sustainable development of synthetic manifestations in the transition-metal catalyzed directing group assisted multiple annulations (L-type, Y-type, and B-type) of inert C(arene)–H bonds.
Rapid preparation of gaseous methanediol (CH2(OH)2)
Authors: Chen Yi-Fang , Chu Li-Kang
Published: March 2022

A simple way to generate gaseous CH2(OH)2via the evaporation of an aqueous formaldehyde solution.
A fluorogenic probe targeting two spatially separated enzymes for selective imaging of cancer cells
Authors: Park Sang-Hyun , Jung Hyoje , Kim Yujun , Shin Injae
Published: March 2022

We describe a fluorogenic probe BocLys(Ac)-AB-FC targeting both histone deacetylases (HDACs) and cathepsin l, which are overexpressed in spatially separated subcellular organelles of cancer cells.
Synthesis, structure and highly selective C3H8/CH4 and C2H6/CH4 adsorption of a (4,8)-c ternary flu-metal–organic framework based upon both [Sc4O2(COO)8] and [Cu4OCl6] clusters
Authors: Ding Min , Wang Qian , Cheng Hongtao , Bai Junfeng
Published: March 2022

A new ternary flu-MOF based upon both the torsional cubic 8-c [Sc4O2(COO)8] cluster and the tetrahedral 4-c [Cu4OCl6] cluster has been successfully synthesized and exhibits highly selective C3H8/CH4 and C2H6/CH4 adsorption.
Synthesis and characterization of thiocarbonato-linked platinum(iv) complexes
Authors: Barth Marie-Christin , Lange Stefanie , Häfner Norman , Ueberschaar Nico , Görls Helmar , Runnebaum Ingo B. , Weigand Wolfgang
Published: March 2022

Novel platinum(iv) complexes with thiocarbonate linkage were synthesized and their cytotoxic activity against ovarian carcinoma cell lines was investigated. Insights into the reaction with ascorbic acid were provided by UHPLC-HRMS.
The Co(ii)/spiroBox-catalyzed enantioselective Mukaiyama-Mannich reaction for the synthesis of quaternary α-amino acid derivatives
Authors: Li Yanshun , Gao Nanxing , Cao Guorui , Teng Dawei
Published: March 2022

Co(ii)/spiroBox-catalyzed Mukaiyama-Mannich reactions of enol silyl ethers with cyclic N-sulfonyl ketimino esters were examined and showed excellent yields and enantioselectivity values.
Mixed AgBiS2 nanocrystals for photovoltaics and photodetectors
Authors: Burgués-Ceballos Ignasi , Wang Yongjie , Konstantatos Gerasimos
Published: March 2022

We mix small-size and large-size AgBiS2 nanocrystals in a gradient fashion to judiciously favour the band alignment and maximise charge transport. Thin film solar cells show 7.3% efficiency and visible-near infrared photodetectors yield EQE >40%.
Convergent biomimetic semisynthesis of disesquiterpenoid rumphellolide J
Authors: Stakanovs Georgijs , Belyakov Sergey , Jirgensons Aigars , Rasina Dace
Published: March 2022

The gram-scale synthesis of disesquiterpenoid ester rumphellolide J (5) from (−)-β-caryophyllene (1) and (−)-caryophyllene oxide (3) via natural products 4β,8β-epoxycaryophyllan-5-ol (2) and (+)-rumphellaoic acid A (4) is demonstrated.
Targeting ASCT2-mediated glutamine metabolism inhibits proliferation and promotes apoptosis of pancreatic cancer cells
Authors: Wang Wenbin , Pan Haihua , Ren Feihua , Chen Hongxia , Ren Ping
Published: March 2022

Some tumor cells have a high rate of glutamine uptake and exhibit glutamine addiction. Alanine-serine cysteine-preferring transporter 2 (ASCT2) is a major mediator of glutamine supply in many tumor cells, but the underlying effects and mechanisms of ASCT2 in pancreatic cancer (PC) are largely unknown. Our results show that ASCT2 expression is significantly higher in PC than in normal pancreatic duct cells and pancreas. Utilizing the Kaplan–Meier Plotter database, a high expression of SLC1A5 mRNA was significantly associated with poor overall survival (OS) in patients with PC. shRNA-mediated inhibition of ASCT2 function in vitro can significantly decrease glutamine consumption, α-ketoglutarate (α-KG) production and ATP generation and increase the reactive oxygen species (ROS) level. Moreover, the antioxidant N-acetylcysteine partially attenuated the increase in the ROS levels and reduced ATP generation. These data suggest that ASCT2 mediates glutamine metabolism and maintains redox homeostasis in PC. To further investigate whether ASCT2 is involved in PC cell growth, we blocked ASCT2 activity with the ASCT2 inhibitor l-γ-glutamyl-p-nitroanilide (GPNA) and silenced the expression of ASCT2 with specific shRNAs. We found that the growth of PC cells was significantly inhibited. Additionally, knockdown of ASCT2 induced apoptosis through the Akt/mTOR signaling pathway. Furthermore, the loss of ASCT2 in BxPC-3 cell xenografts significantly inhibited tumor growth in vivo, and this effect was associated with an increase in cleaved caspase-3 expression and a decrease in Ki67 staining. Taken together, our results show that ASCT2 may be utilized as a putative therapeutic target for PC.
The histological type of endometrial cancer is not associated with menopause status at diagnosis
Authors: Sun Xinyi , Zhang Yi , Shen Fang , Liu Yang , Chen George Qiaoqi , Zhao Min , Chen Qi
Published: March 2022

The latest evidence suggests that type 2 endometrial cancer may not be completely oestrogen-independent, indicating that the status of hormonal change may not be associated with the traditional classification of endometrial cancer, including the histological subtypes. However, this has not been investigated. Menopause is commonly considered a state of hormonal change in women. In the present study, we investigated the association of menopause with the histological types of endometrial cancer. Data on the histological type, menopause status at diagnosis, age at diagnosis, parity, body mass index (BMI), and overall survival rate from 2122 cases were collected. The difference in risk in developing type 1 or type 2 endometrial cancer between premenopausal and postmenopausal patients was 5.457%. A statistical difference in the association of menopause with the histological types between the two groups was seen in endometrioid and serous carcinoma, with a risk difference of 5.6 or 3.8%. A statistical difference in the association of menopause with parity between the groups was only seen in endometrioid and adenosquamous carcinoma, with a risk difference of 7.1 or 3.7%. However, BMI was not associated with histological type and the overall survival rate was not associated with menopause (P=0.764). We reported a relatively small difference in the association of menopause with type 1 or type 2, or the histological types of endometrial cancer. The survival rate was not associated with menopause. Our study suggests that menopause status at diagnosis was not strongly associated with the histological subtypes of endometrial cancer.
Interpolated reference model based fault tolerant sliding mode control for an octorotor
Authors: Vile Liam , Alwi Halim , Edwards Christopher
Published: March 2022

In this paper, a quasi‐linear parameter varying sliding mode control allocation law is proposed for the fault tolerant control of an octorotor. In the event of rotor faults/failures, an allocation law redistributes the control effort among the remaining healthy rotors. The sliding mode control law is designed to guarantee asymptotic tracking of a reference model which is tuned on‐line, through an interpolated feedback gain, to ensure that the control signals remain within their saturation limits. A method for designing the parameterised feedback gain is proposed which is shown to maximise a defined stability criteria whilst preventing undesirable performance characteristics in the reference model. The proposed scheme is tested on a non‐linear octorotor model in the presence of severe rotor failures and uncertainty/disturbances.
Finite‐time attitude stabilization of rigid spacecrafts based on control Lyapunov functions
Authors: Wu Yu‐Yao , Zhang Ying , Wu Ai‐Guo
Published: March 2022

In this paper, the control Lyapunov function (CLF) approach is adopted to investigate the finite‐time attitude control of rigid spacecraft subject to parameter uncertainty and external disturbance. By using an extended state observer to estimate the parameter uncertainty and external disturbance, a finite‐time CLF controller is proposed for attitude stabilization of the spacecraft system. The designed finite‐time CLF controller includes two parts. The first part is a classical CLF based attitude controller, which is proposed to ensure the globally asymptotical stability of the nominal spacecraft system. The second one is a sliding mode controller, which is used to ensure the finite‐time convergence performance of the spacecraft control system. The advantage of the designed controller is that the states of the system can converge into a small neighourhood of zero in finite time, and simultaneously the given performance index can be minimized. The practical finite‐time stability of the resulted closed‐loop system is proven via Lyapunov stability theory. Finally, simulation results illustrate the effectiveness of the developed finite‐time controller.
Improved cross entropy loss for noisy labels in vision leaf disease classification
Authors: Chen Yipeng , Xu Ke , Zhou Peng , Ban Xiaojuan , He Di
Published: March 2022

The predictive performance of supervised learning algorithms depends on the quality of labels. In a typical label collection process, multiple annotators provide subjective noisy estimates of the “truth” under the influence of their varying skill‐levels and biases. Blindly treating these noisy labels as the ground truth limits the accuracy of learning algorithms in the presence of strong disagreement. This problem is critical for applications in domains where the annotation cost is high. Such problems are extremely serious in the domain of agricultural imaging in leaf disease classification. Due to the limitation of acquisition methods, noisy examples are often not only the normal mislabelled ones, but also the samples which contain more than one instance. To cope with the combination of the two noises, label smoothing is blended in the point of increasing entropy for uncertain labels, with Taylor cross entropy loss, which is proved to be efficient to solve the problem of artificial noisy labels on public datasets. And the proposed method is called smooth‐Taylor cross entropy loss, which can deal with the real‐world noises in vision leaf disease dataset. Extensive experimental results on cassava leaf disease dataset demonstrate that our proposed approach significantly outperforms the state‐of‐the‐art counterparts.
The Association of Serum Electrolytes with Disease Severity and Obstetric Complications in Pregnant Women with COVID-19: a Prospective Cohort Study from a Tertiary Reference
Center
Authors: Tanacan Atakan , Erol Seyit Ahmet , Anuk Ali Taner , Yetiskin Fatma Didem Yucel , Tokalioglu Eda Ozden , Sahin Selin , Unlu Serpil , Keskin Huseyin Levent , Surel Aziz Ahmet , Tekin Ozlem Moraloglu , Sahin Dilek
Published: March 2022

Introduction To evaluate the association of serum electrolytes with disease severity and obstetric complications in pregnant women with Coronavirus disease 2019 (COVID-19).

Materials and Methods This prospective cohort study was conducted on pregnant women with confirmed COVID-19. Study population was divided into two groups: 1) Mild COVID-19 group
(n = 811) and 2) Moderate/severe COVID-19 group (n = 52). Demographic features, clinical characteristics, obstetric complications, and serum electrolytes were compared between the groups.
Afterward, a correlation analysis was performed to investigate the association between serum electrolyte disturbances with COVID-19 severity and obstetric complications.

Results Highest serum sodium, hypernatremia, potassium replacement, hypopotassemia, hyperchloremia, initial serum magnesium, hypermagnesemia, and hypocalcemia were significantly
higher in the moderate/severe COVID-19 group. The lowest serum sodium, lowest serum potassium, and initial serum calcium were significantly higher in the mild COVID-19 group (p < 0.05).
Statistically significant positive weak correlations were found between hypernatremia, hypopotassemia, hyperchloremia, hypermagnesemia, hypocalcemia and COVID-19 severity (r values were
0.27, 0.20, 0.12, 0.18 and 0.12, p values were < 0.001, < 0.001, 0.02, 0.03 and 0.03, respectively). Furthermore, statistically significant positive weak correlations were found
between hypopotassemia, hypochloremia, hypermagnesemia, and obstetric complications (r values were 0.10, 0.10, and 0.28, p values were 0.004, 0.03, and 0.001, respectively). A statistically
significant negative weak correlation was found between hypomagnesemia and obstetric complications (r = − 0.23 and p = 0.01, respectively).

Conclusion Electrolyte disturbances in pregnant women with COVID-19 seem to be associated with disease severity and obstetric complications.
Inadequate Timing Limits the Benefit of Antenatal Corticosteroids on Neonatal Outcome: Retrospective Analysis of a High-Risk Cohort of Preterm Infants in a Tertiary Center in
Germany
Authors: Biedermann Richard , Schleussner Ekkehard , Lauten Angela , Heimann Yvonne , Lehmann Thomas , Proquitté Hans , Weschenfelder Friederike
Published: March 2022

Introduction A common problem in the treatment of threatened preterm birth is the timing and the unrestricted use of antenatal corticosteroids (ACS). This study was performed to
evaluate the independent effects of the distinct timing of antenatal corticosteroids on neonatal outcome parameters in a cohort of very low (VLBW; 1000 – 1500 g) and extreme low birth weight
infants (ELBW; < 1000 g). We hypothesize that a prolonged ACS-to-delivery interval leads to an increase in respiratory complications.

Materials and Methods Main data source was the prospectively collected single center data for the German nosocomial infection surveillance system (KISS) between 2015 and 2018.
Multivariate regression analysis was performed to determine independent effects of the ACS-to-delivery interval on the need for ventilation, surfactant or the occurrence of bronchopulmonary
dysplasia, neonatal sepsis or necrotizing enterocolitis. Subgroup analysis was performed for ELBW and VLBW neonates.

Results A total of 239 neonates were included. We demonstrate a significantly increased risk of respiratory distress characterized by the need for ventilation (OR 1.045; CI
1.011 – 1.080) and surfactant administration (OR 1.050, CI 1.018 – 1.083) depending on the ACS-to-delivery interval irrespective of other confounders. Every additional day between ACS and
delivery increased the risk for ventilation by 4.5% and for surfactant administration by 5%. Subgroup analysis revealed significant differences of respiratory complications in VLBW
infants.

Conclusions Our data strongly support the deliberate use and timing of antenatal corticosteroids in pregnancies with threatened preterm birth versus a liberal strategy. When given
more than 7 days before birth, each day between application and delivery increases is relevant concerning major effects on the infant. Especially VLBW preterm neonates benefit from optimal
timing.