bluuebunny/crossref_metadata_2025 huggingface dataset:
Extraordinary evanescent field confinement waveguide sensor for mid-infrared trace gas spectroscopy
Authors: Vlk Marek , Datta Anurup , Alberti Sebastián , Yallew Henock Demessie , Mittal Vinita , Murugan Ganapathy Senthil , Jágerská Jana
Published: January 2021

Nanophotonic waveguides are at the core of a great variety of optical sensors. These structures confine light along defined paths on photonic chips and provide light–matter interaction via an evanescent field. However, waveguides still lag behind free-space optics for sensitivity-critical applications such as trace gas detection. Short optical pathlengths, low interaction strengths, and spurious etalon fringes in spectral transmission are among the main reasons why on-chip gas sensing is still in its infancy. In this work, we report on a mid-infrared integrated waveguide sensor that successfully addresses these drawbacks. This sensor operates with a 107% evanescent field confinement factor in air, which not only matches but also outperforms free-space beams in terms of the per-length optical interaction. Furthermore, negligible facet reflections result in a flat spectral background and record-low absorbance noise that can finally compete with free-space spectroscopy. The sensor performance was validated at 2.566 μm, which showed a 7 ppm detection limit for acetylene with only a 2 cm long waveguide.
No difference in survival after HLA mismatched versus HLA matched allogeneic stem cell transplantation in Ewing sarcoma patients with advanced disease
Authors: Thiel U. , Schober S. J. , Ranft A. , Gassmann H. , Jabar S. , Gall K. , von Lüttichau I. , Wawer A. , Koscielniak E. , Diaz M. A. , Ussowicz M. , Kazantsev I. , Afanasyev B. , Merker M. , Klingebiel T. , Prete A. , Gruhn B. , Bader P. , Jürgens H. , Dirksen U. , Handgretinger R. , Burdach S. , Lang P.
Published: January 2021

Patients with advanced Ewing sarcoma (AES) carry a poor prognosis. Retrospectively, we analyzed 66 AES patients treated with allogeneic stem cell transplantation (allo-SCT) receiving HLA-mismatched (group A, n = 39) versus HLA-matched grafts (group B, n = 27). Median age at diagnosis was 13 years, and 15 years (range 3–49 years) at allo-SCT. The two groups did not differ statistically in distribution of gender, age, remission status/number of relapses at allo-SCT, or risk stratum. 9/39 (23%) group A versus 2/27 (7%) group B patients developed severe acute graft versus host disease (GvHD). Of patients alive at day 100, 7/34 (21%) group A versus 9/19 (47%) group B patients had developed chronic GvHD. In group A, 33/39 (85%) versus 20/27 (74%) group B patients died of disease and 1/39 (3%) versus 1/27 (4%) patients died of complications, respectively. Altogether 12/66 (18%) patients survived in CR. Median EFS 24 months after allo-SCT was 20% in both groups, median OS was 27% (group A) versus 17% (group B), respectively. There was no difference in EFS and OS in AES patients transplanted with HLA-mismatched versus HLA-matched graft in univariate and multivariate analyses. In this analysis, CR at allo-SCT is a condition for survival (p < 0.02).
A new immunotherapy strategy targeted CD30 in peripheral T-cell lymphomas: CAR-modified T-cell therapy based on CD30 mAb
Authors: Wu Yang , Chen Dan , Lu Ya , Dong Shu-Chen , Ma Rong , Tang Wei-yan , Wu Jian-qiu , Feng Ji-Feng , Wu Jian-Zhong
Published: January 2021

Chimeric antigen receptor T-cell immunotherapy (CAR-T) has shown remarkable efficacy in treating tumors of lymphopoietic origin. Herein, we demonstrate an effective CAR-T cell treatment for recurrent and malignant CD30-positive peripheral T-cell lymphomas (PTCL) has been demonstrated. The extracellular fragment gene sequences of CD30 were obtained from tumor tissues of PTCL patients and cloned into a plasmid vector to express the CD30 antigen. The CD30 targeting single-chain antibody fragment (scFv) was obtained from CD30-positive monoclonal hybridoma cells, which were obtained from CD30 antigen immunized mice. After a second-generation of CAR lentiviral construction, CD30 CAR T cells were produced and used to determine the cytotoxicity of this construct toward Karpas 299 cells. The results of CD30 CAR T-mediated cell lysis show that 9C11-2 CAR T cells could significantly promote the lysis of CD30-positive Karpas 299 cells in both LDH and real-time cell electronic sensing (RTCA) assays. In vivo data show that 9C11-2 CAR T cells effectively suppress the tumor growth in a Karpas 299 cell xenograft NCG mouse model. The CD30 CAR T cells exhibited an efficient cytotoxic effect after being co-cultured with the target cells and they also exhibited a significant tumor-inhibiting ability after being intravenously injected into PTCL xenograft tumors; these observations suggest that the new CD30 CAR-T cell may be a promising therapeutic candidate for cancer therapy.
High proportion of thiamine deficiency in referred cancer patients with delirium: a retrospective descriptive study
Authors: Onishi Hideki , Sato Izumi , Uchida Nozomu , Takahashi Takao , Furuya Daisuke , Ebihara Yasuhiro , Yoshioka Akira , Ito Hiroshi , Ishida Mayumi
Published: January 2021

Background/Objectives

Recent studies have revealed thiamine deficiency (TD) as a cause of delirium in cancer patients. However, the extent to which Wernicke encephalopathy is present and in what patients is not well understood.

Subjects/Methods

In this retrospective descriptive study, we investigated referred cancer patients who were diagnosed with delirium by a psycho-oncologist to clarify the proportion of TD, the therapeutic effect of thiamine administration, and the factors involved in its onset.

Results

Among 71 patients diagnosed with delirium by a psycho-oncologist, TD was found in 45% of the patients. Intravenous administration of thiamine led to a recovery in about 60% of these patients. We explored the factors associated with TD using a multivariable regression model with a Markov chain Monte Carlo imputation procedure. We found an association between TD and chemotherapy (adjusted odds ratio, 1.98 [95% confidence interval, 1.04–3.77]); however, there were no significant associations between TD and the other factors we considered.

Conclusions

TD is not particularly rare in delirium patients undergoing psychiatric consultation. The delirium was resolved in more than half of these patients by intravenous administration of thiamine. Oncologists should consider TD as a cause of delirium in cancer patients. Further prospective study is needed to clarify the relationship between TD and delirium in cancer patients.
Ocular manifestations of emerging viral diseases
Authors: Venkatesh Ashwin , Patel Ravi , Goyal Simran , Rajaratnam Timothy , Sharma Anant , Hossain Parwez
Published: January 2021

Emerging infectious diseases (EIDs) are an increasing threat to public health on a global scale. In recent times, the most prominent outbreaks have constituted RNA viruses, spreading via droplets (COVID-19 and Influenza A H1N1), directly between humans (Ebola and Marburg), via arthropod vectors (Dengue, Zika, West Nile, Chikungunya, Crimean Congo) and zoonotically (Lassa fever, Nipah, Rift Valley fever, Hantaviruses). However, specific approved antiviral therapies and vaccine availability are scarce, and public health measures remain critical. Patients can present with a spectrum of ocular manifestations. Emerging infectious diseases should therefore be considered in the differential diagnosis of ocular inflammatory conditions in patients inhabiting or returning from endemic territories, and more general vigilance is advisable in the context of a global pandemic. Eye specialists are in a position to facilitate swift diagnosis, improve clinical outcomes, and contribute to wider public health efforts during outbreaks. This article reviews those emerging viral diseases associated with reports of ocular manifestations and summarizes details pertinent to practicing eye specialists.
Automated MRI-based quantification of posterior ocular globe flattening and recovery after long-duration spaceflight
Authors: Sater Stuart H. , Sass Austin M. , Rohr Jesse J. , Marshall-Goebel Karina , Ploutz-Snyder Robert J. , Ethier C. Ross , Stenger Michael B. , Kramer Larry A. , Martin Bryn A. , Macias Brandon R.
Published: January 2021

Background/Objectives

Spaceflight associated neuro-ocular syndrome (SANS), a health risk related to long-duration spaceflight, is hypothesized to result from a headward fluid shift that occurs with the loss of hydrostatic pressure gradients in weightlessness. Shifts in the vascular and cerebrospinal fluid compartments alter the mechanical forces at the posterior eye and lead to flattening of the posterior ocular globe. The goal of the present study was to develop a method to quantify globe flattening observed by magnetic resonance imaging after spaceflight.

Subjects/Methods

Volumetric displacement of the posterior globe was quantified in 10 astronauts at 5 time points after spaceflight missions of ~6 months.

Results

Mean globe volumetric displacement was 9.88 mm3 (95% CI 4.56–15.19 mm3, p < 0.001) on the first day of assessment after the mission (R[return]+ 1 day); 9.00 mm3 (95% CI 3.73–14.27 mm3, p = 0.001) at R + 30 days; 6.53 mm3 (95% CI 1.24–11.83 mm3, p < 0.05) at R + 90 days; 4.45 mm3 (95% CI −0.96 to 9.86 mm3, p = 0.12) at R + 180 days; and 7.21 mm3 (95% CI 1.82–12.60 mm3, p < 0.01) at R + 360 days.

Conclusions

There was a consistent inward displacement of the globe at the optic nerve, which had only partially resolved 1 year after landing. More pronounced globe flattening has been observed in previous studies of astronauts; however, those observations lacked quantitative measures and were subjective in nature. The novel automated method described here allows for detailed quantification of structural changes in the posterior globe that may lead to an improved understanding of SANS.
Neighbor GWAS: incorporating neighbor genotypic identity into genome-wide association studies of field herbivory
Authors: Sato Yasuhiro , Yamamoto Eiji , Shimizu Kentaro K. , Nagano Atsushi J.
Published: January 2021

An increasing number of field studies have shown that the phenotype of an individual plant depends not only on its genotype but also on those of neighboring plants; however, this fact is not taken into consideration in genome-wide association studies (GWAS). Based on the Ising model of ferromagnetism, we incorporated neighbor genotypic identity into a regression model, named “Neighbor GWAS”. Our simulations showed that the effective range of neighbor effects could be estimated using an observed phenotype when the proportion of phenotypic variation explained (PVE) by neighbor effects peaked. The spatial scale of the first nearest neighbors gave the maximum power to detect the causal variants responsible for neighbor effects, unless their effective range was too broad. However, if the effective range of the neighbor effects was broad and minor allele frequencies were low, there was collinearity between the self and neighbor effects. To suppress the false positive detection of neighbor effects, the fixed effect and variance components involved in the neighbor effects should be tested in comparison with a standard GWAS model. We applied neighbor GWAS to field herbivory data from 199 accessions of Arabidopsis thaliana and found that neighbor effects explained 8% more of the PVE of the observed damage than standard GWAS. The neighbor GWAS method provides a novel tool that could facilitate the analysis of complex traits in spatially structured environments and is available as an R package at CRAN (https://cran.rproject.org/package=rNeighborGWAS).
Direct control of CAR T cells through small molecule-regulated antibodies
Authors: Park Spencer , Pascua Edward , Lindquist Kevin C. , Kimberlin Christopher , Deng Xiaodi , Mak Yvonne S. L. , Melton Zea , Johnson Theodore O. , Lin Regina , Boldajipour Bijan , Abraham Robert T. , Pons Jaume , Sasu Barbra Johnson , Van Blarcom Thomas J. , Chaparro-Riggers Javier
Published: January 2021

Antibody-based therapeutics have experienced a rapid growth in recent years and are now utilized in various modalities spanning from conventional antibodies, antibody-drug conjugates, bispecific antibodies to chimeric antigen receptor (CAR) T cells. Many next generation antibody therapeutics achieve enhanced potency but often increase the risk of adverse events. Antibody scaffolds capable of exhibiting inducible affinities could reduce the risk of adverse events by enabling a transient suspension of antibody activity. To demonstrate this, we develop conditionally activated, single-module CARs, in which tumor antigen recognition is directly modulated by an FDA-approved small molecule drug. The resulting CAR T cells demonstrate specific cytotoxicity of tumor cells comparable to that of traditional CARs, but the cytotoxicity is reversibly attenuated by the addition of the small molecule. The exogenous control of conditional CAR T cell activity allows continual modulation of therapeutic activity to improve the safety profile of CAR T cells across all disease indications.
Electronic spin separation induced by nuclear motion near conical intersections
Authors: Wu Yanze , Subotnik Joseph E.
Published: January 2021

Though the concept of Berry force was proposed thirty years ago, little is known about the practical consequences of this force as far as chemical dynamics are concerned. Here, we report that when molecular dynamics pass near a conical intersection, a massive Berry force can appear as a result of even a small amount of spin-orbit coupling (<10−3eV), and this Berry force can in turn dramatically change pathway selection. In particular, for a simple radical reaction with two outgoing reaction channels, an exact quantum scattering solution in two dimensions shows that the presence of a significant Berry force can sometimes lead to spin selectivity as large as 100%. Thus, this article opens the door for organic chemists to start designing spintronic devices that use nuclear motion and conical intersections (combined with standard spin-orbit coupling) in order to achieve spin selection. Vice versa, for physical chemists, this article also emphasizes that future semiclassical simulations of intersystem crossing (which have heretofore ignored Berry force) should be corrected to account for the spin polarization that inevitably arises when dynamics pass near conical intersections.
Single cell sequencing reveals endothelial plasticity with transient mesenchymal activation after myocardial infarction
Authors: Tombor Lukas S. , John David , Glaser Simone F. , Luxán Guillermo , Forte Elvira , Furtado Milena , Rosenthal Nadia , Baumgarten Nina , Schulz Marcel H. , Wittig Janina , Rogg Eva-Maria , Manavski Yosif , Fischer Ariane , Muhly-Reinholz Marion , Klee Kathrin , Looso Mario , Selignow Carmen , Acker Till , Bibli Sofia-Iris , Fleming Ingrid , Patrick Ralph , Harvey Richard P. , Abplanalp Wesley T. , Dimmeler Stefanie
Published: January 2021

Endothelial cells play a critical role in the adaptation of tissues to injury. Tissue ischemia induced by infarction leads to profound changes in endothelial cell functions and can induce transition to a mesenchymal state. Here we explore the kinetics and individual cellular responses of endothelial cells after myocardial infarction by using single cell RNA sequencing. This study demonstrates a time dependent switch in endothelial cell proliferation and inflammation associated with transient changes in metabolic gene signatures. Trajectory analysis reveals that the majority of endothelial cells 3 to 7 days after myocardial infarction acquire a transient state, characterized by mesenchymal gene expression, which returns to baseline 14 days after injury. Lineage tracing, using the Cdh5-CreERT2;mT/mG mice followed by single cell RNA sequencing, confirms the transient mesenchymal transition and reveals additional hypoxic and inflammatory signatures of endothelial cells during early and late states after injury. These data suggest that endothelial cells undergo a transient mes-enchymal activation concomitant with a metabolic adaptation within the first days after myocardial infarction but do not acquire a long-term mesenchymal fate. This mesenchymal activation may facilitate endothelial cell migration and clonal expansion to regenerate the vascular network.
H3K27me3-rich genomic regions can function as silencers to repress gene expression via chromatin interactions
Authors: Cai Yichao , Zhang Ying , Loh Yan Ping , Tng Jia Qi , Lim Mei Chee , Cao Zhendong , Raju Anandhkumar , Lieberman Aiden Erez , Li Shang , Manikandan Lakshmanan , Tergaonkar Vinay , Tucker-Kellogg Greg , Fullwood Melissa Jane
Published: January 2021

The mechanisms underlying gene repression and silencers are poorly understood. Here we investigate the hypothesis that H3K27me3-rich regions of the genome, defined from clusters of H3K27me3 peaks, may be used to identify silencers that can regulate gene expression via proximity or looping. We find that H3K27me3-rich regions are associated with chromatin interactions and interact preferentially with each other. H3K27me3-rich regions component removal at interaction anchors by CRISPR leads to upregulation of interacting target genes, altered H3K27me3 and H3K27ac levels at interacting regions, and altered chromatin interactions. Chromatin interactions did not change at regions with high H3K27me3, but regions with low H3K27me3 and high H3K27ac levels showed changes in chromatin interactions. Cells with H3K27me3-rich regions knockout also show changes in phenotype associated with cell identity, and altered xenograft tumor growth. Finally, we observe that H3K27me3-rich regions-associated genes and long-range chromatin interactions are susceptible to H3K27me3 depletion. Our results characterize H3K27me3-rich regions and their mechanisms of functioning via looping.
Real-time interleaved spectroscopic photoacoustic and ultrasound (PAUS) scanning with simultaneous fluence compensation and motion correction
Authors: Jeng Geng-Shi , Li Meng-Lin , Kim MinWoo , Yoon Soon Joon , Pitre John J. , Li David S. , Pelivanov Ivan , O’Donnell Matthew
Published: January 2021

For over two decades photoacoustic imaging has been tested clinically, but successful human trials have been limited. To enable quantitative clinical spectroscopy, the fundamental issues of wavelength-dependent fluence variations and inter-wavelength motion must be overcome. Here we propose a real-time, spectroscopic photoacoustic/ultrasound (PAUS) imaging approach using a compact, 1-kHz rate wavelength-tunable laser. Instead of illuminating tissue over a large area, the fiber-optic delivery system surrounding an US array sequentially scans a narrow laser beam, with partial PA image reconstruction for each laser pulse. The final image is then formed by coherently summing partial images. This scheme enables (i) automatic compensation for wavelength-dependent fluence variations in spectroscopic PA imaging and (ii) motion correction of spectroscopic PA frames using US speckle tracking in real-time systems. The 50-Hz video rate PAUS system is demonstrated in vivo using a murine model of labelled drug delivery.
DutaFabs are engineered therapeutic Fab fragments that can bind two targets simultaneously
Authors: Beckmann Roland , Jensen Kristian , Fenn Sebastian , Speck Janina , Krause Katrin , Meier Anastasia , Röth Melanie , Fauser Sascha , Kimbung Raymond , Logan Derek T. , Steegmaier Martin , Kettenberger Hubert
Published: January 2021

We report the development of a platform of dual targeting Fab (DutaFab) molecules, which comprise two spatially separated and independent binding sites within the human antibody CDR loops: the so-called H-side paratope encompassing HCDR1, HCDR3 and LCDR2, and the L-side paratope encompassing LCDR1, LCDR3 and HCDR2. Both paratopes can be independently selected and combined into the desired bispecific DutaFabs in a modular manner. X-ray crystal structures illustrate that DutaFabs are able to bind two target molecules simultaneously at the same Fv region comprising a VH-VL heterodimer. In the present study, this platform is applied to generate DutaFabs specific for VEGFA and PDGF-BB, which show high affinities, physico-chemical stability and solubility, as well as superior efficacy over anti-VEGF monotherapy in vivo. These molecules exemplify the usefulness of DutaFabs as a distinct class of antibody therapeutics, which is currently being evaluated in patients.
Deep convolutional neural networks to predict cardiovascular risk from computed tomography
Authors: Zeleznik Roman , Foldyna Borek , Eslami Parastou , Weiss Jakob , Alexander Ivanov , Taron Jana , Parmar Chintan , Alvi Raza M. , Banerji Dahlia , Uno Mio , Kikuchi Yasuka , Karady Julia , Zhang Lili , Scholtz Jan-Erik , Mayrhofer Thomas , Lyass Asya , Mahoney Taylor F. , Massaro Joseph M. , Vasan Ramachandran S. , Douglas Pamela S. , Hoffmann Udo , Lu Michael T. , Aerts Hugo J. W. L.
Published: January 2021

Coronary artery calcium is an accurate predictor of cardiovascular events. While it is visible on all computed tomography (CT) scans of the chest, this information is not routinely quantified as it requires expertise, time, and specialized equipment. Here, we show a robust and time-efficient deep learning system to automatically quantify coronary calcium on routine cardiac-gated and non-gated CT. As we evaluate in 20,084 individuals from distinct asymptomatic (Framingham Heart Study, NLST) and stable and acute chest pain (PROMISE, ROMICAT-II) cohorts, the automated score is a strong predictor of cardiovascular events, independent of risk factors (multivariable-adjusted hazard ratios up to 4.3), shows high correlation with manual quantification, and robust test-retest reliability. Our results demonstrate the clinical value of a deep learning system for the automated prediction of cardiovascular events. Implementation into clinical practice would address the unmet need of automating proven imaging biomarkers to guide management and improve population health.
Stromal-driven and Amyloid β-dependent induction of neutrophil extracellular traps modulates tumor growth
Authors: Munir Hafsa , Jones James O. , Janowitz Tobias , Hoffmann Markus , Euler Maximilien , Martins Carla P. , Welsh Sarah J. , Shields Jacqueline D.
Published: January 2021

Tumors consist of cancer cells and a network of non-cancerous stroma. Cancer-associated fibroblasts (CAF) are known to support tumorigenesis, and are emerging as immune modulators. Neutrophils release histone-bound nuclear DNA and cytotoxic granules as extracellular traps (NET). Here we show that CAFs induce NET formation within the tumor and systemically in the blood and bone marrow. These tumor-induced NETs (t-NETs) are driven by a ROS-mediated pathway dependent on CAF-derived Amyloid β, a peptide implicated in both neurodegenerative and inflammatory disorders. Inhibition of NETosis in murine tumors skews neutrophils to an anti-tumor phenotype, preventing tumor growth; reciprocally, t-NETs enhance CAF activation. Mirroring observations in mice, CAFs are detected juxtaposed to NETs in human melanoma and pancreatic adenocarcinoma, and show elevated amyloid and β-Secretase expression which correlates with poor prognosis. In summary, we report that CAFs drive NETosis to support cancer progression, identifying Amyloid β as the protagonist and potential therapeutic target.
Asynchronous release sites align with NMDA receptors in mouse hippocampal synapses
Authors: Li Shuo , Raychaudhuri Sumana , Lee Stephen Alexander , Brockmann Marisa M. , Wang Jing , Kusick Grant , Prater Christine , Syed Sarah , Falahati Hanieh , Ramos Raul , Bartol Tomas M. , Hosy Eric , Watanabe Shigeki
Published: January 2021

Neurotransmitter is released synchronously and asynchronously following an action potential. Our recent study indicates that the release sites of these two phases are segregated within an active zone, with asynchronous release sites enriched near the center in mouse hippocampal synapses. Here we demonstrate that synchronous and asynchronous release sites are aligned with AMPA receptor and NMDA receptor clusters, respectively. Computational simulations indicate that this spatial and temporal arrangement of release can lead to maximal membrane depolarization through AMPA receptors, alleviating the pore-blocking magnesium leading to greater activation of NMDA receptors. Together, these results suggest that release sites are likely organized to activate NMDA receptors efficiently.
Influence of cytochrome P450 2D6 polymorphism on hippocampal white matter and treatment response in schizophrenia
Authors: Shin Wonsuk , Bang Minji , Kim Anhye , Cho Doo-Yeoun , Lee Sang-Hyuk
Published: January 2021

Cytochrome P450 2D6 (CYP2D6) is expressed at high levels in the brain and plays a considerable role in the biotransformation and neurotransmission of dopamine. This raises the question of whether CYP2D6 variations and its impact on the brain can confer susceptibility to schizophrenia. We investigated the possible links among the CYP2D6 genotype, white matter (WM) integrity of the hippocampus, and the treatment response to antipsychotic drugs in Korean patients with schizophrenia (n = 106). Brain magnetic resonance imaging and genotyping for CYP2D6 were conducted at baseline. The severity of clinical symptoms and the treatment response were assessed using the Positive and Negative Syndrome Scale (PANSS). After genotyping, 43 participants were classified as intermediate metabolizers (IM), and the remainder (n = 63) were classified as extensive metabolizers (EM). IM participants showed significantly higher fractional anisotropy (FA) values in the right hippocampus compared to EM participants. Radial diffusivity (RD) values were significantly lower in the overlapping region of the right hippocampus in the IM group than in the EM group. After 4 weeks of antipsychotic treatment, the EM group showed more improvements in positive symptoms than the IM group. FAs and RDs in the CYP2D6-associated hippocampal WM region were significantly correlated with a reduction in the positive symptom subscale of the PANSS. Greater improvements in positive symptoms were negatively associated with FAs, and positively associated with RDs in the right hippocampal region. The findings suggest that CYP26D-associated hippocampal WM alterations could be a possible endophenotype for schizophrenia that accounts for individual differences in clinical features and treatment responses.
Hepatitis A virus knowledge and immunization attitudes and practices in the United Arab Emirates community
Authors: Samara Kamel A. , Barqawi Hiba J. , Aboelsoud Basant H. , AlZaabi Moza A. , Alraddawi Fay T. , Mannaa Ayten A.
Published: January 2021

Annually, 1.5 million cases of hepatitis A infection occur worldwide. The United Arab Emirates (U.A.E.) has seen a decrease in infection rates and seroprevalence coupled with an increase in the average age of infection. This study aimed to assess the U.A.E. society’s hepatitis A knowledge, and attitudes and vaccination practices, with the applicability of its introduction into the local immunization schedule. A self-administered, 50-item questionnaire was used to collect data from the four most populous cities in the U.A.E., between January and March 2020. A total of 458 responses were collected and analysed using IBM-SPSS-26, R-4.0.0 and Matplotlib-v3.2.1. Females had better attitudes (P = 0.036), practices (P < 0.0005), immunization schedule knowledge (AOR = 3.019; CI 1.482–6.678), and appreciation of the immunization schedule (AOR = 2.141; CI 1.310–3.499). A higher level of perceived knowledge was associated with an actual better knowledge (P < 0.0005), better practices (P = 0.011), and increased willingness to get vaccinated (AOR = 1.988; CI 1.032–3.828). Respondents were more likely to vaccinate their children against HAV if the vaccine were introduced into the National Immunization Program (P < 0.0005). Overall, disease knowledge was lacking but with positive attitudes and poor practices. There is high trust in the National Immunization Program and a potential for improving poor practices through local awareness campaigns.
Towards a mechanistic understanding of particle shrinkage during biomass pyrolysis via synchrotron X-ray microtomography and in-situ radiography
Authors: Barr Meredith Rose , Jervis Rhodri , Zhang Yeshui , Bodey Andrew J. , Rau Christoph , Shearing Paul R. , Brett Dan J. L. , Titirici Maria‐Magdalena , Volpe Roberto
Published: January 2021

Accurate modelling of particle shrinkage during biomass pyrolysis is key to the production of biochars with specific morphologies. Such biochars represent sustainable solutions to a variety of adsorption-dependent environmental remediation challenges. Modelling of particle shrinkage during biomass pyrolysis has heretofore been based solely on theory and ex-situ experimental data. Here we present the first in-situ phase-contrast X-ray imaging study of biomass pyrolysis. A novel reactor was developed to enable operando synchrotron radiography of fixed beds of pyrolysing biomass. Almond shell particles experienced more bulk shrinkage and less change in porosity than did walnut shell particles during pyrolysis, despite their similar composition. Alkaline pretreatment was found to reduce this difference in feedstock behaviour. Ex-situ synchrotron X-ray microtomography was performed to study the effects of pyrolysis on pore morphology. Pyrolysis led to a redistribution of pores away from particle surfaces, meaning newly formed surface area may be less accessible to adsorbates.
Design of epidermal growth factor immobilization on 3D biocompatible scaffolds to promote tissue repair and regeneration
Authors: Bavaro Teodora , Tengattini Sara , Rezwan Refaya , Chiesa Enrica , Temporini Caterina , Dorati Rossella , Massolini Gabriella , Conti Bice , Ubiali Daniela , Terreni Marco
Published: January 2021

Exogenous application of human epidermal growth factor (hEGF) stimulates epidermal wound healing. The aim of this study was to develop bioconjugates based on hEGF mimicking the protein in its native state and thus suitable for tissue engineering applications, in particular for treating skin-related disorders as burns. Ribonuclease A (RNase A) was used to investigate a number of different activated-agarose carriers: cyanogen bromide (CNBr)-activated-agarose and glyoxyl-agarose showed to preserve the appropriate orientation of the protein for receptor binding. EGF was immobilized on these carriers and immobilization yield was evaluated (100% and 12%, respectively). A peptide mapping of unbound protein regions was carried out by LC–MS to take evidence of the residues involved in the immobilization and, consequently, the flexibility and surface accessibility of immobilized EGF. To assess cell proliferative activities, 10, 25, 50, and 100 ng/mL of each immobilized EGF sample were seeded on fibroblast cells and incubated for 24, 48 and 72 h. The immobilized growth factor showed significantly high cell proliferative activity at 50 and 100 ng/mL compared to control and soluble EGF. Although both of the immobilized samples show dose-dependency when seeded with high number of fibroblast cells, CNBr-agarose-EGF showed a significantly high activity at 100 ng/mL and 72 h incubation, compared to glyoxyl-agarose-EGF.
Signalling pathways and mechanistic cues highlighted by transcriptomic analysis of primordial, primary, and secondary ovarian follicles in domestic cat
Authors: Kehoe Shauna , Jewgenow Katarina , Johnston Paul R. , Mbedi Susan , Braun Beate C.
Published: January 2021

In vitro growth (IVG) of dormant primordial ovarian follicles aims to produce mature competent oocytes for assisted reproduction. Success is dependent on optimal in vitro conditions complemented with an understanding of oocyte and ovarian follicle development in vivo. Complete IVG has not been achieved in any other mammalian species besides mice. Furthermore, ovarian folliculogenesis remains sparsely understood overall. Here, gene expression patterns were characterised by RNA-sequencing in primordial (PrF), primary (PF), and secondary (SF) ovarian follicles from Felis catus (domestic cat) ovaries. Two major transitions were investigated: PrF-PF and PF-SF. Transcriptional analysis revealed a higher proportion in gene expression changes during the PrF-PF transition. Key influencing factors during this transition included the interaction between the extracellular matrix (ECM) and matrix metalloproteinase (MMPs) along with nuclear components such as, histone HIST1H1T (H1.6). Conserved signalling factors and expression patterns previously described during mammalian ovarian folliculogenesis were observed. Species-specific features during domestic cat ovarian folliculogenesis were also found. The signalling pathway terms “PI3K-Akt”, “transforming growth factor-β receptor”, “ErbB”, and “HIF-1” from the functional annotation analysis were studied. Some results highlighted mechanistic cues potentially involved in PrF development in the domestic cat. Overall, this study provides an insight into regulatory factors and pathways during preantral ovarian folliculogenesis in domestic cat.
The usefulness of SwiftScan technology for bone scintigraphy using a novel anthropomorphic phantom
Authors: Shibutani Takayuki , Onoguchi Masahisa , Naoi Yuka , Yoneyama Hiroto , Konishi Takahiro , Tatami Ringo , Nakajima Kenichi
Published: January 2021

The aim of this study was to demonstrate the usefulness of SwiftScan with a low-energy high-resolution and sensitivity (LEHRS) collimator for bone scintigraphy using a novel bone phantom simulating the human body. SwiftScan planar image of lateral view was acquired in clinical condition; thereafter, each planar image of different blend ratio (0–80%) of Crality 2D processing were created. SwiftScan planar images with reduced acquisition time by 25–75% were created by Poisson’s resampling processing. SwiftScan single photon emission computed tomography (SPECT) was acquired with step-and-shoot and continuous mode, and SPECT images were reconstructed using a three-dimensional ordered subset expectation maximization incorporating attenuation, scatter and spatial resolution corrections. SwiftScan planar image showed a high contrast to noise ratio (CNR) and low percent of the coefficient of variance (%CV) compared with conventional planar image. The CNR of the tumor parts in SwiftScan SPECT was higher than that of the conventional SPECT image of step and shoot acquisition, while the %CV showed the lowest value in all systems. In conclusion, SwiftScan planar and SPECT images were able to reduce the image noise compared with planar and SPECT image with a low-energy high-resolution collimator, so that SwiftScan planar and SPECT images could be obtained a high CNR. Furthermore, the SwiftScan planar image was able to reduce the acquisition time by 25% when the blend ratio of Clarity 2D processing set to more than 40%.
A multilayer multimodal detection and prediction model based on explainable artificial intelligence for Alzheimer’s disease
Authors: El-Sappagh Shaker , Alonso Jose M. , Islam S. M. Riazul , Sultan Ahmad M. , Kwak Kyung Sup
Published: January 2021

Alzheimer’s disease (AD) is the most common type of dementia. Its diagnosis and progression detection have been intensively studied. Nevertheless, research studies often have little effect on clinical practice mainly due to the following reasons: (1) Most studies depend mainly on a single modality, especially neuroimaging; (2) diagnosis and progression detection are usually studied separately as two independent problems; and (3) current studies concentrate mainly on optimizing the performance of complex machine learning models, while disregarding their explainability. As a result, physicians struggle to interpret these models, and feel it is hard to trust them. In this paper, we carefully develop an accurate and interpretable AD diagnosis and progression detection model. This model provides physicians with accurate decisions along with a set of explanations for every decision. Specifically, the model integrates 11 modalities of 1048 subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) real-world dataset: 294 cognitively normal, 254 stable mild cognitive impairment (MCI), 232 progressive MCI, and 268 AD. It is actually a two-layer model with random forest (RF) as classifier algorithm. In the first layer, the model carries out a multi-class classification for the early diagnosis of AD patients. In the second layer, the model applies binary classification to detect possible MCI-to-AD progression within three years from a baseline diagnosis. The performance of the model is optimized with key markers selected from a large set of biological and clinical measures. Regarding explainability, we provide, for each layer, global and instance-based explanations of the RF classifier by using the SHapley Additive exPlanations (SHAP) feature attribution framework. In addition, we implement 22 explainers based on decision trees and fuzzy rule-based systems to provide complementary justifications for every RF decision in each layer. Furthermore, these explanations are represented in natural language form to help physicians understand the predictions. The designed model achieves a cross-validation accuracy of 93.95% and an F1-score of 93.94% in the first layer, while it achieves a cross-validation accuracy of 87.08% and an F1-Score of 87.09% in the second layer. The resulting system is not only accurate, but also trustworthy, accountable, and medically applicable, thanks to the provided explanations which are broadly consistent with each other and with the AD medical literature. The proposed system can help to enhance the clinical understanding of AD diagnosis and progression processes by providing detailed insights into the effect of different modalities on the disease risk.
Reduction of 5G cellular network radiation in wireless mobile phone using an asymmetric square shaped passive metamaterial design
Authors: Ramachandran Tayaallen , Faruque Mohammad Rashed Iqbal , Siddiky Air Mohammad , Islam Mohammad Tariqul
Published: January 2021

This study aims to demonstrate the feasibility of metamaterial application in absorption reduction of 5G electromagnetic (EM) energy in the human head tissue. In a general sense, the radio frequency (RF) energy that received by wireless mobile phone from the base station, will emit to surrounding when the devices are in active mode. Since the latest fifth generation technology standard for cellular networks is upon us, the emission of radiation from any wireless devices needs to be taken into consideration. This motivation helps to prepare this paper that focuses on construction of novel and compact square-shaped metamaterial (SM) design to reduce electromagnetic exposure to humans. The commercially available substrate material known as FR-4 with thickness of 1.6 mm was selected to place the metamaterial design on it. The electromagnetic properties and Specific Absorption Rate (SAR) analyses were carried out numerically by utilising high-performance 3D EM analysis, Computer Simulation Technology Studio (CST) software. Meanwhile, for the validation purpose, the metamaterial designs for both unit and array cells were fabricated to measure the electromagnetic properties of the material. From the numerical simulation, the introduced SM design manifested quadruple resonance frequencies in multi bands precisely at 1.246 (at L-band), 3.052, 3.794 (at S-band), and 4.858 (C-band) GHz. However, the comparison of numerically simulated and measured data reveals a slight difference between them where only the second resonance frequency was decreased by 0.009 GHz while other frequencies were increased by 0.002, 0.045, and 0.117 GHz in sequential order. Moreover, the SAR analysis recorded high values at 3.794 GHz with 61.16% and 70.33% for 1 g and 10 g of tissue volumes, respectively. Overall, our results demonstrate strong SAR reduction effects, and the proposed SM design may be considered a promising aspect in the telecommunication field.
Ethnicity influences the gut microbiota of individuals sharing a geographical location: a cross-sectional study from a middle-income country
Authors: Dwiyanto Jacky , Hussain M. H. , Reidpath D. , Ong K. S. , Qasim A. , Lee S. W. H. , Lee S. M. , Foo S. C. , Chong C. W. , Rahman Sadequr
Published: January 2021

No studies have investigated the influence of ethnicity in a multi-ethnic middle-income country with a long-standing history of co-habitation. Stool samples from 214 Malaysian community members (46 Malay, 65 Chinese, 49 Indian, and 54 Jakun) were collected. The gut microbiota of the participants was investigated using 16S amplicon sequencing. Ethnicity exhibited the largest effect size across participants (PERMANOVA Pseudo-F = 4.24, R2 = 0.06, p = 0.001). Notably, the influence of ethnicity on the gut microbiota was retained even after controlling for all demographic, dietary factors and other covariates which were significantly associated with the gut microbiome (PERMANOVA Pseudo-F = 1.67, R2 = 0.02, p = 0.002). Our result suggested that lifestyle, dietary, and uncharacterized differences collectively drive the gut microbiota variation across ethnicity, making ethnicity a reliable proxy for both identified and unidentified lifestyle and dietary variation across ethnic groups from the same community.
Author Correction: Mito-oncology agent: fermented extract suppresses the Warburg effect, restores oxidative mitochondrial activity, and inhibits in vivo tumor growth
Authors: Bencze Gyula , Bencze Szilvia , Rivera Keith D. , Watson James D. , Hidvegi Mate , Orfi Laszlo , Tonks Nicholas K. , Pappin Darryl J.
Published: January 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
FANCD2 modulates the mitochondrial stress response to prevent common fragile site instability
Authors: Fernandes Philippe , Miotto Benoit , Saint-Ruf Claude , Said Maha , Barra Viviana , Nähse Viola , Ravera Silvia , Cappelli Enrico , Naim Valeria
Published: January 2021

Common fragile sites (CFSs) are genomic regions frequently involved in cancer-associated rearrangements. Most CFSs lie within large genes, and their instability involves transcription- and replication-dependent mechanisms. Here, we uncover a role for the mitochondrial stress response pathway in the regulation of CFS stability in human cells. We show that FANCD2, a master regulator of CFS stability, dampens the activation of the mitochondrial stress response and prevents mitochondrial dysfunction. Genetic or pharmacological activation of mitochondrial stress signaling induces CFS gene expression and concomitant relocalization to CFSs of FANCD2. FANCD2 attenuates CFS gene transcription and promotes CFS gene stability. Mechanistically, we demonstrate that the mitochondrial stress-dependent induction of CFS genes is mediated by ubiquitin-like protein 5 (UBL5), and that a UBL5-FANCD2 dependent axis regulates the mitochondrial UPR in human cells. We propose that FANCD2 coordinates nuclear and mitochondrial activities to prevent genome instability.
Author Correction: Stochastic dynamics and pattern formation of geometrically confined skyrmions
Authors: Schäffer Alexander F. , Rózsa Levente , Berakdar Jamal , Vedmedenko Elena Y. , Wiesendanger Roland
Published: January 2021

A Correction to this paper has been published: https://doi.org/10.1038/s42005-021-00523-5.
Construction of an MnO2 nanosheet array 3D integrated electrode for sensitive enzyme-free glucose sensing
Authors: Huang M. , Feng S. , Yang C. , Wen F. , He D. , Jiang P.
Published: January 2021

MnO2 NS/NF was facilely prepared and utilized as an efficient integrated electrode for enzyme-free glucose sensing.
Synthesis of deuterated γ-linolenic acid and application for biological studies: metabolic tuning and Raman imaging
Authors: Dodo Kosuke , Sato Ayato , Tamura Yuki , Egoshi Syusuke , Fujiwara Koichi , Oonuma Kana , Nakao Shuhei , Terayama Naoki , Sodeoka Mikiko
Published: January 2021

γ-Linolenic acid (GLA) is reported to show tumor-selective cytotoxicity via unidentified mechanisms. We introduced deuterium into GLA as a dual functional tag for metabolic inhibition and Raman imaging and applied for mechanistic studies.
Boron-modulated surface of hollow nickel framework for improved hydrogen evolution
Authors: Gu Weishi , Pan Zhongqin , Tao Han , Guo Yanling , Pu Jun , Zhong Chenglin , Li Jiachen , Ye Changqing , Zhou Qingwen
Published: January 2021

Taking advantage of micro/nano structure engineering and surface boron modulation, we developed a binder-free and support-free electrode to enrich and optimize active sites of Ni.
A valuable strategy to improve ferroelectric performance significantly via metallic ion doping in the lattice nodes of metal–organic frameworks
Authors: Liang Jingjing , Liu Meiying , Xu Xuebin , Liu Zhiliang
Published: January 2021

The ferroelectricity is enhanced significantly after doping of Mg2+ cations in the lattice nodes of Ni-MOF.
Theoretical modeling of the singlet–triplet spin transition in different Ni(ii)-diketo-pyrphyrin-based metal–ligand octahedral complexes
Authors: Farcaş Alex-Adrian , Bende Attila
Published: January 2021

The structural stability, charge transfer effects and strength of the spin–orbit couplings in different Ni(ii)–ligand complexes have been studied at the DFT (B3LYP and CAM-B3LYP) and coupled cluster (DLPNO-CCSD(T)) levels of theory.
Quantum and classical effects in DNA point mutations: Watson–Crick tautomerism in AT and GC base pairs
Authors: Slocombe L. , Al-Khalili J. S. , Sacchi M.
Published: January 2021

Proton transfer along the hydrogen bonds of DNA can lead to the creation of short-lived, but biologically relevant point mutations that can further lead to gene mutation and, potentially, cancer.
Understanding the nature of NH3-coordinated active sites and the complete reaction schemes for NH3-SCR using Cu-SAPO-34 catalysts
Authors: Yang Guangpeng , Ran Jingyu , Du Xuesen , Wang Xiangmin , Ran Zhilin , Chen Yanrong , Zhang Li , Crittenden John
Published: January 2021

Cu-SAPO-34 zeolite catalysts show excellent NH3-SCR performance at low temperature, which is due to the catalytic capacity of copper species.
Enhanced Li-ion transport in divalent metal-doped Li2SnO3
Authors: Zulueta Yohandys A. , Nguyen Minh Tho
Published: January 2021

The improvement of Li-ion transport properties and doping engineering in Li-ion batteries are currently active research topics in the search for next-generation energy storage devices.
α-Substituted phthalocyanines based on metal-induced H- or J-type aggregation for silver and palladium ions: synthesis, fluorescence, and antimicrobial and antioxidant properties
Authors: Alici Esma H. , Bilgiçli Ahmet T. , Günsel Armağan , Arabaci Gulnur , Nilüfer Yarasir M.
Published: January 2021

In this study, new tetra substituted phthalocyanines were synthesized. Their precious metal ion sensitivity, antioxidant and antimicrobial properties were investigated.
Ultrafine CoRu alloy nanoparticles in situ embedded in Co4N porous nanosheets as high-efficient hydrogen evolution electrocatalysts
Authors: Zhang Meilin , Wang Jinlei , Zhang Yeqing , Ye Lei , Gong Yaqiong
Published: January 2021

The synthesized CoRu@Co4N electrode exhibited distinguished electrocatalytic performance toward HER over a broad pH range.
Enhanced bio-production from CO2by microbial electrosynthesis (MES) with continuous operational mode
Authors: Izadi Paniz , Fontmorin Jean-Marie , Lim Swee Su , Head Ian M. , Yu Eileen H.
Published: January 2021

Continuous operational mode increased systems efficiency compared to fed-batch mode. Hydraulic retention time (HRT) affected the production pattern. Short and long HRT increased acetate production rate and products diversity, respectively.
Levulinic acid hydrogenation to γ-valerolactone over single Ru atoms on a TiO2@nitrogen doped carbon support
Authors: Zhang Kaili , Meng Qinglei , Wu Haihong , Yuan Tongying , Han Shitao , Zhai Jianxin , Zheng Bingxiao , Xu Caiyun , Wu Wei , He Mingyuan , Han Buxing
Published: January 2021

TiO2@nitrogen doped porous carbon dispersed single Ru atom catalyst (Ru/TiO2@CN) efficiently transforms levulinic acid into γ-valerolactone at room temperature in water with a turnover frequency of 278 molGVL molRu−1 h−1 at complete conversion.