bluuebunny/crossref_metadata_2025 huggingface dataset:
A 2D material–based transparent hydrogel with engineerable interference colours
Authors: Ding Baofu , Zeng Pengyuan , Huang Ziyang , Dai Lixin , Lan Tianshu , Xu Hao , Pan Yikun , Luo Yuting , Yu Qiangmin , Cheng Hui-Ming , Liu Bilu
Published: March 2022

Transparent hydrogels are key materials for many applications, such as contact lens, imperceptible soft robotics and invisible wearable devices. Introducing large and engineerable optical anisotropy offers great prospect for endowing them with extra birefringence-based functions and exploiting their applications in see-through flexible polarization optics. However, existing transparent hydrogels suffer from limitation of low and/or non-fine engineerable birefringence. Here, we invent a transparent magneto-birefringence hydrogel with large and finely engineerable optical anisotropy. The large optical anisotropy factor of the embedded magnetic two-dimensional material gives rise to the large magneto-birefringence of the hydrogel in the transparent condition of ultra-low concentration, which is several orders of magnitude larger than usual transparent magnetic hydrogels. High transparency, large and tunable optical anisotropy cooperatively permit the magnetic patterning of interference colours in the hydrogel. The hydrogel also shows mechanochromic and thermochromic property. Our finding provides an entry point for applying hydrogel in optical anisotropy and colour centred fields, with several proof-of-concept applications been demonstrated.
Kinetic model of GPCR-G protein interactions reveals allokairic modulation of signaling
Authors: Culhane Kelly J. , Gupte Tejas M. , Madhugiri Indrani , Gadgil Chetan J. , Sivaramakrishnan Sivaraj
Published: March 2022

Established models of ternary complex formation between hormone, G protein coupled receptor (GPCR), and G protein assume that all interactions occur under equilibrium conditions. However, recent studies have established that the lifetimes of these interactions are comparable to the duration of hormone activated GPCR signaling. To simulate interactions during such non-equilibrium conditions, we propose a kinetic model wherein the receptor undergoes rate-limiting transitions between two hormone-bound active states. Simulations, using experimentally measured parameters, demonstrate transient states in ternary complex formation, and delineate the phenomenon of GPCR priming, wherein non-cognate G proteins substantially enhance cognate G protein signaling. Our model reveals that kinetic barriers of slow receptor interconversion can be overcome through allokairic modulation, a regulatory mechanism of ternary complex formation and downstream signaling.
Bacterial F-type ATP synthases follow a well-choreographed assembly pathway
Authors: Vu Huu Khanh , Zangl Rene , Hoffmann Jan , Just Alicia , Morgner Nina
Published: March 2022

F-type ATP synthases are multiprotein complexes composed of two separate coupled motors (F1 and FO) generating adenosine triphosphate (ATP) as the universal major energy source in a variety of relevant biological processes in mitochondria, bacteria and chloroplasts. While the structure of many ATPases is solved today, the precise assembly pathway of F1FO-ATP synthases is still largely unclear. Here, we probe the assembly of the F1 complex from Acetobacterium woodii. Using laser induced liquid bead ion desorption (LILBID) mass spectrometry, we study the self-assembly of purified F1 subunits in different environments under non-denaturing conditions. We report assembly requirements and identify important assembly intermediates in vitro and in cellula. Our data provide evidence that nucleotide binding is crucial for in vitro F1 assembly, whereas ATP hydrolysis appears to be less critical. We correlate our results with activity measurements and propose a model for the assembly pathway of a functional F1 complex.
Spatial and temporal expansion of global wildland fire activity in response to climate change
Authors: Senande-Rivera Martín , Insua-Costa Damián , Miguez-Macho Gonzalo
Published: March 2022

Global warming is expected to alter wildfire potential and fire season severity, but the magnitude and location of change is still unclear. Here, we show that climate largely determines present fire-prone regions and their fire season. We categorize these regions according to the climatic characteristics of their fire season into four classes, within general Boreal, Temperate, Tropical and Arid climate zones. Based on climate model projections, we assess the modification of the fire-prone regions in extent and fire season length at the end of the 21st century. We find that due to global warming, the global area with frequent fire-prone conditions would increase by 29%, mostly in Boreal (+111%) and Temperate (+25%) zones, where there may also be a significant lengthening of the potential fire season. Our estimates of the global expansion of fire-prone areas highlight the large but uneven impact of a warming climate on Earth’s environment.
MQuad enables clonal substructure discovery using single cell mitochondrial variants
Authors: Kwok Aaron Wing Cheung , Qiao Chen , Huang Rongting , Sham Mai-Har , Ho Joshua W. K. , Huang Yuanhua
Published: March 2022

Mitochondrial mutations are increasingly recognised as informative endogenous genetic markers that can be used to reconstruct cellular clonal structure using single-cell RNA or DNA sequencing data. However, identifying informative mtDNA variants in noisy and sparse single-cell sequencing data is still challenging with few computation methods available. Here we present an open source computational tool MQuad that accurately calls clonally informative mtDNA variants in a population of single cells, and an analysis suite for complete clonality inference, based on single cell RNA, DNA or ATAC sequencing data. Through a variety of simulated and experimental single cell sequencing data, we showed that MQuad can identify mitochondrial variants with both high sensitivity and specificity, outperforming existing methods by a large extent. Furthermore, we demonstrate its wide applicability in different single cell sequencing protocols, particularly in complementing single-nucleotide and copy-number variations to extract finer clonal resolution.
Differential recognition of canonical NF-κB dimers by Importin α3
Authors: Florio Tyler J. , Lokareddy Ravi K. , Yeggoni Daniel P. , Sankhala Rajeshwer S. , Ott Connor A. , Gillilan Richard E. , Cingolani Gino
Published: March 2022

Nuclear translocation of the p50/p65 heterodimer is essential for NF-κB signaling. In unstimulated cells, p50/p65 is retained by the inhibitor IκBα in the cytoplasm that masks the p65-nuclear localization sequence (NLS). Upon activation, p50/p65 is translocated into the nucleus by the adapter importin α3 and the receptor importin β. Here, we describe a bipartite NLS in p50/p65, analogous to nucleoplasmin NLS but exposed in trans. Importin α3 accommodates the p50- and p65-NLSs at the major and minor NLS-binding pockets, respectively. The p50-NLS is the predominant binding determinant, while the p65-NLS induces a conformational change in the Armadillo 7 of importin α3 that stabilizes a helical conformation of the p65-NLS. Neither conformational change was observed for importin α1, which makes fewer bonds with the p50/p65 NLSs, explaining the preference for α3. We propose that importin α3 discriminates between the transcriptionally active p50/p65 heterodimer and p50/p50 and p65/65 homodimers, ensuring fidelity in NF-κB signaling.
Cas9 exo-endonuclease eliminates chromosomal translocations during genome editing
Authors: Yin Jianhang , Lu Rusen , Xin Changchang , Wang Yuhong , Ling Xinyu , Li Dong , Zhang Weiwei , Liu Mengzhu , Xie Wutao , Kong Lingyun , Si Wen , Wei Ping , Xiao Bingbing , Lee Hsiang-Ying , Liu Tao , Hu Jiazhi
Published: March 2022

The mechanism underlying unwanted structural variations induced by CRISPR-Cas9 remains poorly understood, and no effective strategy is available to inhibit the generation of these byproducts. Here we find that the generation of a high level of translocations is dependent on repeated cleavage at the Cas9-targeting sites. Therefore, we employ a strategy in which Cas9 is fused with optimized TREX2 to generate Cas9TX, a Cas9 exo-endonuclease, which prevents perfect DNA repair and thereby avoids repeated cleavage. In comparison with CRISPR-Cas9, CRISPR-Cas9TX greatly suppressed translocation levels and enhanced the editing efficiency of single-site editing. The number of large deletions associated with Cas9TX was also reduced to very low level. The application of CRISPR-Cas9TX for multiplex gene editing in chimeric antigen receptor T cells nearly eliminated deleterious chromosomal translocations. We report the mechanism underlying translocations induced by Cas9, and propose a general strategy for reducing chromosomal abnormalities induced by CRISPR-RNA-guided endonucleases.
Liquid metal-tailored gluten network for protein-based e-skin
Authors: Chen Bin , Cao Yudong , Li Qiaoyu , Yan Zhuo , Liu Rui , Zhao Yunjiao , Zhang Xiang , Wu Minying , Qin Yixiu , Sun Chang , Yao Wei , Cao Ziyi , Ajayan Pulickel M. , Chee Mason Oliver Lam , Dong Pei , Li Zhaofen , Shen Jianfeng , Ye Mingxin
Published: March 2022

Designing electronic skin (e-skin) with proteins is a critical way to endow e-skin with biocompatibility, but engineering protein structures to achieve controllable mechanical properties and self-healing ability remains a challenge. Here, we develop a hybrid gluten network through the incorporation of a eutectic gallium indium alloy (EGaIn) to design a self-healable e-skin with improved mechanical properties. The intrinsic reversible disulfide bond/sulfhydryl group reconfiguration of gluten networks is explored as a driving force to introduce EGaIn as a chemical cross-linker, thus inducing secondary structure rearrangement of gluten to form additional β-sheets as physical cross-linkers. Remarkably, the obtained gluten-based material is self-healing, achieves synthetic material-like stretchability (>1600%) and possesses the ability to promote skin cell proliferation. The final e-skin is biocompatible and biodegradable and can sense strain changes from human motions of different scales. The protein network microregulation method paves the way for future skin-like protein-based e-skin.
In situ-formed tetrahedrally coordinated double-helical metal complexes for improved coordination-activated n-doping
Authors: Liu Ziyang , Li Xiao , Lu Yang , Zhang Chen , Zhang Yuewei , Huang Tianyu , Zhang Dongdong , Duan Lian
Published: March 2022

In situ coordination-activated n-doping by air-stable metals in electron-transport organic ligands has proven to be a viable method to achieve Ohmic electron injection for organic optoelectronics. However, the mutual exclusion of ligands with high nucleophilic quality and strong electron affinity limits the injection efficiency. Here, we propose meta-linkage diphenanthroline-type ligands, which not only possess high electron affinity and good electron transport ability but also favour the formation of tetrahedrally coordinated double-helical metal complexes to decrease the ionization energy of air-stable metals. An electron injection layer (EIL) compatible with various cathodes and electron transport materials is developed with silver as an n-dopant, and the injection efficiency outperforms conventional EILs such as lithium compounds. A deep-blue organic light-emitting diode with an optimized EIL achieves a high current efficiency calibrated by the y colour coordinate (0.045) of 237 cd A−1 and a superb LT95 of 104.1 h at 5000 cd m−2.
Regulation of protein secretion through chemical regulation of endoplasmic reticulum retention signal cleavage
Authors: Praznik Arne , Fink Tina , Franko Nik , Lonzarić Jan , Benčina Mojca , Jerala Nina , Plaper Tjaša , Roškar Samo , Jerala Roman
Published: March 2022

Secreted proteins, such as hormones or cytokines, are key mediators in multicellular organisms. Response of protein secretion based on transcriptional control is rather slow, as it requires transcription, translation and transport from the endoplasmic reticulum (ER) to the plasma membrane via the conventional protein secretion (CPS) pathway. An alternative regulation to provide faster response would be valuable. Here we present two genetically encoded orthogonal regulatory secretion systems, which rely on the retention of pre-synthesized proteins on the ER membrane (membER, released by a cytosolic protease) or inside the ER lumen (lumER, released by an ER-luminal protease), respectively, and their release by the chemical signal-regulated proteolytic removal of an ER-retention signal, without triggering ER stress due to protein aggregates. Design of orthogonal chemically-regulated split proteases enables the combination of signals into logic functions. Its application was demonstrated on a chemically regulated therapeutic protein secretion and regulated membrane translocation of a chimeric antigen receptor (CAR) targeting cancer antigen. Regulation of the ER escape represents a platform for the design of fast-responsive and tightly-controlled modular and scalable protein secretion system for mammalian cells.
Tocilizumab overcomes chemotherapy resistance in mesenchymal stem-like breast cancer by negating autocrine IL-1A induction of IL-6
Authors: Chung Andrew W. , Kozielski Anthony J. , Qian Wei , Zhou Jianying , Anselme Ann C. , Chan Alfred A. , Pan Ping-Ying , Lee Delphine J. , Chang Jenny C.
Published: March 2022

Triple-negative breast cancer (TNBC) patients with mesenchymal stem-like (MSL) subtype have responded poorly to chemotherapy whereas patients with basal-like 1 (BL1) subtype achieved the best clinical response. In order to gain insight into pathways that may contribute to the divergent sensitivity to chemotherapy, we compared the inflammatory profile of the two TNBC subtypes treated with docetaxel. Cellular signaling analysis determined that docetaxel activated MAPK pathway in MSL TNBCs but not BL1 TNBCs. The subsequent MAPK pathway activation in MSL TNBCs led to an IL-1A mediated cascade of autocrine inflammatory mediators including IL-6. Utilizing the humanized IL-6R antibody, tocilizumab, our in vitro and in vivo data show that MSL TNBCs treated with tocilizumab together with chemotherapy results in delayed tumor progression compared to MSL TNBCs treated with docetaxel alone. Our study highlights a molecular subset of TNBC that may be responsive to tocilizumab therapy for potential translational impact.
Assessment and diagnosis of chronic dyspnoea: a literature review
Authors: Sunjaya Anthony Paulo , Homaira Nusrat , Corcoran Kate , Martin Allison , Berend Norbert , Jenkins Christine
Published: March 2022

Dyspnoea or breathlessness is a common presenting symptom among patients attending primary care services. This review aimed to determine whether there are clinical tools that can be incorporated into a clinical decision support system for primary care for efficient and accurate diagnosis of causes of chronic dyspnoea. We searched MEDLINE, EMBASE and Google Scholar for all literature published between 1946 and 2020. Studies that evaluated a clinical algorithm for assessment of chronic dyspnoea in patients of any age group presenting to physicians with chronic dyspnoea were included. We identified 326 abstracts, 55 papers were reviewed, and eight included. A total 2026 patients aged between 20–80 years were included, 60% were women. The duration of dyspnoea was three weeks to 25 years. All studies undertook a stepwise or algorithmic approach to the assessment of dyspnoea. The results indicate that following history taking and physical examination, the first stage should include simply performed tests such as pulse oximetry, spirometry, and electrocardiography. If the patient remains undiagnosed, the second stage includes investigations such as chest x-ray, thyroid function tests, full blood count and NT-proBNP. In the third stage patients are referred for more advanced tests such as echocardiogram and thoracic CT. If dyspnoea remains unexplained, the fourth stage of assessment will require secondary care referral for more advanced diagnostic testing such as exercise tests. Utilising this proposed stepwise approach is expected to ascertain a cause for dyspnoea for 35% of the patients in stage 1, 83% by stage 3 and >90% of patients by stage 4.
Three doses of BNT162b2 vaccine confer neutralising antibody capacity against the SARS-CoV-2 Omicron variant
Authors: Ariën Kevin K. , Heyndrickx Leo , Michiels Johan , Vereecken Katleen , Van Lent Kurt , Coppens Sandra , Willems Betty , Pannus Pieter , Martens Geert A. , Van Esbroeck Marjan , Goossens Maria E. , Marchant Arnaud , Bartholomeeusen Koen , Desombere Isabelle
Published: March 2022

We report the levels of neutralising antibodies against Wuhan, Delta and Omicron variants in unimmunized infected (group 1), immunised and boosted (group 2) and infected immunised and boosted (group 3) adult individuals. Our observations support the rapid administration of a booster vaccine dose to prevent infection and disease caused by Omicron.
Portable real-time colorimetric LAMP-device for rapid quantitative detection of nucleic acids in crude samples
Authors: Papadakis G. , Pantazis A. K. , Fikas N. , Chatziioannidou S. , Tsiakalou V. , Michaelidou K. , Pogka V. , Megariti M. , Vardaki M. , Giarentis K. , Heaney J. , Nastouli E. , Karamitros T. , Mentis A. , Zafiropoulos A. , Sourvinos G. , Agelaki S. , Gizeli E.
Published: March 2022

Loop-mediated isothermal amplification is known for its high sensitivity, specificity and tolerance to inhibiting-substances. In this work, we developed a device for performing real-time colorimetric LAMP combining the accuracy of lab-based quantitative analysis with the simplicity of point-of-care testing. The device innovation lies on the use of a plastic tube anchored vertically on a hot surface while the side walls are exposed to a mini camera able to take snapshots of the colour change in real time during LAMP amplification. Competitive features are the rapid analysis (< 30 min), quantification over 9 log-units, crude sample-compatibility (saliva, tissue, swabs), low detection limit (< 5 copies/reaction), smartphone-operation, fast prototyping (3D-printing) and ability to select the dye of interest (Phenol red, HNB). The device’s clinical utility is demonstrated in cancer mutations-analysis during the detection of 0.01% of BRAF-V600E-to-wild-type molecules from tissue samples and COVID-19 testing with 97% (Ct < 36.8) and 98% (Ct < 30) sensitivity when using extracted RNA and nasopharyngeal-swabs, respectively. The device high technology-readiness-level makes it a suitable platform for performing any colorimetric LAMP assay; moreover, its simple and inexpensive fabrication holds promise for fast deployment and application in global diagnostics.
Naïve-like pluripotency to pave the way for saving the northern white rhinoceros from extinction
Authors: Zywitza Vera , Rusha Ejona , Shaposhnikov Dmitry , Ruiz-Orera Jorge , Telugu Narasimha , Rishko Valentyna , Hayashi Masafumi , Michel Geert , Wittler Lars , Stejskal Jan , Holtze Susanne , Göritz Frank , Hermes Robert , Wang Jichang , Izsvák Zsuzsanna , Colleoni Silvia , Lazzari Giovanna , Galli Cesare , Hildebrandt Thomas B. , Hayashi Katsuhiko , Diecke Sebastian , Drukker Micha
Published: March 2022

The northern white rhinoceros (NWR) is probably the earth’s most endangered mammal. To rescue the functionally extinct species, we aim to employ induced pluripotent stem cells (iPSCs) to generate gametes and subsequently embryos in vitro. To elucidate the regulation of pluripotency and differentiation of NWR PSCs, we generated iPSCs from a deceased NWR female using episomal reprogramming, and observed surprising similarities to human PSCs. NWR iPSCs exhibit a broad differentiation potency into the three germ layers and trophoblast, and acquire a naïve-like state of pluripotency, which is pivotal to differentiate PSCs into primordial germ cells (PGCs). Naïve culturing conditions induced a similar expression profile of pluripotency related genes in NWR iPSCs and human ESCs. Furthermore, naïve-like NWR iPSCs displayed increased expression of naïve and PGC marker genes, and a higher integration propensity into developing mouse embryos. As the conversion process was aided by ectopic BCL2 expression, and we observed integration of reprogramming factors, the NWR iPSCs presented here are unsuitable for gamete production. However, the gained insights into the developmental potential of both primed and naïve-like NWR iPSCs are fundamental for in future PGC-specification in order to rescue the species from extinction using cryopreserved somatic cells.
Automated detection of celiac disease using Machine Learning Algorithms
Authors: Stoleru Cristian-Andrei , Dulf Eva H. , Ciobanu Lidia
Published: March 2022

Celiac disease is a disorder of the immune system that mainly affects the small intestine but can also affect the skeletal system. The diagnosis relies on histological assessment of duodenal biopsies acquired by upper digestive endoscopy. Immunological tests involve collecting a blood sample to detect if the antibodies have been produced in the body. Endoscopy is invasive and histology is time-consuming. In recent years there have been various algorithms that use artificial intelligence (AI) and neural convolutions (CNN, Convolutional Neural Network) to process images from capsule endoscopy, a non-invasive endoscopy approach, that provides magnified, high qualitative images of the small bowel mucosa, to quickly establish a diagnosis. The proposed innovative approach do not use complex learning algorithms, instead it find some artefacts in the endoscopies using kernels and use classified machine learning algorithms. Each used artefacts have a psychical meaning: atrophies of the mucosa with a visible submucosal vascular pattern; the presence of cracks (depressions) that have an appearance similar to that of dry land; reduction or complete loss of folds in the duodenum; the presence of a submerged appearance at the Kerckring folds and a low number of villi. The results obtained for video capsule endoscopy images processing reveal an accuracy of 94.1% and F1 score of 94%, which is competitive with other complex algorithms. The main goal of the present research was to demonstrate that computer-aided diagnosis of celiac disease is possible even without the use of very complex algorithms, which require expensive hardware and a lot of processing time. The use of the proposed automated images processing acquired noninvasively by capsule endoscopy would be assistive in detecting the subtle presence of villous atrophy not evident by visual inspection. It may also be useful to assess the degree of improvement of celiac. Patients on a gluten-free diet, the main treatment method for stopping the autoimmune process and improving the state of the small intestinal villi. The novelty of the work is that the algorithm uses two modified filters to properly analyse the intestine wall texture. It is proved that using the right filters, the proper diagnostic can be obtained by image processing, without the use of a complicated machine learning algorithm.
Multi-modal self-adaptation during object recognition in an artificial cognitive system
Authors: Miralles David , Garrofé Guillem , Parés Carlota , González Alejandro , Serra Gerard , Soto Alberto , Sevillano Xavier , de Beeck Hans Op , Masson Haemy Lee
Published: March 2022

The cognitive connection between the senses of touch and vision is probably the best-known case of multimodality. Recent discoveries suggest that the mapping between both senses is learned rather than innate. This evidence opens the door to a dynamic multimodality that allows individuals to adaptively develop within their environment. By mimicking this aspect of human learning, we propose a new multimodal mechanism that allows artificial cognitive systems (ACS) to quickly adapt to unforeseen perceptual anomalies generated by the environment or by the system itself. In this context, visual recognition systems have advanced remarkably in recent years thanks to the creation of large-scale datasets together with the advent of deep learning algorithms. However, this has not been the case for the haptic modality, where the lack of two-handed dexterous datasets has limited the ability of learning systems to process the tactile information of human object exploration. This data imbalance hinders the creation of synchronized datasets that would enable the development of multimodality in ACS during object exploration. In this work, we use a multimodal dataset recently generated from tactile sensors placed on a collection of objects that capture haptic data from human manipulation, together with the corresponding visual counterpart. Using this data, we create a multimodal learning transfer mechanism capable of both detecting sudden and permanent anomalies in the visual channel and maintaining visual object recognition performance by retraining the visual mode for a few minutes using haptic information. Our proposal for perceptual awareness and self-adaptation is of noteworthy relevance as can be applied by any system that satisfies two very generic conditions: it can classify each mode independently and is provided with a synchronized multimodal data set.
Iran to achieve the SDG 3.4 at national and sub-national levels
Authors: Haghdoost Ali Akbar , Farzadfar Farshad , Yoosefi Moein , Mansori Kamyar , Larijani Bagher , Baneshi Mohammad Reza , Shadmani Fatemeh Khosravi
Published: March 2022

The present study investigates different scenarios to project the chance of achieving SDG 3.4 in Iran. In this study, the Iranian Death Registry System data was employed to estimate the Unconditional Probability of Dying (UPoD) for the four major categories of NCDs; then, the Bayesian model averaging was used to project the UPoD at the national and sub-national levels. Also, the prevalence of the risk factors was projected by 2030 based on STEPs as well as some other study data. Plus, UPoD and the possibility of achieving the target were estimated once again based on the assumption that the global reduction in risk factors proposed by WHO would be adopted in Iran. The UPoDs for the four NCDs in Iran were 17.5% (95% UI: 16.3–19.2) and 14.7% (13.3–16.2) in 2010 and 2015 respectively and if the current trend continues, 2030 will mark the UPoD of 10.8% (7.9–14.3). However, If the risk factors are reduced to the WHO target level by 2030, the UPoDs will be reduced to 5.44% (3.51–7.39) and 6.55% (5.00–8.13) of the 2010 and 2015 baseline scenarios, respectively, to enable some provinces to meet SDG 3.4. If the current trend continues, Iran will and will not achieve the SDG 3.4 in 2010 and 2015 baseline scenarios, respectively. However, if the global target set for reducing risk factors is achieved, Iran will meet all expectations in SDG 3.4 except in Asthma and COPD. Therefore, effective interventions are recommended to be designed and followed to reduce Asthma and COPD.
Understanding health problems in people with extremely low health-related quality of life in Korea
Authors: Tran Thi Xuan Mai , Lee Sanghee , Oh Chang-Mo , Chang Yoon Jung , Cho Hyunsoon
Published: March 2022

Little is known about patients reporting extremely poor health-related quality of life (HRQoL). This study targeted population with inferior HRQoL and examined their problems experienced with HRQoL dimensions, and impacts of different morbidities on these problems. Data were obtained from a population-based survey in Korea. HRQoL was measured by EQ-5D questionnaire and low-HRQoL population was defined as individuals whose EQ-5D utility score was among the lowest 5% of total survey population. Logistic regression models were used to evaluate the impact of fifteen morbidities on HRQoL dimensions. Of 2976 low-HRQoL participants, females and low socioeconomic individuals were predominant. They experienced significantly more problems in all dimensions, with pain/discomfort, and mobility as the most frequently reported problems. Problems in HRQoL dimensions diverged according to diseases. Individuals with arthritis experienced more difficulties with mobility (aOR 2.62, 95% CI 1.77–3.87) and pain/discomfort (aOR 2.86, 95% CI 1.78–4.60). Stroke patients experienced more problems in self-care (aOR 2.24, 95% CI 1.59–3.15) and usual activities (aOR 1.87, 95% CI 1.11–3.14). Having two or more diseases was associated with worse outcomes in usual activities and increased risk of depression. Thus, efforts to improve status of low-HRQoL should be customized to fulfil unmet needs corresponding to various diseases, and depression prevention is needed for those with multimorbidity status.
Ethnic disparities in hospitalisation and hospital-outcomes during the second wave of COVID-19 infection in east London
Authors: Wan Y. I. , Apea V. J. , Dhairyawan R. , Puthucheary Z. A. , Pearse R. M. , Orkin C. M. , Prowle J. R.
Published: March 2022

It is unclear if changes in public behaviours, developments in COVID-19 treatments, improved patient care, and directed policy initiatives have altered outcomes for minority ethnic groups in the second pandemic wave. This was a prospective analysis of patients aged ≥ 16 years having an emergency admission with SARS-CoV-2 infection between 01/09/2020 and 17/02/2021 to acute NHS hospitals in east London. Multivariable survival analysis was used to assess associations between ethnicity and mortality accounting for predefined risk factors. Age-standardised rates of hospital admission relative to the local population were compared between ethnic groups. Of 5533 patients, the ethnic distribution was White (n = 1805, 32.6%), Asian/Asian British (n = 1983, 35.8%), Black/Black British (n = 634, 11.4%), Mixed/Other (n = 433, 7.8%), and unknown (n = 678, 12.2%). Excluding 678 patients with missing data, 4855 were included in multivariable analysis. Relative to the White population, Asian and Black populations experienced 4.1 times (3.77–4.39) and 2.1 times (1.88–2.33) higher rates of age-standardised hospital admission. After adjustment for various patient risk factors including age, sex, and socioeconomic deprivation, Asian patients were at significantly higher risk of death within 30 days (HR 1.47 [1.24–1.73]). No association with increased risk of death in hospitalised patients was observed for Black or Mixed/Other ethnicity. Asian and Black ethnic groups continue to experience poor outcomes following COVID-19. Despite higher-than-expected rates of hospital admission, Black and Asian patients also experienced similar or greater risk of death in hospital since the start of the pandemic, implying a higher overall risk of COVID-19 associated death in these communities.
Ultra-shallow dopant profiles as in-situ electrodes in scanning probe microscopy
Authors: Kölker Alexander , Wolf Martin , Koch Matthias
Published: March 2022

The application of nano materials to control advanced functionality in semiconductor devices has reached the atomic scale. At this dimension the exact chemical and structural composition of a device is crucial for its performance. Rapid inspection techniques are required to find the optimal combination among numerous materials. However, to date the earliest electrical inspection is carried out after multiple fabrication processes. This delay makes the fabrication of atomically designed components very challenging. Here, we propose a sample system to chemically characterize nanoscale devices in-operando. We introduce ion-implanted contacts which embedded in the sample serve as additional electrodes to carry out scanning gate experiments. We demonstrate that the presence of these electrodes does not deteriorate the surface quality. The potential of this approach is highlighted by controlling the charge state of single dangling bonds on the silicon surface. Apart from our novel sample holder, the experimental setup was not modified making this approach compatible to most commercial low-temperature scanning probe microscopes. For silicon based devices, the versatility of this method is a promising avenue to gain a detailed and rapid understanding of functionalized atomic devices and quantum interactions at the atomic level.
Comparative assessment of motion averaged free-breathing or breath-held cardiac magnetic resonance imaging protocols in a porcine myocardial infarction model
Authors: Selvakumar Dinesh , Deshmukh Tejas , Foster Sheryl L. , Sanaei Naeim N. , Min Anthea L. L. , Grieve Stuart M. , Pathan Faraz , Chong James J. H.
Published: March 2022

Breath-held (BH) cardiac magnetic resonance imaging (CMR) is the gold standard for volumetric quantification. However, large animals for pre-clinical research are unable to voluntarily breath-hold, necessitating general anaesthesia and mechanical ventilation, increasing research costs and affecting cardiovascular physiology. Conducting CMR in lightly sedated, free-breathing (FB) animal subjects is an alternative strategy which can overcome these constraints, however, may result in poorer image quality due to breathing motion artefact. We sought to assess the reproducibility of CMR metrics between FB and BH CMR in a porcine model of ischaemic cardiomyopathy. FB or BH CMR was performed in 38 porcine subjects following percutaneous induction of myocardial infarction. Analysis was performed by two independent, blinded observers according to standard reporting guidelines. Subjective and objective image quality was significantly improved in the BH cohort (image quality score: 3.9/5 vs. 2.4/5; p < 0.0001 and myocardium:blood pool intensity ratio: 2.6–3.3 vs. 1.9–2.3; p < 0.001), along with scan acquisition time (4 min 06 s ± 1 min 55 s vs. 8 min 53 s ± 2 min 39 s; p < 0.000). Intra- and inter-observer reproducibility of volumetric analysis was substantially improved in BH scans (correlation coefficients: 0.94–0.99 vs. 0.76–0.91; coefficients of variation: < 5% in BH and > 5% in FB; Bland–Altman limits of agreement: < 10 in BH and > 10 in FB). Interstudy variation between approaches was used to calculate sample sizes, with BH CMR resulting in greater than 85% reduction in animal numbers required to show clinically significant treatment effects. In summary, BH porcine CMR produces superior image quality, shorter scan acquisition, greater reproducibility, and requires smaller sample sizes for pre-clinical trials as compared to FB acquisition.
Exploring metallic and plastic 3D printed photochemical reactors for customizing chemical synthesis
Authors: Gordeev Evgeniy G. , Erokhin Kirill S. , Kobelev Andrey D. , Burykina Julia V. , Novikov Pavel V. , Ananikov Valentine P.
Published: March 2022

Visible light photocatalysis is a rapidly developing branch of chemical synthesis with outstanding sustainable potential and improved reaction design. However, the challenge is that many particular chemical reactions may require dedicated tuned photoreactors to achieve maximal efficiency. This is a critical stumbling block unless the possibility for reactor design becomes available directly in the laboratories. In this work, customized laboratory photoreactors were developed with temperature stabilization and the ability to adapt different LED light sources of various wavelengths. We explore two important concepts for the design of photoreactors: reactors for performing multiple parallel experiments and reactors suitable for scale-up synthesis, allowing a rapid increase in the product amount. Reactors of the first type were efficiently made of metal using metal laser sintering, and reactors of the second type were successfully manufactured from plastic using fused filament fabrication. Practical evaluation has shown good accuracy of the temperature stabilization in the range typically required for organic synthesis for both types of reactors. Synthetic application of 3D printed reactors has shown good utility in test reactions—furan C–H arylation and thiol-yne coupling. The critical effect of temperature stabilization was established for the furan arylation reaction: heating of the reaction mixture may lead to the total vanishing of photochemical effect.
Alterations to cavefish red blood cells provide evidence of adaptation to reduced subterranean oxygen
Authors: Boggs Tyler E. , Friedman Jessica S. , Gross Joshua B.
Published: March 2022

Animals inhabiting extreme environments allow the powerful opportunity to examine adaptive evolution in response to diverse pressures. One such pressure is reduced oxygen, commonly present at high-altitude and subterranean environments. Cave-dwelling animals must also deal with darkness and starvation, both of which have been rigorously studied as key forces driving the evolution of cave-associated traits. Interestingly, hypoxia as an environmental pressure has received less attention. Here we examined putatively adaptive phenotypes evolving in a freshwater teleost fish, Astyanax mexicanus, which includes both surface- and cave-dwelling forms. This model system also provides the opportunity to identify convergent responses to hypoxia, owing to the presence of numerous natural and independently-colonised cave populations, alongside closely-related surface conspecifics. The focus of this study is hemoglobin, an essential molecule for oxygen transport and delivery. We found that multiple cave populations harbor a higher concentration of hemoglobin in their blood, which is coincident with an increase in cave morph erythrocyte size compared to surface fish. Interestingly, both cave and surface morphs have comparable numbers of erythrocytes per unit of blood, suggesting elevated hemoglobin is not due to overproduction of red blood cells. Alternatively, owing to an increased cell area of erythrocytes in cavefish, we reason that they contain more hemoglobin per erythrocyte. These findings support the notion that cavefish have adapted to hypoxia in caves through modulation of both hemoglobin production and erythrocyte size. This work reveals an additional adaptive feature of Astyanax cavefish, and demonstrates that coordinated changes between cellular architecture and molecular changes are necessary for organisms evolving under intense environmental pressure.
A systematic approach for evaluating the role of surface-exposed loops in trypsin-like serine proteases applied to the 170 loop in coagulation factor VIIa
Authors: Sorensen Anders B. , Greisen Per , Madsen Jesper J. , Lund Jacob , Andersen Gorm , Wulff-Larsen Pernille G. , Pedersen Anette A. , Gandhi Prafull S. , Overgaard Michael T. , Østergaard Henrik , Olsen Ole H.
Published: March 2022

Proteases play a major role in many vital physiological processes. Trypsin-like serine proteases (TLPs), in particular, are paramount in proteolytic cascade systems such as blood coagulation and complement activation. The structural topology of TLPs is highly conserved, with the trypsin fold comprising two β-barrels connected by a number of variable surface-exposed loops that provide a surprising capacity for functional diversity and substrate specificity. To expand our understanding of the roles these loops play in substrate and co-factor interactions, we employ a systematic methodology akin to the natural truncations and insertions observed through evolution of TLPs. The approach explores a larger deletion space than classical random or directed mutagenesis. Using FVIIa as a model system, deletions of 1–7 amino acids through the surface exposed 170 loop, a vital allosteric regulator, was introduced. All variants were extensively evaluated by established functional assays and computational loop modelling with Rosetta. The approach revealed detailed structural and functional insights recapitulation and expanding on the main findings in relation to 170 loop functions elucidated over several decades using more cumbersome crystallization and single deletion/mutation methodologies. The larger deletion space was key in capturing the most active variant, which unexpectedly had a six-amino acid truncation. This variant would have remained undiscovered if only 2–3 deletions were considered, supporting the usefulness of the methodology in general protease engineering approaches. Our findings shed further light on the complex role that surface-exposed loops play in TLP function and supports the important role of loop length in the regulation and fine-tunning of enzymatic function throughout evolution.
Application of ammonium to a N limited arable soil enriches a succession of bacteria typically found in the rhizosphere
Authors: Hernández-Guzmán Mario , Pérez-Hernández Valentín , Navarro-Noya Yendi E. , Luna-Guido Marco L. , Verhulst Nele , Govaerts Bram , Dendooven Luc
Published: March 2022

Crop residue management and tillage are known to affect the soil bacterial community, but when and which bacterial groups are enriched by application of ammonium in soil under different agricultural practices from a semi-arid ecosystem is still poorly understood. Soil was sampled from a long-term agronomic experiment with conventional tilled beds and crop residue retention (CT treatment), permanent beds with crop residue burned (PBB treatment) or retained (PBC) left unfertilized or fertilized with 300 kg urea-N ha−1 and cultivated with wheat (Triticum durum L.)/maize (Zea mays L.) rotation. Soil samples, fertilized or unfertilized, were amended or not (control) with a solution of (NH4)2SO4 (300 kg N ha−1) and were incubated aerobically at 25 ± 2 °C for 56 days, while CO2 emission, mineral N and the bacterial community were monitored. Application of NH4+ significantly increased the C mineralization independent of tillage-residue management or N fertilizer. Oxidation of NH4+ and NO2− was faster in the fertilized soil than in the unfertilized soil. The relative abundance of Nitrosovibrio, the sole ammonium oxidizer detected, was higher in the fertilized than in the unfertilized soil; and similarly, that of Nitrospira, the sole nitrite oxidizer. Application of NH4+ enriched Pseudomonas, Flavisolibacter, Enterobacter and Pseudoxanthomonas in the first week and Rheinheimera, Acinetobacter and Achromobacter between day 7 and 28. The application of ammonium to a soil cultivated with wheat and maize enriched a sequence of bacterial genera characterized as rhizospheric and/or endophytic independent of the application of urea, retention or burning of the crop residue, or tillage.
A self-powered wireless motion sensor based on a high-surface area reverse electrowetting-on-dielectric energy harvester
Authors: Tasneem Nishat T. , Biswas Dipon K. , Adhikari Pashupati R. , Gunti Avinash , Patwary Adnan B. , Reid Russell C. , Mahbub Ifana
Published: March 2022

This paper presents a motion-sensing device with the capability of harvesting energy from low-frequency motion activities. Based on the high surface area reverse electrowetting-on-dielectric (REWOD) energy harvesting technique, mechanical modulation of the liquid generates an AC signal, which is modeled analytically and implemented in Matlab and COMSOL. A constant DC voltage is produced by using a rectifier and a DC–DC converter to power up the motion-sensing read-out circuit. A charge amplifier converts the generated charge into a proportional output voltage, which is transmitted wirelessly to a remote receiver. The harvested DC voltage after the rectifier and DC–DC converter is found to be 3.3 V, having a measured power conversion efficiency (PCE) of the rectifier as high as 40.26% at 5 Hz frequency. The energy harvester demonstrates a linear relationship between the frequency of motion and the generated output power, making it highly suitable as a self-powered wearable motion sensor.
Which-way identification by an asymmetrical double-slit experiment with monochromatic photons
Authors: Vo Van Thuan , Vu Duc Vinh
Published: March 2022

Recently, a laser beam asymmetrical double-slit experiment was proposed and performed, concerning ontological physical reality in quantum mechanics, under an assumption of single-photon interference. In the present study, by controlling better for saturation effects and upgrading the slit’s shape, we succeed in producing new interference samples with acceptable quality. Applying almost the same geometrical set-up, the present experiment makes the ”which-way” identification with higher experimental confidence. In the results, the ontological which-way effect observed in our recent experiment is well reconfirmed without any additional measurement of relative integral intensity.
Engineering an acetoacetyl-CoA reductase from Cupriavidus necator toward NADH preference under physiological conditions
Authors: Olavarria Karel , Pijman Yared O. , Cabrera Ricardo , van Loosdrecht Mark C. M. , Wahl S. Aljoscha
Published: March 2022

The coupling of PHB generation with NADH reoxidation is required to generate PHB as a fermentation product. A fundamental trait to accomplish this feature is to express a functional NADH-preferring acetoacetyl-CoA reductase, engaged in PHB accumulation. One way to obtain such a reductase is by engineering the cofactor preference of the acetoacetyl-CoA reductase encoded by the phaB1 gene from Cupriavidus necator (AARCn1). Aiming to have a deeper understanding of the structural determinants of the cofactor preference in AARCn1, and to obtain an NADH-preferring acetoacetyl-CoA reductase derived from this protein, some engineered enzymes were expressed, purified and kinetically characterized, together with the parental AARCn1. One of these engineered enzymes, Chimera 5, experimentally showed a selectivity ratio ((kcat/KM)NADH/(kcat/KM)NADPH) ≈ 18, which is 160 times higher than the selectivity ratio experimentally observed in the parental AARCn1. A thermodynamic-kinetic approach was employed to estimate the cofactor preference and flux capacity of Chimera 5 under physiological conditions. According to this approach, Chimera 5 could prefer NADH over NADPH between 25 and 150 times. Being a derivative of AARCn1, Chimera 5 should be readily functional in Escherichia coli and C. necator. Moreover, with the expected expression level, its activity should be enough to sustain PHB accumulation fluxes similar to the fluxes previously observed in these biotechnologically relevant cell factories.
Histone H2AX promotes metastatic progression by preserving glycolysis via hexokinase-2
Authors: Liu Yue , Li Haojian , Wilson Crystal N. , Bai Hui Jen , Boufraqech Myriem , Weyemi Urbain
Published: March 2022

Genomic stability is essential for organismal development, cellular homeostasis, and survival. The DNA double-strand breaks are particularly deleterious, creating an environment prone to cellular transformation and oncogenic activation. The histone variant H2AX is an essential component of the nucleosome responsible for initiating the early steps of the DNA repair process. H2AX maintains genomic stability by initiating a signaling cascade that collectively functions to promote DNA double-strand breaks repair. Recent advances have linked genomic stability to energetic metabolism, and alterations in metabolism were found to interfere with genome maintenance. Utilizing genome-wide transcripts profiling to identify differentially-expressed genes involved in energetic metabolism, we compared control and H2AX-deficient metastatic breast cancer cell lines, and found that H2AX loss leads to the repression of key genes regulating glycolysis, with a prominent effect on hexokinase-2 (HK2). These observations are substantiated by evidence that H2AX loss compromises glycolysis, effect which was reversed by ectopic expression of HK2. Utilizing models of experimental metastasis, we found that H2AX silencing halts progression of metastatic breast cancer cells MDA-MB-231. Most interestingly, ectopic expression of HK2 in H2AX-deficient cells restores their metastatic potential. Using multiple publicly available datasets, we found a significantly strong positive correlation between H2AX expression levels in patients with invasive breast cancer, and levels of glycolysis genes, particularly HK2. These observations are consistent with the evidence that high H2AX expression is associated with shorter distant metastasis-free survival. Our findings reveal a role for histone H2AX in controlling the metastatic ability of breast cancer cells via maintenance of HK2-driven glycolysis.