bluuebunny/crossref_metadata_2025 huggingface dataset:
A framework for reconstructing SARS-CoV-2 transmission dynamics using excess mortality data
Authors: Ghafari Mahan , Watson Oliver J. , Karlinsky Ariel , Ferretti Luca , Katzourakis Aris
Published: May 2022

The transmission dynamics and burden of SARS-CoV-2 in many regions of the world is still largely unknown due to the scarcity of epidemiological analyses and lack of testing to assess the prevalence of disease. In this work, we develop a quantitative framework based on excess mortality data to reconstruct SARS-CoV-2 transmission dynamics and assess the level of underreporting in infections and deaths. Using weekly all-cause mortality data from Iran, we are able to show a strong agreement between our attack rate estimates and seroprevalence measurements in each province and find significant heterogeneity in the level of exposure across the country with 11 provinces reaching near 100% attack rates. Despite having a young population, our analysis reveals that incorporating limited access to medical services in our model, coupled with undercounting of COVID-19-related deaths, leads to estimates of infection fatality rate in most provinces of Iran that are comparable to high-income countries.
Cryo-EM structures of human A2ML1 elucidate the protease-inhibitory mechanism of the A2M family
Authors: Nielsen Nadia Sukusu , Zarantonello Alessandra , Harwood Seandean Lykke , Jensen Kathrine Tejlgård , Kjøge Katarzyna , Thøgersen Ida B. , Schauser Leif , Karlsen Jesper Lykkegaard , Andersen Gregers R. , Enghild Jan J.
Published: May 2022

A2ML1 is a monomeric protease inhibitor belonging to the A2M superfamily of protease inhibitors and complement factors. Here, we investigate the protease-inhibitory mechanism of human A2ML1 and determine the structures of its native and protease-cleaved conformations. The functional inhibitory unit of A2ML1 is a monomer that depends on covalent binding of the protease (mediated by A2ML1’s thioester) to achieve inhibition. In contrast to the A2M tetramer which traps proteases in two internal chambers formed by four subunits, in protease-cleaved monomeric A2ML1 disordered regions surround the trapped protease and may prevent substrate access. In native A2ML1, the bait region is threaded through a hydrophobic channel, suggesting that disruption of this arrangement by bait region cleavage triggers the extensive conformational changes that result in protease inhibition. Structural comparisons with complement C3/C4 suggest that the A2M superfamily of proteins share this mechanism for the triggering of conformational change occurring upon proteolytic activation.
Modular (de)construction of complex bacterial phenotypes by CRISPR/nCas9-assisted, multiplex cytidine base-editing
Authors: Volke Daniel C. , Martino Román A. , Kozaeva Ekaterina , Smania Andrea M. , Nikel Pablo I.
Published: May 2022

CRISPR/Cas technologies constitute a powerful tool for genome engineering, yet their use in non-traditional bacteria depends on host factors or exogenous recombinases, which limits both efficiency and throughput. Here we mitigate these practical constraints by developing a widely-applicable genome engineering toolset for Gram-negative bacteria. The challenge is addressed by tailoring a CRISPR base editor that enables single-nucleotide resolution manipulations (C·G → T·A) with >90% efficiency. Furthermore, incorporating Cas6-mediated processing of guide RNAs in a streamlined protocol for plasmid assembly supports multiplex base editing with >85% efficiency. The toolset is adopted to construct and deconstruct complex phenotypes in the soil bacterium Pseudomonas putida. Single-step engineering of an aromatic-compound production phenotype and multi-step deconstruction of the intricate redox metabolism illustrate the versatility of multiplex base editing afforded by our toolbox. Hence, this approach overcomes typical limitations of previous technologies and empowers engineering programs in Gram-negative bacteria that were out of reach thus far.
BRD4 promotes resection and homology-directed repair of DNA double-strand breaks
Authors: Barrows John K. , Lin Baicheng , Quaas Colleen E. , Fullbright George , Wallace Elizabeth N. , Long David T.
Published: May 2022

Double-strand breaks (DSBs) are one of the most toxic forms of DNA damage and represent a major source of genomic instability. Members of the bromodomain and extra-terminal (BET) protein family are characterized as epigenetic readers that regulate gene expression. However, evidence suggests that BET proteins also play a more direct role in DNA repair. Here, we establish a cell-free system using Xenopus egg extracts to elucidate the gene expression-independent functions of BET proteins in DSB repair. We identify the BET protein BRD4 as a critical regulator of homologous recombination and describe its role in stimulating DNA processing through interactions with the SWI/SNF chromatin remodeling complex and resection machinery. These results establish BRD4 as a multifunctional regulator of chromatin binding that links transcriptional activity and homology-directed repair.
Efficacy, T cell activation and antibody responses in accelerated Plasmodium falciparum sporozoite chemoprophylaxis vaccine regimens
Authors: Ibanez Javier , Fendel Rolf , Lorenz Freia-Raphaella , Granados-Bayon Patricia , Brückner Sina , Esen Meral , Sulyok Mihály , Sulyok Zita , Borrmann Steffen , Bacher Petra , Scheffold Alexander , Hoffman Stephen L. , Kremsner Peter G. , Mordmüller Benjamin
Published: May 2022

Repeated direct venous inoculation of Plasmodium falciparum sporozoites (PfSPZ) together with antimalarial chemoprophylaxis (PfSPZ–CVac) is the most potent way to induce sterile immunity against P. falciparum infection in malaria-naive volunteers. However, established schedules are complex and long. Here, we tested two accelerated three-dose schedules (28- and 10-day regimen) assessing efficacy by controlled human malaria infection (CHMI) against placebo, comparing vaccine-specific T cell and antibody responses by antigen-reactive T cell enrichment (ARTE) and protein microarray, respectively. Both regimens were similarly efficacious (67 and 63% vaccine efficacy) but different in the induction of vaccine-specific T cells and antibodies. The 10-day regimen resulted in higher numbers of antigen-specific CD4+ effector memory pro-inflammatory T cells and a broader antibody response compared with the 28-day regimen. Usually in nature, P. falciparum liver stage lasts about 6.5 days. The short vaccination-interval of the 10-day regimen prolongs the time of continuous exposure to liver-stage parasites, which may explain the stronger response. Besides dose and number of vaccinations, duration of liver-stage exposure is a factor to optimize PfSPZ–CVac immunogenicity.
A benchmark study on economic impact of Neem Coated Urea on Indian agriculture
Authors: Ramappa K. B. , Jadhav Vilas , Manjunatha A. V.
Published: May 2022

The policy of mandatory production and distribution of Neem Coated Urea (NCU) was implemented by the Government of India since 2015. In this article, authors have made an attempt to explore the benefits of NCU recognized by the producers of six major crops such as paddy, maize, sugarcane, tur, jute and soybean across six major states viz., Karnataka, Maharashtra, Madhya Pradesh, Bihar, Punjab and Assam. The results reveal that NCU use has contributed positively in terms of increasing the yield levels of main product and by-products, as well as net returns with regard to almost all reference crops however; the extent varies from crop to crop. Moreover, NCU has helped reduce the cost of production by minimizing the cost of urea as well as other fertilizers and pesticides usage. Interestingly, the diversion of urea has stopped completely, post the production and distribution of NCU. Hence, it is concluded that the application of NCU has a positive impact on Indian agriculture, by way of increasing yield levels & returns for the farming community. These results are in line with the PM's vision of doubling farmers’ income by 2022 and Sustainable Development Goals of the Country.
Optogenetic modulation of electroacupuncture analgesia in a mouse inflammatory pain model
Authors: Hsiao I-Han , Liao Hsien-Yin , Lin Yi‑Wen
Published: May 2022

Peripheral tissue damage and associated inflammation can trigger neuroplastic changes in somatic pain pathways, such as reduced neuronal firing thresholds and synaptic potentiation, that ultimately lead to peripheral sensitization and chronic pain. Electroacupuncture (EA) can relieve chronic inflammatory pain, but the underlying mechanisms are unknown, including the contributions of higher pain centers such as somatosensory cortex (SSC). We investigated these mechanisms using optogenetic modulation of SSC activity in a mouse inflammatory pain model. Injection of Complete Freund's Adjuvant into the hind paw reliably induced inflammation accompanied by reduced mechanical and thermal pain thresholds (hyperalgesia) within three days (mechanical: 1.54 ± 0.13 g; thermal: 3.94 ± 0.43 s). Application of EA produced significant thermal and mechanical analgesia, but these responses were reversed by optogenetic activation of SSC neurons, suggesting that EA-induced analgesia involves modulation of central pain pathways. Western blot and immunostaining revealed that EA also attenuated CaMKIIα signaling in the dorsal root ganglion, central spinal cord, SSC, and anterior cingulate cortex (ACC). In contrast, optogenetic activation of the SSC induced CaMKIIα signaling in SSC and ACC. These findings suggest that AE can relieve inflammatory pain by suppressing CaMKIIα-dependent plasticity in cortical pain pathways. The SSC and ACC CaMKIIα signaling pathways may be valuable therapeutic targets for chronic inflammatory pain treatment.
Scale, context, and heterogeneity: the complexity of the social space
Authors: Balsa-Barreiro José , Menendez Mónica , Morales Alfredo J.
Published: May 2022

The social space refers to physical or virtual places where people interact with one another. It decisively influences the emergence of human behaviors. However, little is known about the nature and complexity of the social space, nor its relationship to context and spatial scale. Recently, the science of complex systems has bridged between fields of knowledge to provide quantitative responses to fundamental sociological questions. In this paper, we analyze the shifting behavior of social space in terms of human interactions and wealth distribution across multiple scales using fine-grained data collected from both official (US Census Bureau) and unofficial data sources (social media). We use these data to unveil how patterns strongly depend upon the observation scale. Therefore, it is crucial for any analysis to be framed within the appropriate context to avoid biased results and/or misleading conclusions. Biased data analysis may lead to the adoption of fragile and poor decisions. Including context and a proper understanding of the spatial scale are essential nowadays, especially with the pervasive role of data-driven tools in decision-making processes.
Necrolytic migratory erythema is an important visual cutaneous clue of glucagonoma
Authors: Li Wei , Yang Xue , Deng Yuan , Jiang Yina , Xu Guiping , Li Enxiao , Wu Yinying , Ren Juan , Ma Zhenhua , Dong Shunbin , Han Liang , Ma Qingyong , Wu Zheng , Wang Zheng
Published: May 2022

Glucagonoma is an extremely rare neuroendocrine tumor that arises from pancreatic islet alpha cells. Although glucagonoma is usually accompanied by a variety of characteristic clinical symptoms, early diagnosis is still difficult due to the scarcity of the disease. In this study, we present the cumulative experiences, clinical characteristics and treatments of seven patients diagnosed with glucagonoma during the past 10 years at the First Affiliated Hospital of Xi’an Jiaotong University. The seven patients in our cohort consisted of six females and one male with an average diagnosis age of 40.1 years (range 23–51). The average time from onset of symptoms to diagnosis of glucagonoma was 14 months (range 2–36 months). All the patients visited dermatology first for necrolytic migratory erythema (NME) 7/7 (100%), and other presenting symptoms included diabetes mellitus (DM) 4/7 (57%), stomatitis 2/7 (28%), weight loss 4/7 (57%), anemia 4/7 (57%), diarrhea 1/7 (14%), and DVT1/7 (14%). Plasma glucagon levels were increased in all patients (range 216.92–3155 pg/mL) and declined after surgery. Imaging studies revealed that four of seven patients had liver metastasis. Six of seven patients received surgical resection, and all of them received somatostatin analog therapy. Symptoms improved significantly in 6 out of 7 patients. Three of seven patients died of this disease by the time of follow-up. Our data suggest that if persistent NME is associated with DM and high glucagon levels, timely abdominal imaging should be performed to confirm glucagonoma. Once diagnosed, surgery and somatostatin analogs are effective for symptom relief and tumor control.
Nanofibrous materials affect the reaction of cytotoxicity assays
Authors: Podgórski Rafał , Wojasiński Michał , Ciach Tomasz
Published: May 2022

Nanofibrous materials are widely investigated as a replacement for the extracellular matrix, the 3D foundation for cells in all tissues. However, as with every medical material, nanofibers too must pass all safety evaluations like in vitro cytotoxicity assays or in vivo animal tests. Our literature research showed that differences in results of widely used cytotoxicity assays applied to evaluate nanofibrous materials are poorly understood. To better explore this issue, we prepared three nanofibrous materials with similar physical properties made of poly-L-lactic acid, polyurethane, and polycaprolactone. We tested five metabolic cytotoxicity assays (MTT, XTT, CCK-8, alamarBlue, PrestoBlue) and obtained different viability results for the same nanofibrous materials. Further, the study revealed that nanofibrous materials affect the reaction of cytotoxicity assays. Considering the results of both described experiments, it is evident that validating all available cytotoxicity assays for nanofibrous materials and possibly other highly porous materials should be carefully planned and verified using an additional analytical tool, like scanning electron microscopy or, more preferably, confocal microscopy.
Development of gut microbiota during the first 2 years of life
Authors: Wernroth Mona-Lisa , Peura Sari , Hedman Anna M. , Hetty Susanne , Vicenzi Silvia , Kennedy Beatrice , Fall Katja , Svennblad Bodil , Andolf Ellika , Pershagen Göran , Theorell-Haglöw Jenny , Nguyen Diem , Sayols-Baixeras Sergi , Dekkers Koen F. , Bertilsson Stefan , Almqvist Catarina , Dicksved Johan , Fall Tove
Published: May 2022

Although development of microbiota in childhood has been linked to chronic immune-related conditions, early childhood determinants of microbiota development have not been fully elucidated. We used 16S rRNA sequencing to analyse faecal and saliva samples from 83 children at four time-points during their first 2 years of life and from their mothers. Our findings confirm that gut microbiota in infants have low diversity and highlight that some properties are shared with the oral microbiota, although inter-individual differences are present. A considerable convergence in gut microbiota composition was noted across the first 2 years of life, towards a more diverse adult-like microbiota. Mode of delivery accounted for some of the inter-individual variation in early childhood, but with a pronounced attenuation over time. Our study extends previous research with further characterization of the major shift in gut microbiota composition during the first 2 years of life.
Chromatic discrimination measures in mature observers depend on the response window
Authors: Fars Julien , Fernandes Thiago P. , Huchzermeyer Cord , Kremers Jan , Paramei Galina V.
Published: May 2022

Our past anecdotal evidence prompted that a longer response window (RW) in the Trivector test (Cambridge Colour Test) improved mature observers’ estimates of chromatic discrimination. Here, we systematically explored whether RW variation affects chromatic discrimination thresholds measured by the length of Protan, Deutan and Tritan vectors. We employed the Trivector test with three RWs: 3 s, 5 s, and 8 s. Data of 30 healthy normal trichromats were stratified as age groups: ‘young’ (20–29 years), ‘middle-aged’ (31–48 years), and ‘mature’ (57–64 years). We found that for the ‘young’ and ‘middle-aged’, the thresholds were comparable at all tested RWs. However, the RW effect was apparent for the ‘mature’ observers: their Protan and Tritan thresholds decreased at 8-s RW compared to 3-s RW; moreover, their Tritan threshold decreased at 5-s RW compared to 3-s RW. Elevated discrimination thresholds at shorter RWs imply that for accurate performance, older observers require longer stimulus exposure and are indicative of ageing effects manifested by an increase in critical processing duration. Acknowledging low numbers in our ‘middle-aged’ and ‘mature’ samples, we consider our study as pilot. Nonetheless, our findings encourage us to advocate a RW extension in the Trivector protocol for testing mature observers, to ensure veridical measures of their chromatic discrimination by disentangling these from other ageing effects—slowing down of both motor responses and visual processing.
Potential future malaria transmission in Odisha due to climate change
Authors: Parihar Ruchi Singh , Bal Prasanta Kumar , Saini Atul , Mishra Saroj Kanta , Thapliyal Ashish
Published: May 2022

Future projections of malaria transmission is made for Odisha, a highly endemic region of India, through numerical simulations using the VECTRI dynamical model. The model is forced with bias-corrected temperature and rainfall from a global climate model (CCSM4) for the baseline period 1975–2005 and for the projection periods 2020s, 2050s, and 2080s under RCP8.5 emission scenario. The temperature, rainfall, mosquito density and entomological inoculation rate (EIR), generated from the VECTRI model are evaluated with the observation and analyzed further to estimate the future malaria transmission over Odisha on a spatio-temporal scale owing to climate change. Our results reveal that the malaria transmission in Odisha as a whole during summer and winter monsoon seasons may decrease in future due to the climate change except in few districts with the high elevations and dense forest regions such as Kandhamal, Koraput, Raygada and Mayurbhanj districts where an increase in malaria transmission is found. Compared to the baseline period, mosquito density shows decrease in most districts of the south, southwest, central, north and northwest regions of Odisha in 2030s, 2050s and 2080s. An overall decrease in malaria transmission of 20–40% (reduction in EIR) is seen during the monsoon season (June-Sept) over Odisha with the increased surface temperature of 3.5–4 °C and with the increased rainfall of 20–35% by the end of the century with respect to the baseline period. Furthermore, malaria transmission is likely to reduce in future over most of the Odisha regions with the increase in future warm and cold nights temperatures.
Cellular engagement and interaction in the tumor microenvironment predict non-response to PD-1/PD-L1 inhibitors in metastatic non-small cell lung cancer
Authors: Qin Angel , Lima Fatima , Bell Samantha , Kalemkerian Gregory P. , Schneider Bryan J. , Ramnath Nithya , Lew Madelyn , Krishnan Santhoshi , Mohammed Shariq , Rao Arvind , Frankel Timothy L.
Published: May 2022

Immune checkpoint inhibitors (ICI) with anti-PD-1/PD-L1 agents have improved the survival of patients with metastatic non-small cell lung cancer (mNSCLC). Tumor PD-L1 expression is an imperfect biomarker as it does not capture the complex interactions between constituents of the tumor microenvironment (TME). Using multiplex fluorescent immunohistochemistry (mfIHC), we modeled the TME to study the influence of cellular distribution and engagement on response to ICI in mNSCLC. We performed mfIHC on pretreatment tissue from patients with mNSCLC who received ICI. We used primary antibodies against CD3, CD8, CD163, PD-L1, pancytokeratin, and FOXP3; simple and complex phenotyping as well as spatial analyses was performed. We analyzed 68 distinct samples from 52 patients with mNSCLC. Patients were 39–79 years old (median 67); 44% were male and 75% had adenocarcinoma histology. The most used ICI was atezolizumab (48%). The percentage of PD-L1 positive epithelial tumor cells (EC), degree of cytotoxic T lymphocyte (CTL) engagement with EC, and degree of CTL engagement with helper T lymphocytes (HTL) were significantly lower in non-responders versus responders (p = 0.0163, p = 0.0026 and p = 0.0006, respectively). The combination of these 3 characteristics generated the best sensitivity and specificity to predict non-response to ICI and was also associated with shortened overall survival (p = 0.0271). The combination of low CTL engagement with EC and HTL along with low expression of EC PD-L1 represents a state of impaired endogenous immune reactivity. Together, they more precisely identified non-responders to ICI compared to PD-L1 alone and illustrate the importance of cellular interactions in the TME.
Clinical artificial intelligence quality improvement: towards continual monitoring and updating of AI algorithms in healthcare
Authors: Feng Jean , Phillips Rachael V. , Malenica Ivana , Bishara Andrew , Hubbard Alan E. , Celi Leo A. , Pirracchio Romain
Published: May 2022

Machine learning (ML) and artificial intelligence (AI) algorithms have the potential to derive insights from clinical data and improve patient outcomes. However, these highly complex systems are sensitive to changes in the environment and liable to performance decay. Even after their successful integration into clinical practice, ML/AI algorithms should be continuously monitored and updated to ensure their long-term safety and effectiveness. To bring AI into maturity in clinical care, we advocate for the creation of hospital units responsible for quality assurance and improvement of these algorithms, which we refer to as “AI-QI” units. We discuss how tools that have long been used in hospital quality assurance and quality improvement can be adapted to monitor static ML algorithms. On the other hand, procedures for continual model updating are still nascent. We highlight key considerations when choosing between existing methods and opportunities for methodological innovation.
Deconvolution improves the detection and quantification of spike transmission gain from spike trains
Authors: Spivak Lidor , Levi Amir , Sloin Hadas E. , Someck Shirly , Stark Eran
Published: May 2022

Accurate detection and quantification of spike transmission between neurons is essential for determining neural network mechanisms that govern cognitive functions. Using point process and conductance-based simulations, we found that existing methods for determining neuronal connectivity from spike times are highly affected by burst spiking activity, resulting in over- or underestimation of spike transmission. To improve performance, we developed a mathematical framework for decomposing the cross-correlation between two spike trains. We then devised a deconvolution-based algorithm for removing effects of second-order spike train statistics. Deconvolution removed the effect of burst spiking, improving the estimation of neuronal connectivity yielded by state-of-the-art methods. Application of deconvolution to neuronal data recorded from hippocampal region CA1 of freely-moving mice produced higher estimates of spike transmission, in particular when spike trains exhibited bursts. Deconvolution facilitates the precise construction of complex connectivity maps, opening the door to enhanced understanding of the neural mechanisms underlying brain function.
Functional and phylogenetic analysis of TetX variants to design a new classification system
Authors: Cheng Qipeng , Cheung Yanchu , Liu Chenyu , Chan Edward Wai Chi , Wong Kwok Yin , Zhang Rong , Chen Sheng
Published: May 2022

Recently, many TetX variants such as Tet(X3~14) were reported to confer resistance to tigecycline which is a last-resort antibiotic used to treat infections caused by multidrug-resistant bacteria. In this study, we identified essential residues including 329, 339, 340, 350, and 351 in TetX variants that mediated the evolution of the tigecycline-inactive Tet(X2) enzyme to the active forms of Tet(X3) and Tet(X4). Based on their amino acid sequences and functional features, we classified TetX variants into TetX-A class, TetX-B class and TetX-C class. We further found that TetX-A class variants originated from Bacteroidetes, with some variants further evolving to TetX-C class and acquired by Enterobacteriaceae. On the other hand, our data showed that some variants genes belonging to TetX-A class evolved directly to TetX-B class, which was further transmitted to Acinetobacter spp. This new classification system may facilitate better clinical management of patients infected by TetX-producing strains.
Short-chain fatty acids promote the effect of environmental signals on the gut microbiome and metabolome in mice
Authors: Marrocco Francesco , Delli Carpini Mary , Garofalo Stefano , Giampaoli Ottavia , De Felice Eleonora , Di Castro Maria Amalia , Maggi Laura , Scavizzi Ferdinando , Raspa Marcello , Marini Federico , Tomassini Alberta , Nicolosi Roberta , Cason Carolina , Trettel Flavia , Miccheli Alfredo , Iebba Valerio , D’Alessandro Giuseppina , Limatola Cristina
Published: May 2022

Gut microorganisms and the products of their metabolism thoroughly affect host brain development, function and behavior. Since alterations of brain plasticity and cognition have been demonstrated upon motor, sensorial and social enrichment of the housing conditions, we hypothesized that gut microbiota and metabolome could be altered by environmental stimuli, providing part of the missing link among environmental signals and brain effects. In this preliminary study, metagenomic and metabolomic analyses of mice housed in different environmental conditions, standard and enriched, identify environment-specific microbial communities and metabolic profiles. We show that mice housed in an enriched environment have distinctive microbiota composition with a reduction in gut bacterial richness and biodiversity and are characterized by a metabolomic fingerprint with the increase of formate and acetate and the decrease of bile salts. We demonstrate that mice treated with a mixture of formate and acetate recapitulate some of the brain plasticity effects modulated by environmental enrichment, such as hippocampal neurogenesis, neurotrophin production, short-term plasticity and cognitive behaviors, that can be further exploited to decipher the mechanisms involved in experience-dependent brain plasticity.
Quantifying the role of the lattice in metal–insulator phase transitions
Authors: Georgescu Alexandru B. , Millis Andrew J.
Published: May 2022

Many materials exhibit phase transitions at which both the electronic properties and the crystal structure change. Some authors have argued that the change in electronic order is primary, with the lattice distortion a relatively minor side-effect, and others have argued that the lattice distortions play an essential role in the energetics of the transition. In this paper, we introduce a formalism that resolves this long-standing problem. The methodology works with any electronic structure method that produces solutions of the equation of state determining the electronic order parameter as a function of lattice distortion. We use the formalism to settle the question of the physics of the metal–insulator transitions in the rare-earth perovskite nickelates (RNiO3) and Ruddlesden–Popper calcium ruthenates (Ca2RuO4) in bulk, heterostructure, and epitaxially strained thin film forms, finding that electron-lattice coupling is key to stabilizing the insulating state in both classes of materials.
Optimal Channel Networks accurately model ecologically-relevant geomorphological features of branching river networks
Authors: Carraro Luca , Altermatt Florian
Published: May 2022

River networks’ universal fractal structure not only defines their hydrology and connectivity, but has also profound biological consequences, especially regarding stability and persistence of organismal populations. While rivers’ scaling features are captured by Optimal Channel Networks, knowledge on adequate network topologies has hitherto been only partially transferred across geo- and biosciences. Consequently, ecologists have often studied riverine populations via random networks not respecting real rivers’ scaling character. Here we show that branching probability of random networks is a scale-dependent quantity in that it varies with the length scale or spatial resolution of observations. Therefore, our findings suggest that this property is not a robust driver of ecological dynamics. Moreover, we show that random networks lead to biased estimates of population stability and persistence, while only Optimal Channel Networks yield estimates comparable to real rivers. We hence advocate Optimal Channel Networks as model landscapes for realistic and generalizable projections of ecohydrological dynamics in riverine networks.
Landscaping macrocyclic peptides: stapling hDM2-binding peptides for helicity, protein affinity, proteolytic stability and cell uptake
Authors: de Araujo Aline D. , Lim Junxian , Wu Kai-Chen , Hoang Huy N. , Nguyen Huy T. , Fairlie David P.
Published: May 2022

Surveying macrocycles for mimicking a helical tumor suppressor protein, resisting breakdown by proteases, and entering cancer cells.
Simple synthesis of green luminescent N-doped carbon dots for malachite green determination
Authors: Cheng Sijie , Wang Xin , Yan Xuerong , Xiao Yanteng , Zhang Yong
Published: May 2022

N-CDs with green emission for MG sensitive and fast sensing were synthesized.
Complete utilization of waste lignin: preparation of lignin-derived carbon supports and conversion of lignin-derived guaiacol to nylon precursors
Authors: Lee Jun Gyeong , Lee Shinjae , Lee Hojeong , Kurisingal Jintu Francis , Han Seung Hyun , Kim Yong Hwan , An Kwangjin
Published: May 2022

A new catalytic process was developed to produce raw materials for nylon production utilizing 100% of waste lignin emitted from industrial processes.
Single- and double-bridged PNP ligands in chromium-catalysed ethylene oligomerisation
Authors: Lo Quintin , Pye Dominic , Gesslbauer Sami , Sim Ying , García Felipe , White Andrew J. P. , Britovsek George J. P.
Published: May 2022

Chromium catalysts with diazaphospholane ligands have shown good activities and selectivities for ethylene tri- and tetramerisation. Oligomerisations with a doubly N-bridged cyclodiphosphazane result in a Schulz–Flory distribution of α-olefins.
Effects of energetic disorder in bulk heterojunction organic solar cells
Authors: Yuan Jun , Zhang Chujun , Qiu Beibei , Liu Wei , So Shu Kong , Mainville Mathieu , Leclerc Mario , Shoaee Safa , Neher Dieter , Zou Yingping
Published: May 2022

The energetic disorder can be reduced by developing new photovoltaic materials, especially non-fullerene acceptors, and significant progress in the PCEs of OSCs has been made.
A Zn–nitrite battery as an energy-output electrocatalytic system for high-efficiency ammonia synthesis using carbon-doped cobalt oxide nanotubes
Authors: Zhang Rong , Zhang Shaoce , Guo Ying , Li Chuan , Liu Jiahua , Huang Zhaodong , Zhao Yuwei , Li Yangyang , Zhi Chunyi
Published: May 2022

A Zn-NO2−battery with C/Co3O4catalyst cathode is developed as an energy-output electrocatalytic system that can simultaneously convert NO2−to NH3with high faradaic efficiency and supply electricity with a power density of 6.03 mW cm−2.
Critical role of acceptor dopants in designing highly stable and compatible proton-conducting electrolytes for reversible solid oxide cells
Authors: Luo Zheyu , Zhou Yucun , Hu Xueyu , Kane Nichloas , Li Tongtong , Zhang Weilin , Liu Zhijun , Ding Yong , Liu Ying , Liu Meilin
Published: May 2022

BaHf0.1Ce0.7Yb0.2O3−δ proton-conducting electrolyte exhibits high conductivity, excellent ionic transference number, remarkable chemical stability, and great compatibility with NiO, as confirmed by experimental and computational results.
Calibration and standardization of extracellular vesicle measurements by flow cytometry for translational prostate cancer research
Authors: Kim Yohan , van der Pol Edwin , Arafa Ali , Thapa Ishwor , J. Britton Cameron , Kosti Jorgena , Song Siyang , Joshi Vidhu B. , M. Erickson Ree , Ali Hesham , Lucien Fabrice
Published: May 2022

Higher levels of tumor-derived extracellular vesicles are detected in metastatic prostate cancer compared to localized prostate cancer by standardized and calibrated flow cytometry.
Poly(lactic acid)-hyperbranched polyglycerol nanoparticles enhance bioadhesive treatment of esophageal disease and reduce systemic drug exposure
Authors: Mai Yang , Ouyang Yaqi , Qin Yujia , Jia Changchang , McCoubrey Laura E. , Basit Abdul W. , Nie Yichu , Jia Yizhen , Yu Liu , Dou Liu , Deng Wenbin , Deng Yang , Liu Yang
Published: May 2022

Bioadhesive nanoparticles were developed for local drug delivery to esophagus, which elongated drug release time and enhanced esophageal drug exposure, providing significant therapeutic efficacy on achalasia.
Probing the serum albumin binding site of fenamates and photochemical protein labeling with a fluorescent dye
Authors: Deng Tao , Zhao Jing , Peng Danfeng , He Xinqian , Huang Xin-an , Lin Chaozhan , Zhu Chenchen , Wang Lei , Liu Fang
Published: May 2022

A fluorescent probe TTPy has been prepared that can target the HSA binding site of fenamates, a group of non-steroidal anti-inflammatory drugs (NSAIDs). In addition, TTPy enables HSA fluorescent labeling upon visible light irradiation.
Direct Z-scheme of n-type CuS/p-type ZnS@electrospun PVP nanofiber for the highly efficient catalytic reduction of 4-nitrophenol and mixed dyes
Authors: Sitinjak Elvri Melliaty , Masmur Indra , Marbun New Vita Mey Destty , Hutajulu Poltak Evencus , Gultom Golfrid , Sitanggang Yenny
Published: May 2022

Z-type CuS/ZnS@PVP nanofibers are synthesized for the photocatalytic reduction of 4-nitrophenol and for mixed-dyes degradation under mild conditions.
In vitrotoxicity of carbon nanotubes: a systematic review
Authors: Chetyrkina Margarita R. , Fedorov Fedor S. , Nasibulin Albert G.
Published: May 2022

Carbon nanotube (CNT) toxicity-related issues provoke many debates. This review sheds light on the current knowledge about CNTin vitrotoxicity and offers possible directions for subsequent studies based on the demonstrated here statistical data.
Closing the gap of organic chemistry students’ performance with an adaptive scaffold for argumentation patterns
Authors: Lieber Leonie Sabine , Ibraj Krenare , Caspari-Gnann Ira , Graulich Nicole
Published: May 2022

Building reasonable scientific arguments is a fundamental skill students need to participate in scientific discussions. In organic chemistry, students’ argumentation and reasoning skills on reaction mechanisms are described as indicators of success. However, students often experience challenges with how to structure their arguments, use scientific principles appropriately and engage in multivariate, instead of one-reason decision-making. Since every student experiences their individual challenges with a multitude of expectations, we hypothesise that students would benefit from scaffolding that is adapted to their needs. In the present study, we investigated how 64 chemistry students interacted with an adaptive scaffold that offered different ways of support based on students’ strengths and limitations with structural and conceptual aspects that are needed to build a scientific argument in organic chemistry. Based on the students’ performance in a diagnostic scaffold in which they were asked to judge the plausibility of alternative organic reaction pathways by building arguments, the students were assigned to one of four support groups that received a scaffold adapted to their respective needs. Comparing students’ performance in the diagnostic and adapted scaffolds allows us to determine quantitatively (1) to what extent the adaptive scaffold closes the gap in students’ performance and (2) whether an adaptive scaffold improves the students’ performance in their respective area of support (argumentation and/or concept knowledge). The results of this study indicate that the adaptive scaffold can adaptively advance organic chemistry students’ argumentation patterns.
Enantiomeric β-sheet peptides from Aβ form homochiral pleated β-sheets rather than heterochiral rippled β-sheets
Authors: Li Xingyue , Rios Stephanie E. , Nowick James S.
Published: May 2022

In aqueous solution, mixtures ofl- andd- macrocyclic β-sheet peptides derived from Aβ self-assemble to form homochiral pleated β-sheets but do not co-assemble to form heterochiral rippled β-sheets.
TiO2-enhanced in situ electrochemical activation of Co3O4 for the alkaline hydrogen evolution reaction
Authors: Yuan Ling , Boukhvalov Danil W. , Lv Cuncai , Dong Jie , He Tong , Yu Zhiyang , Luo Wenjie , Cheng Chuanwei , Humphrey Mark G. , Zhang Chi , Huang Zhipeng
Published: May 2022

In situ electrochemical activation results in high-valent metal compounds (with a composite of Co3O4 and TiO2 as a prototype) that exhibit outstanding catalytic performance in the alkaline HER.
Diagnostic accuracy of fluorescence flow-cytometry technology using Sysmex XN-31 for imported malaria in a non-endemic setting
Authors: Picot Stéphane , Perpoint Thomas , Chidiac Christian , Sigal Alain , Javouhey Etienne , Gillet Yves , Jacquin Laurent , Douplat Marion , Tazarourte Karim , Argaud Laurent , Wallon Martine , Miossec Charline , Bonnot Guillaume , Bienvenu Anne-Lise
Published: May 2022

Malaria diagnosis based on microscopy is impaired by the gradual disappearance of experienced microscopists in non-endemic areas. Aside from the conventional diagnostic methods, fluorescence flow cytometry technology using Sysmex XN-31, an automated haematology analyser, has been registered to support malaria diagnosis. The aim of this prospective, monocentric, non-interventional study was to evaluate the diagnostic accuracy of the XN-31 for the initial diagnosis or follow-up of imported malaria cases compared to the reference malaria tests including microscopy, loop mediated isothermal amplification, and rapid diagnostic tests. Over a one-year period, 357 blood samples were analysed, including 248 negative and 109 positive malaria samples. Compared to microscopy, XN-31 showed sensitivity of 100% (95% CI: 97.13–100) and specificity of 98.39% (95% CI: 95.56–100) for the initial diagnosis of imported malaria cases. Moreover, it provided accurate species identification asfalciparumor non-falciparumand parasitaemia determination in a very short time compared to other methods. We also demonstrated that XN-31 was a reliable method for patient follow-up on days 3, 7, and 28. Malaria diagnosis can be improved in non-endemic areas by the use of dedicated haematology analysers coupled with standard microscopy or other methods in development, such as artificial intelligence for blood slide reading. Given that XN-31 provided an accurate diagnosis in 1 min, it may reduce the time interval before treatment and thus improve the outcome of patient who have malaria.
Nexus between financial development, FDI, industrial structure change and innovation in the post-financial crisis era: Evidence from China
Authors: Liu Hongyan , Ma Yan , Song Yanrong
Published: May 2022

China began to strive for innovation-driven economic growth by encouraging technological progress since the recent world financial crisis. Further, Chinese economy exhibited several different features since the crisis. Its financial credits surged. Meanwhile, it began to adjust its industrial structures. In order to test the effect of these policies, this paper investigates whether financial development, FDI and industrial structure changes affect innovation in this new era. The results find that provincial variation in innovation performance enlarged during this period. Further, financial development significantly improves innovation. However, FDI hampers innovation. Lastly, industrial structure adjustment promotes innovation. The paper suggests that China improve the technological skills of local firms and its human capital and introduce high-quality and efficient foreign direct investment to achieve an innovation-driven economic growth.
A Questionnaire Survey of German Thyroidologists on the Use of
Thyroid Hormones in Hypothyroid and Euthyroid Patients: The THESIS (Treatment of
Hypothyroidism in Europe by Specialists: An International Survey)
Collaborative
Authors: Vardarli Irfan , Brandenburg Tim , Hegedüs Laszlo , Attanasio Roberto , Nagy EndreV. , Papini Enrico , Perros Petros , Weidemann Frank , Herrmann Ken , Führer Dagmar
Published: May 2022

Objective To identify the attitudes of German thyroid specialists towards
the clinical treatment of hypothyroidism using thyroid hormones (TH).

Methods All members of the thyroid section of the German Endocrine Society
(DGE) were e-mailed an invitation to participate in a web-based survey about
substitution with TH.

Results Out of 206 members of the DGE’s thyroid section, 163
(79.1%) responses were received and included in the analysis. Of
responding members, 98.6% used levothyroxine (LT4) as the treatment of
choice, and 45.4% also prescribed combination therapy with liothyronine
(LT4+LT3) in their clinical practice (p<0.001). LT4+LT3
combination was favored in patients with persistent hypothyroidism symptoms
despite biochemical euthyroidism on LT4 treatment (p<0.001). Of all
respondents, 26.4% never indicated TH therapy for euthyroid patients
(p<0.001), while the remainder would consider THs for one or more
indications (62.9% for euthyroid infertile women with high anti-thyroid
antibody levels (p<0.001), 7.1% in patients with severe
hypercholesterolemia, as complementary treatment (p=0.007), and
57.1% in patients with simple goiter (p<0.001)). In conditions
that could interfere with LT4 absorption, most respondents still preferred
tablets and did not expect a significant difference when switching from one LT4
formulation to another.

Conclusion For German thyroid specialists, LT4 is the treatment of choice
for hypothyroidism. Combination therapy with LT4+LT3 was considered for
patients with persistent symptoms. Even in conditions that could affect
bioavailability, German thyroid specialists prefer LT4 tablets rather than other
LT4 formulations, such as liquid or soft-gel capsules. The widespread use of
thyroid hormone for non-hypothyroid conditions is not consistent with current
evidence and needs further study.
Transferência do segundo dedo do pé para tratamento de amputação traumática do polegar em uma criança de quatro anos: Relato de caso
Authors: Nakamoto Hugo Alberto , Gonçalves Reinaldo Borges , Nakamoto João Carlos , Iwase Fernanda do Carmo , Pessa Mariana Miranda Nicolosi , Rezende Marcelo Rosa de
Published: May 2022

A transferência microcirúrgica do dedo do pé para a reconstrução do polegar é um procedimento desafiador, considerando-se a habilidade técnica necessária para realizá-la e a difícil avaliação pós-operatória dos aspectos estéticos e funcionais. Este é um relato do caso de uma criança de 3 anos que sofreu uma amputação traumática do polegar. A reconstrução do polegar foi realizada por meio de transferência microcirúrgica do dedo do pé, meses após a falha do reimplante. Uma avaliação subjetiva e outra objetiva dos resultados foram realizadas cinco anos após o procedimento. O resultado funcional foi avaliado por meio do Questionário de Avaliação da Saúde na Infância (Childhood Health Assessment Questionnaire, CHAQ, em inglês) e o Teste Funcional da Mão de Jebsen-Taylor (Jebsen-Taylor Hand Function Test, JTHFT, em inglês). Foram usados o dinamômetro Jamar (Sammons Preston, Bolingbrook, IL, EUA) e os instrumentos de medição Jamar Pinch Gauge (Sammons Preston) para avaliar as forças de preensão palmar e de pinças, respectivamente. Foram realizados os testes de monofilamento e de discriminação de dois pontos de Semmes-Weinstein. O paciente apresentou excelente resultado funcional, recuperação parcial da força, recuperação sensitiva completa, e mínima morbidade do sítio doador. Foi realizada também uma avaliação radiográfica, que demonstrou a preservação da placa epifisária e do potencial de crescimento no dedo do pé transplantado. Em todos os aspectos, os dados observados reforçam os benefícios e as indicações da transferência do dedo do pé para a reconstrução do polegar em crianças.
Does Music during Image-Guided Procedures Reduce Patient Anxiety Levels?
Authors: Mohamed Fahd , DSouza Lenon , Mijar Mahesh
Published: May 2022

Purpose The aim of the study was to evaluate the role of music in alleviating anxiety in patients undergoing image guided procedures.

Materials and Methods A total of 129 patients were included in this prospective study after obtaining clearance from the Institutional Ethics Committee. Patients were randomized into control (n = 59, median age 46, 30 males) and music (n = 70, median age 46.5, 33 males) groups. Procedures included thoracocentesis, paracentesis, fine needle aspiration cytology and biopsies of the breast, liver, thyroid and lymph nodes. It was performed over a period of 4 months, between September 2020 and December 2020. Pre- and intra procedure recordings of systolic blood pressure, diastolic blood pressure and heart rate were recorded. Circumstantial anxiety was evaluated using the Spielberg State-Trait Anxiety Inventory before and after the procedure.

Results There was a statistically significant reduction (p = 0.001) in the rise of systolic blood pressure, diastolic blood pressure and heart rate in the music group as compared to the control group. There was also a statistically significant reduction (p = 0.001) in the State-Trait Anxiety Inventory scale values in the music group as compared to the control group during the procedure.

Conclusion Patients undergoing image-guided procedures may be offered a choice to listen to music of their preference to reduce situational anxiety.
Analysis of rock microseismic signal based on blind source wavelet decomposition algorithm
Authors: Peng Guili , Liu Dewen , Lu Jing , Shen Tong , Wang Shoubin
Published: May 2022

At present, microseismic technology is a widely used method for monitoring the rock burst phenomenon during the construction of deep-buried tunnels. The rock fracture in the tunnel will generate seismic waves. The seismic wave has strong randomness and low energy and is usually mixed with environmental noise, which is called the microseismic signal. The microseismic signal received by the geophone will contain other noises. So, there is an urgent need for an algorithm that can quickly decompose the mixed signal. To solve this problem, this paper proposes a blind source wavelet algorithm to extract the rock fracture signal. First, the signal is preprocessed, and the mixed signal matrix is established. Second, the blind source decomposition algorithm is used to process the signal, and the effective signal is reconstructed. Finally, the wavelet algorithm is used to further remove the noise to enhance the microseismic signal. The proposed method is compared with the wavelet decomposition method and the empirical mode decomposition (EMD) method through the laboratory simulation data and the actual signal of Baihetan Hydropower Station. It is concluded that the proposed algorithm can effectively decompose and remove the noise in the mixed signal, and the decomposition accuracy is better than the wavelet decomposition method and the EMD method. The proposed algorithm has certain practical significance for the identification of microseismic signals of rock fracture and for rock burst early warning.