bluuebunny/crossref_metadata_2025 huggingface dataset:
Therapeutisches Drug Monitoring zur Optimierung der Psychopharmakotherapie von Kindern und Jugendlichen
Authors: Egberts Karin , Fekete Stefanie , Häge Alexander , Hiemke Christoph , Scherf-Clavel Maike , Taurines Regina , Unterecker Stefan , Gerlach Manfred , Romanos Marcel
Published: March 2022

Zusammenfassung. Trotz verbesserter Evidenzbasis bestehen in der kinder- und jugendpsychiatrischen Pharmakotherapie viele Unsicherheiten über die Wirkung und Verträglichkeit der häufig off-label oder in Kombinationstherapie verordneten Medikamente. Gerade auch vor dem Hintergrund der in vielen Fällen notwendigen mittel- bis langfristigen Einnahme sollen unerwünschte Arzneimittelwirkungen in dieser Altersstufe möglichst minimiert und eine auf die individuellen Charakteristika der Patientin oder des Patienten zugeschnittene, effektive Dosierung gefunden werden. Kinder und Jugendliche scheinen nicht nur besonders anfällig für bestimmte unerwünschte Arzneimittelwirkungen, sondern sind auch iatrogenen Risiken durch Dosierungs- oder Applikationsfehler ausgesetzt, die zu Unter- oder Überdosierungen führen können mit entsprechend negativen Auswirkungen auf den Therapieerfolg. Neben einer strengen Indikationsstellung sind daher eine präzise Dosisfindung sowie systematische Überwachung der Sicherheit der Psychopharmakotherapie unverzichtbar. In diesem Artikel wird Therapeutisches Drug Monitoring als hilfreiches klinisches Instrument vorgestellt und beschrieben, wie dessen richtige Anwendung sowohl die Wirksamkeit als auch die Sicherheit und Verträglichkeit einer Psychopharmakotherapie im Kindes- und Jugendalter zum unmittelbaren Nutzen für die Patientinnen und Patienten verbessern kann.
Regional Index Insurance Using Satellite‐Based Fractional Flooded Area
Authors: Tellman Beth , Lall Upmanu , Islam A. K. M. Saiful , Bhuyan Md Ariffuzaman
Published: March 2022

Emerging parametric insurance products targeted at regional governments consider an index of flooding as the instrument for payoff and rate setting. Inundation extent from satellite remote sensing may provide a more direct measure of flood risk in this context than hydraulic modeling of flow and inundation. Here, we examine satellite‐based fractional inundated area as a proxy for flood impact that can be used for index insurance payment at a regional scale. Typical methods for estimating return periods from unbounded distributions such as the Generalized Extreme Value distribution are not appropriate for fractional flooded area, which is bounded by 0 and 1. Here we examine alternative bounded distributions (2 parameter and a 4 parameter Beta) to estimate return periods and quantify uncertainty using a bootstrap sampling procedure for the short duration satellite record of fractional flooded area. We consider two examples with distinct flood dynamics (a) a country (Bangladesh) where a flood can cover the majority of the land surface, and (b) a river basin (the Rio Salado basin in Argentina) where the worst flood covered only a modest fraction of the watershed. We explore how a parametric insurance policy based on fractional flooded area could be priced based on a typical approach used in the industry, that accounts for uncertainty for small sample estimation. Our exploratory approach to model selection illustrates how estimating the uncertainty price influences insurance contract pricing and is important to consider the choice of distribution beyond just the traditional measures of goodness of fit.
Weak, Seismogenic Faults Inherited From Mesozoic Rifts Control Mountain Building in the Andean Foreland
Authors: Wimpenny Sam
Published: March 2022

New earthquake focal mechanism and centroid depth estimates show that the deformation style in the forelands of the Andes is spatially correlated with rift systems that stretched the South American lithosphere in the Mesozoic. Where the rifts trend sub‐parallel to the Andean range front, normal faults inherited from the rifts are being reactivated as reverse faults, causing the 30–45 km thick seismogenic layer to break up. Where the rift systems are absent from beneath the range front, the seismogenic layer is bending and being thrust beneath the Andes like a rigid plate. Force‐balance calculations show that the faults inerhited from former rift zones have an effective coefficient of static friction μ′ < 0.2. In order for these frictionally weak faults to remain seismogenic in the lower crust, their wall rocks are likely to be formed of dry granulite. Xenolith data support this view, and suggest that parts of the lower crust are now mostly metastable, having experienced temperatures at least 75–250°C hotter than present. The conditions in the lower crust make it unlikely that highly pressurized free water, or networks of intrinsically weak phyllosilicate minerals, are the cause of their low effective friction, as, at such high temperatures, both mechanisms would cause the faults to deform through viscous creep and not frictional slip. Therefore pre‐existing faults in the Andean forelands have remained weak and seismogenic after reactivation, and have influenced the style of mountain building in South America. However, the controls on their mechanical properties in the lower crust remain unclear.
Effect of Impurities on Polycrystal Anelasticity
Authors: Takei Yasuko
Published: March 2022

Rock anelasticity causes seismic low velocity and high attenuation if, and only if, attenuation spectrum has a large “high‐frequency peak” superposed on the monotonic background. As a result, it is critical to define the conditions for peak existence. It is known that a large and broad high‐frequency peak exists at near solidus temperatures because grain boundary sliding is enhanced by the significant increase in grain boundary disorder called pre‐melting. The current study experimentally investigated the high‐frequency peak caused by impurities using organic polycrystals as an analog to mantle rock. A method for removing impurities was developed and anelasticity, viscosity, and grain growth rate of polycrystalline borneol with and without impurities were measured. The results showed that impurities can also significantly disorder the grain boundaries and cause a large and broad high‐frequency peak. This impurity‐induced peak disappeared, when the impurities were removed. On the basis of these results, this study draws a conclusion that the existence or non‐existence of the high‐frequency peak is strongly coupled with the grain boundary structure. This study also shows that the underlying mechanism of the peak is diffusionally accommodated grain boundary sliding, which is different from the prediction of existing models, and that further refinement of the models is needed. I further confirmed that the effects of impurities were minor in the published data which demonstrated the mechanical effects of premelting.
Insignia of the Royal Army Dental Corps and Commonwealth Dental Corps
Authors: Radford David R.
Published: March 2022

The insignia worn by the British and Commonwealth Armed Services are rich in symbolism and meaning to the corps and regiments that wear them. Originally, before the adoption of national uniforms pre-1700s, there was little to distinguish friend from foe. To overcome that problem, certainly in battle, it was common practice to wear some sort of distinctive emblem, such as a sprig of a native plant. This then developed, in the reign of Charles II, to the custom of individual regiments or corps adopting devices and designs of their 'colours', through to modern cap and collar badges.

On the centenary of the Royal Army Dental Corps, this paper gives some insight into those designs adopted by the Royal and Commonwealth Dental Corps, when a distinct service of dental care was recognised. They give a fascinating insight into the adoption and amalgamation of both national and dental symbols. The Dental Corps, separate from Army Medical Corps, went on to develop the vital provision of dental healthcare, both in the field and at home.
A qualitative exploration of decisions about dental recall intervals - Part 1: attitudes of NHS general dental practitioners to NICE guideline CG19 on the interval between oral health reviews
Authors: Scott Hannah , Cope Anwen L. , Wood Fiona , Joseph-Williams Natalie , Karki Anup , Roberts Emyr M. , Lovell-Smith Candida , Chestnutt Ivor G.
Published: March 2022

Introduction The National Institute for Health and Care Excellence (NICE) Guideline CG19 recommends that the intervals between oral health reviews should be tailored to patients' disease risk. However, evidence suggests that most patients still attend at six-monthly intervals.

Aim To explore facilitators and barriers to the implementation of CG19 in general dental practice.

Methods Semi-structured telephone interviews were conducted with 25 NHS general dental practitioners (GDPs) in Wales, UK. Transcripts were thematically analysed.

Results Dentists described integrating information on clinical risk, patients' social and dental history, and professional judgement when making decisions about recall interval. Although most GDPs reported routinely using risk-based recall intervals, a number of barriers exist to recall intervals at the extremes of the NICE recommendations. Many practitioners were unwilling to extend recall intervals to 24 months, even for the lowest-risk patients. Conversely, dentists described how it could be challenging to secure the agreement of high-risk patients to three-month recalls. In addition, time and workload pressures, the need to meet contractual obligations, pressure from contracting organisations and the fear of litigation also influenced the implementation of risk-based recalls.

Conclusions Although awareness of the NICE Guideline CG19 was high, there is a need to explore how risk-based recalls may be best supported through contractual mechanisms.
Novel anti-apoptotic L-DOPA precursors SuperDopa and SuperDopamide as potential neuroprotective agents for halting/delaying progression of Parkinson’s disease
Authors: Wiesen Tom , Atlas Daphne
Published: March 2022

Parkinson’s disease (PD) is characterized by a gradual degeneration of the dopaminergic neurons in the substantia nigra pars compacta (SNpC). Levodopa, the standard PD treatment, provides the missing dopamine in SNpC, but ultimately after a honeymoon with levodopa treatment the neurodegenerative process and the progression of the disease continue. Aimed at prolonging the life of dopaminergic cells, we prepared the levodopa precursors SuperDopa (SD) and SueprDopamide (SDA), in which levodopa is merged with the antioxidant N-acetylcysteine (NAC) into a single molecule. Rotenone is a mitochondrial complex inhibitor often used as experimental model of PD. In vivo, SD and SDA treatment show a significant relief of motor disabilities in rotenone-injected rats. SD and SDA also lower rotenone-induced-α-synuclein (α-syn) expression in human SH-SY5Y cells, and α-syn oligomerization in α-syn-overexpressing-HEK293 cells. In the neuronal SH-SY5Y cells, SD and SDA reverse oxidative stress-induced phosphorylation of cJun-N-terminal kinase (JNK) and p38-mitogen-activated kinase (p38MAPK). Attenuation of the MAPK-inflammatory/apoptotic pathway in SH-SY5Y cells concurrent with protection of rotenone-triggered motor impairment in rats, is a manifestation of the combined antioxidant/anti-inflammatory activity of SD and SDA together with levodopa release. The concept of joined therapies into a single molecule, where levodopa precursors confer antioxidant activity by enabling NAC delivery across the BBB, provides a potential disease-modifying treatment for slowing PD progression.
Super-enhancers and novel therapeutic targets in colorectal cancer
Authors: Liu Qian , Guo Lijuan , Lou Zhiyuan , Xiang Xueping , Shao Jimin
Published: March 2022

Transcription factors, cofactors, chromatin regulators, and transcription apparatuses interact with transcriptional regulatory elements, including promoters, enhancers, and super-enhancers (SEs), to coordinately regulate the transcription of target genes and thereby control cell behaviors. Among these transcriptional regulatory components and related elements, SEs often play a central role in determining cell identity and tumor initiation and progression. Therefore, oncogenic SEs, which are generated within cancer cells in oncogenes and other genes important in tumor pathogenesis, have emerged as attractive targets for novel cancer therapeutic strategies in recent years. Herein, we review the identification, formation and activation modes, and regulatory mechanisms for downstream genes and pathways of oncogenic SEs. We also review the therapeutic strategies and compounds targeting oncogenic SEs in colorectal cancer and other malignancies.
ALKBH3-dependent m1A demethylation of Aurora A mRNA inhibits ciliogenesis
Authors: Kuang Wenjun , Jin Hao , Yang Feng , Chen Xiying , Liu Jianzhao , Li Ting , Chang Yongxia , Liu Min , Xu Zhangqi , Huo Chunxiao , Yan Xiaoyi , Yang Yuehong , Liu Wei , Shu Qiang , Xie Shanshan , Zhou Tianhua
Published: March 2022

Primary cilia are antenna-like subcellular structures to act as signaling platforms to regulate many cellular processes and embryonic development. m1A RNA modification plays key roles in RNA metabolism and gene expression; however, the physiological function of m1A modification remains largely unknown. Here we find that the m1A demethylase ALKBH3 significantly inhibits ciliogenesis in mammalian cells by its demethylation activity. Mechanistically, ALKBH3 removes m1A sites on mRNA of Aurora A, a master suppressor of ciliogenesis. Depletion of ALKBH3 enhances Aurora A mRNA decay and inhibits its translation. Moreover, alkbh3 morphants exhibit ciliary defects, including curved body, pericardial edema, abnormal otoliths, and dilation in pronephric ducts in zebrafish embryos, which are significantly rescued by wild-type alkbh3, but not by its catalytically inactive mutant. The ciliary defects caused by ALKBH3 depletion in both vertebrate cells and embryos are also significantly reversed by ectopic expression of Aurora A mRNA. Together, our data indicate that ALKBH3-dependent m1A demethylation has a crucial role in the regulation of Aurora A mRNA, which is essential for ciliogenesis and cilia-associated developmental events in vertebrates.
Light-dependent ionic-electronic conduction in an amorphous octahedral molybdenum cluster thin film
Authors: Harada Kenshi , Nguyen Thi Kim Ngan , Grasset Fabien , Comby-Zerbino Clothilde , MacAleese Luke , Chirot Fabien , Dugourd Philippe , Dumait Noée , Cordier Stéphane , Ohashi Naoki , Matsuda Motohide , Uchikoshi Tetsuo
Published: March 2022

We developed a new environment-sensing device based on the opto-ionic-electronic phenomena of an octahedral molybdenum metal (Mo6) cluster. When the Mo6 cluster is electrochemically deposited on a transparent electrode in an organic solvent containing a trace amount of water, the water permeates the deposited film. During the process, some ligand species that stabilize the frame structure of the Mo6 cluster are substituted with hydroxyl groups, and the negatively charged frame structure of the Mo6 cluster unit is stabilized by hydronium counterions. As a result, the transparent film of the Mo6 cluster fabricated by this method exhibits ionic-electronic mixed conduction of the hydronium ion. The ionic conduction greatly changes depending on the temperature and humidity in the atmosphere, and the electrical conductivity greatly changes depending on the wavelength and intensity of the irradiated light. These unique multisensing properties present new possibilities for environmental sensing applications.
The structural basis for regulation of the glutathione transporter Ycf1 by regulatory domain phosphorylation
Authors: Khandelwal Nitesh Kumar , Millan Cinthia R. , Zangari Samantha I. , Avila Samantha , Williams Dewight , Thaker Tarjani M. , Tomasiak Thomas M.
Published: March 2022

Yeast Cadmium Factor 1 (Ycf1) sequesters heavy metals and glutathione into the vacuole to counter cell stress. Ycf1 belongs to the ATP binding cassette C-subfamily (ABCC) of transporters, many of which are regulated by phosphorylation on intrinsically-disordered domains. The regulatory mechanism of phosphorylation is still poorly understood. Here, we report two cryo-EM structures of Ycf1 at 3.4 Å and 4.0 Å resolution in inward-facing open conformations that capture previously unobserved ordered states of the intrinsically disordered regulatory domain (R-domain). R-domain phosphorylation is clearly evident and induces a topology promoting electrostatic and hydrophobic interactions with Nucleotide Binding Domain 1 (NBD1) and the Lasso motif. These interactions stay constant between the structures and are related by rigid body movements of the NBD1/R-domain complex. Biochemical data further show R-domain phosphorylation reorganizes the Ycf1 architecture and is required for maximal ATPase activity. Together, we provide insights into how R-domains control ABCC transporter activity.
A zirconium metal-organic framework with SOC topological net for catalytic peptide bond hydrolysis
Authors: Wang Sujing , Ly Hong Giang T. , Wahiduzzaman Mohammad , Simms Charlotte , Dovgaliuk Iurii , Tissot Antoine , Maurin Guillaume , Parac-Vogt Tatjana N. , Serre Christian
Published: March 2022

The discovery of nanozymes for selective fragmentation of proteins would boost the emerging areas of modern proteomics, however, the development of efficient and reusable artificial catalysts for peptide bond hydrolysis is challenging. Here we report the catalytic properties of a zirconium metal-organic framework, MIP-201, in promoting peptide bond hydrolysis in a simple dipeptide, as well as in horse-heart myoglobin (Mb) protein that consists of 153 amino acids. We demonstrate that MIP-201 features excellent catalytic activity and selectivity, good tolerance toward reaction conditions covering a wide range of pH values, and importantly, exceptional recycling ability associated with easy regeneration process. Taking into account the catalytic performance of MIP-201 and its other advantages such as 6-connected Zr6 cluster active sites, the green, scalable and cost-effective synthesis, and good chemical and architectural stability, our findings suggest that MIP-201 may be a promising and practical alternative to commercially available catalysts for peptide bond hydrolysis.
Inhibition allocates spikes during hippocampal ripples
Authors: Noguchi Asako , Huszár Roman , Morikawa Shota , Buzsáki György , Ikegaya Yuji
Published: March 2022

Sets of spikes emitted sequentially across neurons constitute fundamental pulse packets in neural information processing, including offline memory replay during hippocampal sharp-wave ripples (SWRs). The relative timing of neuronal spikes is fine-tuned in each spike sequence but can vary between different sequences. However, the microcircuitry mechanism that enables such flexible spike sequencing remains unexplored. We recorded the membrane potentials of multiple hippocampal CA1 pyramidal cells in mice and found that the neurons were transiently hyperpolarized prior to SWRs. The pre-SWR hyperpolarizations were spatiotemporally heterogeneous, and larger hyperpolarizations were associated with later spikes during SWRs. Intracellular blockade of Cl−-mediated inhibition reduced pre-SWR hyperpolarizations and advanced spike times. Single-unit recordings also revealed that the pre-SWR firing rates of inhibitory interneurons predicted the SWR-relevant spike times of pyramidal cells. Thus, pre-SWR inhibitory activity determines the sequential spike times of pyramidal cells and diversifies the repertoire of sequence patterns.
De novo inter-regional coactivations of preconfigured local ensembles support memory
Authors: Miyawaki Hiroyuki , Mizuseki Kenji
Published: March 2022

Neuronal ensembles in the amygdala, ventral hippocampus, and prefrontal cortex are involved in fear memory; however, how inter-regional ensemble interactions support memory remains elusive. Using multi-regional large-scale electrophysiology in the aforementioned structures of fear-conditioned rats, we found that the local ensembles activated during fear memory acquisition are inter-regionally coactivated during the subsequent sleep period, which relied on brief bouts of fast network oscillations. During memory retrieval, the coactivations reappeared, together with fast oscillations. Coactivation-participating-ensembles were configured prior to memory acquisition in the amygdala and prefrontal cortex but developed through experience in the hippocampus. Our findings suggest that elements of a given memory are instantly encoded within various brain regions in a preconfigured manner, whereas hippocampal ensembles and the network for inter-regional integration of the distributed information develop in an experience-dependent manner to form a new memory, which is consistent with the hippocampal memory index hypothesis.
Coincidence of cholinergic pauses, dopaminergic activation and depolarisation of spiny projection neurons drives synaptic plasticity in the striatum
Authors: Reynolds John N. J. , Avvisati Riccardo , Dodson Paul D. , Fisher Simon D. , Oswald Manfred J. , Wickens Jeffery R. , Zhang Yan-Feng
Published: March 2022

Dopamine-dependent long-term plasticity is believed to be a cellular mechanism underlying reinforcement learning. In response to reward and reward-predicting cues, phasic dopamine activity potentiates the efficacy of corticostriatal synapses on spiny projection neurons (SPNs). Since phasic dopamine activity also encodes other behavioural variables, it is unclear how postsynaptic neurons identify which dopamine event is to induce long-term plasticity. Additionally, it is unknown how phasic dopamine released from arborised axons can potentiate targeted striatal synapses through volume transmission. To examine these questions we manipulated striatal cholinergic interneurons (ChIs) and dopamine neurons independently in two distinct in vivo paradigms. We report that long-term potentiation (LTP) at corticostriatal synapses with SPNs is dependent on the coincidence of pauses in ChIs and phasic dopamine activation, critically accompanied by SPN depolarisation. Thus, the ChI pause defines the time window for phasic dopamine to induce plasticity, while depolarisation of SPNs constrains the synapses eligible for plasticity.
A dual-function liquid electrolyte additive for high-energy non-aqueous lithium metal batteries
Authors: Zhang Yuji , Wu Yuan , Li Huiyi , Chen Jinghao , Lei Danni , Wang Chengxin
Published: March 2022

Engineering the formulation of non-aqueous liquid electrolytes is a viable strategy to produce high-energy lithium metal batteries. However, when the lithium metal anode is combined with a Ni-rich layered cathode, the (electro)chemical stability of both electrodes could be compromised. To circumvent this issue, we report a combination of aluminum ethoxide (0.4 wt.%) and fluoroethylene carbonate (5 vol.%) as additives in a conventional LiPF6-containing carbonate-based electrolyte solution. This electrolyte formulation enables the formation of mechanically robust and ionically conductive interphases on both electrodes’ surfaces. In particular, the alumina formed at the interphases prevents the formation of dendritic structures on the lithium metal anode and mitigate the stress-induced cracking and phase transformation in the Ni-rich layered cathode. By coupling a thin (i.e., about 40 μm) lithium metal anode with a high-loading (i.e., 21.5 mg cm−2) LiNi0.8Co0.1Mn0.1O2-based cathode in coin cell configuration and lean electrolyte conditions, the engineered electrolyte allows a specific discharge capacity retention of 80.3% after 130 cycles at 60 mA g−1 and 30 °C which results in calculated specific cell energy of about 350 Wh kg−1.
Protruding Pt single-sites on hexagonal ZnIn2S4 to accelerate photocatalytic hydrogen evolution
Authors: Shi Xiaowei , Dai Chao , Wang Xin , Hu Jiayue , Zhang Junying , Zheng Lingxia , Mao Liang , Zheng Huajun , Zhu Mingshan
Published: March 2022

Single-site cocatalysts engineered on supports offer a cost-efficient pathway to utilize precious metals, yet improving the performance further with minimal catalyst loading is still highly desirable. Here we have conducted a photochemical reaction to stabilize ultralow Pt co-catalysts (0.26 wt%) onto the basal plane of hexagonal ZnIn2S4 nanosheets (PtSS-ZIS) to form a Pt-S3 protrusion tetrahedron coordination structure. Compared with the traditional defect-trapped Pt single-site counterparts, the protruding Pt single-sites on h-ZIS photocatalyst enhance the H2 evolution yield rate by a factor of 2.2, which could reach 17.5 mmol g−1 h−1 under visible light irradiation. Importantly, through simple drop-casting, a thin PtSS-ZIS film is prepared, and large amount of observable H2 bubbles are generated, providing great potential for practical solar-light-driven H2 production. The protruding single Pt atoms in PtSS-ZIS could inhibit the recombination of electron-hole pairs and cause a tip effect to optimize the adsorption/desorption behavior of H through effective proton mass transfer, which synergistically promote reaction thermodynamics and kinetics.
Circadian humidity fluctuation induced capillary flow for sustainable mobile energy
Authors: Tang Jiayue , Zhao Yuanyuan , Wang Mi , Wang Dianyu , Yang Xuan , Hao Ruiran , Wang Mingzhan , Wang Yanlei , He Hongyan , Xin John H. , Zheng Shuang
Published: March 2022

Circadian humidity fluctuation is an important factor that affects human life all over the world. Here we show that spherical cap-shaped ionic liquid drops sitting on nanowire array are able to continuously output electricity when exposed to outdoor air, which we attribute to the daily humidity fluctuation induced directional capillary flow. Specifically, ionic liquid drops could absorb/desorb water around the liquid/vapor interface and swell/shrink depending on air humidity fluctuation. While pinning of the drop by nanowire array suppresses advancing/receding of triple-phase contact line. To maintain the surface tension-regulated spherical cap profile, inward/outward flow arises for removing excess fluid from the edge or filling the perimeter with fluid from center. This moisture absorption/desorption-caused capillary flow is confirmed by in-situ microscope imaging. We conduct further research to reveal how environmental humidity affects flow rate and power generation performance. To further illustrate feasibility of our strategy, we combine the generators to light up a red diode and LCD screen. All these results present the great potential of tiny humidity fluctuation as an easily accessible anytime-and-anywhere small-scale green energy resource.
In vivo three-dimensional multispectral photoacoustic imaging of dual enzyme-driven cyclic cascade reaction for tumor catalytic therapy
Authors: Lei Shan , Zhang Jing , Blum Nicholas Thomas , Li Meng , Zhang Dong-Yang , Yin Weimin , Zhao Feng , Lin Jing , Huang Peng
Published: March 2022

Non-invasive visualization of dynamic molecular events in real-time via molecular imaging may enable the monitoring of cascade catalytic reactions in living systems, however effective imaging modalities and a robust catalytic reaction system are lacking. Here we utilize three-dimensional (3D) multispectral photoacoustic (PA) molecular imaging to monitor in vivo cascade catalytic therapy based on a dual enzyme-driven cyclic reaction platform. The system consists of a two-dimensional (2D) Pd-based nanozyme conjugated with glucose oxidase (GOx). The combination of nanozyme and GOx can induce the PA signal variation of endogenous molecules. Combined with the PA response of the nanozyme, we can simultaneously map the 3D PA signals of dynamic endogenous and exogenous molecules associated with the catalytic process, thus providing a real-time non-invasive visualization. We can also treat tumors under the navigation of the PA imaging. Therefore, our study demonstrates the imaging-guided potential of 3D multispectral PA imaging in feedback-looped cascade catalytic therapy.
A graph based approach to model charge transport in semiconducting polymers
Authors: Noruzi Ramin , Lim Eunhee , Pokuri Balaji Sesha Sarath , Chabinyc Michael L. , Ganapathysubramanian Baskar
Published: March 2022

Charge transport in molecular solids, such as semiconducting polymers, is strongly affected by packing and structural order over several length scales. Conventional approaches to modeling these phenomena range from analytical models to numerical models using quantum mechanical calculations. While analytical approaches cannot account for detailed structural effects, numerical models are expensive for exhaustive (and statistically significant) analysis. Here, we report a computationally scalable methodology using graph theory to explore the influence of molecular ordering on charge mobility. This model accurately reproduces the analytical results for transport in nematic and isotropic systems, as well as experimental results of the dependence of the charge carrier mobility on orientation correlation length for polymers. We further model how defect distribution (correlated and uncorrelated) in semiconducting polymers can modify the mobility, predicting a critical defect density above which the mobility plummets. This work enables rapid (and computationally extensible) evaluation of charge mobility semiconducting polymer devices.
FAIRly big: A framework for computationally reproducible processing of large-scale data
Authors: Wagner Adina S. , Waite Laura K. , Wierzba Małgorzata , Hoffstaedter Felix , Waite Alexander Q. , Poldrack Benjamin , Eickhoff Simon B. , Hanke Michael
Published: March 2022

Large-scale datasets present unique opportunities to perform scientific investigations with unprecedented breadth. However, they also pose considerable challenges for the findability, accessibility, interoperability, and reusability (FAIR) of research outcomes due to infrastructure limitations, data usage constraints, or software license restrictions. Here we introduce a DataLad-based, domain-agnostic framework suitable for reproducible data processing in compliance with open science mandates. The framework attempts to minimize platform idiosyncrasies and performance-related complexities. It affords the capture of machine-actionable computational provenance records that can be used to retrace and verify the origins of research outcomes, as well as be re-executed independent of the original computing infrastructure. We demonstrate the framework’s performance using two showcases: one highlighting data sharing and transparency (using the studyforrest.org dataset) and another highlighting scalability (using the largest public brain imaging dataset available: the UK Biobank dataset).
Global monthly gridded atmospheric carbon dioxide concentrations under the historical and future scenarios
Authors: Cheng Wei , Dan Li , Deng Xiangzheng , Feng Jinming , Wang Yongli , Peng Jing , Tian Jing , Qi Wei , Liu Zhu , Zheng Xinqi , Zhou Demin , Jiang Sijian , Zhao Haipeng , Wang Xiaoyu
Published: March 2022

Increases in atmospheric carbon dioxide (CO2) concentrations is the main driver of global warming due to fossil fuel combustion. Satellite observations provide continuous global CO2 retrieval products, that reveal the nonuniform distributions of atmospheric CO2 concentrations. However, climate simulation studies are almost based on a globally uniform mean or latitudinally resolved CO2 concentrations assumption. In this study, we reconstructed the historical global monthly distributions of atmospheric CO2 concentrations with 1° resolution from 1850 to 2013 which are based on the historical monthly and latitudinally resolved CO2 concentrations accounting longitudinal features retrieved from fossil-fuel CO2 emissions from Carbon Dioxide Information Analysis Center. And the spatial distributions of nonuniform CO2 under Shared Socio-economic Pathways and Representative Concentration Pathways scenarios were generated based on the spatial, seasonal and interannual scales of the current CO2 concentrations from 2015 to 2150. Including the heterogenous CO2 distributions could enhance the realism of global climate modeling, to better anticipate the potential socio-economic implications, adaptation practices, and mitigation of climate change.
Optimized office lighting advances melatonin phase and peripheral heat loss prior bedtime
Authors: Benedetti Marta , Maierová Lenka , Cajochen Christian , Scartezzini Jean-Louis , Münch Mirjam
Published: March 2022

Improving indoor lighting conditions at the workplace has the potential to support proper circadian entrainment of hormonal rhythms, sleep, and well-being. We tested the effects of optimized dynamic daylight and electric lighting on circadian phase of melatonin, cortisol and skin temperatures in office workers. We equipped one office room with an automated controller for blinds and electric lighting, optimized for dynamic lighting (= Test room), and a second room without any automated control (= Reference room). Young healthy participants (n = 34) spent five consecutive workdays in each room, where individual light exposure data, skin temperatures and saliva samples for melatonin and cortisol assessments were collected. Vertical illuminance in the Test room was 1177 ± 562 photopic lux (mean  ± SD) , which was 320 lux higher than in the Reference room (p < 0.01). Melanopic equivalent daylight (D65) illuminance was 931 ± 484 melanopic lux in the Test room and 730 ± 390 melanopic lux in the Reference room (p < 0.01). Individual light exposures resulted in a 50 min earlier time of half-maximum accumulated illuminance in the Test than the Reference room (p < 0.05). The melatonin secretion onset and peripheral heat loss in the evening occurred significantly earlier with respect to habitual sleeptime in the Test compared to the Reference room (p < 0.05). Our findings suggest that optimized dynamic workplace lighting has the potential to promote earlier melatonin onset and peripheral heat loss prior bedtime, which may be beneficial for persons with a delayed circadian timing system.
Genetic analysis of the cold-sensitive growth phenotype of Burkholderia pseudomallei/thailandensis bacteriophage AMP1
Authors: Letarov Andrey V. , Letarova Maria A. , Ivanov Pavel A. , Belalov Ilya S. , Clokie Martha R. J. , Galyov Edouard E.
Published: March 2022

Bacteriophages related to phage Bp_AMP1 are the most widely spread group of phages infecting Burkholderia pseudomallei—the causative agent of melioidosis. These viruses are also infective against the nonpathogenic host Burkholderia thailandensis, allowing experimental work with them without any special safety precautions. The indirect data as well as the results of the mathematical modelling suggest that the AMP1-like viruses may act as natural biocontrol agents influencing the population levels of B. pseudomallei in soil and water habitats in endemic regions. The cold sensitivity of the lytic growth (CSg) of these phages was suggested to be an important feature modulating the effect of viral infection on host populations in nature. We performed genetic analysis to determine the molecular background of the CSg phenotype of the AMP1 phage. The results indicate that CSg is not due to the lack of any function or product missing at low temperature (25 °C) but results in growth inhibition by a phage-encoded temperature-sensitive genetic switch. We identified phage ORF3 and ORF14 to be involved in the genetic determination of this mechanism.
Heterogeneous climate change impacts on electricity demand in world cities circa mid-century
Authors: Romitti Yasmin , Sue Wing Ian
Published: March 2022

Rising ambient temperatures due to climate change will increase urban populations’ exposures to extreme heat. During hot hours, a key protective adaptation is increased air conditioning and associated consumption of electricity for cooling. But during cold hours, milder temperatures have the offsetting effect of reducing consumption of electricity and other fuels for heating. We elucidate the net consequences of these opposing effects in 36 cities in different world regions. We couple reduced-form statistical models of cities’ hourly responses of electric load to temperature with temporally downscaled projections of temperatures simulated by 21 global climate models (GCMs), projecting the effects of warming on the demand for electricity circa 2050. Cities' responses, temperature exposures and impacts are heterogeneous, with changes in total annual consumption ranging from $$-2.7$$

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2.7

to 5.7%, and peak power demand increasing by as much as 9.5% at the multi-GCM median. The largest increases are concentrated in more economically developed mid-latitude cities, with less developed urban areas in the tropics exhibiting relatively small changes. The results highlight the important role of the structure of electricity demand: large temperature increases in tropical cities are offset by their inelastic responses, which can be attributed to lower air-conditioning penetration.
Mild chronic exposure to pesticides alters physiological markers of honey bee health without perturbing the core gut microbiota
Authors: Almasri Hanine , Liberti Joanito , Brunet Jean-Luc , Engel Philipp , Belzunces Luc P.
Published: March 2022

Recent studies highlighted that exposure to glyphosate can affect specific members of the core gut microbiota of honey bee workers. However, in this study, bees were exposed to relatively high glyphosate concentrations. Here, we chronically exposed newly emerged honey bees to imidacloprid, glyphosate and difenoconazole, individually and in a ternary mixture, at an environmental concentration of 0.1 µg/L. We studied the effects of these exposures on the establishment of the gut microbiota, the physiological status, the longevity, and food consumption of the host. The core bacterial species were not affected by the exposure to the three pesticides. Negative effects were observed but they were restricted to few transient non-core bacterial species. However, in the absence of the core microbiota, the pesticides induced physiological disruption by directly altering the detoxification system, the antioxidant defenses, and the metabolism of the host. Our study indicates that even mild exposure to pesticides can directly alter the physiological homeostasis of newly emerged honey bees and particularly if the individuals exhibit a dysbiosis (i.e. mostly lack the core microbiota). This highlights the importance of an early establishment of a healthy gut bacterial community to strengthen the natural defenses of the honey bee against xenobiotic stressors.
Inflammatory burden and persistent CT lung abnormalities in COVID-19 patients
Authors: Besutti Giulia , Giorgi Rossi Paolo , Ottone Marta , Spaggiari Lucia , Canovi Simone , Monelli Filippo , Bonelli Efrem , Fasano Tommaso , Sverzellati Nicola , Caruso Andrea , Facciolongo Nicola , Ghidoni Giulia , Simonazzi Anna , Iori Mauro , Nitrosi Andrea , Fugazzaro Stefania , Costi Stefania , Croci Stefania , Teopompi Elisabetta , Gallina Annalisa , Massari Marco , Dolci Giovanni , Sampaolesi Fabio , Pattacini Pierpaolo , Salvarani Carlo
Published: March 2022

Inflammatory burden is associated with COVID-19 severity and outcomes. Residual computed tomography (CT) lung abnormalities have been reported after COVID-19. The aim was to evaluate the association between inflammatory burden during COVID-19 and residual lung CT abnormalities collected on follow-up CT scans performed 2–3 and 6–7 months after COVID-19, in severe COVID-19 pneumonia survivors. C-reactive protein (CRP) curves describing inflammatory burden during the clinical course were built, and CRP peaks, velocities of increase, and integrals were calculated. Other putative determinants were age, sex, mechanical ventilation, lowest PaO2/FiO2 ratio, D-dimer peak, and length of hospital stay (LOS). Of the 259 included patients (median age 65 years; 30.5% females), 202 (78%) and 100 (38.6%) had residual, predominantly non-fibrotic, abnormalities at 2–3 and 6–7 months, respectively. In age- and sex-adjusted models, best CRP predictors for residual abnormalities were CRP peak (odds ratio [OR] for one standard deviation [SD] increase = 1.79; 95% confidence interval [CI] = 1.23–2.62) at 2–3 months and CRP integral (OR for one SD increase = 2.24; 95%CI = 1.53–3.28) at 6–7 months. Hence, inflammation is associated with short- and medium-term lung damage in COVID-19. Other severity measures, including mechanical ventilation and LOS, but not D-dimer, were mediators of the relationship between CRP and residual abnormalities.
Mitochondrial dysregulation occurs early in ALS motor cortex with TDP-43 pathology and suggests maintaining NAD+ balance as a therapeutic strategy
Authors: Gautam Mukesh , Gunay Aksu , Chandel Navdeep S. , Ozdinler P. Hande
Published: March 2022

Mitochondrial defects result in dysregulation of metabolomics and energy homeostasis that are detected in upper motor neurons (UMNs) with TDP-43 pathology, a pathology that is predominantly present in both familial and sporadic cases of amyotrophic lateral sclerosis (ALS). While same mitochondrial problems are present in the UMNs of ALS patients with TDP-43 pathology and UMNs of TDP-43 mouse models, and since pathologies are shared at a cellular level, regardless of species, we first analyzed the metabolite profile of both healthy and diseased motor cortex to investigate whether metabolomic changes occur with respect to TDP-43 pathology. High-performance liquid chromatography, high-resolution mass spectrometry and tandem mass spectrometry (HPLC–MS/MS) for metabolite profiling began to suggest that reduced levels of NAD+ is one of the underlying causes of metabolomic problems. Since nicotinamide mononucleotide (NMN) was reported to restore NAD+ levels, we next investigated whether NMN treatment would improve the health of diseased corticospinal motor neurons (CSMN, a.k.a. UMN in mice). prpTDP-43A315T-UeGFP mice, the CSMN reporter line with TDP-43 pathology, allowed cell-type specific responses of CSMN to NMN treatment to be assessed in vitro. Our results show that metabolomic defects occur early in ALS motor cortex and establishing NAD+ balance could offer therapeutic benefit to UMNs with TDP-43 pathology.
Clinical features and prognostic impact of asymptomatic pancreatic cancer
Authors: Takikawa Tetsuya , Kikuta Kazuhiro , Hamada Shin , Kume Kiyoshi , Miura Shin , Yoshida Naoki , Tanaka Yu , Matsumoto Ryotaro , Ikeda Mio , Kataoka Fumiya , Sasaki Akira , Nakagawa Kei , Unno Michiaki , Masamune Atsushi
Published: March 2022

Pancreatic ductal adenocarcinoma (PDAC) is highly lethal, and early diagnosis is challenging. Because patients who present with symptoms generally have advanced-stage diseases, analysis of asymptomatic PDAC provides invaluable information for developing strategies for early diagnosis. Here, we reviewed 577 patients with PDAC (372 diagnosed with symptoms [symptomatic group] and 205 without symptoms [asymptomatic group]) diagnosed at our institute. Among the 205 asymptomatic PDAC patients, 109 were detected during follow-up/work-up for other diseases, 61 because of new-onset or exacerbation of diabetes mellitus, and 35 in a medical check-up. Asymptomatic PDAC is characterized by smaller tumor size, earlier disease stage, and higher resectability than those of symptomatic PDAC. In 22.7% of asymptomatic cases, indirect findings, e.g., dilatation of the main pancreatic duct, triggered PDAC detection. Although pancreatic tumors were less frequently detected, overall abnormality detection rates on imaging studies were nearly 100% in asymptomatic PDAC. Asymptomatic PDAC had a better prognosis (median survival time, 881 days) than symptomatic PDAC (342 days, P < 0.001). In conclusion, diagnosis of PDAC in the asymptomatic stage is associated with early diagnosis and a better prognosis. Incidental detection of abnormal findings during the follow-up/work-up for other diseases provides important opportunities for early diagnosis of asymptomatic PDAC.
Pet-directed speech improves horses’ attention toward humans
Authors: Jardat Plotine , Calandreau Ludovic , Ferreira Vitor , Gouyet Chloé , Parias Céline , Reigner Fabrice , Lansade Léa
Published: March 2022

In a recent experiment, we showed that horses are sensitive to pet-directed speech (PDS), a kind of speech used to talk to companion animals that is characterized by high pitch and wide pitch variations. When talked to in PDS rather than adult-directed speech (ADS), horses reacted more favorably during grooming and in a pointing task. However, the mechanism behind their response remains unclear: does PDS draw horses’ attention and arouse them, or does it make their emotional state more positive? In this study, we used an innovative paradigm in which female horses watched videos of humans speaking in PDS or ADS to better understand this phenomenon. Horses reacted differently to the videos of PDS and ADS: they were significantly more attentive and their heart rates increased significantly more during PDS than during ADS. We found no difference in the expressions of negative or positive emotional states during PDS and ADS videos. Thus, we confirm that horses’ perception of humans can be studied by means of video projections, and we conclude that PDS attracts attention and has an arousing effect in horses, with consequences on the use of PDS in daily interactions with them.
Assessing the suitability of self-healing rubber glove for safe handling of pesticides
Authors: Supramaniam Janarthanan , Low Darren Yi Sern , Wong See Kiat , Goh Bey Hing , Leo Bey Fen , Tang Siah Ying
Published: March 2022

Rubber gloves used for protection against chemicals or hazards are generally prone to tearing or leaking after repeated use, exposing the worker to potentially hazardous agents. Self-healing technology promises increased product durability and shelf life appears to be a feasible solution to address these issues. Herein, we aimed to fabricate a novel epoxidized natural rubber-based self-healable glove (SH glove) and investigate its suitability for handling pesticides safely. In this study, breakthrough time analysis and surface morphological observation were performed to determine the SH glove’s ability to withstand dangerous chemicals. The chemical resistance performance of the fabricated SH glove was compared against four different types of commercial gloves at different temperatures. Using malathion as a model pesticide, the results showed that the SH glove presented chemical resistance ability comparable to those gloves made with nitrile and NR latex at room temperature and 37 °C. The self-healing test revealed that the SH glove could be self-healed and retained its chemical resistance ability close to its pre-cut value. Our findings suggested that the developed SH glove with proven chemical resistance capability could be a new suitable safety glove for effectively handling pesticides and reducing glove waste generation.
An emotional discrete controller PSO tuned and designed for a real industrial pumping system
Authors: Marques Davidson C. , Silva Jeydson L. , Lira Milde Maria S. , Aquino Ronaldo R. B.
Published: March 2022

The application of automation techniques to water pump systems, combined with modern control techniques, has been increasing the hydraulic and energy efficiency of such systems. In this context, the objective of this work is to present an intelligent method of flow control based on Brain Emotional Learning Basic Intelligent Control (BELBIC), which will be applied to an experimental workbench of a pumping system, located in the Energy Efficiency and Energy Quality Laboratory (LEEQE) at Federal University of Pernambuco (UFPE). The parameters of this controller are optimized with a particle swarm optimization (PSO) technique with minimization of Integral Absolute Error (IAE). Initial tests were performed in a computational environment so that the system’s performance could be pre-tested, thereby the dynamics of the system was modeled from real data generated in the process. The experimental results were obtained through the implementation of this control system in a programmable logic controller (PLC), which was the device responsible for all the automation of the workbench previously mentioned. The data of this workbench were collected using a supervisory system exclusively developed for this work. These data were then used to analyze the performance of the proposed control system, which demonstrated that its behavior was efficient.