bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and prevention of suicidal ideation among asylum seekers in a high-risk urban post-displacement setting
Authors: Aizik-Reebs A. , Yuval K. , Beyene Kesete Y. , Lurie I. , Bernstein A.
Published: October 2022

Aims

Among asylum seekers in a high-risk unstable post-displacement context, we aimed to investigate the prevalence of and risk for suicidal ideation (study 1), and then to test whether and how Mindfulness-Based Trauma Recovery for Refugees (MBTR-R) may prevent or treat suicidal ideation (study 2).

Methods

Study 1 was conducted among a community sample ofN= 355 (31.8% female) East African asylum seekers in a high-risk urban post-displacement setting in the Middle East (Israel). Study 2 was a secondary analysis of a randomised waitlist-control trial of MBTR-R among 158 asylum-seekers (46.2% female) from the same community and post-displacement setting.

Results

Prevalence of suicidal ideation was elevated (31%). Post-migration living difficulties, as well as posttraumatic stress, depression, anxiety and their multi-morbidity were strongly associated with suicidal ideation severity. Likewise, depression and multi-morbidity prospectively predicted the onset of suicidal ideation. Relative to its incidence among waitlist-control (23.1%), MBTR-R prevented the onset of suicidal ideation at post-intervention assessment (15.6%) and 5-week follow-up (9.8%). Preventive effects of MBTR-R on suicidal ideation were mediated by reduced posttraumatic stress, depression, anxiety and their multi-morbidity. MBTR-R did not therapeutically reduce current suicidal ideation present at the beginning of the intervention.

Conclusions

Findings warn of a public health crisis of suicidality among forcibly displaced people in high-risk post-displacement settings. Although preliminary, novel randomised waitlist-control evidence for preventive effects of MBTR-R for suicidal ideation is promising. Together, findings indicate the need for scientific, applied and policy attention to mental health post-displacement in order to prevent suicide among forcibly displaced people.
Counting the carnivores: Who ate meat in Republican-Era China?
Authors: DuBois Thomas David
Published: October 2022

It is commonly asserted that Chinese diets before the market and production reforms of the 1980s contained little or no meat. Yet this nearly universal assumption remains untested: Unlike other forms of material consumption, the question of meat in Chinese diets has received almost no systematic attention from historians. Focusing on the early twentieth century, this article examines who in China ate meat, and how meat consumption was shaped by regional and household patterns. It combines insights from three sorts of data. First, Japanese price surveys from the 1920s show a high degree of variation in the preference for one type of meat over others, and the price availability of meat versus wages or other food products. Second, production data, including slaughterhouse tallies and industry estimates of animal by-products show the seasonality of animal slaughter and the vast scale and dispersed geography of China’s livestock production. Finally, nutrition and diet studies from the 1920 to the late 1940s examine actual household consumption, emphasizing how social forces and cyclical fortunes shaped individual choices. The composite picture from these three perspectives confirms that China’s meat consumption was hardly inconsequential. But more than simply triangulating a result, the exercise of comparing perspectives of price, production, and nutrition also highlights the collection of survey data as a series of historical moments.
A Coupled River Basin‐Urban Hydrological Model (DRIVE‐Urban) for Real‐Time Urban Flood Modeling
Authors: Chen Weitian , Wu Huan , Kimball John S. , Alfieri Lorenzo , Nanding Nergui , Li Xiaomeng , Jiang Lulu , Wu Wei , Tao Yingchun , Zhao Shihu , Zhong Wenting
Published: October 2022

Reliable urban flood modeling is highly demanded in emergency response, risk management, and urban planning related to urban flooding. In this paper, the Storm Water Management Model (SWMM) is adapted to simulate urban rainfall‐runoff and pipe drainage processes within the Dominant river tracing‐Routing Integrated with VIC Environment (DRIVE) model which accounts for natural river basin runoff generation and routing processes. The integrated DRIVE‐SWMM model (referred to as DRIVE‐Urban) allows to explicitly delineate the mass‐energy interactions between urban drainage system (e.g., pipes and dikes) and river networks. This presents a further step model development for accurate urban flooding prediction which is lacking in existing urban flood models and traditional hydrological models. The validity of the DRIVE‐Urban model is evaluated for three case studies in Haikou City, China, with camera observations of street inundation during typhoon landfalls and heavy rainfall events. The results show that the DRIVE‐Urban model successfully captures 62%, 69%, and 77% of the total observed inundated road‐sections for the three cases respectively. The third case study with severe flooding situation shows that the DRIVE‐Urban performance is further improved when given reliable river and tidal level information, indicating the importance of integrating river‐basin with urban hydrological and hydraulic modeling.
Quasi‐Optical Ray Tracing of Gaussian Beams in the Magnetosphere
Authors: Ling A. G. , Starks M. J. , Albert J. M.
Published: October 2022

A method for tracing rays in tokamak plasmas is applied to tracing rays in the Earth's magnetosphere. The problem of computing power flux from pencil rays using classical geometric optics that occurs when constituent rays exhibit coplanarity is addressed by appealing to complex geometric optics. The construction of Gaussian beams is discussed and the quasi‐optical method of tracing such beams is given. Examples of tracing Gaussian beams from a ground transmitter, a partial beam, and from a satellite location are presented. A median method for dealing with nonviable contributions to the power flux from sections of the beam encountering caustics or otherwise experiencing coplanarity is described. The effect of beam parameter choices on the resulting power flux computation is provided for each of the examples.
Forecasting the Geomagnetic Activity Several Days in Advance Using Neural Networks Driven by Solar EUV Imaging
Authors: Bernoux Guillerme , Brunet Antoine , Buchlin Éric , Janvier Miho , Sicard Angélica
Published: October 2022

Many models of the near‐Earth's space environment (radiation belts, ionosphere, upper atmosphere, etc.) are driven by geomagnetic indices, representing the state of disturbance of the Earth's magnetosphere. Over the past decade, machine learning‐based methods for forecasting geomagnetic indices from near‐Earth solar wind parameters have become popular in the space weather community. These methods often prove to be very accurate and skilled. However, these approaches have the notable drawback of being effective in an operational context only for limited forecasting horizons (often up to a couple of hours ahead at best). In order to increase this prediction horizon, we introduce SERENADE, a novel deep learning‐based proof‐of‐concept model using images delivered by the Atmospheric Imaging Assembly instrument onboard the Solar Dynamics Observatory spacecraft to directly provide probabilistic forecasts of the daily maximum of the geomagnetic index Kp up to a few days ahead. We show in particular that SERENADE is able to capture information on the geomagnetic dynamics from solar imaging alone. In addition, despite it being a prototypical model, our model is more accurate in most situations than three empirical baseline models. However, the model still shows some strong limitations inherent to its structure and the used data set, which could be the focus of future works. This opens the way to a better mid‐to‐long term data‐driven magnetospheric modeling within space weather and geophysical pipelines.
Systematic review of the method and quality of reporting of complications from studies evaluating innovative glaucoma surgical procedures
Authors: Bonnar Jonathan , Azuara-Blanco Augusto
Published: October 2022

The objective of this systematic review is to identify how reporting of micro-invasive glaucoma surgery (MIGS) procedure complications are reported in randomised controlled trials (RCTs) and the quality of this reporting compared to the CONSORT extension for harms. RCTs evaluating MIGS procedures were identified from a database of systematic reviews and from recent literature. Trials were evaluated in comparison to the CONSORT extension for harms to quantify the quality of harms reporting. Simple descriptive statistics were calculated for the CONSORT checklist. 21 trials were identified as eligible for inclusion, 14 were evaluating iStent, one Trabectome, three Hydrus, one Cypass, one Preseflo MicroShunt and one Excimer laser trabeculotomy. The average number of CONSORT for Harms checklist items fulfilled by the studies was 10 out of 16. No studies used a validated instrument to report severity of harms and only 4 had a list or definition of adverse events. An analysis of harm was conducted by 19 of 21 studies (90%). Appropriate metrics were used for reporting rates of adverse events in 19 of 21 studies but in only 4 studies was there an attempt to give these adverse events a grade of seriousness. In conclusion, most studies evaluating MIGS procedures do make an effort to acknowledge harms data, however this is not done uniformly well or in the same manner. A validated instrument to report severity and a standard list of complications for MIGS surgery would go a long way to helping this.
Comprehensive and clinically accurate head and neck cancer organs-at-risk delineation on a multi-institutional study
Authors: Ye Xianghua , Guo Dazhou , Ge Jia , Yan Senxiang , Xin Yi , Song Yuchen , Yan Yongheng , Huang Bing-shen , Hung Tsung-Min , Zhu Zhuotun , Peng Ling , Ren Yanping , Liu Rui , Zhang Gong , Mao Mengyuan , Chen Xiaohua , Lu Zhongjie , Li Wenxiang , Chen Yuzhen , Huang Lingyun , Xiao Jing , Harrison Adam P. , Lu Le , Lin Chien-Yu , Jin Dakai , Ho Tsung-Ying
Published: October 2022

Accurate organ-at-risk (OAR) segmentation is critical to reduce radiotherapy complications. Consensus guidelines recommend delineating over 40 OARs in the head-and-neck (H&N). However, prohibitive labor costs cause most institutions to delineate a substantially smaller subset of OARs, neglecting the dose distributions of other OARs. Here, we present an automated and highly effective stratified OAR segmentation (SOARS) system using deep learning that precisely delineates a comprehensive set of 42 H&N OARs. We train SOARS using 176 patients from an internal institution and independently evaluate it on 1327 external patients across six different institutions. It consistently outperforms other state-of-the-art methods by at least 3–5% in Dice score for each institutional evaluation (up to 36% relative distance error reduction). Crucially, multi-user studies demonstrate that 98% of SOARS predictions need only minor or no revisions to achieve clinical acceptance (reducing workloads by 90%). Moreover, segmentation and dosimetric accuracy are within or smaller than the inter-user variation.
Vesicular release probability sets the strength of individual Schaffer collateral synapses
Authors: Dürst Céline D. , Wiegert J. Simon , Schulze Christian , Helassa Nordine , Török Katalin , Oertner Thomas G.
Published: October 2022

Information processing in the brain is controlled by quantal release of neurotransmitters, a tightly regulated process. From ultrastructural analysis, it is known that presynaptic boutons along single axons differ in the number of vesicles docked at the active zone. It is not clear whether the probability of these vesicles to get released (pves) is homogenous or also varies between individual boutons. Here, we optically measure evoked transmitter release at individual Schaffer collateral synapses at different calcium concentrations, using the genetically encoded glutamate sensor iGluSnFR. Fitting a binomial model to measured response amplitude distributions allowed us to extract the quantal parameters N, pves, and q. We find that Schaffer collateral boutons typically release single vesicles under low pves conditions and switch to multivesicular release in high calcium saline. The potency of individual boutons is highly correlated with their vesicular release probability while the number of releasable vesicles affects synaptic output only under high pves conditions.
Structure of a mitochondrial ribosome with fragmented rRNA in complex with membrane-targeting elements
Authors: Tobiasson Victor , Berzina Ieva , Amunts Alexey
Published: October 2022

Mitoribosomes of green algae display a great structural divergence from their tracheophyte relatives, with fragmentation of both rRNA and proteins as a defining feature. Here, we report a 2.9 Å resolution structure of the mitoribosome from the alga Polytomella magna harbouring a reduced rRNA split into 13 fragments. We found that the rRNA contains a non-canonical reduced form of the 5S, as well as a permutation of the LSU domain I. The mt-5S rRNA is stabilised by mL40 that is also found in mitoribosomes lacking the 5S, which suggests an evolutionary pathway. Through comparison to other ribosomes with fragmented rRNAs, we observe that the pattern is shared across large evolutionary distances, and between cellular compartments, indicating an evolutionary convergence and supporting the concept of a primordial fragmented ribosome. On the protein level, eleven peripherally associated HEAT-repeat proteins are involved in the binding of 3′ rRNA termini, and the structure features a prominent pseudo-trimer of one of them (mL116). Finally, in the exit tunnel, mL128 constricts the tunnel width of the vestibular area, and mL105, a homolog of a membrane targeting component mediates contacts with an inner membrane bound insertase. Together, the structural analysis provides insight into the evolution of the ribosomal machinery in mitochondria.
Online single-cell data integration through projecting heterogeneous datasets into a common cell-embedding space
Authors: Xiong Lei , Tian Kang , Li Yuzhe , Ning Weixi , Gao Xin , Zhang Qiangfeng Cliff
Published: October 2022

Computational tools for integrative analyses of diverse single-cell experiments are facing formidable new challenges including dramatic increases in data scale, sample heterogeneity, and the need to informatively cross-reference new data with foundational datasets. Here, we present SCALEX, a deep-learning method that integrates single-cell data by projecting cells into a batch-invariant, common cell-embedding space in a truly online manner (i.e., without retraining the model). SCALEX substantially outperforms online iNMF and other state-of-the-art non-online integration methods on benchmark single-cell datasets of diverse modalities, (e.g., single-cell RNA sequencing, scRNA-seq, single-cell assay for transposase-accessible chromatin use sequencing, scATAC-seq), especially for datasets with partial overlaps, accurately aligning similar cell populations while retaining true biological differences. We showcase SCALEX’s advantages by constructing continuously expandable single-cell atlases for human, mouse, and COVID-19 patients, each assembled from diverse data sources and growing with every new data. The online data integration capacity and superior performance makes SCALEX particularly appropriate for large-scale single-cell applications to build upon previous scientific insights.
Accelerated pyro-catalytic hydrogen production enabled by plasmonic local heating of Au on pyroelectric BaTiO3 nanoparticles
Authors: You Huilin , Li Siqi , Fan Yulong , Guo Xuyun , Lin Zezhou , Ding Ran , Cheng Xin , Zhang Hao , Lo Tsz Woon Benedict , Hao Jianhua , Zhu Ye , Tam Hwa-Yaw , Lei Dangyuan , Lam Chi-Hang , Huang Haitao
Published: October 2022

The greatest challenge that limits the application of pyro-catalytic materials is the lack of highly frequent thermal cycling due to the enormous heat capacity of ambient environment, resulting in low pyro-catalytic efficiency. Here, we introduce localized plasmonic heat sources to rapidly yet efficiently heat up pyro-catalytic material itself without wasting energy to raise the surrounding temperature, triggering a significantly expedited pyro-catalytic reaction and enabling multiple pyro-catalytic cycling per unit time. In our work, plasmonic metal/pyro-catalyst composite is fabricated by in situ grown gold nanoparticles on three-dimensional structured coral-like BaTiO3 nanoparticles, which achieves a high hydrogen production rate of 133.1 ± 4.4 μmol·g−1·h−1 under pulsed laser irradiation. We also use theoretical analysis to study the effect of plasmonic local heating on pyro-catalysis. The synergy between plasmonic local heating and pyro-catalysis will bring new opportunities in pyro-catalysis for pollutant treatment, clean energy production, and biological applications.
Brain milieu induces early microglial maturation through the BAX-Notch axis
Authors: Zhao Fangying , He Jiangyong , Tang Jun , Cui Nianfei , Shi Yanyan , Li Zhifan , Liu Shengnan , Wang Yazhou , Ma Ming , Zhao Congjian , Luo Lingfei , Li Li
Published: October 2022

Microglia are derived from primitive myeloid cells and gain their early identity in the embryonic brains. However, the mechanism by which the brain milieu confers microglial maturation signature remains elusive. Here, we demonstrate that the baxcq55 zebrafish and Baxtm1Sjk mouse embryos exhibit similarly defective early microglial maturation. BAX, a typical pro-apoptotic factor, is highly enriched in neuronal cells and regulates microglial maturation through both pro-apoptotic and non-apoptotic mechanisms. BAX regulates dlb via the CaMKII-CREB axis calcium-dependently in living neurons while ensuring the efficient Notch activation in the immigrated pre-microglia by apoptotic neurons. Notch signaling is conserved in supporting embryonic microglia maturation. Compromised microglial development occurred in the Cx3cr1Cre/+Rbpjfl/fl embryonic mice; however, microglia acquire their appropriate signature when incubated with DLL3 in vitro. Thus, our findings elucidate a BAX-CaMKII-CREB-Notch network triggered by the neuronal milieu in microglial development, which may provide innovative insights for targeting microglia in neuronal disorder treatment.
Actin polymerization promotes invagination of flat clathrin-coated lattices in mammalian cells by pushing at lattice edges
Authors: Yang Changsong , Colosi Patricia , Hugelier Siewert , Zabezhinsky Daniel , Lakadamyali Melike , Svitkina Tatyana
Published: October 2022

Clathrin-mediated endocytosis (CME) requires energy input from actin polymerization in mechanically challenging conditions. The roles of actin in CME are poorly understood due to inadequate knowledge of actin organization at clathrin-coated structures (CCSs). Using platinum replica electron microscopy of mammalian cells, we show that Arp2/3 complex-dependent branched actin networks, which often emerge from microtubule tips, assemble along the CCS perimeter, lack interaction with the apical clathrin lattice, and have barbed ends oriented toward the CCS. This structure is hardly compatible with the widely held “apical pulling” model describing actin functions in CME. Arp2/3 complex inhibition or epsin knockout produce large flat non-dynamic CCSs, which split into invaginating subdomains upon recovery from Arp2/3 inhibition. Moreover, epsin localization to CCSs depends on Arp2/3 activity. We propose an “edge pushing” model for CME, wherein branched actin polymerization promotes severing and invagination of flat CCSs in an epsin-dependent manner by pushing at the CCS boundary, thus releasing forces opposing the intrinsic curvature of clathrin lattices.
Anaerobic oxidation of propane coupled to nitrate reduction by a lineage within the class Symbiobacteriia
Authors: Wu Mengxiong , Li Jie , Leu Andy O. , Erler Dirk V. , Stark Terra , Tyson Gene W. , Yuan Zhiguo , McIlroy Simon J. , Guo Jianhua
Published: October 2022

Anaerobic microorganisms are thought to play a critical role in regulating the flux of short-chain gaseous alkanes (SCGAs; including ethane, propane and butane) from terrestrial and aquatic ecosystems to the atmosphere. Sulfate has been confirmed to act as electron acceptor supporting microbial anaerobic oxidation of SCGAs, yet several other energetically more favourable acceptors co-exist with these gases in anaerobic environments. Here, we show that a bioreactor seeded with biomass from a wastewater treatment facility can perform anaerobic propane oxidation coupled to nitrate reduction to dinitrogen gas and ammonium. The bioreactor was operated for more than 1000 days, and we used13C- and15N-labelling experiments, metagenomic, metatranscriptomic, metaproteomic and metabolite analyses to characterize the microbial community and the metabolic processes. The data collectively suggest that a species representing a novel order within the bacterial class Symbiobacteriia is responsible for the observed nitrate-dependent propane oxidation. The closed genome of this organism, which we designate as ‘CandidatusAlkanivorans nitratireducens’, encodes pathways for oxidation of propane to CO2via fumarate addition, and for nitrate reduction, with all the key genes expressed during nitrate-dependent propane oxidation. Our results suggest that nitrate is a relevant electron sink for SCGA oxidation in anaerobic environments, constituting a new microbially-mediated link between the carbon and nitrogen cycles.
Cryo-EM structures of the translocational binary toxin complex CDTa-bound CDTb-pore from Clostridioides difficile
Authors: Kawamoto Akihiro , Yamada Tomohito , Yoshida Toru , Sato Yusui , Kato Takayuki , Tsuge Hideaki
Published: October 2022

Some bacteria express a binary toxin translocation system, consisting of an enzymatic subunit and translocation pore, that delivers enzymes into host cells through endocytosis. The most clinically important bacterium with such a system is Clostridioides difficile (formerly Clostridium). The CDTa and CDTb proteins from its system represent important therapeutic targets. CDTb has been proposed to be a di-heptamer, but its physiological heptameric structure has not yet been reported. Here, we report the cryo-EM structure of CDTa bound to the CDTb-pore, which reveals that CDTa binding induces partial unfolding and tilting of the first CDTa α-helix. In the CDTb-pore, an NSS-loop exists in ‘in’ and ‘out’ conformations, suggesting its involvement in substrate translocation. Finally, 3D variability analysis revealed CDTa movements from a folded to an unfolded state. These dynamic structural information provide insights into drug design against hypervirulent C. difficile strains.
Sirtuin5 protects colorectal cancer from DNA damage by keeping nucleotide availability
Authors: Wang Hao-Lian , Chen Yan , Wang Yun-Qian , Tao En-Wei , Tan Juan , Liu Qian-Qian , Li Chun-Min , Tong Xue-Mei , Gao Qin-Yan , Hong Jie , Chen Ying-Xuan , Fang Jing-Yuan
Published: October 2022

In our previous study, we reported that sirtuin5 (SIRT5), a member of the NAD+-dependent class III histone deacetylase family, is highly expressed in colorectal cancer (CRC). Herein we show that SIRT5 knockdown impairs the production of ribose-5-phosphate, which is essential for nucleotide synthesis, resulting in continuous and irreparable DNA damage and consequently leading to cell cycle arrest and enhanced apoptosis in CRC cells. These SIRT5 silencing-induced effects can be reversed by nucleoside supplementation. Mechanistically, SIRT5 activates transketolase (TKT), a key enzyme in the non-oxidative pentose phosphate pathway, in a demalonylation-dependent manner. Furthermore, TKT is essential for SIRT5-induced malignant phenotypes of CRC both in vivo and in vitro. Altogether, SIRT5 silencing induces DNA damage in CRC via post-translational modifications and inhibits tumor growth, suggesting that SIRT5 can serve as a promising target for CRC treatment.
Organic radicals stabilization above 300 °C in Eu-based coordination polymers for solar steam generation
Authors: Ye Xinhe , Chung Lai-Hon , Li Kedi , Zheng Saili , Wong Yan-Lung , Feng Zihao , He Yonghe , Chu Dandan , Xu Zhengtao , Yu Lin , He Jun
Published: October 2022

Organic radicals feature unpaired electrons, and these compounds may have applications in biomedical technology and as materials for solar energy conversion. However, unpaired electrons tend to pair up (to form chemical bonds), making radicals unstable and hampering their applications. Here we report an organic radical system that is stable even at 350 °C, surpassing the upper temperature limit (200 °C) observed for other organic radicals. The system reported herein features a sulfur-rich organic linker that facilitates the formation of the radical centers; on the solid-state level, the molecules are crystallized with Eu(III) ions to form a 3D framework featuring stacks of linker molecules. The stacking is, however, somewhat loose and allows the molecules to wiggle and transform into sulfur-stabilized radicals at higher temperatures. In addition, the resulting solid framework remains crystalline, and it is stable to water and air. Moreover, it is black and features strong broad absorption in the visible and near IR region, thereby enhancing both photothermal conversion and solar-driven water evaporation.
On-site colorimetric detection of Salmonella typhimurium
Authors: Wei Shengnan , Su Zhenyue , Bu Xiangong , Shi Xuening , Pang Bo , Zhang Liang , Li Juan , Zhao Chao
Published: October 2022

Rapid qualitative and quantitative detection ofSalmonella typhimurium(S. typhimurium) takes an important role in ensuring food safety. Herein, a colorimetric assay aptasensor forS. typhimuriumutilizing intrinsic peroxidase-like activity of gold nanoparticles embedded spherical covalent organic framework and the affinity and specificity ofS. typhimurium-aptamer has been explored. This aptasensor can capture theS. typhimuriumvia the selective binding effect of aptamer, and the catalytically active sites were shielded. As a result, the colorimetric signals of the 3,3′,5,5′-tetramethylbenzidine-H2O2system were turned off. Under optimum conditions, the aptasensor gave a linear response over the range of 10 to 107CFU/mL forS. typhimurium. The detection limit of 7 CFU/mL was obtained within 45 min and was effectively applied to detectS. typhimuriumin milk and lake water samples with recoveries in the range from 96.4 to 101.0%. More importantly, combined with a self-developed smartphone-based image analysis system, the proposed aptasensor can be used for point-of-care testing applications.
Estimation of skeletal kinematics in freely moving rodents
Authors: Monsees Arne , Voit Kay-Michael , Wallace Damian J. , Sawinski Juergen , Charyasz Edyta , Scheffler Klaus , Macke Jakob H. , Kerr Jason N. D.
Published: October 2022

Forming a complete picture of the relationship between neural activity and skeletal kinematics requires quantification of skeletal joint biomechanics during free behavior; however, without detailed knowledge of the underlying skeletal motion, inferring limb kinematics using surface-tracking approaches is difficult, especially for animals where the relationship between the surface and underlying skeleton changes during motion. Here we developed a videography-based method enabling detailed three-dimensional kinematic quantification of an anatomically defined skeleton in untethered freely behaving rats and mice. This skeleton-based model was constrained using anatomical principles and joint motion limits and provided skeletal pose estimates for a range of body sizes, even when limbs were occluded. Model-inferred limb positions and joint kinematics during gait and gap-crossing behaviors were verified by direct measurement of either limb placement or limb kinematics using inertial measurement units. Together we show that complex decision-making behaviors can be accurately reconstructed at the level of skeletal kinematics using our anatomically constrained model.
Omnipose: a high-precision morphology-independent solution for bacterial cell segmentation
Authors: Cutler Kevin J. , Stringer Carsen , Lo Teresa W. , Rappez Luca , Stroustrup Nicholas , Brook Peterson S. , Wiggins Paul A. , Mougous Joseph D.
Published: October 2022

Advances in microscopy hold great promise for allowing quantitative and precise measurement of morphological and molecular phenomena at the single-cell level in bacteria; however, the potential of this approach is ultimately limited by the availability of methods to faithfully segment cells independent of their morphological or optical characteristics. Here, we present Omnipose, a deep neural network image-segmentation algorithm. Unique network outputs such as the gradient of the distance field allow Omnipose to accurately segment cells on which current algorithms, including its predecessor, Cellpose, produce errors. We show that Omnipose achieves unprecedented segmentation performance on mixed bacterial cultures, antibiotic-treated cells and cells of elongated or branched morphology. Furthermore, the benefits of Omnipose extend to non-bacterial subjects, varied imaging modalities and three-dimensional objects. Finally, we demonstrate the utility of Omnipose in the characterization of extreme morphological phenotypes that arise during interbacterial antagonism. Our results distinguish Omnipose as a powerful tool for characterizing diverse and arbitrarily shaped cell types from imaging data.
CSF GAP-43 as a biomarker of synaptic dysfunction is associated with tau pathology in Alzheimer’s disease
Authors: Qiang Qiang , Skudder-Hill Loren , Toyota Tomoko , Wei Wenshi , Adachi Hiroaki
Published: October 2022

To test whether cerebrospinal fluid (CSF) growth-associated protein 43 (GAP-43) concentration is elevated in Alzheimer’s disease (AD) dementia and its associations with other hallmarks of AD, we examined the CSF GAP-43 measurements of 787 participants (245 cognitively normal (CN), 415 individuals with mild cognitive impairment (MCI) and 127 individuals with AD dementia) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) study. Associations were investigated between CSF GAP-43 and clinical diagnosis, Aβ/tau/neurodegeneration (AT(N)) status, CSF and blood biomarkers of AD, cognitive measurements and brain neuroimaging findings. CSF GAP-43 levels were increased in patients with AD dementia (mean, 6331.05 pg/ml) compared with the CN (mean, 5001.05 pg/ml) and MCI (mean, 5118.8 pg/ml) (P < 0.001) groups. CSF GAP-43 correlated with CSF phosphorylated tau 181(p-tau) (r = 0.768, P < 0.001), and had high diagnostic accuracy in differentiating tau positive status vs. tau negative status (area under the receiver operating characteristic curve, 0.8606). CSF GAP-43 was particularly elevated among individuals with tau positive status. High CSF GAP-43 was associated with longitudinal deterioration of cognitive scores and brain neuroimaging findings. CSF GAP-43 was associated with a clinical diagnosis of AD dementia and with an individual’s tau status, cognitive measurements and findings from neuroimaging. This study implies that CSF GAP-43 as a biomarker of synaptic dysfunction could predict the disease progression of AD patients.
A digital platform for the design of patient-centric supply chains
Authors: Triantafyllou Niki , Bernardi Andrea , Lakelin Matthew , Shah Nilay , Papathanasiou Maria M.
Published: October 2022

Chimeric Antigen Receptor (CAR) T cell therapies have received increasing attention, showing promising results in the treatment of acute lymphoblastic leukaemia and aggressive B cell lymphoma. Unlike typical cancer treatments, autologous CAR T cell therapies are patient-specific; this makes them a unique therapeutic to manufacture and distribute. In this work, we focus on the development of a computer modelling tool to assist the design and assessment of supply chain structures that can reliably and cost-efficiently deliver autologous CAR T cell therapies. We focus on four demand scales (200, 500, 1000 and 2000 patients annually) and we assess the tool’s capabilities with respect to the design of responsive supply chain candidate solutions while minimising cost.
An 80-million-year sulphur isotope record of pyrite burial over the Permian–Triassic
Authors: Salisbury Jack , Gröcke Darren R. , Cheung H. D. R. Ashleigh , Kump Lee R. , McKie Tom , Ruffell Alastair
Published: October 2022

Despite the extensive use of sulphur isotope ratios (δ34S) for understanding ancient biogeochemical cycles, many studies focus on specific time-points of interest, such as the end-Permian mass extinction (EPME). We have generated an 80 million-year Permian–Triassic δ34Sevap curve from the Staithes S-20 borehole, Yorkshire, England. The Staithes δ34Sevap record replicates the major features of the global curve, while confirming a new excursion at the Olenekian/Anisian boundary at ~ 247 million years ago. We incorporate the resultant δ34Sevap curve into a sulphur isotope box model. Our modelling approach reveals three significant pyrite burial events (i.e. PBEs) in the Triassic. In particular, it predicts a significant biogeochemical response across the EPME, resulting in a substantial increase in pyrite burial, possibly driven by Siberian Traps volcanism. Our model suggests that after ~ 10 million years pyrite burial achieves relative long-term stability until the latest Triassic.
Characterizing the composition of iPSC derived cells from bulk transcriptomics data with CellMap
Authors: Ouyang Zhengyu , Bourgeois-Tchir Nathanael , Lyashenko Eugenia , Cundiff Paige E. , Cullen Patrick F. , Challa Ravi , Li Kejie , Zhang Xinmin , Casey Fergal , Engle Sandra J. , Zhang Baohong , Zavodszky Maria I.
Published: October 2022

Induced pluripotent stem cell (iPSC) derived cell types are increasingly employed as in vitro model systems for drug discovery. For these studies to be meaningful, it is important to understand the reproducibility of the iPSC-derived cultures and their similarity to equivalent endogenous cell types. Single-cell and single-nucleus RNA sequencing (RNA-seq) are useful to gain such understanding, but they are expensive and time consuming, while bulk RNA-seq data can be generated quicker and at lower cost. In silico cell type decomposition is an efficient, inexpensive, and convenient alternative that can leverage bulk RNA-seq to derive more fine-grained information about these cultures. We developed CellMap, a computational tool that derives cell type profiles from publicly available single-cell and single-nucleus datasets to infer cell types in bulk RNA-seq data from iPSC-derived cell lines.
Comparing three types of data-driven models for monthly evapotranspiration prediction under heterogeneous climatic conditions
Authors: Aghelpour Pouya , Varshavian Vahid , Khodamorad Pour Mehraneh , Hamedi Zahra
Published: October 2022

Evapotranspiration is one of the most important hydro-climatological components which directly affects agricultural productions. Therefore, its forecasting is critical for water managers and irrigation planners. In this study, adaptive neuro-fuzzy inference system (ANFIS) model has been hybridized by differential evolution (DE) optimization algorithm as a novel approach to forecast monthly reference evapotranspiration (ET0). Furthermore, this model has been compared with the classic stochastic time series model. For this, the ET0 rates were calculated on a monthly scale during 1995–2018, based on FAO-56 Penman–Monteith equation and meteorological data including minimum air temperature, maximum air temperature, mean air temperature, minimum relative humidity, maximum relative humidity & sunshine duration. The investigation was performed on 6 stations in different climates of Iran, including Bandar Anzali & Ramsar (per-humid), Gharakhil (sub-humid), Shiraz (semi-arid), Ahwaz (arid), and Yazd (extra-arid). The models’ performances were evaluated by the criteria percent bias (PB), root mean squared error (RMSE), normalized RMSE (NRMSE), and Nash-Sutcliff (NS) coefficient. Surveys confirm the high capability of the hybrid ANFIS-DE model in monthly ET0 forecasting; so that the DE algorithm was able to improve the accuracy of ANFIS, by 16% on average. Seasonal autoregressive integrated moving average (SARIMA) was the most suitable pattern among the time series stochastic models and superior to its competitors, ANFIS and ANFIS-DE. Consequently, the SARIMA was suggested more appropriate for monthly ET0 forecasting in all the climates, due to its simplicity and parsimony. Comparison between the different climates confirmed that the climate type significantly affects the forecasting accuracies: it’s revealed that all the models work better in extra-arid, arid and semi-arid climates, than the humid and per-humid areas.
Finite element analysis and optimization of tractor gearbox body under various kinds of working conditions
Authors: Dong Sihui , Li Shiqun , Fu Shenghui , Wang Kang
Published: October 2022

As the main component of the tractor gearbox, the box has the functions of shifting operation and carrying the cab, it also carries part of the framework function. If the strength, stiffness, or vibration characteristics of the box do not meet the allowable requirements, large vibration and noise may occur, and even there is the possibility of fracture in some limiting conditions. To solve this problem, according to the structural parameters of a gearbox, the three-dimensional model of the box was established by using the three-dimensional modeling software Creo. According to the dangerous degree of the transmission load when the tractor is working normally, three vehicle working conditions are selected: a round of suspension conditions, farm tool lifting conditions, and emergency turning conditions. In addition, according to the transmission ratio of each gear meshing inside the gearbox, two gear conditions are selected: gear condition one and reverse gear condition one. The forces of the box under these extreme conditions are analyzed. The static analysis and modal analysis of the tractor gearbox are carried out by using the Static Structural module of ANSYS Workbanch. The deformation, equivalent stress distribution, and modal vibration frequency of the gearbox are tested. The topology optimization method is used to improve structural defects and reduce box quality. The results show that the weight of the optimized box reduces by 8.44%, the deformation decreased by 15.89%, and the equivalent stress decreased by 18.34%. The strength and stiffness of the box are improved, the quality is lightweight, the waste of resources is reduced, and the heat dissipation performance and fracture resistance of the box are enhanced.
Suppressed renoprotective purines in COVID-19 patients with acute kidney injury
Authors: Jackson Edwin K. , Kitsios Georgios D. , Lu Michael Y. , Schaefer Caitlin M. , Kessinger Cathy J. , McVerry Bryan J. , Morris Alison , Macatangay Bernard J. C.
Published: October 2022

Acute kidney injury (AKI) is common in patients hospitalized for COVID-19, complicating their clinical course and contributing to worse outcomes. Animal studies show that adenosine, inosine and guanosine protect the kidney against some types of AKI. However, until now there was no evidence in patients supporting the possibility that abnormally low kidney levels of adenosine, inosine and guanosine contribute to AKI. Here, we addressed the question as to whether these renoprotective purines are altered in the urine of COVID-19 patients with AKI. Purines were measured by employing ultra-high-performance liquid chromatography-tandem mass spectrometry with stable-isotope-labeled internal standards for each purine of interest. Compared with COVID-19 patients without AKI (n = 23), COVID-19 patients with AKI (n = 20) had significantly lower urine levels of adenosine (P < 0.0001), inosine (P = 0.0008), and guanosine (P = 0.0008) (medians reduced by 85%, 48% and 61%, respectively) and lower levels (P = 0.0003; median reduced by 67%) of the 2nd messenger for A2A and A2B adenosine receptors, i.e., 3’,5’-cAMP. Moreover, in COVID-19 patients with AKI, urine levels of 8-aminoguanine (endogenous inhibitor of inosine and guanosine metabolism) were nearly abolished (P < 0.0001). In contrast, the “upstream” precursors of renoprotective purines, namely 5’-AMP and 5’-GMP, were not significantly altered in COVID-19 patients with AKI, suggesting defective conversion of these precursors by CD73 (converts 5’-AMP to adenosine and 5’-GMP to guanosine). These findings imply that an imbalance in renoprotective purines may contribute to AKI in COVID-19 patients and that pharmacotherapy targeted to restore levels of renoprotective purines may attenuate the risk of AKI in susceptible patients with COVID-19.
Formation of orogenic gold deposits by progressive movement of a fault-fracture mesh through the upper crustal brittle-ductile transition zone
Authors: Tavares Nassif Miguel , Monecke Thomas , Reynolds T. James , Kuiper Yvette D. , Goldfarb Richard J. , Piazolo Sandra , Lowers Heather A.
Published: October 2022

Orogenic gold deposits are comprised of complex quartz vein arrays that form as a result of fluid flow along transcrustal fault zones in active orogenic belts. Mineral precipitation in these deposits occurs under variable pressure conditions, but a mechanism explaining how the pressure regimes evolve through time has not previously been proposed. Here we show that extensional quartz veins at the Garrcon deposit in the Abitibi greenstone belt of Canada preserve petrographic characteristics suggesting that the three recognized paragenetic stages formed within different pressure regimes. The first stage involved the growth of interlocking quartz grains competing for space in fractures held open by hydrothermal fluids at supralithostatic pressures. Subsequent fluid flow at fluctuating pressure conditions caused recrystallization of the vein quartz and the precipitation of sulfide minerals through wall-rock sulfidation, with some of the sulfide minerals containing microscopic gold. These pressure fluctuations between supralithostatic to near-hydrostatic conditions resulted in the post-entrapment modification of the fluid inclusion inventory of the quartz. Late fluid flow occurred at near-hydrostatic conditions and resulted in the formation of fluid inclusions that have not been affected by post-entrapment modification as pressure conditions never returned to supralithostatic conditions. This late fluid flow is interpreted to have formed the texturally late, coarse native gold that occurs along quartz grain boundaries and in open spaces. The systematic evolution of the pressure regimes in orogenic gold deposits such as Garrcon can be explained by relative movement of fault-fracture meshes across the base of the upper crustal brittle-ductile transition zone. We conclude that early vein quartz in orogenic deposits is precipitated at near-lithostatic conditions whereas the paragenetically late gold is introduced at distinctly lower pressure.
Differentiation of human induced pluripotent stem cells into hypothalamic vasopressin neurons with minimal exogenous signals and partial conversion to the naive state
Authors: Ozaki Hajime , Suga Hidetaka , Sakakibara Mayu , Soen Mika , Miyake Natsuki , Miwata Tsutomu , Taga Shiori , Nagai Takashi , Kano Mayuko , Mitsumoto Kazuki , Miyata Takashi , Kobayashi Tomoko , Sugiyama Mariko , Onoue Takeshi , Takagi Hiroshi , Hagiwara Daisuke , Iwama Shintaro , Banno Ryoichi , Iguchi Genzo , Takahashi Yutaka , Muguruma Keiko , Inoue Haruhisa , Arima Hiroshi
Published: October 2022

Familial neurohypophyseal diabetes insipidus (FNDI) is a degenerative disease of vasopressin (AVP) neurons. Studies in mouse in vivo models indicate that accumulation of mutant AVP prehormone is associated with FNDI pathology. However, studying human FNDI pathology in vivo is technically challenging. Therefore, an in vitro human model needs to be developed. When exogenous signals are minimized in the early phase of differentiation in vitro, mouse embryonic stem cells (ESCs)/induced pluripotent stem cells (iPSCs) differentiate into AVP neurons, whereas human ESCs/iPSCs die. Human ESCs/iPSCs are generally more similar to mouse epiblast stem cells (mEpiSCs) compared to mouse ESCs. In this study, we converted human FNDI-specific iPSCs by the naive conversion kit. Although the conversion was partial, we found improved cell survival under minimal exogenous signals and differentiation into rostral hypothalamic organoids. Overall, this method provides a simple and straightforward differentiation direction, which may improve the efficiency of hypothalamic differentiation.
Impact of body weight change on clinical outcomes in patients with idiopathic pulmonary fibrosis receiving pirfenidone
Authors: Kim Tae Hun , Shin Yune-Young , Kim Hyung-Jun , Song Myung Jin , Kim Yeon Wook , Lim Sung Yoon , Lee Yeon Joo , Park Jong Sun , Cho Young-Jae , Lee Jae Ho , Lee Choon-Taek , Kwon Byoung Soo
Published: October 2022

There have been limited studies on the association between prognosis and body weight change in patients with idiopathic pulmonary fibrosis (IPF). This single-center retrospective observational study evaluated the impact of weight loss on outcomes in Korean patients with IPF receiving pirfenidone at a tertiary medical institution. We analyzed 215 IPF patients prescribed pirfenidone from January 1st, 2015 to December 31st, 2019. The patients were categorized into maintained weight (MW; weight gain or loss < 5%/year) and reduced weight (RW; weight loss ≥ 5%/year) groups. The mean age was 71.8 years and 175 (81.4%) were male. There were 54 (25.1%) patients in the RW group. All patients showed a decrease in body weight (baseline vs. after 1 year; 64.1 kg vs. 62.8 kg, P < 0.001). Although baseline lung function showed a difference, there was no difference in the rate of change (forced vital capacity [% of predicted]; P = 0.221, diffusing capacity of the lung for carbon monoxide [% of predicted]; P = 0.973). The MW group had a lower risk of all-cause mortality (P < 0.001). Weight loss appeared to be a significant risk factor for mortality in patients with IPF. Not only disease control with antifibrotic agents, but also efforts to prevent weight loss may be necessary.
Clear-sky control of anvils in response to increased CO2 or surface warming or volcanic eruptions
Authors: Saint-Lu Marion , Bony Sandrine , Dufresne Jean-Louis
Published: October 2022

Anvil clouds produced by deep convection cover extensive areas of the tropics, and their response to external perturbations matters for the Earth’s climate sensitivity. It has been suggested that variations in the height and spatial extent of these clouds can be understood from basic physical arguments related to the conservation of mass and energy in the clear-sky areas of the tropics. Based on satellite observations, meteorological reanalyses, and climate model simulations, we show that these arguments can be used to interpret the response of anvil cloud fraction to a range of perturbations in the current climate and under climate change. This includes the response to interannual and long-term surface temperature changes, to the direct effect of carbon dioxide, and the decrease of anvil cloud fraction after explosive volcanic eruptions. Therefore, the control of tropical anvils by clear-sky radiative cooling and static stability in the upper troposphere can explain a large diversity of the responses of anvil cloud fraction to natural and anthropogenic perturbations. These findings should also be considered when assessing the impacts of geo-engineering techniques.