bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporal Changes in Epinephrine Dosing in Out-of-Hospital Cardiac Arrest: A Review of EMS Protocols across the United States
Authors: Garfinkel Eric , Michelsen Katelyn , Johnson Benjamin , Margolis Asa , Levy Matthew
Published: October 2022

Background:

Administration of epinephrine has been associated with worse neurological outcomes for survivors of out-of-hospital cardiac arrest. The publication of the 2018 PARAMEDIC-2 trial, a randomized and double-blind study of epinephrine in out-of-hospital cardiac arrest, provides the strongest evidence to date that epinephrine increases return of spontaneous circulation (ROSC) but not neurologically intact survival. This study aims to determine if Emergency Medical Services (EMS) cardiac arrest protocols have changed since the publication of PARAMEDIC-2.

Methods:

States in the US utilizing mandatory or model state-wide EMS protocols, including Washington DC, were included in this study. The nontraumatic cardiac arrest protocol as of January 1, 2018 was compared to the protocol in effect on January 1, 2021 to determine if there was a change in the administration of epinephrine. Protocols were downloaded from the relevant state EMS website. If a protocol could not be obtained, the state medical director was contacted.

Results:

A 2021 state-wide protocol was found for 32/51 (62.7%) states. Data from 2018 were available for 21/51 (41.2%) states. Of the 11 states without data from 2018, all follow Advanced Cardiac Life Support (ACLS) guidelines in the 2021 protocol. Five (15.6%) of the states with a state-wide protocol made a change in the cardiac arrest protocols. Maximum cumulative epinephrine dose was limited to 4mg in Maryland and 3mg in Vermont. Rhode Island changed epinephrine in shockable rhythms to be administered after three cycles of cardiopulmonary resuscitation (CPR) and an anti-arrhythmic. Rhode Island also added an epinephrine infusion as an option. No states removed epinephrine administration from their cardiac arrest protocol. Simple statistical analysis was performed with Microsoft Excel.

Conclusion:

Several states have adjusted cardiac arrest protocols since 2018. The most frequent change was limiting the maximum cumulative dosage of epinephrine. One state changed timing of epinephrine dosing depending on the rhythm and also provided an option of an epinephrine infusion in place of bolus dosing. While the sample size is small, these changes may reflect the future direction of prehospital cardiac arrest protocols. Significant limitations apply, including the exclusion of local and regional protocols which are more capable of quickly adjusting to new research. Additionally, this study is only focused on EMS in the United States.
A Novel Technique for Producing Three-Dimensional Data Using Serial Sectioning and Semi-Automatic Image Classification
Authors: Mehra Akshay , Howes Bolton , Manzuk Ryan , Spatzier Alex , Samuels Bradley M , Maloof Adam C
Published: October 2022

The three-dimensional characterization of internal features, via metrics such as orientation, porosity, and connectivity, is important to a wide variety of scientific questions. Many spatial and morphological metrics only can be measured accurately through direct in situ three-dimensional observations of large (i.e., big enough to be statistically representative) volumes. For samples that lack material contrast between phases, serial grinding and imaging—which relies solely on color and textural characteristics to differentiate features—is a viable option for extracting such information. Here, we present the Grinding, Imaging, Reconstruction Instrument (GIRI), which automatically serially grinds and photographs centimeter-scale samples at micron resolution. Although the technique is destructive, GIRI produces an archival digital image stack. This digital image stack is run through a supervised machine-learning-based image processing technique that quickly and accurately segments data into predefined classes. These classified data then can be loaded into three-dimensional visualization software for measurement. We share three case studies to illustrate how GIRI can address questions with a significant morphological component for which two-dimensional or small-volume three-dimensional measurements are inadequate. The analyzed metrics include: the morphologies of objects and pores in a granular material, the bulk mineralogy of polyminerallic solids, and measurements of the internal angles and symmetry of crystals.
Long-Gone Moon Could Explain Birth of Saturn’s Rings
Authors: Benningfield Damond
Published: October 2022

Named Chrysalis, the moon could have disintegrated during a close encounter with the gas giant roughly 100 million years ago.
Measurements of Mesospheric Water Vapor From 1992 to 2021 at Three Stations From the Network for the Detection of Atmospheric Composition Change
Authors: Nedoluha Gerald E. , Gomez R. Michael , Boyd Ian , Neal Helen , Allen Douglas R. , Siskind David E. , Lambert Alyn , Livesey Nathaniel J.
Published: October 2022

We present ground‐based microwave measurements of mesospheric water vapor made by the Water Vapor Millimeter‐wave Spectrometer (WVMS) instruments since the early 1990s from sites in California, Hawaii, and New Zealand. These measurements are compared with coincident measurements from the Halogen Occultation Experiment, the Aura Microwave Limb Sounder, and Sounding of the Atmosphere using Broadband Emission Radiometry; all of which combine to cover the entire time period of the ground‐based measurements. Comparisons are presented both on ∼weekly timescales in order to better identify discontinuities in the relative differences and on annual timescales in order to better study geophysical variations. The WVMS retrievals shown here are available on the Network for the Detection of Atmospheric Composition Change database. The range of WVMS trends and the differences from the satellite trends, with the latter varying over a range of ∼3%/decade, provide an estimate of how accurately it would be possible to determine multidecadal trends using ground‐based microwave instruments in a postsatellite era. This uncertainty is comparable to the trend in mesospheric water vapor that is expected to have occurred since the early 1990s.
Detection technologies for RNA modifications
Authors: Zhang Yan , Lu Liang , Li Xiaoyu
Published: October 2022

To date, more than 170 chemical modifications have been characterized in RNA, providing a new layer of gene expression regulation termed the ‘epitranscriptome’. RNA modification detection methods and tools advance the functional studies of the epitranscriptome. According to the detection throughput and principles, existing RNA modification detection technologies can be categorized into four classes, including quantification methods, locus-specific detection methods, next-generation sequencing-based detection technologies and nanopore direct RNA sequencing-based technologies. In this review, we summarize the current knowledge about these RNA modification detection technologies and discuss the challenges for the existing detection tools, providing information for a comprehensive understanding of the epitranscriptome.
High-speed magnetic control of water transport in superhydrophobic tubular actuators
Authors: Xiong Fangyihan , Zhang Liyun , Xu Lei , Zhao Huan , Lan Jianyang , Ji Chenhao , Chen Linfeng , Xia Fan
Published: October 2022

Directed transport of a small amount of water is a basic issue and has attracted extensive attention due to its importance in a wide range of applications, such as water collection, microfluidics, printing, bioanalysis, and microchemical reactions. Various strategies based on constructing a surface tension gradient or Laplace pressure gradient have been developed to realize directional water transport. Typically, electrostatic forces and magnetic fields are utilized to achieve high-speed water transport on open superhydrophobic surfaces. However, these methods suffer from water evaporation or contamination. Here, we report a magnetic superhydrophobic tubular PDMS actuator for directional water transport. The actuator deformed under an applied external magnetic field and actuated the water droplet to transport along the moving direction of the magnet. The water transport velocity reached 16.1 cm/s. In addition, as the inner surface of the actuator is superhydrophobic, the water droplet showed weak interactions with the surface and presented negligible mass loss during the transport process. The results of this work may inspire new design of actuators for directional water transport with high speeds.
Incorporating evolutionary and threat processes into crop wild relatives conservation
Authors: Tobón-Niedfeldt Wolke , Mastretta-Yanes Alicia , Urquiza-Haas Tania , Goettsch Bárbara , Cuervo-Robayo Angela P. , Urquiza-Haas Esmeralda , Orjuela-R M. Andrea , Acevedo Gasman Francisca , Oliveros-Galindo Oswaldo , Burgeff Caroline , Rivera-Rodríguez Diana M. , Sánchez González José de Jesús , Alarcón-Guerrero Jesús , Aguilar-Meléndez Araceli , Aragón Cuevas Flavio , Alavez Valeria , Alejandre-Iturbide Gabriel , Avendaño-Arrazate Carlos-H. , Azurdia Pérez César , Delgado-Salinas Alfonso , Galán Pablo , González-Ledesma Manuel , Hernández-Ruíz Jesús , Lorea-Hernández Francisco G. , Lira Saade Rafael , Rodríguez Aarón , Rodríguez Delcid Dagoberto , Ruiz-Corral José Ariel , Santos Pérez Juan José , Vargas-Ponce Ofelia , Vega Melania , Wegier Ana , Quintana-Camargo Martín , Sarukhán José , Koleff Patricia
Published: October 2022

Crop wild relatives (CWR) intra- and interspecific diversity is essential for crop breeding and food security. However, intraspecific genetic diversity, which is central given the idiosyncratic threats to species in landscapes, is usually not considered in planning frameworks. Here, we introduce an approach to develop proxies of genetic differentiation to identify conservation areas, applying systematic conservation planning tools that produce hierarchical prioritizations of the landscape. It accounts for: (i) evolutionary processes, including historical and environmental drivers of genetic diversity, and (ii) threat processes, considering taxa-specific tolerance to human-modified habitats, and their extinction risk status. Our analyses can be used as inputs for developing national action plans for the conservation and use of CWR. Our results also inform public policy to mitigate threat processes to CWR (like crops living modified organisms or agriculture subsidies), and could advise future research (e.g. for potential germplasm collecting). Although we focus on Mesoamerican CWR within Mexico, our methodology offers opportunities to effectively guide conservation and monitoring strategies to safeguard the evolutionary resilience of any taxa, including in regions of complex evolutionary histories and mosaic landscapes.
Two-dimensional mineral hydrogel-derived single atoms-anchored heterostructures for ultrastable hydrogen evolution
Authors: Lyu Fucong , Zeng Shanshan , Jia Zhe , Ma Fei-Xiang , Sun Ligang , Cheng Lizi , Pan Jie , Bao Yan , Mao Zhengyi , Bu Yu , Li Yang Yang , Lu Jian
Published: October 2022

Hydrogen energy is critical for achieving carbon neutrality. Heterostructured materials with single metal-atom dispersion are desirable for hydrogen production. However, it remains a great challenge to achieve large-scale fabrication of single atom-anchored heterostructured catalysts with high stability, low cost, and convenience. Here, we report single iron (Fe) atom-dispersed heterostructured Mo-based nanosheets developed from a mineral hydrogel. These rationally designed nanosheets exhibit excellent hydrogen evolution reaction (HER) activity and reliability in alkaline condition, manifesting an overpotential of 38.5 mV at 10 mA cm−2, and superior stability without performance deterioration over 600 h at current density up to 200 mA cm−2, superior to most previously reported non-noble-metal electrocatalysts. The experimental and density functional theory results reveal that the O-coordinated single Fe atom-dispersed heterostructures greatly facilitated H2O adsorption and enabled effective adsorbed hydrogen (H*) adsorption/desorption. The green, scalable production of single-atom-dispersed heterostructured HER electrocatalysts reported here is of great significance in promoting their large-scale implementation.
Translational reprogramming in response to accumulating stressors ensures critical threshold levels of Hsp90 for mammalian life
Authors: Bhattacharya Kaushik , Maiti Samarpan , Zahoran Szabolcs , Weidenauer Lorenz , Hany Dina , Wider Diana , Bernasconi Lilia , Quadroni Manfredo , Collart Martine , Picard Didier
Published: October 2022

The cytosolic molecular chaperone Hsp90 is essential for eukaryotic life. Although reduced Hsp90 levels correlate with aging, it was unknown whether eukaryotic cells and organisms can tune the basal Hsp90 levels to alleviate physiologically accumulated stress. We have investigated whether and how mice adapt to the deletion of three out of four alleles of the two genes encoding cytosolic Hsp90, with one Hsp90β allele being the only remaining one. While the vast majority of such mouse embryos die during gestation, survivors apparently manage to increase their Hsp90β protein to at least wild-type levels. Our studies reveal an internal ribosome entry site in the 5’ untranslated region of the Hsp90β mRNA allowing translational reprogramming to compensate for the genetic loss of Hsp90 alleles and in response to stress. We find that the minimum amount of total Hsp90 required to support viability of mammalian cells and organisms is 50–70% of what is normally there. Those that fail to maintain a threshold level are subject to accelerated senescence, proteostatic collapse, and ultimately death. Therefore, considering that Hsp90 levels can be reduced ≥100-fold in the unicellular budding yeast, critical threshold levels of Hsp90 have markedly increased during eukaryotic evolution.
The cholesterol transport protein GRAMD1C regulates autophagy initiation and mitochondrial bioenergetics
Authors: Ng Matthew Yoke Wui , Charsou Chara , Lapao Ana , Singh Sakshi , Trachsel-Moncho Laura , Schultz Sebastian W. , Nakken Sigve , Munson Michael J. , Simonsen Anne
Published: October 2022

During autophagy, cytosolic cargo is sequestered into double-membrane vesicles called autophagosomes. The contributions of specific lipids, such as cholesterol, to the membranes that form the autophagosome, remain to be fully characterized. Here, we demonstrate that short term cholesterol depletion leads to a rapid induction of autophagy and a corresponding increase in autophagy initiation events. We further show that the ER-localized cholesterol transport protein GRAMD1C functions as a negative regulator of starvation-induced autophagy and that both its cholesterol transport VASt domain and membrane binding GRAM domain are required for GRAMD1C-mediated suppression of autophagy initiation. Similar to its yeast orthologue, GRAMD1C associates with mitochondria through its GRAM domain. Cells lacking GRAMD1C or its VASt domain show increased mitochondrial cholesterol levels and mitochondrial oxidative phosphorylation, suggesting that GRAMD1C may facilitate cholesterol transfer at ER-mitochondria contact sites. Finally, we demonstrate that expression of GRAMD family proteins is linked to clear cell renal carcinoma survival, highlighting the pathophysiological relevance of cholesterol transport proteins.
Single cell transcriptomic profiling of a neuron-astrocyte assembloid tauopathy model
Authors: Rickner Hannah Drew , Jiang Lulu , Hong Rui , O’Neill Nicholas K. , Mojica Chromewell A. , Snyder Benjamin J. , Zhang Lushuang , Shaw Dipan , Medalla Maria , Wolozin Benjamin , Cheng Christine S.
Published: October 2022

The use of iPSC derived brain organoid models to study neurodegenerative disease has been hampered by a lack of systems that accurately and expeditiously recapitulate pathogenesis in the context of neuron-glial interactions. Here we report development of a system, termed AstTau, which propagates toxic human tau oligomers in iPSC derived neuron-astrocyte assembloids. The AstTau system develops much of the neuronal and astrocytic pathology observed in tauopathies including misfolded, phosphorylated, oligomeric, and fibrillar tau, strong neurodegeneration, and reactive astrogliosis. Single cell transcriptomic profiling combined with immunochemistry characterizes a model system that can more closely recapitulate late-stage changes in adult neurodegeneration. The transcriptomic studies demonstrate striking changes in neuroinflammatory and heat shock protein (HSP) chaperone systems in the disease process. Treatment with the HSP90 inhibitor PU-H71 is used to address the putative dysfunctional HSP chaperone system and produces a strong reduction of pathology and neurodegeneration, highlighting the potential of AstTau as a rapid and reproducible tool for drug discovery.
Micro-scale functional modules in the human temporal lobe
Authors: Chapeton Julio I. , Wittig John H. , Inati Sara K. , Zaghloul Kareem A.
Published: October 2022

The sensory cortices of many mammals are often organized into modules in the form of cortical columns, yet whether modular organization at this spatial scale is a general property of the human neocortex is unknown. The strongest evidence for modularity arises when measures of connectivity, structure, and function converge. Here we use microelectrode recordings in humans to examine functional connectivity and neuronal spiking responses in order to assess modularity in submillimeter scale networks. We find that the human temporal lobe consists of temporally persistent spatially compact modules approximately 1.3mm in diameter. Functionally, the information coded by single neurons during an image categorization task is more similar for neurons belonging to the same module than for neurons from different modules. The geometry, connectivity, and spiking responses of these local cortical networks provide converging evidence that the human temporal lobe is organized into functional modules at the micro scale.
Giant ferroelectric polarization in a bilayer graphene heterostructure
Authors: Niu Ruirui , Li Zhuoxian , Han Xiangyan , Qu Zhuangzhuang , Ding Dongdong , Wang Zhiyu , Liu Qianling , Liu Tianyao , Han Chunrui , Watanabe Kenji , Taniguchi Takashi , Wu Menghao , Ren Qi , Wang Xueyun , Hong Jiawang , Mao Jinhai , Han Zheng , Liu Kaihui , Gan Zizhao , Lu Jianming
Published: October 2022

At the interface of van der Waals heterostructures, the crystal symmetry and the electronic structure can be reconstructed, giving rise to physical properties superior to or absent in parent materials. Here by studying a Bernal bilayer graphene moiré superlattice encapsulated by 30°-twisted boron nitride flakes, we report an unprecedented ferroelectric polarization with the areal charge density up to 1013 cm−2, which is far beyond the capacity of a moiré band. The translated polarization ~5 pC m−1is among the highest interfacial ferroelectrics engineered by artificially stacking van der Waals crystals. The gate-specific ferroelectricity and co-occurring anomalous screening are further visualized via Landau levels, and remain robust for Fermi surfaces outside moiré bands, confirming their independence on correlated electrons. We also find that the gate-specific resistance hysteresis loops could be turned off by the other gate, providing an additional control knob. Furthermore, the ferroelectric switching can be applied to intrinsic properties such as topological valley current. Overall, the gate-specific ferroelectricity with strongly enhanced charge polarization may encourage more explorations to optimize and enrich this novel class of ferroelectricity, and promote device applications for ferroelectric switching of various quantum phenomena.
Thiazolidinedione use and risk of Parkinson’s disease in patients with type 2 diabetes mellitus
Authors: Zhao Houyu , Zhuo Lin , Sun Yexiang , Shen Peng , Lin Hongbo , Zhan Siyan
Published: October 2022

The health burden of Parkinson’s disease (PD) and diabetes increases rapidly in China. However, no population-based study of the association between glucose lowering agents and PD incidence has been conducted in mainland Chinese population. Preclinical studies indicate that thiazolidinediones (TZDs) have neuroprotective effects against PD through stimulating peroxisome proliferator-activated receptor gamma. Nevertheless, debate remains in human studies. We assembled a retrospective cohort of type 2 diabetes mellitus (T2DM) patients who were new users of TZDs or alpha glucosidase inhibitors (AGIs) using the Yinzhou Regional Health Care Database. A Cox model with inverse probability of treatment weighting (IPTW) was applied to estimate the hazard ratio (HR) of PD incidence associated with the use of TZDs compared with AGIs. The final cohort included 12,704 new users of TZDs and 49,696 new users of AGIs. The incidence of PD was 135 per 100,000 person-years in TZD users and 203 per 100,000 person-years in the AGI group. An inverse association between use of TZDs and incidence of PD, with a HR of 0.74 (95% confidence interval, 0.59–0.92), was observed after adjusting for potential confounding using IPTW. The results of various subgroup analyses and sensitivity analyses were consistent with the findings of the primary analysis. Our results indicated that the use of TZD is associated with a decreased risk of PD incidence in a mainland Chinese population with T2DM. Given the heavy disease burden of PD and diabetes in China, these findings could provide some evidence for developing effective prevention and control measures to reduce the future incidence of PD in China.
Documentation of smoking in scheduled asthma contacts in primary health care: a 12-year follow-up study
Authors: Takala Jaana , Vähätalo Iida , Tuomisto Leena E. , Niemelä Onni , Ilmarinen Pinja , Kankaanranta Hannu
Published: October 2022

Smoking among asthmatics is common and associates with poorer asthma control, more rapid lung function decline and higher health care costs in dose-dependent manner. No previous real-life studies exist, however, on how smoking status and pack-years are documented in scheduled asthma contacts in primary health care (PHC) during long-term follow-up, and how often patients are advised to quit smoking. In this real-life 12-year follow-up study, we showed that out of all scheduled PHC asthma contacts (n = 603) smoking was mentioned only in 17.2% and pack-years only in 6.5%. Smoking data was not recorded even once in 70.9% of never smokers, 64.7% of ex-smokers and 27.3% of current smokers. Smoking including pack-years were mentioned more often if nurse took part on the scheduled contact. For current smokers, smoking cessation was recommended only in 21.7% of their scheduled contacts. Current smokers used more antibiotics and had more unscheduled health care contacts during follow-up.
Understanding relationships between asthma medication use and outcomes in a SABINA primary care database study
Authors: Vervloet Marcia , van Dijk Liset , Weesie Yvette M. , Kocks Janwillem W. H. , Dima Alexandra L. , Korevaar Joke C.
Published: October 2022

Adherence to inhaled corticosteroids (ICS) in asthma is suboptimal. Patients may rely more on their short-acting beta-agonist (SABA) to control symptoms, which may increase their risk of exacerbations and uncontrolled asthma. Our objective is to describe ICS adherence and SABA use among Dutch primary care patients with asthma, and how these are related to exacerbations and self-reported asthma control. Patients aged ≥12 years diagnosed with asthma who received ≥2 inhalation medication prescriptions in 2016 were selected from the Nivel Primary Care Database. ICS adherence (continuous measure of medication availability), SABA use (number of prescriptions), exacerbations (short courses of oral corticosteroids with daily dose ≥20 mg), and asthma control (self-reported with the Asthma Control Questionnaire; ACQ) were computed. Multilevel logistic regression analyses, to account for clustering of patients within practices, were used to model associations between ICS adherence, SABA use, and asthma outcomes. Prescription data of 13,756 patients were included. ICS adherence averaged 62% (SD: 32.7), 14% of patients received ≥3 SABA prescriptions, and 13% of patients experienced ≥1 exacerbation. Self-reported asthma control was available for 2183 patients of whom 51% reported controlled asthma (ACQ-5 score <0.75). A higher number of SABA prescriptions was associated with a higher risk of exacerbations and uncontrolled asthma, even with high ICS adherence (>90%). ICS adherence was not associated with exacerbations, whilst poor ICS adherence (≤50%) was associated with uncontrolled asthma. In conclusion, increased SABA use is an important and easily identifiable signal for general practitioners to discuss asthma self-management behavior with their patients.
Severe testing with high-dimensional omics data for enhancing biomedical scientific discovery
Authors: Emmert-Streib Frank
Published: October 2022

High-throughput omics experiments provide a wealth of data for exploring biomedical questions and for advancing translational research. However, despite this great potential, results that enter the clinical practice are scarce even twenty years after the completion of the human genome project. For this reason in this paper, we revisit problems with scientific discovery commonly summarized under the term reproducibility crisis. We will argue that the major problem that hampers progress in translational research is threefold. First, in order to establish biological foundations of disorders or general complex phenotypes, one needs to embrace emergence. Second, there seems to be confusion about the underlying hypotheses tested by omics studies. Third, most contemporary omics studies are designed to perform what can be seen as incremental corroborations of a hypothesis. In order to improve upon these shortcomings, we define a severe testing framework (STF) that can be applied to a large number of omics studies for enhancing scientific discovery in the biomedical sciences. Briefly, STF provides systematic means to trim wild-grown omics studies in a constructive way.
Comparative transcriptomic analysis of whole blood mycobacterial growth assays and tuberculosis patients’ blood RNA profiles
Authors: Bachanová Petra , Cheyne Ashleigh , Broderick Claire , Newton Sandra M. , Levin Michael , Kaforou Myrsini
Published: October 2022

In vitro whole blood infection models are used for elucidating the immune response to Mycobacterium tuberculosis (Mtb). They exhibit commonalities but also differences, to the in vivo blood transcriptional response during natural human Mtb disease. Here, we present a description of concordant and discordant components of the immune response in blood, quantified through transcriptional profiling in an in vitro whole blood infection model compared to whole blood from patients with tuberculosis disease. We identified concordantly and discordantly expressed gene modules and performed in silico cell deconvolution. A high degree of concordance of gene expression between both adult and paediatric in vivo–in vitro tuberculosis infection was identified. Concordance in paediatric in vivo vs in vitro comparison is largely characterised by immune suppression, while in adults the comparison is marked by concordant immune activation, particularly that of inflammation, chemokine, and interferon signalling. Discordance between in vitro and in vivo increases over time and is driven by T-cell regulation and monocyte-related gene expression, likely due to apoptotic depletion of monocytes and increasing relative fraction of longer-lived cell types, such as T and B cells. Our approach facilitates a more informed use of the whole blood in vitro model, while also accounting for its limitations.
A stacking-based artificial intelligence framework for an effective detection and localization of colon polyps
Authors: Albuquerque Carina , Henriques Roberto , Castelli Mauro
Published: October 2022

Polyp detection through colonoscopy is a widely used method to prevent colorectal cancer. The automation of this process aided by artificial intelligence allows faster and improved detection of polyps that can be missed during a standard colonoscopy. In this work, we propose to implement various object detection algorithms for polyp detection. To improve the mean average precision (mAP) of the detection, we combine the baseline models through a stacking approach. The experiments demonstrate the potential of this new methodology, which can reduce the workload for oncologists and increase the precision of the localization of polyps. Our proposal achieves a mAP of 0.86, translated into an improvement of 34.9% compared to the best baseline model and 28.8% with respect to the weighted boxes fusion ensemble technique.
Construction of a bioluminescence-based assay for bitter taste receptors (TAS2Rs)
Authors: Tan Shi Min , Seetoh Wei-Guang
Published: October 2022

In humans, a family of 25 bitter taste receptors (TAS2Rs) mediates bitter taste perception. A common approach to characterize bitter causative agents involves expressing TAS2Rs and the appropriate signal transducers in heterologous cell systems, and monitoring changes in the intracellular free calcium levels upon ligand exposure using a fluorescence-based modality, which typically suffers from a low signal window, and is susceptible to interference by autofluorescence, therefore prohibiting its application to screening of plant or food extracts, which are likely to contain autofluorescent compounds. The aim of this study is to develop and validate a bioluminescence-based intracellular calcium release assay for TAS2Rs that has a better assay performance than a fluorescence-based assay. Furthermore, the bioluminescence-based assay enabled the evaluation of TAS2R agonists within an autofluorescent matrix, highlighting its potential utility in the assessment of the bitterness-inducing properties of plant or food fractions by the food industry. Additionally, improvement to the bioluminescence-based assay for some TAS2Rs was achieved by altering their N-terminal signal sequences, leading to signal window enhancement. Altogether, the bioluminescence-based TAS2R assay can be used to perform functional studies of TAS2Rs, evaluate TAS2R-modulating properties of autofluorescent samples, and facilitate the discovery of compounds that can function as promising bitter taste modulators.
Active inference and the two-step task
Authors: Gijsen Sam , Grundei Miro , Blankenburg Felix
Published: October 2022

Sequential decision problems distill important challenges frequently faced by humans. Through repeated interactions with an uncertain world, unknown statistics need to be learned while balancing exploration and exploitation. Reinforcement learning is a prominent method for modeling such behaviour, with a prevalent application being the two-step task. However, recent studies indicate that the standard reinforcement learning model sometimes describes features of human task behaviour inaccurately and incompletely. We investigated whether active inference, a framework proposing a trade-off to the exploration-exploitation dilemma, could better describe human behaviour. Therefore, we re-analysed four publicly available datasets of the two-step task, performed Bayesian model selection, and compared behavioural model predictions. Two datasets, which revealed more model-based inference and behaviour indicative of directed exploration, were better described by active inference, while the models scored similarly for the remaining datasets. Learning using probability distributions appears to contribute to the improved model fits. Further, approximately half of all participants showed sensitivity to information gain as formulated under active inference, although behavioural exploration effects were not fully captured. These results contribute to the empirical validation of active inference as a model of human behaviour and the study of alternative models for the influential two-step task.
Contrast volume and in-hospital outcomes of dialysis patients undergoing percutaneous coronary intervention
Authors: Kuno Toshiki , Numasawa Yohei , Shoji Satoshi , Ueda Ikuko , Suzuki Masahiro , Noma Shigetaka , Fukuda Keiichi , Kohsaka Shun
Published: October 2022

Toxicity resulting from retained contrast media may cause adverse cardiovascular outcomes (e.g., heart failure and cardiogenic shock) for dialysis patients. However, the association between the administered contrast volume and outcomes of dialysis patients after percutaneous coronary intervention (PCI) has not been sufficiently investigated. We evaluated 953 consecutive dialysis patients (age, 67.9 ± 9.9 years; 30.1% with acute coronary syndrome) who underwent PCI between September 2008 and March 2019. Patients were divided into two groups: those with a contrast volume ≥ 200 ml and those with a contrast volume < 200 ml. The cutoff was 200 ml because 100 ml increment of contrast volume is known to raise the risk of acute kidney injury, and 200 ml is more than the average volume used at most PCI centers. The primary endpoint was a composite of in-hospital death, post-PCI cardiogenic shock and post-PCI heart failure. A multivariable logistic regression model and smooth spline curve were constructed to assess the association between contrast volume and the primary endpoint. The median contrast volume was 157 ml (interquartile range, 115–210 ml). The overall primary endpoint incidence was 6.8% (N = 65). A contrast volume ≥ 200 ml was associated with a higher risk of the primary endpoint (odds ratio 2.91; 95% confidence interval 1.42–6.05; P = 0.004). The smooth spline curve demonstrated a linear relationship between the contrast volume and primary endpoint. In conclusions, the contrast volume was associated with adverse in-hospital outcomes of dialysis patients undergoing PCI. Attention should be focused on the contrast volume used for dialysis patients undergoing PCI.
Utilization trends for endoscopic ablation therapy and esophagectomy in Barrett’s esophagus from 2005 to 2019
Authors: Trindade Arvind J. , Zhang Jianying , Raphael Kara L. , Qiu Jiejing , Hauschild John , Benias Petros C.
Published: October 2022

Guidelines have shifted to now recommend endoscopic eradication therapy for Barrett’s esophagus (BE) with low and high-grade dysplasia. Previously, esophagectomy was the standard therapy for high-grade dysplasia. However, it is unclear to what degree ablation therapy has affected utilization of esophagectomy. In this retrospective observational cohort study of BE patients without cancer from the Premier Healthcare Database, the prevalence of utilization of endoscopic ablation therapy and of esophagectomy in BE were calculated and temporal trends were evaluated. A total of 938, 333 BE cases were included in the study. There was a significantly increasing trend of ablation over the period 2006 to 2010 (Annual Percentage Change (APC); 95% CI 0.56% [0.51%, 0.61%]), a significantly decreasing trend for the period 2011 to 2015 (APC; 95% CI − 0.15% [− 0.20%, − 0.11%]), and a shallow increasing trend for the period 2016 to 2019 (APC; 95% CI 0.09% [0.06%, 0.11%]). For esophagectomy, there was a significantly decreasing trend for the period 2006 to 2009 (APC; 95% CI − 0.03% [− 0.04%, − 0.02%]; P < 0.001) that corresponded to the uptrend in utilization of endoscopic ablation. There was a stable trend of esophagectomy over the period 2010 to 2019 (APC; 95% CI − 0.0006% [− 0.0002%, 0.0005%]; P = 0.1947). Adoption and increased utilization of endoscopic ablation therapy for BE has coincided with a decrease in esophagectomy, and is the predominate method of therapy for BE with dysplasia.
Structure of the pre-mRNA leakage 39-kDa protein reveals a single domain of integrated zf-C3HC and Rsm1 modules
Authors: Hashimoto Hideharu , Ramirez Daniel H. , Lautier Ophélie , Pawlak Natalie , Blobel Günter , Palancade Benoît , Debler Erik W.
Published: October 2022

In Saccharomyces cerevisiae, the pre-mRNA leakage 39-kDa protein (ScPml39) was reported to retain unspliced pre-mRNA prior to export through nuclear pore complexes (NPCs). Pml39 homologs outside the Saccharomycetaceae family are currently unknown, and mechanistic insight into Pml39 function is lacking. Here we determined the crystal structure of ScPml39 at 2.5 Å resolution to facilitate the discovery of orthologs beyond Saccharomycetaceae, e.g. in Schizosaccharomyces pombe or human. The crystal structure revealed integrated zf-C3HC and Rsm1 modules, which are tightly associated through a hydrophobic interface to form a single domain. Both zf-C3HC and Rsm1 modules belong to the Zn-containing BIR (Baculovirus IAP repeat)-like super family, with key residues of the canonical BIR domain being conserved. Features unique to the Pml39 modules refer to the spacing between the Zn-coordinating residues, giving rise to a substantially tilted helix αC in the zf-C3HC and Rsm1 modules, and an extra helix αAB′ in the Rsm1 module. Conservation of key residues responsible for its distinct features identifies S. pombe Rsm1 and Homo sapiens NIPA/ZC3HC1 as structural orthologs of ScPml39. Based on the recent functional characterization of NIPA/ZC3HC1 as a scaffold protein that stabilizes the nuclear basket of the NPC, our data suggest an analogous function of ScPml39 in S. cerevisiae.
Clinical frailty assessment might be associated with mortality in incident dialysis patients
Authors: Oki Rikako , Hamasaki Yoshifumi , Tsuji Shiho , Suzuki Kana , Tsuneishi Sayaka , Imafuku Mikie , Komaru Yohei , Miyamoto Yoshihisa , Matsuura Ryo , Doi Kent , Nangaku Masaomi
Published: October 2022

Frailty is associated with mortality in maintenance dialysis patients. For incident dialysis patients, we used the clinical frailty scale (CFS) to investigate frailty as related to mortality or hospitalization within 2 years. We retrospectively reviewed the medical records of patients initiating hemodialysis or peritoneal dialysis during 2016–2018. Based on those records, two dialysis nurses independently used a 9-point CFS (1 = “Very fit” to 9 = “Terminally ill”) to assess each patient’s frailty at dialysis initiation. Patients with a mean CFS value of 5 or higher were classified into the frail group. The 2-year survival rates or hospitalization-free rates after the initiation of dialysis were compared between the frail (mean CFS score ≥ 5) and non-frail (mean CFS score < 5) groups. The analysis included 155 incident dialysis patients with mean age of 66.7 ± 14.1 (71% male). Frailty was inferred for 39 (25%) patients at dialysis initiation. Kaplan–Meier analyses showed that the survival rate and hospitalization-free rate within 2 years were significantly lower in the frail group than in the non-frail group (p < 0.01). Cox proportional hazards regression analyses revealed the CFS score as associated with the occurrence of a composite outcome, independently of age (hazard ratio 1.34, 95% confidence interval 1.04–1.72). Frailty assessment based on clinical judgment using CFS might predict adverse outcomes in dialysis-initiated patients.
Characterization of Pseudoterranova ceticola (Nematoda: Anisakidae) larvae from meso/bathypelagic fishes off Macaronesia (NW Africa waters)
Authors: Bao Miguel , Olsen Kaja M. , Levsen Arne , Cipriani Paolo , Giulietti Lucilla , Storesund Julia E. , García-Seoane Eva , Karlsbakk Egil
Published: October 2022

The genus Pseudoterranova includes parasite species of cetaceans and pinnipeds. The third stage larva (L3) of seal-infecting species occur in second intermediate or paratenic fish hosts mainly in neritic waters. This study firstly describes a Pseudoterranova L3 from meso/bathypelagic fishes off Macaronesia. L3s were morphologically and genetically studied by light microscopy and sequencing of the mtDNA cox2 and entire ITS rDNA genes. Bayesian inferences were performed with sequences from the larvae and selected sequences from GenBank. The nematode L3s were molecularly identified as Pseudoterranova ceticola, a parasite of kogiid whales. Such larvae were collected from Bolinichthys indicus, Chauliodus danae, Eupharynx pelecanoides, Diaphus rafinesquii, D. mollis, Diretmus argenteus and Maulisia argipalla. They mainly occurred in the viscera of these fishes. Pseudoterranova ceticola L3 were small (< 12 mm) and whitish, and a prominent characteristic is a circumoral ridge extending from the ventral boring tooth which differentiate them from Pseudoterranova spp. L3 maturing in pinnipeds and Terranova sensu lato larvae that mature in poikilotherms. The shape of the tail: conical, long, pointed, ventrally curved and lacking mucron also distinguish these larvae from those of the pinniped-infecting Pseudoterranova spp. Phylogenetic analyses based on mtDNA cox2 and ITS rDNA sequences suggest that P. ceticola is closely related to Skrjabinisakis spp., and not with Pseudoterranova spp. parasitizing pinnipeds. The related species Skrjabinisakis paggiae, S. brevispiculata and S. physeteris (until recently belonging to genus Anisakis), are as P. ceticola also parasites of physeteroid cetaceans. The morphology and morphological variation of the larvae of the cetacean parasite P. ceticola is thoroughly described for the first time. These L3 can readily be morphologically distinguished from those of the pinniped-infecting Pseudoterranova spp. The parasite likely completes its life cycle in the mesopelagic and bathypelagic realm, with meso/bathypelagic fish as 2nd intermediate or paratenic hosts and kogiids as final host. Thus, Pseudoterranova from cetaceans appear to be morphologically, genetically, and ecologically differentiated to those from pinnipeds, suggesting that they are not congeneric.
Effectiveness of COVID-19 vaccination in healthcare workers in Shiga Prefecture, Japan
Authors: Chano Tokuhiro , Yamashita Tomoko , Fujimura Hirokazu , Kita Hiroko , Ikemoto Toshiyuki , Kume Shinji , Morita Shin-ya , Suzuki Tomoyuki , Kakuno Fumihiko
Published: October 2022

This study, which included serological and cellular immunity tests, evaluated whether coronavirus disease 2019 (COVID-19) vaccination adequately protected healthcare workers (HCWs) from COVID-19. Serological investigations were conducted among 1600 HCWs (mean ± standard deviation, 7.4 ± 1.4 months after the last COVID-19 vaccination). Anti-SARS-CoV-2 antibodies N-Ig, Spike-Ig (Roche), N-IgG, Spike-IgM, and -IgG (Abbott), were evaluated using a questionnaire of health condition. 161 HCWs were analyzed for cellular immunity using T-SPOT® SARS-CoV-2 kit before, and 52 HCWs were followed up until 138.3 ± 15.7 days after their third vaccination. Spike-IgG value was 954.4 ± 2282.6 AU/mL. Forty-nine of the 1600 HCWs (3.06%) had pre-existing SARS-CoV-2 infection. None of the infectious seropositive HCWs required hospitalization. T-SPOT value was 85.0 ± 84.2 SFU/106 cells before the third vaccination, which increased to 219.4 ± 230.4 SFU/106 cells immediately after, but attenuated later (to 111.1 ± 133.6 SFU/106 cells). Poor counts (< 40 SFU/106 cells) were present in 34.8% and 38.5% of HCWs before and after the third vaccination, respectively. Our findings provide insights into humoral and cellular immune responses to repeated COVID-19 vaccinations. COVID-19 vaccination was effective in protecting HCWs from serious illness during the original Wuhan-1, Alpha, Delta and also ongoing Omicron-predominance periods. However, repeated vaccinations using current vaccine versions may not induce sufficient cellular immunity in all HCWs.
A Mendelian randomization study of genetic predisposition to autoimmune diseases and COVID-19
Authors: Li Shun , Yuan Shuai , Schooling C. M. , Larsson Susanna C.
Published: October 2022

Autoimmune diseases and coronavirus disease 2019 (COVID-19) share many similarities. Concerns have arisen that autoimmune diseases may increase the susceptibility and severity of COVID-19. We used Mendelian randomization to investigate whether liability to autoimmune diseases is related to COVID-19 susceptibility and severity. Genetic instruments for 8 autoimmune diseases, including type 1 diabetes mellitus, rheumatoid arthritis, systemic lupus erythematosus, psoriasis, multiple sclerosis, primary sclerosing cholangitis, primary biliary cirrhosis and juvenile idiopathic arthritis, were obtained from published genome-wide association studies. Two-sample Mendelian randomization analyses of the associations of liability to each autoimmune disease with COVID-19 infection, hospitalized COVID-19, and very severe COVID-19 were performed using the latest publicly available genome-wide association study for COVID-19. Genetic liability to each of the autoimmune diseases was largely not associated with COVID-19 infection, hospitalized COVID-19, or very severe COVID-19 after accounting for multiple comparison. Sensitivity analysis excluding genetic variants in the human leukocyte antigen gene, which has an important role in the immune response, showed similar results. The autoimmune diseases examined were largely not genetically associated with the susceptibility or severity of COVID-19. Further investigations are warranted.
Sustained release of drug-loaded nanoparticles from injectable hydrogels enables long-term control of macrophage phenotype
Authors: Soni Shreya S. , D'Elia Arielle M. , Alsasa Abdulrahman , Cho Sylvia , Tylek Tina , O'Brien Erin M. , Whitaker Ricardo , Spiller Kara L. , Rodell Christopher B.
Published: October 2022

Polymer-nanoparticle hydrogels are assembled by guest–host interactions that also enable drug encapsulation. Surface erosion of celastrol-loaded nanoparticles from injectable hydrogels enables macrophage-targeted delivery to modulate cell phenotype.
Photocatalytic C–H activation for C–C/CN/C–S bond formation over CdS: effect of morphological regulation and S vacancies
Authors: Hu Zujie , Li Yue , Gan Chuan , Sheng Meilin , Sun Bin , Jiang Heyan
Published: October 2022

CdS catalytic materials were utilized to fabricate C–C, CN and C–S bonds for drug intermediates or other value-added products through the high bond energy, low polarity and strong inertia C–H bonds activation.
Anti-aging potency correlates with metabolites from in vitro fermentation of edible fungal polysaccharides using human fecal intestinal microflora
Authors: Zhang Xiaomei , Liu Liu , Luo Jianming , Peng Xichun
Published: October 2022

Aging is a natural process in which the structural integrity of an organism declines over time.
Fracture behavior of metallic sodium and implications for battery applications
Authors: Shin Jungho , Pharr Matt
Published: October 2022

We report fracture behavior of sodium metal and discover that Na is nearly insensitive to the presence of flaws. We also identify microstructural features of the fracture process and discuss the corresponding implications for battery applications.
Anion recognition by silanetriol in acetonitrile
Authors: Kondo Shin-ichi , Okada Natsumi , Abe Shiori , Tanaka Ryoji , Yamamura Masaki , Unno Masafumi
Published: October 2022

Anion recognition ability and organocatalytic activity of a silanetriol are firstly presented by comparing with those of a series of silanol derivatives.
Assessing the local structure and quantifying defects in Ca4Fe9O17 combining STEM and FAULTS
Authors: Serrano-Sevillano Jon , Oró-Solé Judith , Gázquez Jaume , Frontera Carlos , Black Ashley P. , Casas-Cabanas Montse , Palacín M. Rosa
Published: October 2022

Defects in crystalline structures play a vital role in their properties, so their proper characterization is essential to understanding and improving the behaviour of the materials.
Pd/Cu catalyzed carbonylation of α-aminoaryl-tethered alkylidenecyclopropanes: synthesis of furoquinoline derivatives
Authors: Li Lin , Zeng Hui-Hui , Zhang You-Ya , Liang Jin-Yan , Zhang Xiang-Zhi , Peng Jin-Bao
Published: October 2022

A Pd/Cu catalyzed carbonylation of α-aminoaryl-tethered ACPs for the synthesis of furoquinoline derivatives has been developed. Oxygen was used as the terminal oxidant.