bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expanding luciferase reporter systems for cell-free protein expression
Authors: Sato Wakana , Rasmussen Melanie , Deich Christopher , Engelhart Aaron E. , Adamala Katarzyna P. 
Published: July 2022

AbstractLuciferases are often used as a sensitive, versatile reporter in cell-free transcription-translation (TXTL) systems, for research and practical applications such as engineering genetic parts, validating genetic circuits, and biosensor outputs. Currently, only two luciferases (Firefly and Renilla) are commonly used without substrate cross-talk. Here we demonstrate the expansion of the cell-free luciferase reporter system, with two orthogonal luciferase reporters: N. nambi luciferase (Luz) and LuxAB. These luciferases do not have cross-reactivity with the Firefly and Renilla substrates. We also demonstrate a substrate regeneration pathway for one of the new luciferases, enabling long-term time courses of protein expression monitoring in the cell-free system. Furthermore, we reduced the number of genes required in TXTL expression, by engineering a cell extract containing part of the luciferase enzymes. Our findings lead to an expanded platform with multiple orthogonal luminescence translation readouts for in vitro protein expression.
Extreme value theory inspires explainable machine learning approach for seizure detection
Authors: Karpov Oleg E. , Grubov Vadim V. , Maksimenko Vladimir A. , Kurkin Semen A. , Smirnov Nikita M. , Utyashev Nikita P. , Andrikov Denis A. , Shusharina Natalia N. , Hramov Alexander E. 
Published: July 2022

AbstractEpilepsy is one of the brightest manifestations of extreme behavior in living systems. Extreme epileptic events are seizures, that arise suddenly and unpredictably. Usually, treatment strategies start by analyzing brain activity during the seizures revealing their type and onset mechanisms. This approach requires collecting data for a representative number of events which is only possible during the continuous EEG monitoring over several days. A big part of the further analysis is searching for seizures on these recordings. An experienced medical specialist spends hours checking the data of a single patient and needs assistance from the automative systems for seizure detection. Machine learning methods typically address this issue in a supervised fashion and exhibit a lack of generalization. The extreme value theory allows addressing this issue with the unsupervised machine learning methods of outlier detection. Here, we make the first step toward using this approach for the seizure detection. Based on our recent work, we specified the EEG features showing extreme behavior during seizures and loaded them to the one-class SVM, a popular outlier detection algorithm. Testing the proposed approach on 83 patients, we reported 77% sensitivity and 12% precision. In 60 patients, sensitivity was 100%. In the rest 23 subjects, we observed deviations from the extreme behavior. The one-class SVM used a single subject’s data for training; therefore, it was stable against between-subject variability. Our results demonstrate an effective convergence between the extreme value theory, a physical concept, and the outlier detection algorithms, a machine learning concept, toward solving the meaningful task of medicine.
Endothelial reactive oxygen-forming NADPH oxidase 5 is a possible player in diabetic aortic aneurysm but not atherosclerosis
Authors: Ho Florence , Watson Anna M. D. , Elbatreek Mahmoud H. , Kleikers Pamela W. M. , Khan Waheed , Sourris Karly C. , Dai Aozhi , Jha Jay , Schmidt Harald H. H. W. , Jandeleit-Dahm Karin A. M. 
Published: July 2022

AbstractAtherosclerosis and its complications are major causes of cardiovascular morbidity and death. Apart from risk factors such as hypercholesterolemia and inflammation, the causal molecular mechanisms are unknown. One proposed causal mechanism involves elevated levels of reactive oxygen species (ROS). Indeed, early expression of the ROS forming NADPH oxidase type 5 (Nox5) in vascular endothelial cells correlates with atherosclerosis and aortic aneurysm. Here we test the pro-atherogenic Nox5 hypothesis using mouse models. Because Nox5 is missing from the mouse genome, a knock-in mouse model expressing human Nox5 in its physiological location of endothelial cells (eNOX5ki/ki) was tested as a possible new humanised mouse atherosclerosis model. However, whether just on a high cholesterol diet or by crossing in aortic atherosclerosis-prone ApoE−/− mice with and without induction of diabetes, Nox5 neither induced on its own nor aggravated aortic atherosclerosis. Surprisingly, however, diabetic ApoE−/− x eNOX5ki/ki mice developed aortic aneurysms more than twice as often correlating with lower vascular collagens, as assessed by trichrome staining, without changes in inflammatory gene expression, suggesting that endothelial Nox5 directly affects extracellular matrix remodelling associated with aneurysm formation in diabetes. Thus Nox5-derived reactive oxygen species are not a new independent mechanism of atherosclerosis but may enhance the frequency of abdominal aortic aneurysms in the context of diabetes. Together with similar clinical findings, our preclinical target validation opens up a first-in-class mechanism-based approach to treat or even prevent abdominal aortic aneurysms.
Prior exposure to microcystin alters host gut resistome and is associated with dysregulated immune homeostasis in translatable mouse models
Authors: Saha Punnag , Bose Dipro , Stebliankin Vitalii , Cickovski Trevor , Seth Ratanesh K. , Porter Dwayne E. , Brooks Bryan W. , Mathee Kalai , Narasimhan Giri , Colwell Rita , Scott Geoff I. , Chatterjee Saurabh 
Published: July 2022

AbstractA strong association between exposure to the common harmful algal bloom toxin microcystin and the altered host gut microbiome has been shown. We tested the hypothesis that prior exposure to the cyanotoxin microcystin-LR may alter the host resistome. We show that the mice exposed to microcystin-LR had an altered microbiome signature that harbored antibiotic resistance genes. Host resistome genotypes such as mefA, msrD, mel, ant6, and tet40 increased in diversity and relative abundance following microcystin-LR exposure. Interestingly, the increased abundance of these genes was traced to resistance to common antibiotics such as tetracycline, macrolides, glycopeptide, and aminoglycosides, crucial for modern-day treatment of several diseases. Increased abundance of these genes was positively associated with increased expression of PD1, a T-cell homeostasis marker, and pleiotropic inflammatory cytokine IL-6 with a concomitant negative association with immunosurveillance markers IL-7 and TLR2. Microcystin-LR exposure also caused decreased TLR2, TLR4, and REG3G expressions, increased immunosenescence, and higher systemic levels of IL-6 in both wild-type and humanized mice. In conclusion, the results show a first-ever characterization of the host resistome following microcystin-LR exposure and its connection to host immune status and antimicrobial resistance that can be crucial to understand treatment options with antibiotics in microcystin-exposed subjects in clinical settings.
Patients deriving long-term benefit from immune checkpoint inhibitors demonstrate conserved patterns of site-specific mutations
Authors: Principe Daniel R. 
Published: July 2022

AbstractImmune checkpoint inhibitors (ICIs) have revolutionized cancer therapy and are now the preferred treatment for several tumor types. Though ICIs have shown remarkable efficacy in several cancer histologies, in many cases providing long-term disease control, not all patients will derive clinical benefit from such approaches. Given the lack of a reliable predictive biomarker for therapeutic responses to ICIs, we conducted a retrospective analysis of publicly available genomic data from a large pan-cancer cohort of patients receiving ICI-based immunotherapy. Consistent with previous results, patients in the combined cohort deriving a long-term survival benefit from ICIs were more likely to have a higher tumor mutational burden (TMB). However, this was not uniform across tumor-types, failing to predict for long-term survivorship in most non-melanoma cancers. Interestingly, long-term survivors in most cancers had conserved patterns of mutations affecting several genes. In melanoma, this included mutations affecting TET1 or PTPRD. In patients with colorectal cancer, mutations affecting TET1, RNF43, NCOA3, LATS1, NOTCH3, or CREBBP were also associated with improved prognosis, as were mutations affecting PTPRD, EPHA7, NTRK3, or ZFHX3 in non-small cell lung cancer, RNF43, LATS1, or CREBBP mutations in bladder cancer, and VHL mutations in renal cell carcinoma patients. Thus, this study identified several genes that may have utility as predictive biomarkers for therapeutic responses in patients receiving ICIs. As many have no known relationship to immunotherapy or ICIs, these genes warrant continued exploration, particularly for cancers in which established biomarkers such as PD-L1 expression or TMB have little predictive value.
Impact of walking speed and motion adaptation on optokinetic nystagmus-like head movements in the blowfly Calliphora
Authors: Longden Kit D. , Schützenberger Anna , Hardcastle Ben J. , Krapp Holger G. 
Published: July 2022

AbstractThe optokinetic nystagmus is a gaze-stabilizing mechanism reducing motion blur by rapid eye rotations against the direction of visual motion, followed by slower syndirectional eye movements minimizing retinal slip speed. Flies control their gaze through head turns controlled by neck motor neurons receiving input directly, or via descending neurons, from well-characterized directional-selective interneurons sensitive to visual wide-field motion. Locomotion increases the gain and speed sensitivity of these interneurons, while visual motion adaptation in walking animals has the opposite effects. To find out whether flies perform an optokinetic nystagmus, and how it may be affected by locomotion and visual motion adaptation, we recorded head movements of blowflies on a trackball stimulated by progressive and rotational visual motion. Flies flexibly responded to rotational stimuli with optokinetic nystagmus-like head movements, independent of their locomotor state. The temporal frequency tuning of these movements, though matching that of the upstream directional-selective interneurons, was only mildly modulated by walking speed or visual motion adaptation. Our results suggest flies flexibly control their gaze to compensate for rotational wide-field motion by a mechanism similar to an optokinetic nystagmus. Surprisingly, the mechanism is less state-dependent than the response properties of directional-selective interneurons providing input to the neck motor system.
Sex-specific cardiometabolic risk markers of left ventricular mass in physically active young adults: the CHIEF heart study
Authors: Tsai Kun-Zhe , Liu Pang-Yen , Huang Wei-Chun , Lima Joao A. C. , Lavie Carl J. , Lin Gen-Min 
Published: July 2022

AbstractGreater physical fitness may lead to greater left ventricular mass (LVM) and reduce the effect of cardiometabolic risk factors on LVM. However, the cardiometabolic biomarkers associations for LVM have not been clarified in physically active young adults. This study included 2019 men and 253 women, aged 18–43 years, from the military in Taiwan. All participants underwent anthropometric and blood metabolic markers measurements, and completed a 3000-m run test for assessing fitness. LVM was calculated on the basis of an echocardiography. Multiple linear regression was used to determine the sex-specific associations between cardiometabolic risk markers and LVM indexed for the body height (g/m2.7). In men, age, systolic blood pressure (SBP), 3000-m running time, serum triglycerides, serum uric acid and waist circumference (WC) were correlated with LVM index (β = 0.07, 0.10, − 0.01, 0.01, 0.24 and 0.24, respectively; all p-values < 0.05). The correlations were not significant for fasting plasma glucose, total cholesterol and high-density lipoprotein cholesterol (HDL-C). In women, SBP, HDL-C and WC were correlated with LVM index in the univariate analysis (β = 0.07, − 0.05 and 0.32, respectively; all p-values < 0.05), whereas the correlation was only significant for WC in the multiple linear regression analysis (β = 0.20; p-value < 0.001). In physically active adults, the associations of cardiometabolic risk markers with LVM might vary by sex. Better endurance exercise performance associated with greater LVM was noted only in men, while greater WC was the only metabolic risk marker for greater LVM in both men and women.
The global, regional and national burden of stomach cancer and its attributable risk factors from 1990 to 2019
Authors: Song Yexun , Liu Xiajing , Cheng Wenwei , Li Heqing , Zhang Decai 
Published: July 2022

AbstractWe aimed to estimate the incidence, mortality, and disability-adjusted life-years (DALYs) of stomach cancer at the global, regional, and national levels. Stomach cancer resulted in 1.3 million (1.2–1.4 million) incident cases, 9.5 hundred thousand (8.7–10.4 hundred thousand) deaths, and 22.2 million (20.3–24.1 million) DALYs in 2019. The age-standardized incidence rate, death rate and DALY rate were 15.6 (14.1–17.2), 11.9 (10.8–12.8), and 268.4 (245.5–290.6) per 100,000 person-years, respectively. Between 1990 and 2019, the global age-standardized incidence rate, death rate, and DALY rate decreased by − 30.5% (− 36.7 to − 22.9), − 41.9% (− 47.2 to − 36.3), and − 45.6% (− 50.8 to − 39.8), respectively. In 2019, most of the global numbers of incidence, death and DALYs were higher among males than females. A considerable burden of stomach cancer was attributable to smoking and a high-sodium diet. Although the global age-standardized incidence and death rates have decreased, continued growth in absolute numbers in some regions, especially in East Asia, poses a major global public health challenge. To address this, public health responses should be tailored to fit each country’s unique situation. Primary and secondary prevention strategies with increased effectiveness are required to reduce the incidence and mortality of stomach cancer, particularly in populations with a high disease burden.
General circulation and global heat transport in a quadrupling CO2 pulse experiment
Authors: An Soon-Il , Park So-Eun , Shin Jongsoo , Yang Young-Min , Yeh Sang-Wook , Son Seok-Woo , Kug Jong-Seong 
Published: July 2022

AbstractTo investigate the response of the general circulation and global transport of heat through both atmosphere and ocean to two-types of carbon dioxide removal scenario, we performed an earth system model experiment in which we imposed a pulse-type quadrupling of CO2 forcing for 50 years and a gradual peak-and-decline of four-time CO2 forcing. We found that the results from two experiments are qualitatively similar to each other. During the forcing-on period, a dominant warming in the upper troposphere over the tropics and on the surface at high latitudes led to a slowdown in the Hadley circulation, but the poleward atmospheric energy transport was enhanced due to an increase in specific humidity. This counteracted the reduction in poleward oceanic energy transport owing to the suppression of the meridional overturning circulation in both Hemispheres. After returning the original CO2 level, the hemispheric thermal contrast was reversed, causing a southward shift of the intertropical convergence zone. To reduce the hemispheric thermal contrast, the northward energy transports in the atmosphere and ocean surface were enhanced while further weakening of the global-scale Atlantic meridional overturning circulation led to southward energy transport in the deep ocean.
Smooth muscle protein 22α-Cre recombination in resting cardiac fibroblasts and hematopoietic precursors
Authors: Ikeda Shinya , Sugioka Sachiko , Kimura Takeshi , Ashida Noboru 
Published: July 2022

AbstractThe Cre-loxP system has been widely used for cell- or organ-specific gene manipulation, but it is important to precisely understand what kind of cells the recombination takes place in. Smooth muscle 22α (SM22α)-Cre mice have been utilized to alter genes in vascular smooth muscle cells (VSMCs), activated fibroblasts or cardiomyocytes (CMs). Moreover, previous reports indicated that SM22α-Cre is expressed in adipocytes, platelets or myeloid cells. However, there have been no report of whether SM22α-Cre recombination takes place in nonCMs in hearts. Thus, we used the double-fluorescent Cre reporter mouse in which GFP is expressed when recombination occurs. Immunofluorescence analysis demonstrated that recombination occurred in resting cardiac fibroblasts (CFs) or macrophages, as well as VSMCs and CMs. Flow cytometry showed that some CFs, resident macrophages, neutrophils, T cells, and B cells were positive for GFP. These results prompted us to analyze bone marrow cells, and we observed GFP-positive hematopoietic precursor cells (HPCs). Taken together, these results indicated that SM22α-Cre-mediated recombination occurs in resting CFs and hematopoietic cell lineages, including HPCs, which is a cautionary point when using SM22α-Cre mice.
Evaluation of polyvinyl chloride adhesion to 2D crystal flakes
Authors: Wakafuji Yusai , Onodera Momoko , Masubuchi Satoru , Moriya Rai , Zhang Yijin , Watanabe Kenji , Taniguchi Takashi , Machida Tomoki 
Published: July 2022

AbstractWe investigated the adhesion of polyvinyl chloride (PVC) to 2D crystal flakes on SiO2/Si substrates. Although the anchoring effect cannot be used to explain adhesion to atomically flat surfaces, PVC is sufficiently strongly adhesive to 2D crystal flake surfaces to allow pickup from SiO2/Si substrates via surface contact alone. Results of the pickup test, whether pickup is possible or impossible, were plotted on a map of contact surface area ratio vs. contact edge length ratio, which allowed us to identify the conditions under which flakes can be picked up using PVC and to discuss the adhesion strengths of the surface and edge. This study provides a method for the evaluation of adhesion forces between polymers and 2D flakes and demonstrates that PVC is a useful polymer for deterministic transfer and versatile manipulation of 2D flakes.
The performance of artificial intelligence-driven technologies in diagnosing mental disorders: an umbrella review
Authors: Abd-alrazaq Alaa , Alhuwail Dari , Schneider Jens , Toro Carla T. , Ahmed Arfan , Alzubaidi Mahmood , Alajlani Mohannad , Househ Mowafa 
Published: July 2022

AbstractArtificial intelligence (AI) has been successfully exploited in diagnosing many mental disorders. Numerous systematic reviews summarize the evidence on the accuracy of AI models in diagnosing different mental disorders. This umbrella review aims to synthesize results of previous systematic reviews on the performance of AI models in diagnosing mental disorders. To identify relevant systematic reviews, we searched 11 electronic databases, checked the reference list of the included reviews, and checked the reviews that cited the included reviews. Two reviewers independently selected the relevant reviews, extracted the data from them, and appraised their quality. We synthesized the extracted data using the narrative approach. We included 15 systematic reviews of 852 citations identified. The included reviews assessed the performance of AI models in diagnosing Alzheimer’s disease (n = 7), mild cognitive impairment (n = 6), schizophrenia (n = 3), bipolar disease (n = 2), autism spectrum disorder (n = 1), obsessive-compulsive disorder (n = 1), post-traumatic stress disorder (n = 1), and psychotic disorders (n = 1). The performance of the AI models in diagnosing these mental disorders ranged between 21% and 100%. AI technologies offer great promise in diagnosing mental health disorders. The reported performance metrics paint a vivid picture of a bright future for AI in this field. Healthcare professionals in the field should cautiously and consciously begin to explore the opportunities of AI-based tools for their daily routine. It would also be encouraging to see a greater number of meta-analyses and further systematic reviews on performance of AI models in diagnosing other common mental disorders such as depression and anxiety.
A kinetic descriptor for the electrolyte effect on the oxygen reduction kinetics on Pt(111)
Authors: Luo Mingchuan , Koper Marc T. M. 
Published: July 2022

AbstractProton-exchange membrane fuel cells demand efficient electrode–electrolyte interfaces to catalyse the oxygen reduction reaction (ORR), the kinetics of which depends on the energetics of surface adsorption and on electrolyte environment. Here we show an unanticipated effect of non-specifically adsorbed anions on the ORR kinetics on a Pt(111) electrode; these trends do not follow the usual ORR descriptor, that is *OH binding energy. We propose a voltammetry-accessible descriptor, namely reversibility of the *O ↔ *OH transition. This descriptor tracks the dependence of ORR rates on electrolyte, including the concentration/identity of anions in acidic media, cations in alkaline media and the effect of ionomers. We propose a model that relates the ORR rate on Pt(111) to the rate of the *O to *OH transition, in addition to the thermodynamic *OH binding energy descriptor. Our model also rationalizes different trends for the ORR rate on stepped Pt surfaces in acidic versus alkaline media.
Min waves without MinC can pattern FtsA-anchored FtsZ filaments on model membranes
Authors: Godino Elisa , Doerr Anne , Danelon Christophe 
Published: July 2022

AbstractAlthough the essential proteins that drive bacterial cytokinesis have been identified, the precise mechanisms by which they dynamically interact to enable symmetrical division are largely unknown. In Escherichia coli, cell division begins with the formation of a proto-ring composed of FtsZ and its membrane-tethering proteins FtsA and ZipA. In the broadly proposed molecular scenario for ring positioning, Min waves composed of MinD and MinE distribute the FtsZ-polymerization inhibitor MinC away from mid-cell, where the Z-ring can form. Therefore, MinC is believed to be an essential element connecting the Min and FtsZ subsystems. Here, by combining cell-free protein synthesis with planar lipid membranes and microdroplets, we demonstrate that MinDE drive the formation of dynamic, antiphase patterns of FtsA-anchored FtsZ filaments even in the absence of MinC. These results suggest that Z-ring positioning may be achieved with a more minimal set of proteins than previously envisaged, providing a fresh perspective about synthetic cell division.
Semaphorin 3A: A potential target for prevention and treatment of nickel allergy
Authors: Liu Lipei , Watanabe Megumi , Minami Norikazu , Yunizar Mohammad Fadyl , Ichikawa Tetsuo 
Published: July 2022

AbstractMetal allergy is one of the typical immune disorders encountered during the application of dental/medical materials and has a highly complex pathogenic mechanism. Semaphorin 3A (Sema3A), a member of the semaphorin family, is reported to be involved in various immune disorders. However, its role in metal allergy has not been clarified yet. Herein, we show that Sema3A expression was upregulated in nickel (Ni) allergy-induced mouse ear tissue and in NiCl2-stimulated mouse keratinocytes. Moreover, Sema3A regulated tumor necrosis factor-alpha production and mitogen-activated protein kinase activation in keratinocytes. The specific deletion of Sema3A in keratinocytes did not affect immune cell infiltration but reduced edema and ear swelling; it also impeded Th1 responses to cause a slight alleviation in Ni allergy in mice. Our results demonstrate that Sema3A promotes the development of metal allergy and should be explored as a potential target for the prevention and treatment of metal allergy.