bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthetic multiantigen MVA vaccine COH04S1 protects against SARS-CoV-2 in Syrian hamsters and non-human primates
Authors: Chiuppesi Flavia , Nguyen Vu H. , Park Yoonsuh , Contreras Heidi , Karpinski Veronica , Faircloth Katelyn , Nguyen Jenny , Kha Mindy , Johnson Daisy , Martinez Joy , Iniguez Angelina , Zhou Qiao , Kaltcheva Teodora , Frankel Paul , Kar Swagata , Sharma Ankur , Andersen Hanne , Lewis Mark G. , Shostak Yuriy , Wussow Felix , Diamond Don J. 
Published: January 2022

AbstractSecond-generation COVID-19 vaccines could contribute to establish protective immunity against SARS-CoV-2 and its emerging variants. We developed COH04S1, a synthetic multiantigen modified vaccinia Ankara-based SARS-CoV-2 vaccine that co-expresses spike and nucleocapsid antigens. Here, we report COH04S1 vaccine efficacy in animal models. We demonstrate that intramuscular or intranasal vaccination of Syrian hamsters with COH04S1 induces robust Th1-biased antigen-specific humoral immunity and cross-neutralizing antibodies (NAb) and protects against weight loss, lower respiratory tract infection, and lung injury following intranasal SARS-CoV-2 challenge. Moreover, we demonstrate that single-dose or two-dose vaccination of non-human primates with COH04S1 induces robust antigen-specific binding antibodies, NAb, and Th1-biased T cells, protects against both upper and lower respiratory tract infection following intranasal/intratracheal SARS-CoV-2 challenge, and triggers potent post-challenge anamnestic antiviral responses. These results demonstrate COH04S1-mediated vaccine protection in animal models through different vaccination routes and dose regimens, complementing ongoing investigation of this multiantigen SARS-CoV-2 vaccine in clinical trials.
AI-based atomic force microscopy image analysis allows to predict electrochemical impedance spectra of defects in tethered bilayer membranes
Authors: Raila Tomas , Penkauskas Tadas , Ambrulevičius Filipas , Jankunec Marija , Meškauskas Tadas , Valinčius Gintaras 
Published: January 2022

AbstractAtomic force microscopy (AFM) image analysis of supported bilayers, such as tethered bilayer membranes (tBLMs) can reveal the nature of the membrane damage by pore-forming proteins and predict the electrochemical impedance spectroscopy (EIS) response of such objects. However, automated analysis involving pore detection in such images is often non-trivial and can require AI-based object detection techniques. The specific object-detection algorithm we used to determine the defect coordinates in real AFM images was a convolutional neural network (CNN). Defect coordinates allow to predict the EIS response of tBLMs populated by the pore-forming toxins using finite element analysis (FEA) modeling. We tested if the accuracy of the CNN algorithm affected the EIS spectral features sensitive to defect densities and other physical parameters of tBLMs. We found that the EIS spectra can be predicted sufficiently well, however, systematic errors of characteristic spectral points were observed and need to be taken into account. Importantly, the comparison of predicted EIS curves with experimental ones allowed to estimate important physical parameters of tBLMs such as the specific resistance of submembrane reservoir. This reservoir separates phospholipid bilayer from the solid support. We found that the specific resistance of the reservoir amounts to $$10^{4.25 \pm 0.10}$$

10

4.25
±
0.10

$$\Omega \cdot cm$$

Ω
·
c
m

which is approximately two orders of a magnitude higher compared to the specific resistance of the buffer bathing tBLMs studied in this work. We hypothesize that such effect may be related in part due to decreased concentration of ionic carriers in the submembrane due to decreased relative dielectric permittivity in this region.
Metabolic adjustments of blood-stage Plasmodium falciparum in response to sublethal pyrazoleamide exposure
Authors: Tewari Shivendra G. , Kwan Bobby , Elahi Rubayet , Rajaram Krithika , Reifman Jaques , Prigge Sean T. , Vaidya Akhil B. , Wallqvist Anders 
Published: January 2022

AbstractDue to the recurring loss of antimalarial drugs to resistance, there is a need for novel targets, drugs, and combination therapies to ensure the availability of current and future countermeasures. Pyrazoleamides belong to a novel class of antimalarial drugs that disrupt sodium ion homeostasis, although the exact consequences of this disruption in Plasmodium falciparum remain under investigation. In vitro experiments demonstrated that parasites carrying mutations in the metabolic enzyme PfATP4 develop resistance to pyrazoleamide compounds. However, the underlying mechanisms that allow mutant parasites to evade pyrazoleamide treatment are unclear. Here, we first performed experiments to identify the sublethal dose of a pyrazoleamide compound (PA21A092) that caused a significant reduction in growth over one intraerythrocytic developmental cycle (IDC). At this drug concentration, we collected transcriptomic and metabolomic data at multiple time points during the IDC to quantify gene- and metabolite-level alterations in the treated parasites. To probe the effects of pyrazoleamide treatment on parasite metabolism, we coupled the time-resolved omics data with a metabolic network model of P. falciparum. We found that the drug-treated parasites adjusted carbohydrate metabolism to enhance synthesis of myoinositol—a precursor for phosphatidylinositol biosynthesis. This metabolic adaptation caused a decrease in metabolite flux through the pentose phosphate pathway, causing a decreased rate of RNA synthesis and an increase in oxidative stress. Our model analyses suggest that downstream consequences of enhanced myoinositol synthesis may underlie adjustments that could lead to resistance emergence in P. falciparum exposed to a sublethal dose of a pyrazoleamide drug.
Grass-roots entrepreneurship complements traditional top-down innovation in lung and breast cancer
Authors: Ramadi Khalil B. , Mehta Rhea , He David , Chao Sichen , Chu Zen , Atun Rifat , Nguyen Freddy T. 
Published: January 2022

AbstractThe majority of biomedical research is funded by public, governmental, and philanthropic grants. These initiatives often shape the avenues and scope of research across disease areas. However, the prioritization of disease-specific funding is not always reflective of the health and social burden of each disease. We identify a prioritization disparity between lung and breast cancers, whereby lung cancer contributes to a substantially higher socioeconomic cost on society yet receives significantly less funding than breast cancer. Using search engine results and natural language processing (NLP) of Twitter tweets, we show that this disparity correlates with enhanced public awareness and positive sentiment for breast cancer. Interestingly, disease-specific venture activity does not correlate with funding or public opinion. We use outcomes from recent early-stage innovation events focused on lung cancer to highlight the complementary mechanism by which bottom-up “grass-roots” initiatives can identify and tackle under-prioritized conditions.
Ex vivo anticoagulants affect human blood platelet biomechanics with implications for high-throughput functional mechanophenotyping
Authors: Sachs Laura , Wesche Jan , Lenkeit Lea , Greinacher Andreas , Bender Markus , Otto Oliver , Palankar Raghavendra 
Published: January 2022

AbstractInherited platelet disorders affecting the human platelet cytoskeleton result in increased bleeding risk. However, deciphering their impact on cytoskeleton-dependent intrinsic biomechanics of platelets remains challenging and represents an unmet need from a diagnostic and prognostic perspective. It is currently unclear whether ex vivo anticoagulants used during collection of peripheral blood impact the mechanophenotype of cellular components of blood. Using unbiased, high-throughput functional mechanophenotyping of single human platelets by real-time deformability cytometry, we found that ex vivo anticoagulants are a critical pre-analytical variable that differentially influences platelet deformation, their size, and functional response to agonists by altering the cytoskeleton. We applied our findings to characterize the functional mechanophenotype of platelets from a patient with Myosin Heavy Chain 9 (MYH9) related macrothrombocytopenia. Our data suggest that platelets from MYH9 p.E1841K mutation in humans affecting platelet non-muscle myosin heavy chain IIa (NMMHC-IIA) are biomechanically less deformable in comparison to platelets from healthy individuals.
Two distinct Notch signals, Delta-like 4/Notch1 and Jagged-1/Notch2, antagonistically regulate chemical hepatocarcinogenesis in mice
Authors: Nakano Yasuhiro , Nakao Sachie , Sueoka Minako , Kasahara Daigo , Tanno Yuri , Sumiyoshi Hideaki , Itoh Tohru , Miyajima Atsushi , Hozumi Katsuto , Inagaki Yutaka 
Published: January 2022

AbstractNotch signaling is one of the most common drivers of carcinogenesis in many types of cancers, including hepatocellular carcinoma (HCC); however, it occasionally suppresses tumor progression. Moreover, it is virtually unknown how different sets of Notch ligands and receptors regulate the HCC development. In this study, we demonstrate that the expression of the Notch ligands, Delta-like 4 (Dll4) and Jagged-1 (Jag1), is upregulated during diethylnitrosamine-induced hepatocarcinogenesis. Dll4 is detected in the preneoplastic hepatocytes and HCC cells, but not in the normal hepatocytes, while Jag1 is expressed in the desmin-positive mesenchymal cells. Hepatocyte-specific Dll4 knockout abolishes the Notch1 signaling and suppresses the tumor progression. In contrast, Jag1 deletion induces the ectopic expression of Dll4 in hepatocytes along with the loss of Notch2 signaling, leading to the tumor progression. These results indicate that the two distinct Notch signals, Dll4/Notch1 and Jag1/Notch2, are antagonistic to each other, exerting opposite effects on HCC progression.
Cryofouling avoidance in the Antarctic scallop Adamussium colbecki
Authors: Wong William S. Y. , Hauer Lukas , Cziko Paul A. , Meister Konrad 
Published: January 2022

AbstractThe presence of supercooled water in polar regions causes anchor ice to grow on submerged objects, generating costly problems for engineered materials and life-endangering risks for benthic communities. The factors driving underwater ice accretion are poorly understood, and passive prevention mechanisms remain unknown. Here we report that the Antarctic scallop Adamussium colbecki appears to remain ice-free in shallow Antarctic marine environments where underwater ice growth is prevalent. In contrast, scallops colonized by bush sponges in the same microhabitat grow ice and are removed from the population. Characterization of the Antarctic scallop shells revealed a hierarchical micro-ridge structure with sub-micron nano-ridges which promotes directed icing. This concentrates the formation of ice on the growth rings while leaving the regions in between free of ice, and appears to reduce ice-to-shell adhesion when compared to temperate species that do not possess highly ordered surface structures. The ability to control the formation of ice may enable passive underwater anti-icing protection, with the removal of ice possibly facilitated by ocean currents or scallop movements. We term this behavior cryofouling avoidance. We posit that the evolution of natural anti-icing structures is a key trait for the survival of Antarctic scallops in anchor ice zones.
NapB Restores cytochrome c biosynthesis in bacterial dsbD-deficient mutants
Authors: Guo Kailun , Feng Xue , Sun Weining , Han Sirui , Wu Shihua , Gao Haichun 
Published: January 2022

AbstractCytochromes c (cyts c), essential for respiration and photosynthesis in eukaryotes, confer bacteria respiratory versatility for survival and growth in natural environments. In bacteria having a cyt c maturation (CCM) system, DsbD is required to mediate electron transport from the cytoplasm to CcmG of the Ccm apparatus. Here with cyt c-rich Shewanella oneidensis as the research model, we identify NapB, a cyt c per se, that suppresses the CCM defect of a dsbD mutant during anaerobiosis, when NapB is produced at elevated levels, a result of activation by cAMP-Crp. Data are then presented to suggest that NapB reduces CcmG, leading to the suppression. We further show that NapB proteins capable of rescuing CCM in the dsbD mutant form a small distinct clade. The study sheds light on multifunctionality of cyts c, and more importantly, unravels a self-salvation strategy through which bacteria have evolved to better adjust to the natural world.
Investigating the detectability of hydrocarbons in exoplanet atmospheres with JWST
Authors: Gasman Danny , Min Michiel , Chubb Katy L. 
Published: January 2022

Aims.We investigate at what abundances various hydrocarbon molecules (e.g. acetylene (C2H2), ethylene (C2H4), and methane (CH4)) become detectable when observing the atmospheres of various planets using theJames WebbSpace Telescope (JWST).Methods.We focused on atmospheric models based on the parameters of a small sample of planets: HD 189733b, HD 209458b (hot Jupiters orbiting bright stars); HD 97658b (a sub-Neptune/super-Earth orbiting a bright star); and Kepler-30c (a warm Jupiter orbiting a faint star). We computed model transmission spectra, assuming equilibrium chemistry and clear atmospheres for all planets apart from HD 189733b, where we also computed spectra with a moderate cloud layer included. We used the Bayesian retrieval package ARCiS for the model atmospheres, and simulated observed spectra from different instruments that will be on board JWST using the PandExo package. We subsequently ran retrievals on these spectra to determine whether the parameters input into the forward models, with a focus on molecular abundances, can be accurately retrieved from these simulated spectra.Results.We find that generally we can detect and retrieve abundances of the hydrocarbon species as long as they have a volume mixing ratio above approximately 1 × 10−7–1 × 10−6, at least for the brighter targets. There are variations based on planet type and instrument(s) used, and these limits will likely change depending on the abundance of other strong absorbers. We also find scenarios where the presence of one hydrocarbon is confused with another, particularly when a small wavelength region is covered; this is often improved when two instruments are combined.Conclusions.The molecules C2H2, CH4, and C2H4will all be detectable with JWST, provided they are present in high enough abundances, and that the optimal instruments are chosen for the exoplanet system being observed. Our results indicate that generally a combination of two instruments, either NIRSpec G395M and MIRI LRS, or NIRCam F322W2 and MIRI LRS, are best for observing these hydrocarbons in bright exoplanet systems with planets of various sizes, with NIRSpec G395M and MIRI LRS the best option for the HD 189733b-like atmosphere with clouds included. The use of NIRSpec Prism is tentatively found to be best for fainter targets, potentially in combination with the MIRI LRS slit mode, although the target we test is too faint to draw any strong conclusions. Instrument sensitivity, noise, and wavelength range are all thought to play a role in being able to distinguish spectral features.
Upstream solar wind speed at comet 67P
Authors: Nilsson H. , Moeslinger A. , Williamson H. N. , Bergman S. , Gunell H. , Stenberg Wieser G. , Futaana Y. , Karlsson T. , Behar E. , Holmström M. 
Published: January 2022

Context.Rosetta followed comet 67P at heliocentric distances from 1.25 to 3.6 au. The solar wind was observed for much of this time, but was significantly deflected and to some extent slowed down by the interaction with the coma.Aims.We use the different changes in the speed of H+and He2+when they interact with the coma to estimate the upstream speed of the solar wind. The different changes in the speed are due to the different mass per charge of the particles, while the electric force per charge due to the interaction is the same. A major assumption is that the speeds of H+and He2+were the same in the upstream region. This is investigated.Methods.We derived a method for reconstructing the upstream solar wind from H+and He2+observations. The method is based on the assumption that the interaction of the comet with the solar wind can be described by an electric potential that is the same for both H+and He2+. This is compared to estimates from the Tao model and to OMNI and Mars Express data that we propagated to the observation point.Results.The reconstruction agrees well with the Tao model for most of the observations, in particular for the statistical distribution of the solar wind speed. The electrostatic potential relative to the upstream solar wind is derived and shows values from a few dozen volts at large heliocentric distances to about 1 kV during solar events and close to perihelion. The reconstructed values of the solar wind for periods of high electrostatic potential also agree well with propagated observations and model results.Conclusions.The reconstructed upstream solar wind speed during the Rosetta mission agrees well with the Tao model. The Tao model captures some slowing down of high-speed streams as compared to observations at Earth or Mars. At low solar wind speeds, below 400 km s−1, the agreement is better between our reconstruction and Mars observations than with the Tao model. The magnitude of the reconstructed electrostatic potential is a good measure of the slowing-down of the solar wind at the observation point.
Plasma Ascorbic Acid Levels in Critically Ill Pediatric Patients
Authors: Choi Daniel Horim , Basu Sonali , Levine Mark , Steinhorn David 
Published: January 2022

AbstractAscorbic acid, or vitamin C, is a physiological antioxidant that has been found to be deficient in critically ill adults with sepsis and acute respiratory distress system. In adults, ascorbic acid supplementation has been shown to reduce the need for vasopressors and mechanical ventilation. This study aimed to describe the prevalence of ascorbic acid deficiency in critically ill pediatric patients. This prospective, single-centered study analyzed 34 patients aged 1 month to 18 years old with septic shock and/or acute respiratory failure requiring mechanical ventilation in a quaternary, urban, pediatric intensive care unit. Plasma ascorbic acid levels were measured by high-performance liquid chromatography within 24 hours of meeting eligibility criteria. The median level was 23.34 µM (IQR [11.45, 39.14]). Twenty-three patients had repeat samples that were collected 3 to 5 days later. The median for repeat samples was higher at 42.41 µM (IQR [13.08, 62.43]). Patients who were enterally fed had significantly higher levels than those who were not (62.4 ± 7.7 µM vs. 32.4 ± 7.1 µM; p = 0.03). Ascorbic acid levels vary widely among critically ill children with septic shock and/or respiratory failure requiring mechanical ventilation, but one-half of our patients had deficient levels that are typically seen in scurvy. Further studies are warranted to investigate the significance of low levels as well as the impact of normalizing levels through nutritional support.
The Decision to Extubate: The Association between Clinician Impressions and Objective Extubation Readiness Criteria in a Pediatric Intensive Care Unit
Authors: Marupudi Neelima K. , Steurer-Muller Martina , Franzon Deborah 
Published: January 2022

Abstract
Objective Objective tools such as spontaneous breathing trials (SBT) aim to identify patients ready for extubation and shorten the length of mechanical ventilation (MV). Despite passing an SBT, patients sometimes are not extubated based on clinicians' subjective impressions. In this article, we explored the factors that influence the decision to extubate among pediatric intensivists and their association with objective criteria.
Design This is a single-center prospective observational study.
Setting This study was conducted in an academic, multidisciplinary 20-bed pediatric intensive care unit (PICU).
Patients The study group involves mechanically ventilated, orally intubated patients admitted to the PICU from January 1 to June 30, 2019.
Measurements and Main Results Objective clinical data were collected for 650 MV days. Attending surveys about extubation readiness were completed for 419 (64.5%) MV days and 63 extubation events. Extubation occurred on 42% of days after passing an SBT. The primary reasons patients who passed an SBT were not extubated on days were unresolved lung pathology (66.6%) and fluid overload (37.6%). On days without extubation, there was no association between a specific reason for not extubating and SBT result (p > 0.05).
Conclusions In this single-center study, the decision to extubate was not strongly associated with passing an SBT, indicating that clinician impressions, namely unresolved lung pathology and fluid overload, outweighed objective measures for determining extubation readiness. To mitigate morbidities and costs associated with unnecessarily prolonged intubations, a better-defined extubation readiness process is needed to guide the decision to extubate in the pediatric population.
Primary Diffuse Leptomeningeal Atypical Teratoid/Rhabdoid Tumor Initially Masquerading as Guillain–Barré Syndrome: A Case Report and Literature Review
Authors: Kobayashi Kenichiro , Tanaka Kuniaki , Iwai Atsushi , Taki Junya , Kitagawa Masashi , Hayashi Tomoko , Tsuzuki Sadatoshi , Yamamoto Tetsuro , Yoshioka Takako , Hirato Junko , Maihara Toshiro , Yamada Keisuke , Usami Ikuya , Heike Toshio 
Published: January 2022

AbstractA 10-year-old male child patient was admitted with a chief complaint of progression of lower limb weakness lasting for 5 weeks. An initial clinical picture was reminiscent of Guillain–Barré syndrome. Repeated cerebrospinal fluid (CSF) cytological examinations were negative for neoplastic cells, but leptomeningeal biopsy targeting positron emission tomography (PET) avid lesion confirmed the invasion of tumor cells which were negatively stained with Brahma-related gene 1. An extensive literature review identified five cases of primary diffuse leptomeningeal atypical teratoid/rhabdoid tumors, and the clinical characteristics, including ours, were characterized as follows: (1) there was a bimodal age distribution in young children and adolescents with a male predominance, (2) roughly half of the patients fulfilled the diagnostic criteria of albuminocytologic dissociation and CSF cytology was neither sensitive nor specific to establish a definitive diagnosis, and (3) cerebrospinal magnetic resonance imaging findings were mostly indistinguishable from those of infectious or inflammatory diseases. We would like to suggest that primary leptomeningeal tumor should be included in the differential diagnosis of progressive polyneuropathy even in the absence of CSF cytological findings and implementation of preoperative PET may enhance the diagnostic accuracy of such a miscellaneous central nervous system tumor.