bluuebunny/crossref_metadata_2025 huggingface dataset:
Fabrication, characterization and antifungal evaluation of polyphenolic extract activated keratin starch coating on infected tomato fruits
Authors: Oluba Olarewaju M. , Obokare Onome , Bayo-Olorunmeke Opeyemi A. , Ojeaburu Samuel I. , Ogunlowo Olayemi M. , Irokanulo Emenike O. , Akpor Oghenerobor B.
Published: March 2022

In recent times, the application of protein-based bio-composite edible films in postharvest preservation of food and agricultural products is attracting increased attention due to their biodegradability, eco-friendliness and sustainability. In this study, an avocado pear peel polyphenolic extract enriched keratin-starch composite film was fabricated, characterized and evaluated for antimicrobial activity against fungal infected tomato fruits after 6 days of storage at room (25 ± 2 °C) temperature. The SEM/EDX and FTIR results revealed the successful film formation with high degree of compatibility and homogeneity. Following a 6-day post-coating loss in weight of the coated tomato fruits decreased significantly (p < 0.05) with increasing extract concentration while titratable acidity showed a significant (p < 0.05) increase with increasing extract load. Ascorbic acid and lycopene contents were significantly (p < 0.05) higher in the avocado pear peel polyphenolic extract-loaded films. No significant effect was observed in catechol oxidase activity of the tomato extract across the different treatment groups. In addition, fungal growth inhibition showed a dose dependent increase consistent with avocado pear peel polyphenolic load in coated tomato fruits compared to control. Results obtained in this study showed that polyphenolic activated keratin-starch coating was able to reduce spoilage-induce weight loss as well as conserve the overall quality (including titratable acid levels, lycopene and ascorbic acid contents) of fungal-infected tomato fruit and reduce microbial growth. Therefore polyphenolic activated keratin-starch coating could serve as a sustainable and ecofriendly postharvest preservation method to prolong the shelf life of tomato fruits.
The effects of socioeconomic and geographic factors on chronic phase long-term survival after stroke in South Korea
Authors: Park Dougho , Lee Su Yun , Jeong Eunhwan , Hong Daeyoung , Kim Mun-Chul , Choi Jun Hwa , Shin Eun Kyong , Son Kang Ju , Kim Hyoung Seop
Published: March 2022

The stroke incidence has increased rapidly in South Korea, calling for a national-wide system for long-term stroke management. We investigated the effects of socioeconomic status (SES) and geographic factors on chronic phase survival after stroke. We retrospectively enrolled 6994 patients who experienced a stroke event in 2009 from the Korean National Health Insurance database. We followed them up from 24 to 120 months after stroke onset. The endpoint was all-cause mortality. We defined SES using a medical-aid group and four groups divided by health insurance premium quartiles. Geographic factors were defined using Model 1 (capital, metropolitan, city, and county) and Model 2 (with or without university hospitals). The higher the insurance premium, the higher the survival rate tended to be (P < 0.001). The patient survival rate was highest in the capital city and lowest at the county level (P < 0.001). Regions with a university hospital(s) showed a higher survival rate (P = 0.006). Cox regression revealed that the medical-aid group was identified as an independent risk factor for chronic phase mortality. Further, NHIP level had a more significant effect than geographic factors on chronic stroke mortality. From these results, long-term nationwide efforts to reduce inter-regional as well as SES discrepancies affecting stroke management are needed.
Proteomic analysis of heat-stable proteins revealed an increased proportion of proteins with compositionally biased regions
Authors: Park Hongsun , Yamanaka Tomoyuki , Nukina Nobuyuki
Published: March 2022

Intrinsically disordered proteins (IDPs) have been in the spotlight for their unique properties, such as their lack of secondary structures and low sequence complexity. Alpha-synuclein and tau are representative disease-related IDPs with low complexity regions in their sequences, accumulating in the brains of patients with Parkinson disease and Alzheimer disease, respectively. Their heat resistance in particular was what attracted our attention. We assumed that there exist many other unidentified proteins that are resistant to heat-treatment, referred to as heat-stable proteins, which would also have low sequence complexity. In this study, we performed proteomic analysis of heat-stable proteins of mouse brains and found that proteins with compositionally biased regions are abundant in the heat-stable proteins. The proteins related to neurodegeneration are known to undergo different types of post-translational modifications (PTMs) such as phosphorylation and ubiquitination. We then investigated the heat-stability and aggregation properties of phosphorylated synuclein and tau with different phosphorylation sites. We suggest that PTMs can be important factors that determine the heat-stability and aggregation properties of a protein. IDPs identified in the heat-stable proteins of mouse brains would be candidates for the pathogenic proteins for neurodegeneration.
Visual consciousness dynamics in adults with and without autism
Authors: Skerswetat Jan , Bex Peter J. , Baron-Cohen Simon
Published: March 2022

Sensory differences between autism and neuro-typical populations are well-documented and have often been explained by either weak-central-coherence or excitation/inhibition-imbalance cortical theories. We tested these theories with perceptual multi-stability paradigms in which dissimilar images presented to each eye generate dynamic cyclopean percepts based on ongoing cortical grouping and suppression processes. We studied perceptual multi-stability with Interocular Grouping (IOG), which requires the simultaneous integration and suppression of image fragments from both eyes, and Conventional Binocular Rivalry (CBR), which only requires global suppression of either eye, in 17 autistic adults and 18 neurotypical participants. We used a Hidden-Markov-Model as tool to analyze the multistable dynamics of these processes. Overall, the dynamics of multi-stable perception were slower (i.e. there were longer durations and fewer transitions among perceptual states) in the autistic group compared to the neurotypical group for both IOG and CBR. The weighted Markovian transition distributions revealed key differences between both groups and paradigms. The results indicate overall lower levels of suppression and decreased levels of grouping in autistic than neurotypical participants, consistent with elements of excitation/inhibition imbalance and weak-central-coherence theories.
Automated computation of nerve fibre inclinations from 3D polarised light imaging measurements of brain tissue
Authors: Menzel Miriam , Reuter Jan A. , Gräßel David , Costantini Irene , Amunts Katrin , Axer Markus
Published: March 2022

The method 3D polarised light imaging (3D-PLI) measures the birefringence of histological brain sections to determine the spatial course of nerve fibres (myelinated axons). While the in-plane fibre directions can be determined with high accuracy, the computation of the out-of-plane fibre inclinations is more challenging because they are derived from the amplitude of the birefringence signals, which depends e.g. on the amount of nerve fibres. One possibility to improve the accuracy is to consider the average transmitted light intensity (transmittance weighting). The current procedure requires effortful manual adjustment of parameters and anatomical knowledge. Here, we introduce an automated, optimised computation of the fibre inclinations, allowing for a much faster, reproducible determination of fibre orientations in 3D-PLI. Depending on the degree of myelination, the algorithm uses different models (transmittance-weighted, unweighted, or a linear combination), allowing to account for regionally specific behaviour. As the algorithm is parallelised and GPU optimised, it can be applied to large data sets. Moreover, it only uses images from standard 3D-PLI measurements without tilting, and can therefore be applied to existing data sets from previous measurements. The functionality is demonstrated on unstained coronal and sagittal histological sections of vervet monkey and rat brains.
Congenitally blind adults can learn to identify face-shapes via auditory sensory substitution and successfully generalize some of the learned features
Authors: Arbel Roni , Heimler Benedetta , Amedi Amir
Published: March 2022

Unlike sighted individuals, congenitally blind individuals have little to no experience with face shapes. Instead, they rely on non-shape cues, such as voices, to perform character identification. The extent to which face-shape perception can be learned in adulthood via a different sensory modality (i.e., not vision) remains poorly explored. We used a visual-to-auditory Sensory Substitution Device (SSD) that enables conversion of visual images to the auditory modality while preserving their visual characteristics. Expert SSD users were systematically taught to identify cartoon faces via audition. Following a tailored training program lasting ~ 12 h, congenitally blind participants successfully identified six trained faces with high accuracy. Furthermore, they effectively generalized their identification to the untrained, inverted orientation of the learned faces. Finally, after completing the extensive 12-h training program, participants learned six new faces within 2 additional hours of training, suggesting internalization of face-identification processes. Our results document for the first time that facial features can be processed through audition, even in the absence of visual experience across the lifespan. Overall, these findings have important implications for both non-visual object recognition and visual rehabilitation practices and prompt the study of the neural processes underlying auditory face perception in the absence of vision.
A data driven approach to identify trajectories of prenatal alcohol consumption in an Australian population-based cohort of pregnant women
Authors: Muggli Evelyne , Hearps Stephen , Halliday Jane , Elliott Elizabeth J. , Penington Anthony , Thompson Deanne K. , Spittle Alicia , Forster Della A. , Lewis Sharon , Anderson Peter J.
Published: March 2022

Accurate information on dose, frequency and timing of maternal alcohol consumption is critically important when investigating fetal risks from prenatal alcohol exposure. Identification of distinct alcohol use behaviours can also assist in developing directed public health messages about possible adverse child outcomes, including Fetal Alcohol Spectrum Disorder. We aimed to determine group-based trajectories of time-specific, unit-level, alcohol consumption using data from 1458 pregnant women in the Asking Questions about Alcohol in Pregnancy (AQUA) longitudinal study in Melbourne, Australia. Six alcohol consumption trajectories were identified incorporating four timepoints across gestation. Labels were assigned based on consumption in trimester one and whether alcohol use was continued throughout pregnancy: abstained (33.8%); low discontinued (trimester one) (14.4%); moderate discontinued (11.7%); low sustained (13.0%); moderate sustained (23.5%); and high sustained (3.6%). Median weekly consumption in trimester one ranged from 3 g (low discontinued) to 184 g of absolute alcohol (high sustained). Alcohol use after pregnancy recognition decreased dramatically for all sustained drinking trajectories, indicating some awareness of risk to the unborn child. Further, specific maternal characteristics were associated with different trajectories, which may inform targeted health promotion aimed at reducing alcohol use in pregnancy.
Characterization of the Portuguese population diagnosed with retinoblastoma
Authors: Castela Guilherme , Providência Joana , Monteiro Madalena , Silva Sonia , Brito Manuel , Sá Joaquim , Oliveiros Barbara , Murta Joaquim Neto , Correa Zelia , Branco Miguel Castelo
Published: March 2022

The purpose of this study is to characterize demographically and genetically the Portuguese population with retinoblastoma; to report the clinical stage at presentation and its impact on survival and ocular preservation rate and, finally, to assess the incidence of retinoblastoma in Portugal. Retrospective observational study including children consecutively diagnosed with retinoblastoma at the Portuguese National Referral Center of Intraocular Tumors, between October 2015 and October 2020. Twenty-eight children were diagnosed with retinoblastoma at our center, 15 hereditary from which 12 presented with bilateral retinoblastoma and 3 were unilateral. The overall mean age at diagnosis was 13.6 ± 11.1 months with hereditary retinoblastomas diagnosed slightly earlier at 9.6 ± 6.3 months. A familial history of retinoblastoma was found in only 4 (14.3%) of the cases. A pathogenic mutation in the RB1 gene was found in 13 (46.4%) of the children. The most frequent sign at referral was leukocoria in 71.4% of patients. Considering the ICRB classification of the tumors, 84.6% of non-hereditable hereditary retinoblastomas were referred to our center in advanced stages. In the group of hereditable retinoblastomas 86.7% presented with one of the eyes with advanced intraocular retinoblastoma. Fourteen children had one eye enucleated due to retinoblastoma. No deaths were registered during the study period. Considering the incidence analysis, we registered a year-of-birth controlled incidence analysis of 4.04 per 100.000 living births (IC 95% 1.59–6.49). This is the first characterization of the Portuguese Population diagnosed with Retinoblastoma in the National Reference Center.
Variation in the dynamic of absorption and efficiency of phosphorus use in tomato
Authors: Marques Douglas José , da Silva Ernani Clarete , Siqueira José Andrés Carreño , Abedi Elham , Veloso Fernanda Rosa , Maciel Gabriel Mascarenhas , Maluf Wilson Roberto
Published: March 2022

Changes in root growth and metabolism of P in tomato cultivars are necessary in acidic soils in tropical and subtropical regions in response to P deficiency. This increase in the efficiency of phosphorus absorption by tomatoes can significantly reduce the doses of phosphate fertilizers used, as well as, possibly, the more immediate use of P fixed in the soil matrix, with favorable effects on agricultural sustainability, promoting the use of marginal areas in terms of soil fertility, and the national fertilizer economy. The tested hypothesis was that there would be no difference in the uptake and utilization of P by tomato cultivars; therefore, this study investigated the variation in the dynamics of absorption and efficiency of P-use through changes in the root, stem, leaf, gas exchange, and P-use efficiency in tomato cultivars contrasting P-absorption. The experimental design comprised a factorial scheme consisting of two cultivars that were tolerant and sensitive to P deficiency and three P concentrations (control, moderate deficiency, and severe deficiency). P limitation in the tolerant cultivar promoted high dry matter concentration (root, stem, and leaf), leaf area, root volume, nutrient translocation, rate of leaf gas exchange, and efficiency under P-deficiency stress. It was concluded from the research that the variation in the dynamics of absorption and efficiency of P use of the tolerant cultivar increased the production of roots, leaves, and leaf gas exchange under P stress conditions.
Slaked lime improves growth, antioxidant capacity and reduces Cd accumulation of peanut (Arachis hypogaea L.) under Cd stress
Authors: Zhang Liqing , Zou Dongsheng , Zeng Ningbo , Li Lin , Xiao Zhihua
Published: March 2022

Slaked lime has been used to remediate contaminated agricultural soils as an in situ chemical immobilization amendment for a long time. However, the effects of slaked lime on peanut and soil cadmium (Cd) levels remain poorly understood with respect to remediating Cd-contaminated soil. In this study, six rates of slaked lime (e.g., 0, 300, 600, 900, 1200 and 1500 kg ha−1) were applied to evaluate the effects of slaked lime treatments on soil pH and the growth, Cd accumulation and physiology characteristics of peanut, which were in Cd-contaminated soil, and 0 kg ha−1 was taken as the control. The results indicated that slaked lime application significantly increased soil pH and reduced total Cd contents in peanut tissues at all growth stages. As the rates of slaked lime were increased, kernel biomass increased in the maturity stage, which increased peanut yields. The irregular variations in catalase, peroxidase, and superoxide dismutase activities and chlorophyll and malondialdehyde contents that were observed at all growth stages may be due to the interactions among soil pH, Ca nutrients and Cd, etc. In summary, slaked lime is suitable as an in situ chemical immobilization amendment to increase Cd immobilization and peanut yields in Cd-contaminated soil.
Tuning wettability and electrical conductivity of single-walled carbon nanotubes by the modified Hummers method
Authors: Stando Grzegorz , Han Sujie , Kumanek Bogumiła , Łukowiec Dariusz , Janas Dawid
Published: March 2022

Partial oxidation of nanocarbon materials is one of the most straightforward methods to improve their compatibility with other materials, which widens its application potential. This work studied how the microstructure and properties of high crystallinity single-walled carbon nanotubes (SWCNTs) can be tailored by applying the modified Hummers method. The influence of temperature (0, 18, 40 °C), reaction time (0 min to 7 h), and the amount of KMnO4 oxidant was monitored. The results showed that depending on the oxidation conditions, the electronic characteristics of the material could be adjusted. After optimizing the parameters, the SWCNTs were much more conductive (1369 ± 84 S/cm with respect to 283 ± 32 S/cm for the untreated material). At the same time, the films made from them exhibited hydrophilic character of the surface (water contact angle changed from 71° to 27°).
Prognostic factor analysis of definitive radiotherapy using intensity-modulated radiation therapy and volumetric modulated arc therapy with boluses for scalp angiosarcomas
Authors: Kashihara Tairo , Igaki Hiroshi , Ogata Dai , Nakayama Hiroki , Nakamura Satoshi , Okuma Kae , Mori Taisuke , Yamakawa Kohei , Takahashi Akira , Namikawa Kenjiro , Takahashi Ayaka , Takahashi Kana , Kaneda Tomoya , Inaba Koji , Murakami Naoya , Nakayama Yuko , Okamoto Hiroyuki , Yamazaki Naoya , Itami Jun
Published: March 2022

Cutaneous angiosarcomas is a rare cancer with poor prognoses. The common radiotherapy techniques that have been reported so far are two pairs of lateral X-ray and electron fields. However, it is quite difficult to irradiate scalp angiosarcomas (SAs) homogeneously with this technique. In this study, safety, effectiveness, and risk factors were assessed for localized SAs ≥ 5 cm treated with intensity-modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT) with boluses. Sixty-eight angiosarcoma patients who had received radiotherapy in our institution between January 2007 and November 2020 were retrieved from our radiotherapy database. Of these patients, 27 localized SA patients were included in the retrospective analysis. The 2-year overall survival, local progression-free rate, and distant metastases-free survival were 41.8%, 48.4%, and 33.1%. All the patients experienced acute radiation dermatitis ≥ grade 2, with18 (66.7%) ≥ grade 3. No nodule lesion was a significant unfavorable predictive factor of acute radiation dermatitis ≥ grade 3. Tumor bleeding at the initiation of radiotherapy and tumor invasion to the face were significant predictive factors of overall survival, and tumor bleeding at the initiation of radiotherapy was also a significant predictive factor of local progression-free rate.
Characterisation of dust emissions from machined engineered stones to understand the hazard for accelerated silicosis
Authors: Ramkissoon Chandnee , Gaskin Sharyn , Thredgold Leigh , Hall Tony , Rowett Shelley , Gun Richard
Published: March 2022

Engineered stones are novel construction materials associated with a recent upsurge in silicosis cases among workers in the stonemason industry. In order to understand the hazard for the short latency of lung disease among stonemasons, we simulated real-time dust exposure scenario by dry-machining engineered stones in controlled conditions, capturing and analysing the respirable dust generated for physical and chemical characteristics. Natural granite and marble were included for comparison. Cutting engineered stones generated high concentrations of very fine particles (< 1 µm) with > 80% respirable crystalline silica content, in the form of quartz and cristobalite. Engineered stones also contained 8–20% resin and 1–8% by weight metal elements. In comparison, natural stones had far lower respirable crystalline silica (4- 30%) and much higher metal content, 29–37%. Natural stone dust emissions also had a smaller surface area than engineered stone, as well as lower surface charge. This study highlighted the physical and chemical variability within engineered stone types as well as between engineered and natural stones. This information will ultimately help understand the unique hazard posed by engineered stone fabrication work and help guide the development of specific engineering control measures targeting lower exposure to respirable crystalline silica.
Immediate complete revascularization showed better outcome in out-of-hospital cardiac arrest survivors with left main or triple-vessel coronary diseases
Authors: Kim Youn-Jung , Park Duk-Woo , Kim Yong Hwan , Choi Minwoo , Kim Su Jin , Lee Gun Tak , Lee Dong Hun , Lee Byung Kook , Oh Joo Suk , Oh Sang Hoon , Lee Dong Hoon , Kim Won Young
Published: March 2022

This study aimed to evaluate the prevalence of left main or triple vessel coronary artery disease (CAD) in comatose out-of-hospital cardiac arrest (OHCA) survivors and assessed their outcome based on the revascularization strategy. This multicenter, retrospective, observational registry-based study was conducted at 9 Korean tertiary care hospitals. Adult comatose OHCA survivors with left main or triple vessel CAD documented by immediate (≤ 2 h) coronary angiography after return of spontaneous circulation between 2011 and 2019 were included. The primary outcome was neurologically intact survival at 1-month. Among 727 OHCA patients, 150 (25%) had left main or triple vessel CAD and underwent complete (N = 32), incomplete (N = 78), and no immediate (N = 40) revascularization, respectively. The rate of neurologically intact survival at 1 month was significantly different among the groups (53%, 32%, and 23% for complete, incomplete, and no immediate revascularization groups, respectively; P = 0.02). After adjustment using the inverse probability of treatment weighting, complete revascularization was associated with neurologically intact survival at 1 month (odds ratio, 2.635; P = 0.01). Left main or triple vessel CAD is not uncommon in OHCA patients. The complete revascularization was associated with better outcome. Further clinical trials to confirm the best revascularization strategy are needed.
Analysis on the characteristics of spatio-temporal evolution and aggregation trend of early COVID-19 in mainland China
Authors: Bi Shengxian , Bie Siyu , Hu Xijian , Zhang Huiguo
Published: March 2022

To analyze the spatio-temporal aggregation of COVID-19 in mainland China within 20 days after the closure of Wuhan city, and provide a theoretical basis for formulating scientific prevention measures in similar major public health events in the future. Draw a distribution map of the cumulative number of COVID-19 by inverse distance weighted interpolation; analyze the spatio-temporal characteristics of the daily number of COVID-19 in mainland China by spatio-temporal autocorrelation analysis; use the spatio-temporal scanning statistics to detect the spatio-temporal clustering area of the daily number of new diagnosed cases. The cumulative number of diagnosed cases obeyed the characteristics of geographical proximity and network proximity to Hubei. Hubei and its neighboring provinces were most affected, and the impact in the eastern China was more dramatic than the impact in the western; the global spatio-temporal Moran’s I index showed an overall downward trend. Since the 10th day of the closure of Wuhan, the epidemic in China had been under effective control, and more provinces had shifted into low-incidence areas. The number of new diagnosed cases had gradually decreased, showing a random distribution in time and space (P< 0.1), and no clusters were formed. Conclusion: the spread of COVID-19 had obvious spatial-temporal aggregation. China’s experience shows that isolation city strategy can greatly contain the spread of the COVID-19 epidemic.
Itaconic acid-modified layered double hydroxide/gellan gum nanocomposites for Congo red adsorption
Authors: Shabani Shirin , Dinari Mohammad
Published: March 2022

Polymer matrix nanocomposites with nanosized fillers are becoming an inseparable part of various industries owing to their unique properties. Among the nanosized fillers, layered double hydroxides are a good candidate due to their fantastic properties such as the ability to ion exchange and adsorption capacity. In the present work, a simple and green synthesis procedure was applied for the preparation of novel modified Cu–Ca–Al-based layered double hydroxide/polymer matrix nanocomposites. Notably, the synthesis was performed in a water medium as solvent. The layered double hydroxide was synthesized and itaconic acid was used for the surface functionalization of the prepared material. The modified material was then incorporated into the natural polymer of gellan gum to produce polymer matrix nanocomposites with different filler contents. The prepared materials were characterized using infrared spectroscopy, X-ray diffraction analysis, scanning and transmission electron microscopy, X-ray diffraction analysis, thermogravimetric analysis, and N2 adsorption/desorption technique. After characterization, the prepared materials were used for the adsorption of Congo red. After investigation of the important experimental parameters, the isotherm and kinetic studies were also performed. Among the studied kinetic models, the pseudo-second-order model and intra-particle diffusion model were obtained the best in the case of Congo red adsorption. The Freundlich isotherm model showed the best results. Finally, maximum adsorption capacities of 80.9, 90.1, and 99.9 mg g−1 were obtained for nanocomposites containing 1%, 3%, and 5 wt% of filler, respectively.
The microwave-absorption properties and mechanism of phenyl silicone rubber/CIPs/graphene composites after thermal-aging in an elevated temperature
Authors: Yan Xiao , Guo Jianhua , Jiang Xinghua
Published: March 2022

Recently, the application and development of flexible microwave-absorption composites based on silicone rubber have gradually become a research hot spot. In this study, methyl vinyl phenyl silicone rubber (MPVQ)/carbonyl iron particles (CIPs)/graphene (GR) composites were prepared by mechanical blending, and the effects of thermal-ageing temperature on the microwave-absorption properties of the composites were investigated. The mechanism of the thermal-ageing temperature’s effects on microwave-absorption behaviour was identified. The results show that unaged composites have superior microwave-absorption properties, with a minimum reflection loss (RLmin) of − 87.73 dB, a lowest thickness of 1.46 mm, and an effective absorption bandwidth (EAB, RL < − 10 dB) reaching 5.8 GHz (9.9–15.7 GHz). With ageing at 240 °C for 24 h, the RLmin at a frequency of 5.48 GHz is − 45.55 dB with a thickness of 2.55 mm, and the EAB value reaches 2 GHz (range 4.6–6.6 GHz). In the thermal-ageing process, a crosslinking reaction occurs in MPVQ with an increase in crosslinking density from 5.88 × 10−5 mol g−1 (unaged) to 4.69 × 10−4 mol g−1 (aged at 240 °C). Simultaneously, thermal degradation of the composites leads to a reduction in the rubber concentration. In addition, a small amount of CIPs are oxidized to Fe3O4, and the remaining CIPs aggregate to generate more electrically conductive pathways. Consequently, the dielectric loss of the composites will be significantly improved, resulting in poor impedance matching. The microwave-absorption properties of the composites gradually decrease with increasing thermal-ageing temperature from 200 to 240 °C.
Circulating linoleic acid at the time of myocardial infarction and risk of primary ventricular fibrillation
Authors: Oliveras Teresa , Lázaro Iolanda , Rueda Ferran , Cediel Germán , Bhatt Deepak L. , Fitó Montserrat , Madrid-Gambin Francisco , Pozo Oscar J. , Harris William S. , García-García Cosme , Sala-Vila Aleix , Bayés-Genís Antoni
Published: March 2022

Primary ventricular fibrillation (PVF) is a major driver of cardiac arrest in the acute phase of ST-segment elevation myocardial infarction (STEMI). Enrichment of cardiomyocyte plasma membranes with dietary polyunsaturated fatty acids (PUFA) reduces vulnerability to PVF experimentally, but clinical data are scarce. PUFA status in serum phospholipids is a valid surrogate biomarker of PUFA status in cardiomyocytes within a wide range of dietary PUFA. In this nested case–control study (n = 58 cases of STEMI-driven PVF, n = 116 control non-PVF STEMI patients matched for age, sex, smoking status, dyslipidemia, diabetes mellitus and hypertension) we determined fatty acids in serum phospholipids by gas-chromatography, and assessed differences between cases and controls, applying the Benjamini–Hochberg procedure on nominal P-values to control the false discovery rate (FDR). Significant differences between cases and controls were restricted to linoleic acid (LA), with PVF patients showing a lower level (nominal P = 0.002; FDR-corrected P = 0.027). In a conditional logistic regression model, each one standard deviation increase in the proportion of LA was related to a 42% lower prevalence of PVF (odds ratio = 0.58; 95% confidence interval, 0.37, 0.90; P = 0.02). The association lasted after the inclusion of confounders. Thus, regular consumption of LA-rich foods (nuts, oils from seeds) may protect against ischemia-driven malignant arrhythmias.
Natural antibody IgG levels are associated with HBeAg-positivity and seroconversion in chronic hepatitis B patients treated with entecavir
Authors: Choi Youkyung H. , Lee Hyun Woong , Purdy Michael A.
Published: March 2022

B1 cell-derived natural antibodies are non-specific polyreactive antibodies and can activate the complement pathway leading to lysis of enveloped virus particles before activation of the adaptive immune response. We investigated the relationship between natural antibody levels and treatment outcomes of 126 treatment-naïve chronic hepatitis B (CHB) patients, who underwent entecavir (ETV) treatment. Serum IgG1-3 and complement C3 levels were significantly higher in HBeAg-positive patients. In pre-treatment, IgG1 (odd ratios [OR] 2.3, p < 0.0001), IgG2 (OR 9.8, p < 0.0001), IgG3 (OR 7.4, p < 0.0001), and C3 (OR 7.2, p < 0.0001) were associated with HBeAg-positive patients. At baseline, IgG2 (OR 10.2, p = 0.025), IgG4, (OR 3.4, p = 0.026), and complement C1q (OR 5.0, p = 0.0068) were associated with seroconverters. Post-treatment levels of IgG1-4 and C3/C1q were also associated with HBeAg-positive patients and seroconverters. High levels of IgG2-4 and C1q were observed in seroconverters but not in virological responders. Thus, high pretreatment and post-treatment levels of natural antibody IgG1-4, complement C3, and/or C1q were significantly associated with HBeAg-positivity and HBeAg seroconverters in CHB patients with ETV treatment. These results suggest that the presence of preexisting host immunity against chronic hepatitis B is closely related to outcome of ETV treatment.
Reconciling historical changes in the hydrological cycle over land
Authors: Hobeichi Sanaa , Abramowitz Gab , Ukkola Anna M. , De Kauwe Martin , Pitman Andy , Evans Jason P. , Beck Hylke
Published: March 2022

The sixth Intergovernmental Panel on Climate Change (IPCC) assessment report confirms that global warming drives widespread changes in the global terrestrial hydrological cycle, and that changes are regionally diverse. However, reported trends and changes in the hydrological cycle suffer from significant inconsistencies. This is associated with the lack of a rigorous observationally-based assessment of simultaneous trends in the different components of the hydrological cycle. Here, we reconcile these different estimates of historical changes by simultaneously analysing trends in all the major components of the hydrological cycle, coupled with vegetation greenness for the period 1980–2012. We use observationally constrained, conserving estimates of the closure of the hydrological cycle, combined with a data assimilation approach and observationally-driven uncertainty estimates. We find robust changes in the hydrological cycle across more than 50% of the land area, with evapotranspiration (ET) changing the most and precipitation (P) the least. We find many instances of unambiguous trends in ET and runoff (Q) without robust trends in P, a result broadly consistent with a “wet gets wetter, but dry does not get drier”. These findings provide important opportunities for water resources management and climate risk assessment over a significant fraction of the land surface where hydrological trends have previously been uncertain.
Artificial intelligence-rationalized balanced PPARα/γ dual agonism resets dysregulated macrophage processes in inflammatory bowel disease
Authors: Katkar Gajanan D. , Sayed Ibrahim M. , Anandachar Mahitha Shree , Castillo Vanessa , Vidales Eleadah , Toobian Daniel , Usmani Fatima , Sawires Joseph R. , Leriche Geoffray , Yang Jerry , Sandborn William J. , Das Soumita , Sahoo Debashis , Ghosh Pradipta
Published: March 2022

A computational platform, Boolean network explorer (BoNE), has recently been developed to infuse AI-enhanced precision into drug discovery; it enables invariant Boolean Implication Networks of disease maps for prioritizing high-value targets. Here we used BoNE to query an Inflammatory Bowel Disease (IBD)-map and prioritize a therapeutic strategy that involves dual agonism of two nuclear receptors, PPARα/γ. Balanced agonism of PPARα/γ was predicted to modulate macrophage processes, ameliorate colitis, ‘reset’ the gene expression network from disease to health. Predictions were validated using a balanced and potent PPARα/γ-dual-agonist (PAR5359) in Citrobacter rodentium- and DSS-induced murine colitis models. Using inhibitors and agonists, we show that balanced-dual agonism promotes bacterial clearance efficiently than individual agonists, both in vivo and in vitro. PPARα is required and sufficient to induce the pro-inflammatory cytokines and cellular ROS, which are essential for bacterial clearance and immunity, whereas PPARγ-agonism blunts these responses, delays microbial clearance; balanced dual agonism achieved controlled inflammation while protecting the gut barrier and ‘reversal’ of the transcriptomic network. Furthermore, dual agonism reversed the defective bacterial clearance observed in PBMCs derived from IBD patients. These findings not only deliver a macrophage modulator for use as barrier-protective therapy in IBD, but also highlight the potential of BoNE to rationalize combination therapy.
Agonistic CD27 antibody potency is determined by epitope-dependent receptor clustering augmented through Fc-engineering
Authors: Heckel Franziska , Turaj Anna H. , Fisher Hayden , Chan H. T. Claude , Marshall Michael J. E. , Dadas Osman , Penfold Christine A. , Inzhelevskaya Tatyana , Mockridge C. Ian , Alvarado Diego , Tews Ivo , Keler Tibor , Beers Stephen A. , Cragg Mark S. , Lim Sean H.
Published: March 2022

Agonistic CD27 monoclonal antibodies (mAb) have demonstrated impressive anti-tumour efficacy in multiple preclinical models but modest clinical responses. This might reflect current reagents delivering suboptimal CD27 agonism. Here, using a novel panel of CD27 mAb including a clinical candidate, we investigate the determinants of CD27 mAb agonism. Epitope mapping and in silico docking analysis show that mAb binding to membrane-distal and external-facing residues are stronger agonists. However, poor epitope-dependent agonism could partially be overcome by Fc-engineering, using mAb isotypes that promote receptor clustering, such as human immunoglobulin G1 (hIgG1, h1) with enhanced affinity to Fc gamma receptor (FcγR) IIb, or hIgG2 (h2). This study provides the critical knowledge required for the development of agonistic CD27 mAb that are potentially more clinically efficacious.
Utilizing wearable sensors for continuous and highly-sensitive monitoring of reactions to the BNT162b2 mRNA COVID-19 vaccine
Authors: Gepner Yftach , Mofaz Merav , Oved Shay , Yechezkel Matan , Constantini Keren , Goldstein Nir , Eisenkraft Arik , Shmueli Erez , Yamin Dan
Published: March 2022

Background

Clinical trial guidelines for assessing the safety of vaccines, are primarily based on self-reported questionnaires. Despite the tremendous technological advances in recent years, objective, continuous assessment of physiological measures post-vaccination is rarely performed.

Methods

We conducted a prospective observational study during the mass vaccination campaign in Israel. 160 participants >18 years who were not previously found to be COVID-19 positive and who received the BNT162b2 COVID-19 (Pfizer BioNTech) vaccine were equipped with an FDA-approved chest-patch sensor and a dedicated mobile application. The chest-patch sensor continuously monitored 13 different cardiovascular, and hemodynamic vitals: heart rate, blood oxygen saturation, respiratory rate, systolic and diastolic blood pressure, pulse pressure, mean arterial pressure, heart rate variability, stroke volume, cardiac output, cardiac index, systemic vascular resistance and skin temperature. The mobile application collected daily self-reported questionnaires on local and systemic reactions.

Results

We identify continuous and significant changes following vaccine administration in nearly all vitals. Markedly, these changes are observed even in presumably asymptomatic participants who did not report any local or systemic reaction. Changes in vitals are more apparent at night, in younger participants, and in participants following the second vaccine dose.

Conclusion

the considerably higher sensitivity of wearable sensors can revolutionize clinical trials by enabling earlier identification of abnormal reactions with fewer subjects.
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