Miracle-dz/UniFAR-FTUs huggingface dataset:
The Spike of Concern—The Novel Variants of SARS-CoV-2

The high sequence identity of the first SARS-CoV-2 samples collected in December 2019 at Wuhan did not foretell the emergence of novel variants in the United Kingdom, North and South America, India, or South Africa that drive the current waves of the pandemic. The viral spike receptor possesses two surface areas of high mutagenic plasticity: the supersite in its N-terminal domain (NTD) that is recognised by all anti-NTD antibodies and its receptor binding domain (RBD) where 17 residues make contact with the human Ace2 protein (angiotensin I converting enzyme 2) and many neutralising antibodies bind. While NTD mutations appear at first glance very diverse, they converge on the structure of the supersite. The mutations within the RBD, on the other hand, hone in on only a small number of key sites (K417, L452, E484, N501) that are allosteric control points enabling spike to escape neutralising antibodies while maintaining or even gaining Ace2-binding activity. The D614G mutation is the hallmark of all variants, as it promotes viral spread by increasing the number of open spike protomers in the homo-trimeric receptor complex. This review discusses the recent spike mutations as well as their evolution.
Incidence trends in lung and bladder cancers in the Nordic Countries before and after the smoking epidemic

Cigarette smoking epidemic, which started before the World War II, completely changed the cancer landscape. Reliable incidence data spanning the stepwise spreading epidemic are rare, but the Nordic cancer registries are unique sources in being able to catch the pre-epidemic situation in the female population where smoking became more prevalent after the War. For Swedish men, smoking prevalence has decease early and cancer rates may herald postsmoking rates. We used data from the NORDCAN database, constructed by the cancer registries of Denmark, Finland, Norway and Sweden, for the analysis of incidence changes in lung and bladder cancers from year 1943 (Denmark), from 1953 (Finland and Norway) and from 1960 (Sweden) until year 2016. The analyses revealed four novel observation relevant to the smoking epidemic. (1) The incidence of lung cancer in Norwegian women in the 1950s, when the smoking prevalence was very low, was 1.8/100 000 (world standard rate), which is at the level of lowest global female rates known to-date; (2) the earliest lung-to-bladder incidence ratio among Norwegian women was 0.64, probably benchmarking the incidence rates prior to the smoking epidemic; (3) bladder cancer incidence for Finnish women diagnosed in the 1950s was 1.2/100 000 which is at the level of the lowest rates currently known and (4) Swedish men with the lowest smoking prevalence in Europe, showed an epochal crossing of lung and bladder cancer incidence rates before year 2015. The data suggest that the approaching of the incidence rates for lung and bladder cancer can be expected in the course of the abating smoking epidemic.
Improved Transfer-Learning-Based Facial Recognition Framework to Detect Autistic Children at an Early Stage

Autism spectrum disorder (ASD) is a complex neuro-developmental disorder that affects social skills, language, speech and communication. Early detection of ASD individuals, especially children, could help to devise and strategize right therapeutic plan at right time. Human faces encode important markers that can be used to identify ASD by analyzing facial features, eye contact, and so on. In this work, an improved transfer-learning-based autism face recognition framework is proposed to identify kids with ASD in the early stages more precisely. Therefore, we have collected face images of children with ASD from the Kaggle data repository, and various machine learning and deep learning classifiers and other transfer-learning-based pre-trained models were applied. We observed that our improved MobileNet-V1 model demonstrates the best accuracy of 90.67% and the lowest 9.33% value of both fall-out and miss rate compared to the other classifiers and pre-trained models. Furthermore, this classifier is used to identify different ASD groups investigating only autism image data using k-means clustering technique. Thus, the improved MobileNet-V1 model showed the highest accuracy (92.10%) for k = 2 autism sub-types. We hope this model will be useful for physicians to detect autistic children more explicitly at the early stage.
Induced Pluripotent Stem Cell-Derived Conditioned Medium Promotes Endogenous Leukemia Inhibitory Factor to Attenuate Endotoxin-Induced Acute Lung Injury

The conditioned medium of induced pluripotent stem cells (iPSC-CM) can attenuate neutrophil recruitment and endothelial leakage of lipopolysaccharide (LPS)-induced acute lung injury (ALI). Therefore, we investigated the mechanisms by which iPSC-CM regulate the interaction between neutrophils and the endothelium in ALI. Murine iPSCs (miPSCs) were delivered intravenously to male C57BL/6 mice (8–12 weeks old) 4 h after intratracheal LPS injection. A miPSC-derived conditioned medium (miPSC-CM) was delivered intravenously to mice after intratracheal LPS injection. DMSO-induced HL-60 cells (D-HL-60, neutrophil-like cells) and human umbilical vein endothelial cells (HUVECs) were used as in vitro models to assess the interaction of neutrophils and endothelial cells. miPSC-CM diminished the histopathological changes in the lungs and the neutrophil count in bronchoalveolar lavage fluids of ALI mice. miPSC-CM attenuated the expression of adhesion molecules in the lungs of ALI mice. Human iPSC conditioned medium (hiPSC-CM) reduced the expression of adhesion molecules in a HUVEC and D-HL-60 co-culture after LPS stimulation, which decreased the transendothelial migration (TEM) of D-HL-60. A human angiogenesis factors protein array revealed that leukemia inhibitory factor (LIF) was not detected in the absence of D-HL-60 and hiPSC-CM groups. hiPSC-CM significantly promoted the production of endogenous LIF in in vitro models. Administration of an anti-LIF antibody not only reversed the effect of iPSC-CM in ALI mice, but also blocked the effect of iPSC-CM on neutrophils TEM in in vitro models. However, a controlled IgG had no such effect. Our study demonstrated that iPSC-CM promoted endogenous LIF to inhibit neutrophils TEM and attenuate the severity of sepsis-induced ALI.
Keap1/Nrf2 Signaling Pathway

Nuclear factor, erythroid 2-like transcription factor 2 (Nrf2) and its cytoplasmic inhibitor, kelch-like ECH-associated protein 1 (Keap1), comprise a redox-responsive endogenous antioxidant defense module that orchestrates the expression of cytoprotective genes to maintain homeostasis [. ].
Near Infrared Fluorescence Imaging of Intraperitoneal Ovarian Tumors in Mice Using Erythrocyte-Derived Optical Nanoparticles and Spatially-Modulated Illumination

Simple Summary Ovarian cancer has a greater mortality rate than all gynecological malignancies combined. While cytoreductive surgery remains the primary therapeutic approach, its success is limited by the inability to visualize all tumor nodules for resection. We developed light activated nano-sized particles derived from red blood cells as potential imaging probes for near infrared fluorescence imaging of tumors during cytoreductive surgery. We present the first demonstration of the use of these nanoparticles in conjunction a spatially-modulated illumination (SMI) modality to image ovarian intraperitoneal tumors in mice. Our findings indicate that, at 24 h post-administration, these nanoparticles accumulated at higher levels in tumors as compared to organs, and that use of SMI enhances the image contrast. Abstract Ovarian cancer is the deadliest gynecological cancer. Cytoreductive surgery to remove primary and intraperitoneal tumor deposits remains as the standard therapeutic approach. However, lack of an intraoperative image-guided approach to enable the visualization of all tumors can result in incomplete cytoreduction and recurrence. We engineered nano-sized particles derived from erythrocytes that encapsulate the near infrared (NIR) fluorochrome, indocyanine green, as potential imaging probes for tumor visualization during cytoreductive surgery. Herein, we present the first demonstration of the use of these nanoparticles in conjunction with spatially-modulated illumination (SMI), at spatial frequencies in the range of 0–0.5 mm−1, to fluorescently image intraperitoneal ovarian tumors in mice. Results of our animal studies suggest that the nanoparticles accumulated at higher levels within tumors 24 h post-intraperitoneal injection as compared to various other organs. We demonstrate that, under the imaging specifications reported here, use of these nanoparticles in conjunction with SMI enhances the fluorescence image contrast between intraperitoneal tumors and liver, and between intraperitoneal tumors and spleen by nearly 2.1, and 3.0 times, respectively, at the spatial frequency of 0.2 mm−1 as compared to the contrast values at spatially-uniform (non-modulated) illumination. These results suggest that the combination of erythrocyte-derived NIR nanoparticles and structured illumination provides a promising approach for intraoperative fluorescence imaging of ovarian tumor nodules at enhanced contrast.
Leukocyte Trafficking via Lymphatic Vessels in Atherosclerosis

In recent years, lymphatic vessels have received increasing attention and our understanding of their development and functional roles in health and diseases has greatly improved. It has become clear that lymphatic vessels are critically involved in acute and chronic inflammation and its resolution by supporting the transport of immune cells, fluid, and macromolecules. As we will discuss in this review, the involvement of lymphatic vessels has been uncovered in atherosclerosis, a chronic inflammatory disease of medium- and large-sized arteries causing deadly cardiovascular complications worldwide. The progression of atherosclerosis is associated with morphological and functional alterations in lymphatic vessels draining the diseased artery. These defects in the lymphatic vasculature impact the inflammatory response in atherosclerosis by affecting immune cell trafficking, lymphoid neogenesis, and clearance of macromolecules in the arterial wall. Based on these new findings, we propose that targeting lymphatic function could be considered in conjunction with existing drugs as a treatment option for atherosclerosis.
Proteoglycan 4 Modulates Osteogenic Smooth Muscle Cell Differentiation during Vascular Remodeling and Intimal Calcification

Calcification is a prominent feature of late-stage atherosclerosis, but the mechanisms driving this process are unclear. Using a biobank of carotid endarterectomies, we recently showed that Proteoglycan 4 (PRG4) is a key molecular signature of calcified plaques, expressed in smooth muscle cell (SMC) rich regions. Here, we aimed to unravel the PRG4 role in vascular remodeling and intimal calcification. PRG4 expression in human carotid endarterectomies correlated with calcification assessed by preoperative computed tomographies. PRG4 localized to SMCs in early intimal thickening, while in advanced lesions it was found in the extracellular matrix, surrounding macro-calcifications. In experimental models, Prg4 was upregulated in SMCs from partially ligated ApoE−/− mice and rat carotid intimal hyperplasia, correlating with osteogenic markers and TGFb1. Furthermore, PRG4 was enriched in cells positive for chondrogenic marker SOX9 and around plaque calcifications in ApoE−/− mice on warfarin. In vitro, PRG4 was induced in SMCs by IFNg, TGFb1 and calcifying medium, while SMC markers were repressed under calcifying conditions. Silencing experiments showed that PRG4 expression was driven by transcription factors SMAD3 and SOX9. Functionally, the addition of recombinant human PRG4 increased ectopic SMC calcification, while arresting cell migration and proliferation. Mechanistically, it suppressed endogenous PRG4, SMAD3 and SOX9, and restored SMC markers’ expression. PRG4 modulates SMC function and osteogenic phenotype during intimal remodeling and macro-calcification in response to TGFb1 signaling, SMAD3 and SOX9 activation. The effects of PRG4 on SMC phenotype and calcification suggest its role in atherosclerotic plaque stability, warranting further investigations.
Extrusion Processing of Rapeseed Press Cake-Starch Blends: Effect of Starch Type and Treatment Temperature on Protein, Fiber and Starch Solubility

For the valorization of oilseed press cakes into food products, extrusion can be used. A common way of applying the protein- and fiber-rich press cakes in directly expanded products is the combination thereof with starch, since starch gives a favourable texture, which correlates directly to expansion. To control product properties like expansion of protein and fiber-rich extruded products, the underlying physicochemical changes of proteins, fibers and starch due to thermomechanical input need to be comprehensively described. In this study, rapeseed press cake (RPC) was extruded and treated under defined thermomechanical conditions in a closed-cavity rheometer, pure and in combination with four starches. The impact of starch type (potato PS, waxy potato WPS, maize MS, high-amylose maize HAMS) and temperature (20/25, 80, 100, 120, 140 °C) on protein solubility, starch gelatinization (Dgel), starch hydrolysis (SH) and fiber solubility of the blends was evaluated. The extrusion process conditions were significantly affected by the starch type. In the extruded blends, the starch type had a significant impact on the protein solubility which decreased with increasing barrel temperature. Increasing barrel temperatures significantly increased the amount of soluble fiber fractions in the blends. At defined thermomechanical conditions, the starch type showed no significant impact on the protein solubility of the blends. Therefore, the observed effects of starch type on the protein solubility of extruded blends could be attributed to the indistinct process conditions due to differences in the rheological properties of the starches rather than to molecular interactions of the starches with the rapeseed proteins in the blends.
Ubiquitin-Specific Protease 3 Deubiquitinates and Stabilizes Oct4 Protein in Human Embryonic Stem Cells

Oct4 is an important mammalian POU family transcription factor expressed by early human embryonic stem cells (hESCs). The precise level of Oct4 governs the pluripotency and fate determination of hESCs. Several post-translational modifications (PTMs) of Oct4 including phosphorylation, ubiquitination, and SUMOylation have been reported to regulate its critical functions in hESCs. Ubiquitination and deubiquitination of Oct4 should be well balanced to maintain the pluripotency of hESCs. The protein turnover of Oct4 is regulated by several E3 ligases through ubiquitin-mediated degradation. However, reversal of ubiquitination by deubiquitinating enzymes (DUBs) has not been reported for Oct4. In this study, we generated a ubiquitin-specific protease 3 (USP3) gene knockout using the CRISPR/Cas9 system and demonstrated that USP3 acts as a protein stabilizer of Oct4 by deubiquitinating Oct4. USP3 interacts with endogenous Oct4 and co-localizes in the nucleus of hESCs. The depletion of USP3 leads to a decrease in Oct4 protein level and loss of pluripotent morphology in hESCs. Thus, our results show that USP3 plays an important role in controlling optimum protein level of Oct4 to retain pluripotency of hESCs.
Purpose in Life of Elite Athletes after Spinal Cord Injury

Background: Searching for the meaning of human existence is man’s fundamental orientation. People are free to find meaning in their lives, and while they are not always free to choose the conditions of life, they are free to choose their attitude toward the conditions in which they find themselves. When people experience an unchangeable situation, the most important thing is the attitude they take toward it. This study aimed to identify the sense of meaning in life among elite athletes after a spinal cord injury (SCI) and to analyze the different aspects contributing to this domain. Methods: The study involved five athletes with at least national-level achievements in sports prior to a SCI. The study consisted of an interview using a communicator and filling out two online questionnaires—a personal questionnaire and the Purpose in Life Scale. Results: Analyzing the quantitative results, four participants achieved results indicating a high sense of meaning in life, while one participant achieved a significantly lower result. Conclusions: What affects one’s purpose in life is not so much the objective physical limitation but how much physicality one perceives to have lost as a result of the injury. Elite athletes stay involved in the sporting environment, which prevents the loss of purpose and maintains a sense of meaning at a high level. Both telling the story of your own illness and listening to the stories of others help the process of self-healing.
Osteoconductivity of Bovine Xenograft Granules of Different Sizes in Sinus Lift: A Histomorphometric Study in Rabbits

Background: Due to the lack of data on bone-to-graft contact (BGC) over time in the various regions within the subantral space of the augmented sinus floor, the present study aimed to evaluate the osteoconductivity of deproteinized bovine bone mineral (DBBM) with granules of different sizes applied in maxillary sinus floor elevation. Methods: A maxillary sinus augmentation was performed bilaterally in 18 rabbits using DBBM with particle dimensions of either 0.125–1.0 mm or 1–2 mm. The antrostomy was covered using a collagen barrier. The animals were euthanized in groups of six after 2, 4, and 8 weeks of healing. MicroCT and histological analyses were performed. Results: After 2 weeks of healing, BGC was 10.9% and 11.9% for the small and large granule sites, respectively. After 8 weeks of healing, the BGC increased to 65% and 62% at the small and large granule sites, respectively. The highest values were located close to the bony walls and the bony window. New bone content developed between 2 and 8 weeks from 7.0% to 27.6% and from 6.1% to 27.6% at the small and large granule sites, respectively. Conclusions: Similar outcomes in osteoconductivity and bone formation were found at both small and large DBBM granule sites.
Spatiotemporal patterns of anuran functional diversity in temperate montane forests

Functional diversity is an integrative approach to better understand biodiversity across space and time. In the present study, we investigated the spatiotemporal patterns (i.e., elevation and season) and environmental determinants of anuran functional diversity on Tianping Mountain, northwest Hunan, China. Specifically, 10 transects were established from low (300 m a.s.l.) to high (1 492 m a.s.l.) elevations, and anuran communities were sampled in spring, early summer, midsummer, and autumn in 2017. Four functional diversity indices were computed for each transect in each season using ecomorphological functional traits. Our results demonstrated that these indices had contrasting responses to increasing elevations. However, they did not differ significantly among seasons in terms of temporal patterns. Interestingly, the unique spatiotemporal functional diversity patterns were impacted by distinct environmental variables, such as leaf litter cover, water temperature, number of trees, and water conductivity.
Compositional Changes in Grapes and Leaves as a Consequence of Smoke Exposure of Vineyards from Multiple Bushfires across a Ripening Season

The negative effects of smoke exposure of grapes in vineyards that are close to harvest are well documented. Volatile phenols in smoke from forest and grass fires can contaminate berries and, upon uptake, are readily converted into a range of glycosylated grape metabolites. These phenolic glycosides and corresponding volatile phenols are extracted into the must and carried through the winemaking process, leading to wines with overtly smoky aromas and flavours. As a result, smoke exposure of grapes can cause significant quality defects in wine, and may render grapes and wine unfit for sale, with substantial negative economic impacts. Until now, however, very little has been known about the impact on grape composition of smoke exposure very early in the season, when grapes are small, hard and green, as occurred with many fires in the 2019–20 Australian grapegrowing season. This research summarises the compositional consequences of cumulative bushfire smoke exposure of grapes and leaves, it establishes detailed profiles of volatile phenols and phenolic glycosides in samples from six commercial Chardonnay and Shiraz blocks throughout berry ripening and examines the observed effects in the context of vineyard location and timing of smoke exposure. In addition, we demonstrate the potential of some phenolic glycosides in leaves to serve as additional biomarkers for smoke exposure of vineyards.
Association between Hepatitis C Virus Infection and Esophageal Cancer: An Asian Nationwide Population-Based Cohort Study

Background: Hepatitis C virus (HCV) infection causes many extrahepatic cancers, and whether HCV infection is associated with esophageal cancer development remains inconclusive. Methods: A nationwide population-based cohort study of the Taiwan National Health Insurance Research Database (TNHIRD) was conducted. Results: From 2003 to 2012, of 11,895,993 patients, three 1:1:1 propensity score-matched cohorts, including HCV-treated (interferon-based therapy ≧6 months, n = 9047), HCV-untreated (n = 9047), and HCV-uninfected cohorts (n = 9047), were enrolled. The HCV-untreated cohort had the highest 9-year cumulative incidence of esophageal cancer among the three cohorts (0.174%; 95% confidence interval (CI): 0.068–0.395) (p = 0.0292). However, no difference in cumulative incidences was identified between the HCV-treated (0.019%; 0.002–0.109%) and HCV-uninfected cohorts (0.035%; 0.007–0.133%) (p = 0.5964). The multivariate analysis showed that HCV positivity (hazard ratio (HR): 5.1, 95% CI HR: 1.39–18.51) and male sex (HR: 8.897; 95% CI HR: 1.194–66.323) were independently associated with the development of esophageal cancer. Of the three cohorts, the HCV-untreated cohort had the highest cumulative incidence of overall mortality at 9 years (21.459%, 95% CI: 18.599–24.460) (p < 0.0001), and the HCV-treated (12.422%, 95% CI: 8.653–16.905%) and HCV-uninfected cohorts (5.545%, 95% CI: 4.225–7.108%) yielded indifferent cumulative mortality incidences (p = 0.1234). Conclusions: Although HCV positivity and male sex were independent factors associated with esophageal cancer development, whether HCV infection is the true culprit or a bystander for developing esophageal cancer remains to be further investigated. Interferon-based anti-HCV therapy might attenuate esophageal risk and decrease overall mortality in HCV-infected patients.