Miracle-dz/UniFAR-FTUs huggingface dataset:
In Silico Antibody Mutagenesis for Optimizing Its Binding to Spike Protein of Severe Acute Respiratory Syndrome Coronavirus 2

Coronavirus disease 2019 (COVID-19) is an ongoing global pandemic, and there are currently no FDA-approved medicines for treatment or prevention. Inspired by promising outcomes for convalescent plasma treatment, the development of antibody drugs (biologics) to block SARS-CoV-2 infection has been the focus of drug discovery, along with tremendous efforts in repurposing small-molecule drugs. In the past several months, experimentally, many human neutralizing monoclonal antibodies (mAbs) were successfully extracted from plasma of recovered COVID-19 patients. Currently, several mAbs targeting the SARS-CoV-2’s spike glycoprotein (S-protein) are in clinical trials. With known atomic structures of the mAb and S-protein complex, it becomes possible to investigate in silico the molecular mechanism of mAb’s binding with S-protein and to design more potent mAbs through protein mutagenesis studies, complementary to existing experimental efforts. Leveraging today’s superb computing power, we propose a fully automated in silico protocol for quickly identifying possible mutations in a mAb (e.g., CB6) to enhance its binding affinity for S-protein for the design of more efficacious therapeutic mAbs.
Xenografted Human Amniotic Membrane–Derived Mesenchymal Stem Cells Are Immunologically Tolerated and Transdifferentiated Into Cardiomyocytes

Rationale: Amniotic membrane is known to have the ability to transdifferentiate into multiple organs and is expected to stimulate a reduced immunologic reaction. Objective: Determine whether human amniotic membrane–derived mesenchymal cells (hAMCs) can be an ideal allograftable stem cell source for cardiac regenerative medicine. Methods and Results: We established hAMCs. After cardiomyogenic induction in vitro, hAMCs beat spontaneously, and the calculated cardiomyogenic transdifferentiation efficiency was 33%. Transplantation of hAMCs 2 weeks after myocardial infarction improved impaired left ventricular fractional shortening measured by echocardiogram (34±2% [n=8] to 39±2% [n=11]; P<0.05) and decreased myocardial fibrosis area (18±1% [n=9] to 13±1% [n=10]; P<0.05), significantly. Furthermore hAMCs transplanted into the infarcted myocardium of Wistar rats were transdifferentiated into cardiomyocytes in situ and survived for more than 4 weeks after the transplantation without using any immunosuppressant. Immunologic tolerance was caused by the hAMC-derived HLA-G expression, lack of MHC expression of hAMCs, and activation of FOXP3-positive regulatory T cells. Administration of IL-10 or progesterone, which is known to play an important role in feto-maternal tolerance during pregnancy, markedly increased HLA-G expression in hAMCs in vitro and, surprisingly, also increased cardiomyogenic transdifferentiation efficiency in vitro and in vivo. Conclusions: Because hAMCs have a high ability to transdifferentiate into cardiomyocytes and to acquire immunologic tolerance in vivo, they can be a promising cellular source for allograftable stem cells for cardiac regenerative medicine.
Association between in-line filtration and Type I hypersensitivity reactions in pediatric oncology patients receiving intravenous etoposide

Abstract The objective of this study was to describe hypersensitivity reactions with and without the use of in-line filters during intravenous etoposide therapy in pediatric oncology patients. This was a retrospective review of all patients treated in the Division of Oncology/Hematology/Bone Marrow Transplant at British Columbia Children’s Hospital with intravenous etoposide between December 1, 2013 and February 1, 2018. Hypersensitivity reactions and anaphylaxis associated with etoposide infusions were compared over time, including 12 months prior to, 27 months during the use of, and for 12 months after the discontinuation of in-line filtration. There were 192 patients (median age 6.0 (IQR 2.8-13.0) years treated with etoposide and 486 etoposide infusions including 137 (28%) before, 261 (54%) during and 88 (18%) after use of in-line filters at our center. Twenty-six of 486 (5%) and 13/486 (3%) of infusions resulted in a type I hypersensitivity reaction and anaphylaxis, respectively. There were 2/137 (1%), 36/261 (14%) and 1/88 (1%) infusion reactions prior to, during and after in-line filter use, respectively. Infusion reactions during the in-line filter period were higher than during the pre-filter (Z = 3.978; p < 0.001) and post-filter (Z = 3.335; p < 0.001) periods of the study. These data suggest that the use of in-line filtration may be associated with increased frequency of hypersensitivity reactions to etoposide in pediatric cancer patients.
Optimal model complexity for terrestrial carbon cycle prediction

Abstract. The terrestrial carbon cycle plays a critical role in modulating the interactions of climate with the Earth system, but different models often make vastly different predictions of its behavior. Efforts to reduce model uncertainty have commonly focused on model structure, namely by introducing additional processes and increasing structural complexity. However, the extent to which increased structural complexity can directly improve predictive skill is unclear. While adding processes may improve realism, the resulting models are often encumbered by a greater number of poorly determined or over-generalized parameters. To guide efficient model development, here we map the theoretical relationship between model complexity and predictive skill. To do so, we developed 16 structurally distinct carbon cycle models spanning an axis of complexity and incorporated them into a model–data fusion system. We calibrated each model at six globally distributed eddy covariance sites with long observation time series and under 42 data scenarios that resulted in different degrees of parameter uncertainty. For each combination of site, data scenario, and model, we then predicted net ecosystem exchange (NEE) and leaf area index (LAI) for validation against independent local site data. Though the maximum model complexity we evaluated is lower than most traditional terrestrial biosphere models, the complexity range we explored provides universal insight into the inter-relationship between structural uncertainty, parametric uncertainty, and model forecast skill. Specifically, increased complexity only improves forecast skill if parameters are adequately informed (e.g., when NEE observations are used for calibration). Otherwise, increased complexity can degrade skill and an intermediate-complexity model is optimal. This finding remains consistent regardless of whether NEE or LAI is predicted. Our COMPLexity EXperiment (COMPLEX) highlights the importance of robust observation-based parameterization for land surface modeling and suggests that data characterizing net carbon fluxes will be key to improving decadal predictions of high-dimensional terrestrial biosphere models.
COVID-19: Pregnant Women’s Knowledge, Perceptions & Fears. First National Data from Lebanon

Background and objective: The world is facing the pandemic of COVID-19 declared on the 11th of March by the World Health Organization caused by the novel corona virus SARS-COV-2.With insufficient worldwide evidence on the effect of COVID-19 on pregnancy, it is critically important to understand pregnant women’s knowledge, perceptions, and fears regarding COVID-19 and to provide them support as far as possible. The aim of the study was to explore pregnant women’s awareness level of COVID-19 risk and its implication during the outbreak. Methods: This was a cross-sectional and observational study conducted on pregnant women living in Lebanon, using an electronic survey (Google form). Questions about demographics, knowledge of the COVID-19, risk perception, precautionary measures, source of information and degree of trust, anxiety levels were asked. Scores were calculated. Data was analysed using the SPSS version 22. Descriptive, bivariate, and multivariate analyses were carried out and p<0.05 was considered statistically significant. Results: With 449 pregnant women enrolled, the mean knowledge score was 4.4 (± 1.17) over 5. The mean perception score was 30.2 (± 5.4) over 51, while the mean precaution score was 19.7(± 3.04) over 25. As for the anxiety, the mean score was 7.1(± 5.8) over 21. Significant correlation was found between knowledge score vs both perception and precaution score (R=-0.213, p<0.001/R=0.465, p<0.00, respectively) between perception score vs knowledge, precaution, and anxiety scores (R= -0.213, p<0.001/ R=0.107, p=0.023/R=0.248, p<0.001, respectively), between precaution score vs knowledge and perception scores (R=0.465, p<0.001/ R=0.107, p=0.023, respectively) and finally between GAD 7 anxiety score vs perception score (R=0.248, p<0.001). Using the Kruskal Wallis, Mann-Whitney, the bivariate analysis showed that pregnant women had higher GAD7 score when they were multiparous (p=0.021) and when they had the Lebanese nationality (p=0.042). Accordingly, lower GAD7 score was noted with higher level of education (p=0.021). As for the two most trusted organizations as a source of information, they were the personal doctor (Mean trust = 4.4 ± 0.9 over 5) and MOPH (Mean trust = 4.2 ± 1.1 over 5). Conclusion: A high knowledge score among pregnant women across Lebanon suggested a strong commitment on the part of these women to gain a better understanding of their health, their responsibilities towards their foetuses, and to counter this pandemic. However, a better communication between pregnant women and their physicians with the help of midwives is encouraged towards better management of care and better support.
SIGNS OF CHANGE: ROLE OF VISUAL INFORMATION IN CONSUMER PERCEPTION

The American Marketing Association emphasizes the role of communication as vital in marketing activities. Research on signage encompasses the ways individuals and businesses use this medium in effective communication (Kellaris and Machleit 2016). For many businesses, the most basic function of an on-premise sign is to communicate its location to customers (Auffrey and Hildebrandt 2017). Taylor et al. (2005) note that communication through signs is fundamental and that “next to the human voice, signage is the most available and ubiquitous form of speech” (xv). Most discussion on the research surrounding the use of signage includes an analysis of signage governance and regulations (Jourdan, Hurd, and Hawkins 2013; Chang and Killion 2015; Connolly 2012). When it comes to sign regulation, aesthetics refers to how signs are visually experienced and appreciated within their environmental context by individual viewers, and will vary based on personal tastes, cultural preferences, socioeconomic background, and education (Hein, Ngalamulume, and Robinson 2010). Researchers have long advocated for effective signage graphics as a way to influence consumer perception (Fontaine and Bradbury 2017). The visual experience of signage includes outcomes on consumer inferences that could be apparently straightforward such as the influence of visual depiction of movement on a sense of belonging in the community (Sundar et al. 2018), to more unintuitive findings such as the role and effect of visual disfluency as it increases sensitivity to missing information (Sundar et. al. 2019).
Vitamin E as promising adjunct treatment option in the combat of infectious diseases caused by bacterial including multi-drug resistant pathogens – Results from a comprehensive literature survey

The use of antibiotics has provoked an emergence of various multidrug-resistant (MDR) bacteria. Infectious diseases that cannot be treated sufficiently with conventional antibiotic intervention strategies anymore constitue serious threats to human health. Therefore, current research focus has shifted to alternative, antibiotic-independent therapeutic approaches. In this context, vitamin E constitutes a promising candidate molecule due to its multi-faceted modes of action. Therefore, we used the PubMed database to perform a comprehensive literature survey reviewing studies addressing the antimicrobial properties of vitamin E against bacterial pathogens including MDR bacteria. The included studies published between 2010 and 2020 revealed that given its potent synergistic antimicrobial effects in combination with distinct antibiotic compounds, vitamin E constitutes a promising adjunct antibiotic treatment option directed against infectious diseases caused by MDR bacteria such as Pseudomonas aeruginosa, Burkholderia cenocepacia and methicillin-resistant Staphylococcus aureus (MRSA). In conclusion, the therapeutic value of vitamin E for the treatment of bacterial infections should therefore be investigated in future clinical studies.
Sitagliptin: a potential drug for the treatment of COVID-19?

Abstract Recently, an outbreak of a fatal coronavirus, SARS-CoV-2, has emerged from China and is rapidly spreading worldwide. Possible interaction of SARS-CoV-2 with DPP4 peptidase may partly contribute to the viral pathogenesis. An integrative bioinformatics approach starting with mining the biomedical literature for high confidence DPP4-protein/gene associations followed by functional analysis using network analysis and pathway enrichment was adopted. The results indicate that the identified DPP4 networks are highly enriched in viral processes required for viral entry and infection, and as a result, we propose DPP4 as an important putative target for the treatment of COVID-19. Additionally, our protein-chemical interaction networks identified important interactions between DPP4 and sitagliptin. We conclude that sitagliptin may be beneficial for the treatment of COVID-19 disease, either as monotherapy or in combination with other therapies, especially for diabetic patients and patients with pre-existing cardiovascular conditions who are already at higher risk of COVID-19 mortality.
Population genomics reveals repeated signals of adaptive divergence in the Atlantic salmon of north‐eastern Europe

Our ability to examine genetic variation across entire genomes has enabled many studies searching for the genetic basis of local adaptation. These studies have identified numerous loci as candidates for differential local selection; however, relatively few have examined the overlap among candidate loci identified from independent studies of the same species in different geographic areas or evolutionary lineages. We used an allelotyping approach with a 220K SNP array to characterize the population genetic structure of Atlantic salmon in north‐eastern Europe and ask whether the same genomic segments emerged as outliers among populations in different geographic regions. Genome‐wide data recapitulated the phylogeographic structure previously inferred from mtDNA and microsatellite markers. Independent analyses of three genetically and geographically distinct groups of populations repeatedly inferred the same 17 haploblocks to contain loci under differential local selection. The most strongly supported of these replicated haploblocks had known strong associations with life‐history variation or immune response in Atlantic salmon. Our results are consistent with these genomic segments harbouring large‐effect loci which have a major role in Atlantic salmon diversification and are ideal targets for validation studies.
The Chicken MHC: Insights into Genetic Resistance, Immunity, and Inflammation Following Infectious Bronchitis Virus Infections

The chicken immune system has provided an immense contribution to basic immunology knowledge by establishing major landmarks and discoveries that defined concepts widely used today. One of many special features on chickens is the presence of a compact and simple major histocompatibility complex (MHC). Despite its simplicity, the chicken MHC maintains the essential counterpart genes of the mammalian MHC, allowing for a strong association to be detected between the MHC and resistance or susceptibility to infectious diseases. This association has been widely studied for several poultry infectious diseases, including infectious bronchitis. In addition to the MHC and its linked genes, other non-MHC loci may play a role in the mechanisms underlying such resistance. It has been reported that innate immune responses, such as macrophage function and inflammation, might be some of the factors driving resistance or susceptibility, consequently influencing the disease outcome in an individual or a population. Information about innate immunity and genetic resistance can be helpful in developing effective preventative measures for diseases such as infectious bronchitis, to which a systemic antibody response is often not associated with disease protection. In this review, we summarize the importance of the chicken MHC in poultry disease resistance, particularly to infectious bronchitis virus (IBV) infections and the role played by innate immunity and inflammation on disease outcome. We highlight how future studies focusing on the MHC and non-MHC genes can potentially bring clarity to observed resistance in some chicken B haplotype lines.
Vulnerability of mountain communities to climate change and natural resources scarcity in Northwest Ethiopia: the case of Debark Woreda

In recent decades, climate change causes distressful shocks upon the poor people’s natural resources and socio-economic processes from local up to global scales. The crisis is more severe in Ethiopia, where harsh ecological changes are frequent. Therefore, the objective of this study was to determine the vulnerability levels of rural communities to climate change and natural resources scarcity in Debark woreda, Northwest Ethiopia. Livelihood Vulnerability Index (LVI) and IPCC methods were used to analyze the data. The meteorological data reveal a declining precipitation trend by 61.13 mm in the past 31 years whilst maximum and minimum temperatures increased by 0.62 0 C and 0.74 0 C respectively. The LVI result indicates that the Debark community is highly vulnerable with land (0.59) and forest (0.57) scarcity. Water scarcity (0.50) and climate exposure (0.30) put them in a vulnerable class. Both the total LVI (0.48) and LVI-IPCC (-0.69) approaches placed the woreda community again in a vulnerable position. The findings imply that climate change should be placed within the broader context of development strategy and rural poverty reduction. Particularly, concerted efforts should be exerted to participatory integrated watershed management strategies supported with farmers training to ensure sustainable development of natural resources. Farmers’ best natural resource conservation practices should be incorporated in the local plans.
Musculoskeletal complications of hand–arm vibration syndrome among tyre shop workers in Kelantan, Malaysia

Objectives. Exposure to hand–arm vibration (HAV) is associated with hand–arm vascular syndrome (HAVS), which is characterized by musculoskeletal complications. However, evidence on this matter has been inconclusive. Therefore, this study aimed to determine and compare the prevalence of musculoskeletal complications of HAVS between a high-exposure (≥5 m·s−2) group and a low–moderate-exposure (<5 m·s−2) group and to explore the factors associated with the musculoskeletal complications of HAVS among tyre shop workers in Kelantan, Malaysia. Methods. A cross-sectional study involving 200 tyre shop workers was carried out. HAV was measured by a vibration meter. The workers were divided into two exposure groups – according to their 8-h time-weighted average, A(8), of vibration exposure – and compared. Results. Almost half of the workers reported musculoskeletal complications of the upper limbs and neck. Only the lifetime vibration dose (LVD) was significantly associated with the development of musculoskeletal complications. Conclusion. The high-exposure group had a higher prevalence of musculoskeletal complications. Only the LVD was significantly associated with complications. However, all factors of the work system, such as ergonomics, handgrip force and posture, might contribute to the development of musculoskeletal complications of HAVS and should be included in assessments.
LENGTH-WEIGHT RELATIONSHIP , CONDITION FACTOR AND SEX RATIO OF TWO CHRYSICHTHYS SPECIES ( PISCES : CLAROTEIDAE ) OF SOCIO-ECONOMIC IMPORTANCE FROM KPONG RESERVOIR IN GHANA

A total of 392 combined samples of Chrysichthys auratus and Chrysichthys nigrodigitatus was obtained from experimental and artisanal fishing from inshore and offshore areas of Kpong Reservoir. C. auratus and C. nigrodigitatus exhibited hyperallometric (b = 3.17–3.23) and hypoallometric (b = 2.79 2.91) growth patterns, respectively. Fluctuating monthly condition factor for males, females and combined sexes observed for the two species based on standard length and total length could be attributed to changes in feeding activity and, or degree of nourishment, food availability, gonadal activity, and season. However, based on total length, October and June were periods of the best physiological condition for C. auratus, while for C. nigrodigitatus, December was the least physiological period. There were significantly more females than males while differences in sex ratio were significant at 95 per cent confidence interval (P = 1.354), indicating departure from the expected sex ratio of 1:1 for the two species. Regular assessment of biological, ecological and environmental characteristics of the species is recommended to provide requisite information for sustainable management of the species for reservoir fishery development and food security.
The Significance of Fibrosis Quantification as a Marker in Assessing Pseudo-Capsule Status and Clear Cell Renal Cell Carcinoma Prognosis

Fibrosis plays an important role in tumor growth and progression, and thus, we aimed to determine whether renal fibrosis is correlated with the clinical and pathological characteristics and prognosis of clear cell renal cell carcinoma (ccRCC). Fibrosis, including intra-tumoral fibrosis (ITF), pseudo-capsule (PC) fibrosis and adjacent normal renal interstitial fibrosis, was evaluated in 73 pairs of ccRCC specimens using second harmonic generation combined with two-photon excitation fluorescence (SHG/TPEF). The clinical and pathological characteristics of the patients who were eligible for the present study were recorded. The associations between fibrosis and clinicopathological parameters were analyzed using a Mann-Whitney U test or logistic regression analysis. Progression-free survival (PFS) was analyzed using the Kaplan-Meier method and a Cox regression model. High-resolution images of fibrosis were captured from unstained slides using the SHG/TPEF approach. Both ITF and PC fibrosis were associated with tumor progression in ccRCC. Multivariate logistic regression analysis revealed a significant inverse association between the PC collagen proportional area (CPA) and PC invasion (p < 0.05), suggesting that PC CPA is an independent risk factor or marker for PC invasion. A significant decrease in progression-free survival (PFS), determined by Kaplan-Meier curves, was observed for patients with higher PC CPA status compared with those with lower PC CPA status (p < 0.05). Similar results were observed in patients with PC invasion. In multivariate Cox regression analysis, PC invasion and intra-tumoral necrosis were identified as independent prognostic factors for PFS. Our data suggest that ITF and PC fibrosis are associated with ccRCC progression. In addition, PC fibrosis may act as a marker of PC invasion and an effective quantitative measurement for assessing prognosis.