Miracle-dz/UniFAR-FTUs huggingface dataset:
A streamlined whole blood CyTOF workflow defines a circulating immune cell signature of COVID‐19

Mass cytometry (CyTOF) represents one of the most powerful tools in immune phenotyping, allowing high throughput quantification of over 40 parameters at single‐cell resolution. However, wide deployment of CyTOF‐based immune phenotyping studies are limited by complex experimental workflows and the need for specialized CyTOF equipment and technical expertise. Furthermore, differences in cell isolation and enrichment protocols, antibody reagent preparation, sample staining, and data acquisition protocols can all introduce technical variation that can confound integrative analyses of large data‐sets of samples processed across multiple labs. Here, we present a streamlined whole blood CyTOF workflow which addresses many of these sources of experimental variation and facilitates wider adoption of CyTOF immune monitoring across sites with limited technical expertise or sample‐processing resources or equipment. Our workflow utilizes commercially available reagents including the Fluidigm MaxPar Direct Immune Profiling Assay (MDIPA), a dry tube 30‐marker immunophenotyping panel, and SmartTube Proteomic Stabilizer, which allows for simple and reliable fixation and cryopreservation of whole blood samples. We validate a workflow that allows for streamlined staining of whole blood samples with minimal processing requirements or expertise at the site of sample collection, followed by shipment to a central CyTOF core facility for batched downstream processing and data acquisition. We apply this workflow to characterize 184 whole blood samples collected longitudinally from a cohort of 72 hospitalized COVID‐19 patients and healthy controls, highlighting dynamic disease‐associated changes in circulating immune cell frequency and phenotype.
Bioactive Secondary Metabolites of the Genus Diaporthe and Anamorph Phomopsis from Terrestrial and Marine Habitats and Endophytes: 2010–2019

The genus Diaporthe and its anamorph Phomopsis are distributed worldwide in many ecosystems. They are regarded as potential sources for producing diverse bioactive metabolites. Most species are attributed to plant pathogens, non-pathogenic endophytes, or saprobes in terrestrial host plants. They colonize in the early parasitic tissue of plants, provide a variety of nutrients in the cycle of parasitism and saprophytism, and participate in the basic metabolic process of plants. In the past ten years, many studies have been focused on the discovery of new species and biological secondary metabolites from this genus. In this review, we summarize a total of 335 bioactive secondary metabolites isolated from 26 known species and various unidentified species of Diaporthe and Phomopsis during 2010–2019. Overall, there are 106 bioactive compounds derived from Diaporthe and 246 from Phomopsis, while 17 compounds are found in both of them. They are classified into polyketides, terpenoids, steroids, macrolides, ten-membered lactones, alkaloids, flavonoids, and fatty acids. Polyketides constitute the main chemical population, accounting for 64%. Meanwhile, their bioactivities mainly involve cytotoxic, antifungal, antibacterial, antiviral, antioxidant, anti-inflammatory, anti-algae, phytotoxic, and enzyme inhibitory activities. Diaporthe and Phomopsis exhibit their potent talents in the discovery of small molecules for drug candidates.
Plasma MicroRNA Profiling of Plasmodium falciparum Biomass and Association with Severity of Malaria Disease

Severe malaria (SM) is a major public health problem in malaria-endemic countries. Sequestration of Plasmodium falciparum–infected erythrocytes in vital organs and the associated inflammation leads to organ dysfunction. MicroRNAs (miRNAs), which are rapidly released from damaged tissues into the host fluids, constitute a promising biomarker for the prognosis of SM. We applied next-generation sequencing to evaluate the differential expression of miRNAs in SM and in uncomplicated malaria (UM. Six miRNAs were associated with in vitro P. falciparum cytoadhesion, severity in children, and P. falciparum biomass. Relative expression of hsa-miR-4497 quantified by TaqMan-quantitative reverse transcription PCR was higher in plasma of children with SM than those with UM (p<0.048) and again correlated with P. falciparum biomass (p = 0.033). These findings suggest that different physiopathological processes in SM and UM lead to differential expression of miRNAs and pave the way for future studies to assess their prognostic value in malaria.
Multiple roles of PP2A binding motif in hepatitis B virus core linker and PP2A in regulating core phosphorylation state and viral replication

Hepatitis B virus (HBV) capsid or core protein (HBc) contains an N-terminal domain (NTD) and a C-terminal domain (CTD) connected by a short linker peptide. HBc plays a critical role in virtually every step of viral replication, which is further modulated by dynamic phosphorylation and dephosphorylation of its CTD. While several cellular kinases have been identified that mediate HBc CTD phosphorylation, there is little information on the cellular phosphatases that mediate CTD dephosphorylation. Herein, a consensus binding motif for the protein phosphatase 2A (PP2A) regulatory subunit B56 was recognized within the HBc linker peptide. Mutations within this motif designed to block or enhance B56 binding showed pleiotropic effects on CTD phosphorylation state as well as on viral RNA packaging, reverse transcription, and virion secretion. Furthermore, linker mutations affected the HBV nuclear episome (the covalently closed circular or CCC DNA) differentially during intracellular amplification vs. infection. The effects of linker mutations on CTD phosphorylation state varied with different phosphorylation sites and were only partially consistent with the linker motif serving to recruit PP2A-B56, specifically, to dephosphorylate CTD, suggesting that multiple phosphatases and/or kinases may be recruited to modulate CTD (de)phosphorylation. Furthermore, pharmacological inhibition of PP2A could decrease HBc CTD dephosphorylation and increase the nuclear HBV episome. These results thus strongly implicate the HBc linker in recruiting PP2A and other host factors to regulate multiple stages of HBV replication.
Content of Phenolic Acids in the Grain of Selected Polish Triticale Cultivars and Its Products

The triticale grain has high nutritive value and good technological suitability. Triticale flour can be a valuable raw material for bread-making. The aim of this work was to determine the profile of phenolic acids in triticale grain of selected Polish cultivars and its products. Ultra-high-performance liquid chromatography (UPLC-PDA-MS/MS) was applied for separation and identification of these constituents. The grain of the examined triticale cultivars contained 13 phenolic acids, of which ferulic acid was determined in the largest amount and was constituted from 42–44% of the total content of phenolic acids in the grain. In addition, due to the large amounts of ferulic, di-ferulic, and sinapic acids, composition of the phenolic acids fraction in triticale grain of the tested cultivars varied in comparison with that of wheat and rye cultivars. In triticale flour, the number of phenolic acids was nearly 4 times lower than in the grain, as phenolic acids were removed along with bran, in which their proportion was almost 9 times higher than in the grain intended for grinding. The application of bran in the bread recipe resulted in a 3.5-fold increase in the fraction of phenolic acids compared to the bread produced from triticale flour without bran addition.
Folic acid supplementation and risk for congenital hydrocephalus in China

Abstract Objective: We examined whether folic acid (FA) supplementation prevented congenital hydrocephalus (CH) in more than 200 000 births in China. Design: A large population-based cohort study. Setting: All births at 20 complete gestational weeks, including live births, stillbirths and pregnancy terminations, and all structural birth defects regardless of gestational week were recorded. The prevalence of births with CH was classified by maternal characteristics and FA supplementation. CH was diagnosed in accordance with code 742.3 of the International Classification of Diseases, Ninth Revision, Clinical Modification, while non-neural tube defect (NTD) CH refers to CH without anencephaly (740), spina bifida (741) or encephalocele (742·0). Participants: A total of 247 831 pregnant women who delivered with known outcomes were included. Results: A total of 206 cases of CH (0·83 per 1000 births) and 170 cases of non-NTD CH (0·69 per 1000 births) were recorded in the study. The prevalence of CH and non-NTD CH was higher in women in the no supplementation group than those in the FA supplementation group (0·92 and 0·72 v. 0·75 and 0·65 per 1000 births, respectively). FA supplementation during the periconceptional period significantly prevented CH (OR = 0·29, 95 % CI 0·12, 0·69) and non-NTD CH (OR = 0·34, 95 % CI 0·12, 0·97) in northern China, especially in a high-compliance group (≥ 80 %). Conclusions: Periconceptional FA supplementation did not significantly prevent CH overall in the current study. However, in the north of China with common maternal folate insufficiency, there was some evidence.
Overproduction of Human Zip (SLC39) Zinc Transporters in Saccharomyces cerevisiae for Biophysical Characterization

Zinc constitutes the second most abundant transition metal in the human body, and it is implicated in numerous cellular processes, including cell division, DNA and protein synthesis as well as for the catalytic activity of many enzymes. Two major membrane protein families facilitate zinc homeostasis in the animal kingdom, i.e., Zrt/Irt-like proteins (ZIPs aka solute carrier 39, SLC39, family) and Zn transporters (ZnTs), essentially conducting zinc flux in the opposite directions. Human ZIPs (hZIPs) regulate import of extracellular zinc to the cytosol, being critical in preventing overaccumulation of this potentially toxic metal, and crucial for diverse physiological and pathological processes, including development of neurodegenerative disorders and several cancers. To date, our understanding of structure–function relationships governing hZIP-mediated zinc transport mechanism is scarce, mainly due to the notorious difficulty in overproduction of these proteins for biophysical characterization. Here we describe employment of a Saccharomyces cerevisiae-based platform for heterologous expression of hZIPs. We demonstrate that yeast is able to produce four full-length hZIP members belonging to three different subfamilies. One target (hZIP1) is purified in the high quantity and homogeneity required for the downstream biochemical analysis. Our work demonstrates the potential of the described production system for future structural and functional studies of hZIP transporters.
Conserved Structural Features of Core Oligosaccharides among the Lipopolysaccharides of Respiratory Pathogens from the Genus Bordetella Analyzed Exclusively by NMR Spectroscopy

Bacterial pathogens expose on the cell surface a variety of complex carbohydrate molecules. Gram-negative bacteria produce lipopolysaccharides, which are the main components of the outer membrane of bacterial envelopes and play a major role in host–pathogen interactions. B. pertussis, B. parapertussis, B. bronchiseptica, and B. holmesii, are mammalian respiratory pathogens, having substantial economic impact on human health and agriculture. B. pertussis is responsible for whooping cough (pertussis) and B. holmesii is the second pertussis etiological factor, but the current anti-pertussis vaccines do not provide cross-protection. The structural data on any given hypothetical carbohydrate antigen is a prerequisite for further analysis of structure-related activities and their interaction with hosts. 1H NMR spectra constitute fingerprints of the analyzed glycans and provide unique identity information. The concept of structure-reporter groups has now been augmented by 1H,13C-correlation spectra of the Bordetella oligosaccharides. The comparative analysis of Bordetellae oligosaccharides (OS) revealed that the hexasaccharide, comprising the α-GlcpN, α-GlcpA, 4,6-disubstituted-β-Glcp, 2,7-disubstituted-l-α-d-Hepp, 3,4-disubstituted-l-α-d-Hepp, and Kdo, constitute the least variable OS segment. This minimal common element in the structure of lipopolysaccharides of Bordetellae could be used to devise a universal cross-protective vaccine component against infections with various bacteria from the genus Bordetella.
Heparan Sulfate Glycosaminoglycans: (Un)Expected Allies in Cancer Clinical Management

In an era when cancer glycobiology research is exponentially growing, we are witnessing a progressive translation of the major scientific findings to the clinical practice with the overarching aim of improving cancer patients’ management. Many mechanistic cell biology studies have demonstrated that heparan sulfate (HS) glycosaminoglycans are key molecules responsible for several molecular and biochemical processes, impacting extracellular matrix properties and cellular functions. HS can interact with a myriad of different ligands, and therefore, hold a pleiotropic role in regulating the activity of important cellular receptors and downstream signalling pathways. The aberrant expression of HS glycan chains in tumours determines main malignant features, such as cancer cell proliferation, angiogenesis, invasion and metastasis. In this review, we devote particular attention to HS biological activities, its expression profile and modulation in cancer. Moreover, we highlight HS clinical potential to improve both diagnosis and prognosis of cancer, either as HS-based biomarkers or as therapeutic targets.
Performance Analyses of Fatty Acids in Reactive Distillation Process for Biodiesel Production

Different materials are used for biodiesel production via esterification or transesterificationprocesses. In esterification reaction, an organic acid is reacted with an alcohol to produce an ester (biodiesel) and water (by-product). It then implies that the fatty acid used determines the type and the purity of the biodiesel obtained. As such, the performances of the fatty acids available and used for biodiesel production are not, of course, likely to be the same. So, i t is good to have some knowledge about the performances of the fatty acids available for biodiesel production so as to know the type of a fatty acid to choose for the production of a particular biodiesel product at any time. Therefore, this work has been carried out to investigate the performances of some fatty acids used for the production of biodiesel using reactive distillation column. The fatty acids considered were oleic acid, which was discovered, according to Kusmiyati and Sugiharto (2010), to give biodiesel that had the quality required to be a diesel substitute, and some other ones (stearic acid, linoleic acid and palmitic acid) found to be present in jatropha oil. Methanol was used as the alcohol of the reaction. The study was carried out with the aid of Aspen HYSYS that was used to develop the model of the reactive distillation column in which both the reaction for biodiesel production and the separation of the unreacted materials and by-products were simultaneously carried out. The results obtained from the study revealed that, among the fatty acids investigated, the one with the highest performance was palmitic acid because it was able
Transferability of Molecular Potentials for 2D Molybdenum Disulphide

An ability of different molecular potentials to reproduce the properties of 2D molybdenum disulphide polymorphs is examined. Structural and mechanical properties, as well as phonon dispersion of the 1H, 1T and 1T’ single-layer MoS2 (SL MoS2) phases, were obtained using density functional theory (DFT) and molecular statics calculations (MS) with Stillinger-Weber, REBO, SNAP and ReaxFF interatomic potentials. Quantitative systematic comparison and discussion of the results obtained are reported.
Music intervention to relieve anxiety and pain in adults undergoing cardiac surgery: a systematic review and meta-analysis

Objectives Previous studies have reported beneficial effects of perioperative music on patients’ anxiety and pain. We performed a systematic review and meta-analysis of randomised controlled trials investigating music interventions in cardiac surgery. Methods Five electronic databases were systematically searched. Primary outcomes were patients’ postoperative anxiety and pain. Secondary outcomes were hospital length of stay, opioid use, vital parameters and time on mechanical ventilation. PRISMA guidelines were followed and PROSPERO database registration was completed (CRD42020149733). A meta-analysis was performed using random effects models and pooled standardised mean differences (SMD) with 95% confidence intervals were calculated. Results Twenty studies were included for qualitative analysis (1169 patients) and 16 (987 patients) for meta-analysis. The first postoperative music session was associated with significantly reduced postoperative anxiety (SMD = –0.50 (95% CI –0.67 to –0.32), p<0.01) and pain (SMD = –0.51 (95% CI –0.84 to –0.19), p<0.01). This is equal to a reduction of 4.00 points (95% CI 2.56 to 5.36) and 1.05 points (95% CI 0.67 to 1.41) on the State-Trait Anxiety Inventory and Visual Analogue Scale (VAS)/Numeric Rating Scale (NRS), respectively, for anxiety, and 1.26 points (95% CI 0.47 to 2.07) on the VAS/NRS for pain. Multiple days of music intervention reduced anxiety until 8 days postoperatively (SMD = –0.39 (95% CI –0.64 to –0.15), p<0.01). Conclusions Offering recorded music is associated with a significant reduction in postoperative anxiety and pain in cardiac surgery. Unlike pharmacological interventions, music is without side effects so is promising in this population.
Inorganic Chemical Composition of Swimming Pools in Amman-Jordan

Monitoring was carried out during summer 2011 in three types of swimming pools in Amman-Jordan. Thirty six water samples, collected from three users type of swimming pools (adults, family and infants), were examined for its major ionic composition (HCO3 - , Cl - , NO3 - , SO4 = , Ca +2 , Mg +2 , Na + , K + and PO4 +4 ) in addition to its BOD and COD content. All of the examined samples from the swimming pools water were acceptable according to the local and WHO standards. The type and number of users as well as the maintenance of the swimming pool water influenced the water quality. The results showed that there was a noticeable increase in NO3, PO4 and Cl than other ions. All of the examined samples from the swimming pools water were acceptable according to the local and WHO standards and although the water of the infant's users changed frequently, it showed the highest concentration of most of the parameters and Adults' pool showed the lowest.
Myocardial Function Imaging in Echocardiography Using Deep Learning

Deformation imaging in echocardiography has been shown to have better diagnostic and prognostic value than conventional anatomical measures such as ejection fraction. However, despite clinical availability and demonstrated efficacy, everyday clinical use remains limited at many hospitals. The reasons are complex, but practical robustness has been questioned, and a large inter-vendor variability has been demonstrated. In this work, we propose a novel deep learning based framework for motion estimation in echocardiography, and use this to fully automate myocardial function imaging. A motion estimator was developed based on a PWC-Net architecture, which achieved an average end point error of (0.06±0.04) mm per frame using simulated data from an open access database, on par or better compared to previously reported state of the art. We further demonstrate unique adaptability to image artifacts such as signal dropouts, made possible using trained models that incorporate relevant image augmentations. Further, a fully automatic pipeline consisting of cardiac view classification, event detection, myocardial segmentation and motion estimation was developed and used to estimate left ventricular longitudinal strain in vivo. The method showed promise by achieving a mean deviation of (−0.7±1.6)% compared to a semi-automatic commercial solution for N=30 patients with relevant disease, within the expected limits of agreement. We thus believe that learning-based motion estimation can facilitate extended use of strain imaging in clinical practice.
“In cities, it’s not far, but it takes long”: comparing estimated and replicated travel times to reach life-saving obstetric care in Lagos, Nigeria

Background Travel time to comprehensive emergency obstetric care (CEmOC) facilities in low-resource settings is commonly estimated using modelling approaches. Our objective was to derive and compare estimates of travel time to reach CEmOC in an African megacity using models and web-based platforms against actual replication of travel. Methods We extracted data from patient files of all 732 pregnant women who presented in emergency in the four publicly owned tertiary CEmOC facilities in Lagos, Nigeria, between August 2018 and August 2019. For a systematically selected subsample of 385, we estimated travel time from their homes to the facility using the cost-friction surface approach, Open Source Routing Machine (OSRM) and Google Maps, and compared them to travel time by two independent drivers replicating women’s journeys. We estimated the percentage of women who reached the facilities within 60 and 120 min. Results The median travel time for 385 women from the cost-friction surface approach, OSRM and Google Maps was 5, 11 and 40 min, respectively. The median actual drive time was 50–52 min. The mean errors were >45 min for the cost-friction surface approach and OSRM, and 14 min for Google Maps. The smallest differences between replicated and estimated travel times were seen for night-time journeys at weekends; largest errors were found for night-time journeys at weekdays and journeys above 120 min. Modelled estimates indicated that all participants were within 60 min of the destination CEmOC facility, yet journey replication showed that only 57% were, and 92% were within 120 min. Conclusions Existing modelling methods underestimate actual travel time in low-resource megacities. Significant gaps in geographical access to life-saving health services like CEmOC must be urgently addressed, including in urban areas. Leveraging tools that generate ‘closer-to-reality’ estimates will be vital for service planning if universal health coverage targets are to be realised by 2030.