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asmaa hamoda, A. Ibrahim, and wael xekry, "INCIDENCE AND OUTCOME OF colorectal carcinoma IN PEDIATRIC CANCER PATIENTS,single center experience", SIOP ASIA, moscow, 24may, Submitted.
asmaa hamoda, A. Ibrahim, and wael xekry, "INCIDENCE AND OUTCOME OF colorectal carcinoma IN PEDIATRIC CANCER PATIENTS,single center experience", SIOP ASIA, moscow, 24may, Submitted.
Guo, W. - B., G. - Q. Xue, X. Li, Y. - A. Liu, L. - C. Sun, Y. - F. Chang, C. - H. Chang, C. - L. Chung, Y. Wang, W. Wang, et al., down there?, : CSIRO, Submitted. Abstract
Zhang, K., Y. Xing, G. Wang, R. Shemi, M. Duan, W. L., and X. Xie, "Ridge-furrow with film mulching practice ameliorates soil microbial metabolic activity and carbon utilization in rhizosphere soil of rapeseed (Brassica napus L.)", Soils and Sediments, vol. 19, pp. 2764–2776, Submitted. zhang-2019-ridge-furrowwithfi.pdf
Xiao, R., A. Ali, Y. Xu, H. Abdelrahman, R. Li, Y. Lin, N. Bolan, S. M. Shaheen, J. Rinklebe, and Z. Zhang, "Earthworms as candidates for remediation of potentially toxic elements contaminated soils and mitigating the environmental and human health risks: A review", Environment International, vol. 158, pp. 106924, 2022. AbstractWebsite

Global concerns towards potentially toxic elements (PTEs) are steadily increasing due to the significant threats that PTEs pose to human health and environmental quality. This calls for immediate, effective and efficient remediation solutions. Earthworms, the 'ecosystem engineers', can modify and improve soil health and enhance plant productivity. Recently, considerable attention has been paid to the potential of earthworms, alone or combined with other soil organisms and/or soil amendments, to remediate PTEs contaminated soils. However, the use of earthworms in the remediation of PTEs contaminated soil (i.e., vermiremediation) has not been thoroughly reviewed to date. Therefore, this review discusses and provides comprehensive insights into the suitability of earthworms as potential candidates for bioremediation of PTEs contaminated soils and mitigating environmental and human health risks. Specifically, we reviewed and discussed: i) the occurrence and abundance of earthworms in PTEs contaminated soils; ii) the influence of PTEs on earthworm communities in contaminated soils; iii) factors affecting earthworm PTEs accumulation and elimination, and iv) the dynamics and fate of PTEs in earthworm amended soils. The technical feasibility, knowledge gaps, and practical challenges have been worked out and critically discussed. Therefore, this review could provide a reference and guidance for bio-restoration of PTEs contaminated soils and shall also help developing innovative and applicable solutions for controlling PTEs bioavailability for the remediation of contaminated soils and the mitigation of the environment and human risks.

Méndez-Sánchez, N., E. Bugianesi, R. G. Gish, F. Lammert, H. Tilg, M. H. Nguyen, S. K. Sarin, N. Fabrellas, S. Zelber-Sagi, J. - G. Fan, et al., "Global multi-stakeholder endorsement of the MAFLD definition", The Lancet Gastroenterology & HepatologyThe Lancet Gastroenterology & Hepatology, vol. 7, issue 5: Elsevier, pp. 388 - 390, 2022. AbstractWebsite
Borayek, R., F. Foroughi, X. Xin, A. M. Mohamed, M. M. Abdelrahman, mostafa zedan, D. Zhang, and J. Ding, "Near-Zero Hysteresis Ionic Conductive Elastomers with Long-Term Stability for Sensing Applications", ACS Applied Materials & InterfacesACS Applied Materials & Interfaces, vol. 14, issue 9: American Chemical Society, pp. 11727 - 11738, 2022. AbstractWebsite
Leng, L., R. Liu, S. Xu, B. A. Mohamed, Z. Yang, Y. Hu, J. Chen, S. Zhao, Z. Wu, H. Peng, et al., An overview of sulfur-functional groups in biochar from pyrolysis of biomass, , vol. 10, issue 2, pp. 107185, 2022. AbstractWebsite

Biochar is a solid material obtained from the pyrolytic carbonization of biomass in an oxygen-free/limited environment. Sulfur-containing biochar has a wide range of applications, such as adsorptive removal of pollutants (e.g., Hg, Cd, and Ni) and acting as a solid acid catalyst or as an electrode of Li-S battery. To date, many methods have been developed to strengthen the function of biochar by introducing sulfur-containing groups to promote the application and commercialization of biochar. This review aims to present the formation, analysis, engineering, and application of sulfur-functional groups in biochar. The sulfur-functional groups such as organic sulfur (e.g., C–S, –C–S–C–, CS, thiophene, and sulfone) and inorganic sulfur (e.g., sulfate, sulfide, sulfite, and elemental S) can be determined through Fourier transform infrared spectrometry (FTIR), X-ray photoelectron spectroscopy (XPS), and X-ray absorption near edge structure (XANES). The sulfur-functional groups can be obtained through selecting biomass composition, pyrolysis process, S-doping, and post-treatment of biochar, but the engineering is challenging. The positive effect of sulfur-functional groups in the application is also analyzed in this paper, such as the complexation and electron transfer between sulfur-functional groups and heavy metal (e.g., Hg, Cd, and Ni) on improving biochar adsorption capacity. However, there are still challenges in directional synthesis, precise determination, and regulation of application performance. Based on the research gaps identified, future prospective investigation directions on analysis, engineering, and application of biochar S-functional groups were presented in this review.

Xie, P., Z. Shi, M. Feng, K. Sun, Y. Liu, K. Yan, C. Liu, T. A. A. Moussa, M. Huang, S. Meng, et al., Recent advances in radio-frequency negative dielectric metamaterials by designing heterogeneous composites, , 2022. AbstractWebsite

Dielectric constant (ε, epsilon) is one of the basic physical parameters for materials, determining the response of materials to electromagnetic waves or electrical field; its value is generally positive. In fact, dielectric constant can also be negative, regarded as supernormal performance to some degree. The negative dielectric property has become research hotspot as an essential key for constructing metamaterials, showing unique and exotic electromagnetic properties not existing in naturally occurring materials, such as negative refraction, perfect troubles, and reverse Doppler effect. Recently, the feasibility is demonstrated to achieve negative dielectric property in conventional heterogeneous composites rather than periodic artificial arrays; drawing great attention from researchers in material science and engineering, many advances have been made and can promote the development of metamaterials and conventional electromagnetic functional materials. Here, we reviewed the recent advances in negative dielectric property designed in some heterogeneous composites, including metal composites, carbon composites, ceramic composites, conducting polymer. Besides, various strategies, including designing different microstructures, changing the working temperatures, choosing flexible matrix or fillers, electro-magnetic coupling, were summarized to precisely adjust negative dielectric property. Finally, the question unsolved and perspectives about negative dielectric property are put forward; we expect to shed light on the mechanism of negative dielectric property as well as its relationship with the material design in composition and microstructure.

Monzur, S., G. Hassan, S. M. Afify, K. Kumon, H. Mansour, H. M. Nawara, M. Sheta, H. A. Abu Quora, M. H. Zahra, Y. Xu, et al., "Diphenyleneiodonium efficiently inhibits the characteristics of a cancer stem cell model derived from induced pluripotent stem cells.", Cell biochemistry and function, vol. 40, issue 3, pp. 310-320, 2022. Abstract

Diphenyleneiodonium (DPI) has long been evaluated as an anticancer drug inhibiting NADPH oxidase, the IC in several cancer cell lines was reported 10 µM, which is too high for efficacy. In this study, we employed miPS-Huh7cmP cells, which we previously established as a cancer stem cell (CSC) model from induced pluripotent stem cells, to reevaluate the efficacy of DPI because CSCs are currently one of the main foci of therapeutic strategy to treat cancer, but generally considered resistant to chemotherapy. As a result, the conventional assay for the cell growth inhibition by DPI accounted for an IC at 712 nM that was not enough to define the effectiveness as an anticancer drug. Simultaneously, the wound-healing assay revealed an IC of approximately 500 nM. Comparatively, the IC values shown on sphere formation, colony formation, and tube formation assays were 5.52, 12, and 8.7 nM, respectively. However, these inhibitory effects were not observed by VAS2780, also a reputed NADPH oxidase inhibitor. It is noteworthy that these three assays are evaluating the characteristic of CSCs and are designed in the three-dimensional (3D) culture methods. We concluded that DPI could be a suitable candidate to target mitochondrial respiration in CSCs. We propose that the 3D culture assays are more efficient to screen anti-CSC drug candidates and better mimic tumor microenvironment when compared to the adherent monolayer of 2D culture system used for a conventional assay, such as cell growth inhibition and wound-healing assays.

Afify, S. M., G. Hassan, H. M. Nawara, M. H. Zahra, Y. Xu, M. J. Alam, K. Saitoh, H. Mansour, H. A. Abu Quora, M. Sheta, et al., "Optimization of production and characterization of a recombinant soluble human Cripto-1 protein inhibiting self-renewal of cancer stem cells.", Journal of cellular biochemistry, 2022. Abstract

Human Cripto-1 is a member of the epidermal growth factor (EGF)-Cripto-FRL-1-Cryptic (CFC) family family and performs critical roles in cancer and various pathological and developmental processes. Recently we demonstrated that a soluble form of Cripto-1 suppresses the self-renewal and enhances the differentiation of cancer stem cells (CSCs). A functional form of soluble Cripto-1 was found to be difficult to obtain because of the 12 cysteine residues in the protein which impairs the folding process. Here, we optimized the protocol for a T7 expression system, purification from inclusion bodies under denatured conditions refolding of a His-tagged Cripto-1 protein. A concentrations of 0.2-0.4 mM isopropyl β-D-1-thiogalactopyranoside (IPTG) at 37°C was found to be the optimal concentration for Cripto-1 expression while imidazole at 0.5 M was the optimum concentration to elute the Cripto-1 protein from a Ni-column in the smallest volume. Cation exchange column chromatography of the Cripto-1 protein in the presence of 8 M urea exhibited sufficient elution profile at pH 5, which was more efficient at recovery. The recovery of the protein reached to more than 26.6% after refolding with arginine. The purified Cripto-1 exhibited high affinity to the anti-ALK-4 antibody and suppressed sphere forming ability of CSCs at high dose and induced cell differentiation.

Goncalves, D. R., J. Leroy, S. Van Hees, I. Xhonneux, P. E. J. Bols, F. Kiekens, and W. F. A. Marei, "Cellular uptake of polymeric nanoparticles by bovine cumulus-oocyte complexes and their effect on in vitro developmental competence", Eur J Pharm Biopharm, 2020/11/29, vol. 158, pp. 143-155, Jan, 2021. AbstractWebsite

Polymeric nanoparticles (NPs) are produced using bio-compatible and bio-degradable materials such as PLGA (Poly(lactic-co-glycolic acid)). This technology provides a valuable tool to deliver molecules to the subcellular level with a relatively low risk of cytotoxicity. However their use in the field of reproductive biotechnology is not yet scientifically substantiated. The aim of the present study was to test if PLGA NPs can be taken-up by cumulus-enclosed oocytes as a first step towards potential oocyte-targeted applications to enhance oocyte quality and fertility. We conducted a series of experiments using bovine in vitro oocyte maturation as a model to study FITC-conjugated PLGA internalization (using laser-scanning confocal microscopy) and the effect of some important physical (particle size) and chemical (conjugation with PEG) modifications. We show evidence that PLGA NPs can be taken-up by cumulus cells and to a less extent by the enclosed oocytes regardless of the NP size. The NP transfer to the oocyte appear to be transcellular (via cumulus cells and transzonal projections) and paracellular (via zona pellucida). The PLGA NPs were detected in the vicinity of the oocyte as quick as 2 h post-exposure in a protein-free medium and did not compromise cumulus cell viability nor subsequent early embryo development or embryo quality. These results suggest that PLGA NPs may have promising applications as carriers for drug or molecule delivery targeting cumulus cells and oocytes.

Sonousi, A., J. C. K. Quirke, P. Waduge, T. Janusic, M. Gysin, K. Haldimann, S. Xu, S. N. Hobbie, S. - H. Sha, J. Schacht, et al., "An Advanced Apralog with Increased in vitro and in vivo Activity toward Gram-negative Pathogens and Reduced ex vivo Cochleotoxicity", ChemMedChem, vol. 16, issue 2: John Wiley & Sons, Ltd, pp. 335 - 339, 2021. AbstractWebsite

Abstract We describe the convergent synthesis of a 5-O-?-D-ribofuranosyl-based apramycin derivative (apralog) that displays significantly improved antibacterial activity over the parent apramycin against wild-type ESKAPE pathogens. In addition, the new apralog retains excellent antibacterial activity in the presence of the only aminoglycoside modifying enzyme (AAC(3)-IV) acting on the parent, without incurring susceptibility to the APH(3?) mechanism that disables other 5-O-?-D-ribofuranosyl 2-deoxystreptamine type aminoglycosides by phosphorylation at the ribose 5-position. Consistent with this antibacterial activity, the new apralog has excellent 30?nM activity (IC50) for the inhibition of protein synthesis by the bacterial ribosome in a cell-free translation assay, while retaining the excellent across-the-board selectivity of the parent for inhibition of bacterial over eukaryotic ribosomes. Overall, these characteristics translate into excellent in?vivo efficacy against E. coli in a mouse thigh infection model and reduced ototoxicity vis à vis the parent in mouse cochlear explants.

Akowuah, E., R. A. Benson, E. J. Caruana, G. Chetty, J. Edwards, S. Forlani, G. Gradinariu, G. J. Murphy, A. Y. Oo, A. J. Patel, et al., "Early outcomes and complications following cardiac surgery in patients testing positive for coronavirus disease 2019: An international cohort study", The Journal of Thoracic and Cardiovascular SurgeryThe Journal of Thoracic and Cardiovascular Surgery, vol. 162, issue 2: Elsevier, pp. e355 - e372, 2021. AbstractWebsite
Glasbey, J., A. Ademuyiwa, A. Adisa, E. Alameer, A. P. Arnaud, F. Ayasra, J. Azevedo, A. Minaya-Bravo, A. Costas-Chavarri, J. Edwards, et al., "Effect of COVID-19 pandemic lockdowns on planned cancer surgery for 15 tumour types in 61 countries: an international, prospective, cohort study", The Lancet OncologyThe Lancet Oncology, vol. 22, issue 11: Elsevier, pp. 1507 - 1517, 2021. AbstractWebsite
Biccard, B. M., L. du Toit, M. Lesosky, T. Stephens, L. Myer, A. B. A. Prempeh, N. Vickery, H. - L. Kluyts, A. Torborg, A. Omigbodun, et al., Enhanced postoperative surveillance versus standard of care to reduce mortality among adult surgical patients in Africa (ASOS-2): a cluster-randomised controlled trial, , vol. 9, issue 10, pp. e1391 - e1401, 2021. AbstractWebsite

Risk of mortality following surgery in patients across Africa is twice as high as the global average. Most of these deaths occur on hospital wards after the surgery itself. We aimed to assess whether enhanced postoperative surveillance of adult surgical patients at high risk of postoperative morbidity or mortality in Africa could reduce 30-day in-hospital mortality.
We did a two-arm, open-label, cluster-randomised trial of hospitals (clusters) across Africa. Hospitals were eligible if they provided surgery with an overnight postoperative admission. Hospitals were randomly assigned through minimisation in recruitment blocks (1:1) to provide patients with either a package of enhanced postoperative surveillance interventions (admitting the patient to higher care ward, increasing the frequency of postoperative nursing observations, assigning the patient to a bed in view of the nursing station, allowing family members to stay in the ward, and placing a postoperative surveillance guide at the bedside) for those at high risk (ie, with African Surgical Outcomes Study Surgical Risk Calculator scores ≥10) and usual care for those at low risk (intervention group), or for all patients to receive usual postoperative care (control group). Health-care providers and participants were not masked, but data assessors were. The primary outcome was 30-day in-hospital mortality of patients at low and high risk, measured at the participant level. All analyses were done as allocated (by cluster) in all patients with available data. This trial is registered with, NCT03853824.
Between May 3, 2019, and July 27, 2020, 594 eligible hospitals indicated a desire to participate across 33 African countries; 332 (56%) were able to recruit participants and were included in analyses. We allocated 160 hospitals (13 275 patients) to provide enhanced postoperative surveillance and 172 hospitals (15 617 patients) to provide standard care. The mean age of participants was 37·1 years (SD 15·5) and 20 039 (69·4%) of 28 892 patients were women. 30-day in-hospital mortality occurred in 169 (1·3%) of 12 970 patients with mortality data in the intervention group and in 193 (1·3%) of 15 242 patients with mortality data in the control group (relative risk 0·96, 95% CI 0·69–1·33; p=0·79). 45 (0·2%) of 22 031 patients at low risk and 309 (5·6%) of 5500 patients at high risk died. No harms associated with either intervention were reported.
This intervention package did not decrease 30-day in-hospital mortality among surgical patients in Africa at high risk of postoperative morbidity or mortality. Further research is needed to develop interventions that prevent death from surgical complications in resource-limited hospitals across Africa.
Bill & Melinda Gates Foundation and the World Federation of Societies of Anaesthesiologists.
For the Arabic, French and Portuguese translations of the abstract see Supplementary Materials section.

Kamran, M., D. Wang, H. A. S. Alhaithloul, S. M. Alghanem, T. Aftab, K. Xie, Y. Lu, C. Shi, J. Sun, and W. Gu, "Jasmonic acid-mediated enhanced regulation of oxidative, glyoxalase defense system and reduced chromium uptake contributes to alleviation of chromium (VI) toxicity in choysum (Brassica parachinensis L.)", Ecotoxicology and Environmental Safety, vol. 208, pp. 111758, 2021. Abstract
Talaat, H., J. Xu, M. Hatzopoulou, and H. Abdelgawad, Mobile monitoring and spatial prediction of black carbon in Cairo, Egypt, , vol. 193, issue 9, pp. 587, 2021. AbstractWebsite

This study harnesses the power of mobile data in developing a spatial model for predicting black carbon (BC) concentrations within one of the most heavily populated regions in the Middle East and North Africa MENA region, Greater Cairo Region (GCR) in Egypt. A mobile data collection campaign was conducted in GCR to collect BC measurements along specific travel routes. In total, 3,300 km were travelled across a widespread 525 km of routes. Reported average BC values were around 20 µg/m3, announcing an alarming order of magnitude value when compared to the maximum reported values in similar studies. A bi-directional stepwise land use regression (LUR) model was developed to select the best combination of explanatory variables and generate an exposure surface for BC, in addition to a number of machine learning models (random forest gradient boost, light gradient boost model (LightGBM), Keras neural network (NN)). Data from 7 air quality (AQ) stations were compared—in terms of mean square error (MSE) and mean absolute error (MAE)—with predictions from the LUR and the NN model. The NN model estimated higher BC concentrations in the downtown areas, while lower concentrations are estimated for the peripheral area at the east side of the city. Such results shed light on the credibility of the LUR models in generating a general spatial trend of BC concentrations while the superiority of NN in BC accuracy estimation (0.023 vs 0.241 in terms of MSE and 0.12 vs 0.389 in terms of MAE; of NN vs LUR respectively).

Wright, N. J., A. J. M. Leather, N. Ade-Ajayi, N. Sevdalis, J. Davies, D. Poenaru, E. Ameh, A. Ademuyiwa, K. Lakhoo, E. R. Smith, et al., Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study, , vol. 398, issue 10297, pp. 325 - 339, 2021. AbstractWebsite

Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality.
We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis.
We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality.
Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030.
Wellcome Trust.

Xiong, G., L. Li, A. W. Mohamed, X. Yuan, and J. Zhang, A new method for parameter extraction of solar photovoltaic models using gaining–sharing knowledge based algorithm, , vol. 7, pp. 3286 - 3301, 2021. AbstractWebsite

For the solar photovoltaic (PV) system to operate efficiently, it is necessary to effectively establish an equivalent model of PV cell and extract the relevant unknown model parameters accurately. This paper introduces a new metaheuristic algorithm, i.e., gaining-sharing knowledge based algorithm (GSK) to solve the solar PV model parameter extraction problem. This algorithm simulates the process of knowledge acquisition and sharing in the human life cycle and is with strong competitiveness in solving optimization problems. It includes two significant phases. The first phase is the beginner–intermediate or junior acquisition and sharing stage, and the second phase is the intermediate–expert or senior acquisition and sharing stage. In order to verify the effectiveness of GSK, it is applied to five PV models including the single diode model, double diode model, and three PV modules. The influence of population size on the algorithm performance is empirically investigated. Besides, it is further compared with some other excellent metaheuristic algorithms including basic algorithms and advanced algorithms. Among the five PV models, the root mean square error values between the measured data and the calculated data of GSK are 9.8602E−04 ± 2.18E−17, 9.8280E−04 ± 8.72E−07, 2.4251E−03 ± 1.04E−09, 1.7298E−03 ± 6.25E−18, and 1.6601E−02 ± 1.44E−16, respectively. The results show that GSK has overall better robustness, convergence, and accuracy.

Qiao, L., L. Xu, L. Yu, J. Wynn, R. Hernan, X. Zhou, C. Farkouh-Karoleski, U. S. Krishnan, J. Khlevner, A. De, et al., Rare and de novo variants in 827 congenital diaphragmatic hernia probands implicate LONP1 as candidate risk gene, , vol. 108, issue 10, pp. 1964 - 1980, 2021. AbstractWebsite

SummaryCongenital diaphragmatic hernia (CDH) is a severe congenital anomaly that is often accompanied by other anomalies. Although the role of genetics in the pathogenesis of CDH has been established, only a small number of disease-associated genes have been identified. To further investigate the genetics of CDH, we analyzed de novo coding variants in 827 proband-parent trios and confirmed an overall significant enrichment of damaging de novo variants, especially in constrained genes. We identified LONP1 (lon peptidase 1, mitochondrial) and ALYREF (Aly/REF export factor) as candidate CDH-associated genes on the basis of de novo variants at a false discovery rate below 0.05. We also performed ultra-rare variant association analyses in 748 affected individuals and 11,220 ancestry-matched population control individuals and identified LONP1 as a risk gene contributing to CDH through both de novo and ultra-rare inherited largely heterozygous variants clustered in the core of the domains and segregating with CDH in affected familial individuals. Approximately 3% of our CDH cohort who are heterozygous with ultra-rare predicted damaging variants in LONP1 have a range of clinical phenotypes, including other anomalies in some individuals and higher mortality and requirement for extracorporeal membrane oxygenation. Mice with lung epithelium-specific deletion of Lonp1 die immediately after birth, most likely because of the observed severe reduction of lung growth, a known contributor to the high mortality in humans. Our findings of both de novo and inherited rare variants in the same gene may have implications in the design and analysis for other genetic studies of congenital anomalies.

Gao, W., A. O. Elnabawy, Z. D. Hood, Y. Shi, X. Wang, L. T. Roling, X. Pan, M. Mavrikakis, Y. Xia, and M. Chi, "Atomistic insights into the nucleation and growth of platinum on palladium nanocrystals", Nature communications, vol. 12, issue 1: Nature Publishing Group, pp. 1-10, 2021. Abstract
Ramos-Casals, M., N. Acar-Denizli, A. Vissink, P. Brito-Zerón, X. Li, F. Carubbi, R. Priori, N. Toplak, C. Baldini, E. Faugier-Fuentes, et al., "Childhood-onset of primary Sjögren's syndrome: phenotypic characterization at diagnosis of 158 children.", Rheumatology (Oxford, England), vol. 60, issue 10, pp. 4558-4567, 2021. Abstract

OBJECTIVES: To characterize the phenotypic presentation at diagnosis of childhood-onset primary SS.

METHODS: The Big Data Sjögren Project Consortium is an international, multicentre registry using worldwide data-sharing cooperative merging of pre-existing clinical SS databases from the five continents. For this study, we selected those patients in whom the disease was diagnosed below the age of 19 years according to the fulfilment of the 2002/2016 classification criteria.

RESULTS: Among the 12 083 patients included in the Sjögren Big Data Registry, 158 (1.3%) patients had a childhood-onset diagnosis (136 girls, mean age of 14.2 years): 126 (80%) reported dry mouth, 111 (70%) dry eyes, 52 (33%) parotid enlargement, 118/122 (97%) positive minor salivary gland biopsy and 60/64 (94%) abnormal salivary US study, 140/155 (90%) positive ANA, 138/156 (89%) anti-Ro/La antibodies and 86/142 (68%) positive RF. The systemic EULAR Sjögren's syndrome disease activity index (ESSDAI) domains containing the highest frequencies of active patients included the glandular (47%), articular (26%) and lymphadenopathy (25%) domains. Patients with childhood-onset primary SS showed the highest mean ESSDAI score and the highest frequencies of systemic disease in 5 (constitutional, lymphadenopathy, glandular, cutaneous and haematological) of the 12 ESSDAI domains, and the lowest frequencies in 4 (articular, pulmonary, peripheral nerve and CNS) in comparison with patients with adult-onset disease.

CONCLUSIONS: Childhood-onset primary SS involves around 1% of patients with primary SS, with a clinical phenotype dominated by sicca features, parotid enlargement and systemic disease. Age at diagnosis plays a key role in modulating the phenotypic expression of the disease.

Kumon, K., S. M. Afify, G. Hassan, S. Ueno, S. Monzur, H. M. Nawara, H. A. A. Quora, M. Sheta, Y. Xu, X. Fu, et al., "Differentiation of cancer stem cells into erythroblasts in the presence of CoCl.", Scientific reports, vol. 11, issue 1, pp. 23977, 2021. Abstract

Cancer stem cells (CSCs) are subpopulations in the malignant tumors that show self-renewal and multilineage differentiation into tumor microenvironment components that drive tumor growth and heterogeneity. In previous studies, our group succeeded in producing a CSC model by treating mouse induced pluripotent stem cells. In the current study, we investigated the potential of CSC differentiation into blood cells under chemical hypoxic conditions using CoCl. CSCs and miPS-LLCcm cells were cultured for 1 to 7 days in the presence of CoCl, and the expression of VEGFR1/2, Runx1, c-kit, CD31, CD34, and TER-119 was assessed by RT-qPCR, Western blotting and flow cytometry together with Wright-Giemsa staining and immunocytochemistry. CoCl induced significant accumulation of HIF-1α changing the morphology of miPS-LLCcm cells while the morphological change was apparently not related to differentiation. The expression of VEGFR2 and CD31 was suppressed while Runx1 expression was upregulated. The population with hematopoietic markers CD34 and c-kit was immunologically detected in the presence of CoCl. Additionally, high expression of CD34 and, a marker for erythroblasts, TER-119, was observed. Therefore, CSCs were suggested to differentiate into erythroblasts and erythrocytes under hypoxia. This differentiation potential of CSCs could provide new insight into the tumor microenvironment elucidating tumor heterogenicity.