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2021
Collaborative, C. O. V. I. D. S., and G. S. Collaborative, "Effects of pre-operative isolation on postoperative pulmonary complications after elective surgery: an international prospective cohort study", AnaesthesiaAnaesthesia, vol. 76, issue 11: John Wiley & Sons, Ltd, pp. 1454 - 1464, 2021. AbstractWebsite

Summary We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05?1.36, p = 0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3 days, with an OR (95%CI) at 4?7 days or ≥ 8 days of 1.25 (1.04?1.48), p = 0.015 and 1.31 (1.11?1.55), p = 0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care.

Mohamed, B. A., N. Ellis, C. S. Kim, X. Bi, and W. - H. Chen, Engineered biochars from catalytic microwave pyrolysis for reducing heavy metals phytotoxicity and increasing plant growth, , vol. 271, pp. 129808, 2021. AbstractWebsite

Pb, Ni, and Co are among the most toxic heavy metals that pose direct risks to humans and biota. There are no published studies on biochars produced at low temperatures (i.e., 300 °C), which possess high sorption capacity for heavy metal remediation and reclamation of contaminated sandy soils. This research studied the effect of catalytic microwave pyrolysis of switchgrass (SG) using bentonite and K3PO4 to produce biochar at low temperature (300 °C) with high sorption capacity for reducing the phytotoxicity of heavy metals, and investigated the synergistic effects of catalyst mixture on biochar sorption capacity. The quality of the biochars was examined in terms of their impacts on plant growth, reducing phytotoxicity and uptake of heavy metals in sandy soil spiked with Pb, Ni, and Co. All catalysts increased the micropore surface area and cation-exchange capacity of biochars, and resulted in biochars rich in plant nutrients, which not only decreased heavy metal phytotoxicity, but also boosted plant growth in the spiked soil by up to 140% compared to the sample without biochar. By mixing bentonite and K3PO4 with SG during microwave pyrolysis, the efficacy of biochar in reducing phytotoxicity and heavy metals uptake was further enhanced because of the highest micropore surface area (402 m2/g), moderate contents of Ca, Mg, K, and Fe for ion-exchange and moderate concentration of phosphorus for the formation of insoluble heavy metal compounds. Generally, the biochar created at 300 °C (300-30KP) showed similar performance to the biochar created at 400 °C (400-30KP) in terms of reducing heavy metal bioavailability.

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

SummaryBackground
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.
Methods
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 ClinicalTrials.gov, NCT03853824.
Findings
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.
Interpretation
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.
Funding
Bill & Melinda Gates Foundation and the World Federation of Societies of Anaesthesiologists.
Translations
For the Arabic, French and Portuguese translations of the abstract see Supplementary Materials section.

Han, L., A. M. E. Khalil, J. Wang, Y. Chen, F. Li, H. Chang, H. Zhang, X. Liu, G. Li, and Q. Jia, "Graphene-boron nitride composite aerogel: a high efficiency adsorbent for ciprofloxacin removal from water", Separation and Purification Technology, vol. 278: Elsevier, pp. 119605, 2021. Abstract

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Khan, A., T. Wang, T. Hussain, Amna, F. Ali, F. Shi, A. Latef, O. Ali, K. Hayat, S. Mehmood, et al., "Halotolerant-Koccuria rhizophila (14asp)-Induced Amendment of Salt Stress in Pea Plants by Limiting Na+ Uptake and Elevating Production of Antioxidants", Agronomy, vol. 11, issue 10, pp. 1907, 2021. AbstractWebsite

Endophytic bacteria are useful for their safe services in plant growth improvement and for ameliorating abiotic and biotic stresses. Salt-tolerant plant-growth-promoting Kocuria rhizophila 14asp (accession number KF 875448) was investigated for its role in pea plants under a saline environment. Salt stress (75 mM and 150 mM NaCl) was subjected to two pea varieties, peas2009 and 9800-10, in a greenhouse under a complete randomized design. Different parameters such as plant growth promotion, relative water content, chlorophyll, antioxidants, and mineral contents were analyzed to elucidate the extent of tolerance persuaded by PGPB (plant-growth-promoting bacteria). Exhibition of adverse effects was noticed in uninoculated varieties. However, inoculation of K. rhizophila improved the morphological parameters, antioxidant enzymes, and minimized the uptake of Na+ in plants under various saline regimes. Pea variety 9800-10 exhibited more tolerance than peas2009 in all traits, such as root and shoot length, fresh and dry biomass, chlorophyll contents, and antioxidant enzymes. Our results showed that halotolerant K. rhizophila inoculation plays a vital role in enhancing plant growth by interacting ingeniously with plants through antioxidant systems, enduring saline conditions.

Mohamed, O. G., Z. G. Khalil, A. A. Salim, H. Cui, A. Blumenthal, and R. J. Capon, "Lincolnenins A–D: Isomeric Bactericidal Bianthracenes from Streptomyces lincolnensis", The Journal of Organic ChemistryThe Journal of Organic Chemistry, vol. 86, issue 16: American Chemical Society, pp. 11011 - 11018, 2021. AbstractWebsite
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Alsherbiny, M. A., D. J. Bhuyan, I. Radwan, D. Chang, and C. - G. Li, Metabolomic identification of anticancer metabolites of australian propolis and proteomic elucidation of its synergistic mechanisms with doxorubicin in the MCF7 Cells, , vol. 22, issue 15: Multidisciplinary Digital Publishing Institute, pp. 7840, 2021. Abstract
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Salim, A. A., Z. G. Khalil, A. H. Elbanna, T. Wu, and R. J. Capon, "Methods in Microbial Biodiscovery", Marine Drugs, vol. 19, issue 9, pp. 503, 2021. Abstract

This review presents an account of the microbial biodiscovery methodology developed and applied in our laboratory at The University of Queensland, Institute for Molecular Bioscience, with examples drawn from our experiences studying natural products produced by Australian marine-derived (and terrestrial) fungi and bacteria.

Leitch, A. C., I. Ibrahim, T. M. Abdelghany, A. Charlton, C. Roper, D. Vidler, J. M. Palmer, C. Wilson, D. E. Jones, P. G. Blain, et al., "The methylimidazolium ionic liquid M8OI is detectable in human sera and is subject to biliary excretion in perfused human liver", Toxicology, vol. 459, 2021. AbstractWebsite
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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

SummaryBackground
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.
Methods
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.
Findings
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.
Interpretation
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.
Funding
Wellcome Trust.

Elbanna, A. H., Z. G. Khalil, P. V. Bernhardt, and R. J. Capon, "Neobulgarones Revisited: Anti and Syn Bianthrones from an Australian Mud Dauber Wasp Nest-Associated Fungus, Penicillium sp. CMB-MD22.", Journal of natural products, vol. 84, issue 3, pp. 762–770, 2021. Abstract

We report on the chemical analysis of a mud dauber wasp nest-associated fungus, Penicillium sp. CMB-MD22, leading to the discovery and structure elucidation of three known (1-3) and two new (4 and 5) anthrones, and a family of new and known bianthrones, neobulgarones 6-23. Detection and structure elucidation of 1-23 was supported by detailed spectroscopic analysis, as well as chemical (thermal) transformations, and global natural products social (GNPS) molecular networking. An empirical approach using HPLC retention times was effective at differentiating anti from syn bianthrone isomers, while a facile thermal equilibration was shown to favor anti over syn isomers. The neobulgarones 6-23 are natural products, and a crude extract rich in 6-23 exhibits selective antifungal activity against a co-isolated mud dauber wasp nest-associated fungus, suggestive of a possible ecological role as an antifungal chemical defense.

Khushi, S., A. A. Salim, A. H. Elbanna, L. Nahar, and R. J. Capon, "New from Old: Thorectandrin Alkaloids in a Southern Australian Marine Sponge, Thorectandra choanoides (CMB-01889)", Marine Drugs, vol. 19, issue 2, pp. 97, 2021. Abstract

Thorectandra choanoides (CMB-01889) was prioritized as a source of promising new chemistry from a library of 960 southern Australian marine sponge extracts, using a global natural products social (GNPS) molecular networking approach. The sponge was collected at a depth of 45 m. Chemical fractionation followed by detailed spectroscopic analysis led to the discovery of a new tryptophan-derived alkaloid, thorectandrin A (1), with the GNPS cluster revealing a halo of related alkaloids 1a–1n. In considering biosynthetic origins, we propose that Thorectandrachoanoides (CMB-01889) produces four well-known alkaloids, 6-bromo-1′,8-dihydroaplysinopsin (2), 6-bromoaplysinopsin (3), aplysinopsin (4), and 1′,8-dihydroaplysinopsin (10), all of which are susceptible to processing by a putative indoleamine 2,3-dioxygenase-like (IDO) enzyme to 1a–1n. Where the 1′,8-dihydroalkaloids 2 and 10 are fully transformed to stable ring-opened thorectandrins 1 and 1a–1b, and 1h–1j, respectively, the conjugated precursors 3 and 4 are transformed to highly reactive Michael acceptors that during extraction and handling undergo complete transformation to artifacts 1c–1g, and 1k–1n, respectively. Knowledge of the susceptibility of aplysinopsins as substrates for IDOs, and the relative reactivity of Michael acceptor transformation products, informs our understanding of the pharmaceutical potential of this vintage marine pharmacophore. For example, the cancer tissue specificity of IDOs could be exploited for an immunotherapeutic response, with aplysinopsins transforming in situ to Michael acceptor thorectandrins, which covalently bind and inhibit the enzyme.

Wang, J., P. R. Ahimaz, S. Hashemifar, J. Khlevner, J. A. Picoraro, W. Middlesworth, M. M. Elfiky, J. Que, Y. Shen, and W. K. Chung, Novel candidate genes in esophageal atresia/tracheoesophageal fistula identified by exome sequencing, , vol. 29, issue 1, pp. 122 - 130, 2021. AbstractWebsite

The various malformations of the aerodigestive tract collectively known as esophageal atresia/tracheoesophageal fistula (EA/TEF) constitute a rare group of birth defects of largely unknown etiology. Previous studies have identified a small number of rare genetic variants causing syndromes associated with EA/TEF. We performed a pilot exome sequencing study of 45 unrelated simplex trios (probands and parents) with EA/TEF. Thirteen had isolated and 32 had nonisolated EA/TEF; none had a family history of EA/TEF. We identified de novo variants in protein-coding regions, including 19 missense variants predicted to be deleterious (D-mis) and 3 likely gene-disrupting (LGD) variants. Consistent with previous studies of structural birth defects, there is a trend of increased burden of de novo D-mis in cases (1.57-fold increase over the background mutation rate), and the burden is greater in constrained genes (2.55-fold, p = 0.003). There is a frameshift de novo variant in EFTUD2, a known EA/TEF risk gene involved in mRNA splicing. Strikingly, 15 out of 19 de novo D-mis variants are located in genes that are putative target genes of EFTUD2 or SOX2 (another known EA/TEF gene), much greater than expected by chance (3.34-fold, p value = 7.20e−5). We estimated that 33% of patients can be attributed to de novo deleterious variants in known and novel genes. We identified APC2, AMER3, PCDH1, GTF3C1, POLR2B, RAB3GAP2, and ITSN1 as plausible candidate genes in the etiology of EA/TEF. We conclude that further genomic analysis to identify de novo variants will likely identify previously undescribed genetic causes of EA/TEF.

Elbanna, A. H., Z. G. Khalil, and R. J. Capon, "Oxandrastins: Antibacterial Meroterpenes from an Australian Mud Dauber Wasp Nest-Associated Fungus, Penicillium sp. CMB-MD14", Molecules, vol. 26, issue 23, pp. 7144, 2021. Abstract

The ethyl acetate extract of an ISP-2 agar cultivation of the wasp nest-associated fungus Penicillium sp. CMB-MD14 exhibited promising antibacterial activity against vancomycin-resistant enterococci (VRE), with a bioassay guided chemical investigation yielding the new meroterpene, oxandrastin A (1), the first andrastin-like metabolite with an extra oxygenation at C-2. A culture media optimisation strategy informed a scaled-up rice cultivation that yielded 1, together with three new oxandrastins B–D (2–4), two known andrastins C (5) and F (6), and a new meroterpene of the austalide family, isoaustalide F (7). Structures of 1–7 were assigned based on detailed spectroscopic analysis and chemical interconversion. A GNPS molecular networking analysis of the rice cultivation extract detected the known austalides B (8), H (9), and H acid (10), tentatively identified based on molecular formulae and co-clustering with 7. That the anti-VRE properties of the CMB-MD14 extract were exclusively attributed to 1 (IC50 6.0 µM, MIC99 13.9 µM), highlights the importance of the 2-OAc and 3-OAc moieties to the oxandrastin anti-VRE pharmacophore.

Zainab, N., Amna, A. A. Khan, M. A. Azeem, B. Ali, T. Wang, F. Shi, S. M. Alghanem, M. F. Hussain Munis, M. Hashem, et al., "PGPR-Mediated Plant Growth Attributes and Metal Extraction Ability of Sesbania sesban L. in Industrially Contaminated Soils", Agronomy, vol. 11, issue 9, pp. 1820, 2021. AbstractWebsite

The release of harmful wastes via different industrial activities is the main cause of heavy metal toxicity. The present study was conducted to assess the effects of heavy metal stress on the plant growth traits, antioxidant enzyme activities, chlorophyll content and proline content of Sesbania sesban with/without the inoculation of heavy-metal-tolerant Bacillus gibsonii and B. xiamenensis. Both PGP strains showed prominent ACC-deaminase, indole acetic acid, exopolysaccharides production and tolerance at different heavy metal concentrations (50–1000 mg/L). Further, in a pot experiment, S. sesban seeds were grown in contaminated and noncontaminated soils. After harvesting, plants were used for the further analysis of growth parameters. The experiment comprised of six different treatments. The effects of heavy metal stress and bacterial inoculation on the plant root length; shoot length; fresh and dry weight; photosynthetic pigments; proline content; antioxidant activity; and absorption of metals were observed at the end of the experiment. The results revealed that industrially contaminated soils distinctly reduced the growth of plants. However, both PGPR strains enhanced the root length up to 105% and 80%. The shoot length was increased by 133% and 75%, and the fresh weight was increased by 121% and 129%. The proline content and antioxidant enzymes posed dual effects on the plants growing in industrially contaminated soil, allowing them to cope with the metal stress, which enhanced the plant growth. The proline content was increased up to 190% and 179% by the inoculation of bacterial strains. Antioxidant enzymes, such as SOD, increased to about 216% and 245%, while POD increased up to 48% and 49%, respectively. The results clearly show that the utilized PGPR strains might be strong candidates to assist S. sesban growth under heavy metal stress conditions. We highly suggest these PGPR strains for further implementation in field experiments.

Elbanna, A. H., A. A. Dewa, Z. G. Khalil, and R. J. Capon, "Precursor-Directed Biosynthesis Mediated Amplification of Minor Aza Phenylpropanoid Piperazines in an Australian Marine Fish-Gut-Derived Fungus, Chrysosporium sp. CMB-F214", Marine Drugs, vol. 19, issue 9, pp. 478, 2021. Abstract

Chemical analysis of an M1 agar plate cultivation of a marine fish-gut-derived fungus, Chrysosporium sp. CMB-F214, revealed the known chrysosporazines A–D (11–14) in addition to a suite of very minor aza analogues 1–6. A microbioreactor (MATRIX) cultivation profiling analysis failed to deliver cultivation conditions that significantly improved the yields of 1–6; however, it did reveal that M2 agar cultivation produced the new natural product 15. A precursor-directed biosynthesis strategy adopting supplementation of a CMB-F214 M1 solid agar culture with sodium nicotinate enhanced production of otherwise inaccessible azachrysposorazines A1 (1), A2 (2), B1 (3), C1 (4), C2 (5) and D1 (6), in addition to four new chrysosporazines; chrysosporazines N–P (7–9) and spirochrysosporazine A (10). Structures inclusive of absolute configurations were assigned to 1–15 based on detailed spectroscopic and chemical analyses, and biosynthetic considerations. Non-cytotoxic to human carcinoma cells, azachrysosporazies 1–5 were capable of reversing doxorubicin resistance in P-glycoprotein (P-gp)-overexpressing human colon carcinoma cells (SW620 Ad300), with optimum activity exhibited by the C-2′ substituted analogues 3–5.

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.

Kumar, A., R. Ishida, T. Strilets, J. Cole, J. Lopez-Orozco, N. Fayad, A. Felix-Lopez, M. Elaish, D. Evseev, and K. E. Magor, SARS-CoV-2 non-structural protein 1 inhibits the interferon response by causing depletion of key host signaling factors., : American Society for Microbiology 1752 N St., NW, Washington, DC, pp. JVI - 00266, 2021. Abstract
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Hasan, M. M., B. M. Alharbi, H. A. S. Alhaithloul, A. M. Abdulmajeed, S. M. Alghanem, A. A. M. Al-Mushhin, M. S. Jahan, F. J. Corpas, X. - W. Fang, and M. H. Soliman, "Spermine-Mediated Tolerance to Selenium Toxicity in Wheat (Triticum aestivum L.) Depends on Endogenous Nitric Oxide Synthesis", Antioxidants, vol. 10, issue 11, pp. 1835, 2021. AbstractWebsite

Excess selenium (Se) causes toxicity, and nitric oxide (NO)’s function in spermine (Spm)-induced tolerance to Se stress is unknown. Using wheat plants exposed to 1 mM sodium selenate—alone or in combination with either 1 mM Spm, 0.1 mM NO donor sodium nitroprusside (SNP) or 0.1 mM NO scavenger cPTIO—the potential beneficial effects of these compounds to palliate Se-induced stress were evaluated at physiological, biochemical and molecular levels. Se-treated plants accumulated Se in their roots (92%) and leaves (95%) more than control plants. Furthermore, Se diminished plant growth, photosynthetic traits and the relative water content and increased the levels of malondialdehyde, H2O2, osmolyte and endogenous NO. Exogenous Spm significantly decreased the levels of malondialdehyde by 28%, H2O2 by 37% and electrolyte leakage by 42%. Combined Spm/NO treatment reduced the Se content and triggered plant growth, photosynthetic traits, antioxidant enzymes and glyoxalase systems. Spm/NO also upregulated MTP1, MTPC3 and HSP70 and downregulated TaPCS1 and NRAMP1 (metal stress-related genes involved in selenium uptake, translocation and detoxification). However, the positive effects of Spm on Se-stressed plants were eliminated by the NO scavenger. Accordingly, data support the notion that Spm palliates selenium-induced oxidative stress since the induced NO elicits antioxidant defence upregulation but downregulates Se uptake and translocation. These findings pave the way for potential biotechnological approaches to supporting sustainable wheat crop production in selenium-contaminated areas.

Alsherbiny, M. A., D. J. Bhuyan, M. N. Low, D. Chang, and C. G. Li, Synergistic interactions of cannabidiol with chemotherapeutic drugs in mcf7 cells: Mode of interaction and proteomics analysis of mechanisms, , vol. 22, issue 18: Multidisciplinary Digital Publishing Institute, pp. 10103, 2021. Abstract
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Alsherbiny, M., I. Radwan, N. Moustafa, D. Bhuyan, M. El-Waisi, D. Chang, and C. G. Li, Trustworthy Deep Neural Network for Inferring Anticancer Synergistic Combinations, : IEEE, 2021. Abstract
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Korai, P. K., T. A. Sial, G. Pan, H. Abdelrahman, A. Sikdar, F. Kumbhar, S. A. Channa, E. F. Ali, J. Zhang, J. Rinklebe, et al., "Wheat and maize-derived water-washed and unwashed biochar improved the nutrients phytoavailability and the grain and straw yield of rice and wheat: A field trial for sustainable management of paddy soils", Journal of Environmental Management, vol. 297, pp. 113250, 2021. AbstractWebsite

A field experiment was carried out to evaluate the effects of different biochars on grain yield and phytoavailability and uptake of macro- and micro-nutrients by rice and wheat grown in a paddy soil in a rotation. Soil was treated with i) maize raw (un-washed) biochar (MRB), ii) maize water-washed biochar (MWB), iii) wheat raw biochar (WRB) or iv) wheat water-washed biochar (WWB) and untreated soil was used as control (CF). Inorganic fertilizers were applied to all soils while biochar treated soils received 20 ton ha−1 of designated biochar before rice cultivation in rice-wheat rotation. The WRB significantly (P < 0.05) increased rice grain yield and straw by up to 49%, compared to the CF. Biochar addition, particularly WRB, significantly increased the availability of N, P, K and their content in the grain (26–37%) and straw (22–37%) of rice and wheat. Also, the availability and grain content of Fe, Mn, Zn, and Cu increased significantly after biochar addition, particularly after the WRB, due to WRB water dissolved C acting as a carrier for micronutrients in soil and plant. However, the water-washing process altered biochar properties, particularly the water extractable C, which decreased its efficiency. Both wheat- and maize-derived biochars, particularly the WRB, are recommended to improve nutrients availability and to improve grain yield in the rice-wheat rotation agro-ecosystem. These results shed light on the importance of crop straw transformation into an important source for soil C and nutrients necessary for sustainable management of wheat-rice agro-ecosystem. However, with the current and future alternative energy demands, the decision on using crop biomass for soil conservation or for bioenergy becomes a challenge reliant on regulatory and policy frameworks.

Collaborative, C. O. V. I. D. S., "{Global wealth disparities drive adherence to COVID-safe pathways in head and neck cancer surgery}", BJS Open, vol. 5, no. 6, 12, 2021. AbstractWebsite

{Dear EditorThe COVID-19 pandemic has had profound impacts on safe healthcare delivery, particularly within surgical specialties1. There has been clear evidence of pulmonary complications and death associated with surgery following perioperative COVID infection2,3. Mitigation of COVID-related risk for patients depends upon several primary tenets of safe surgery, including implementation of appropriate COVID-secure treatment pathways4, provision of adequate testing for patients to ensure COVID-negative status and protection of staff members through suitable personal protective equipment (PPE). Following the initial peaks of SARS-CoV-2 infection, healthcare service provision was afforded time for preparation and reorganization before subsequent waves of infection. An ability to use this window of opportunity was dependent not only on strategic decision making but also national financial resources and healthcare capabilities.}

Collaborative, S. T. A. R. S., and C. O. V. I. D. S. Collaborative, "{Death following pulmonary complications of surgery before and during the SARS-CoV-2 pandemic}", British Journal of Surgery, vol. 108, no. 12, pp. 1448-1464, 11, 2021. AbstractWebsite

{This study aimed to determine the impact of pulmonary complications on death after surgery both before and during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic.This was a patient-level, comparative analysis of two, international prospective cohort studies: one before the pandemic (January–October 2019) and the second during the SARS-CoV-2 pandemic (local emergence of COVID-19 up to 19 April 2020). Both included patients undergoing elective resection of an intra-abdominal cancer with curative intent across five surgical oncology disciplines. Patient selection and rates of 30-day postoperative pulmonary complications were compared. The primary outcome was 30-day postoperative mortality. Mediation analysis using a natural-effects model was used to estimate the proportion of deaths during the pandemic attributable to SARS-CoV-2 infection.This study included 7402 patients from 50 countries; 3031 (40.9 per cent) underwent surgery before and 4371 (59.1 per cent) during the pandemic. Overall, 4.3 per cent (187 of 4371) developed postoperative SARS-CoV-2 in the pandemic cohort. The pulmonary complication rate was similar (7.1 per cent (216 of 3031) versus 6.3 per cent (274 of 4371); P = 0.158) but the mortality rate was significantly higher (0.7 per cent (20 of 3031) versus 2.0 per cent (87 of 4371); P \< 0.001) among patients who had surgery during the pandemic. The adjusted odds of death were higher during than before the pandemic (odds ratio (OR) 2.72, 95 per cent c.i. 1.58 to 4.67; P \< 0.001). In mediation analysis, 54.8 per cent of excess postoperative deaths during the pandemic were estimated to be attributable to SARS-CoV-2 (OR 1.73, 1.40 to 2.13; P \< 0.001).Although providers may have selected patients with a lower risk profile for surgery during the pandemic, this did not mitigate the likelihood of death through SARS-CoV-2 infection. Care providers must act urgently to protect surgical patients from SARS-CoV-2 infection.This study compared death rates in patients who developed pulmonary complications of surgery before and during the pandemic in two large, international studies. Patients who underwent surgery during the pandemic tended to be younger and fitter. Overall, 4.3 per cent were diagnosed with SARS-CoV-2 infection after surgery in the pandemic cohort. Deaths within 30 days after surgery tripled during the first wave of the pandemic (from 0.7 to 2.0 per cent), whereas the rate of pulmonary complications remained the similar (7.1 to 6.3 per cent). Over half of these excess deaths (54.8 per cent) were estimated to be related to SARS-CoV-2 infection.}