When a high need for new residences coincides with an insufficient area of obtainable land within cities, urban sprawl occurs. Although densification is a well-known policy for controlling urban sprawl, one of the main challenges faced by researchers is that of determining urban densification potentials and priorities at the city scale. This paper aims to establish a methodology to facilitate decision-making regarding urban densification using five different methods. The proposed methodology utilizes high-quality city strategic plans (CSPs) and urban regulation documents and adopts geographic information systems (GISs) to determine and map the potential areas for densification. Multiple sustainability parameters, including environmental, economic, and social parameters, are selected, and weighted using an analytical hierarchy process (AHP) to prioritize the densification sites. The proposed method is tested in Tanta, Egypt, which has suffered due to agricultural losses of approximately 10 km2 within the last 50 years. The results credibly demonstrate the means by which to accommodate approximately 428% of the anticipated population increase in Tanta by 2027 and thereby save more than 53% of the approved deducted agricultural lands under the current urban regulations. Generally, this methodology offers a new model to optimize urban densification, which can be effective in urban management to achieve city resilience.

Breast cancer is the first common cause of cancer-related death in women worldwide. Since the malignancy and aggressiveness of breast cancer have been correlated with the presence of breast cancer stem cells, the establishment of a disease model with cancer stem cells is required for the development of a novel therapeutic strategy. Here, we aimed to evaluate the availability of cancer stem cell models developed from mouse induced pluripotent stem cells with the conditioned medium of different subtypes of breast cancer cell lines, the hormonal-responsive T47D cell line and the triple-negative breast cancer BT549 cell line, to generate tumor models. When transplanted into the mammary fat pads of BALB/c nude mice, these two model cells formed malignant tumors exhibiting pronounced histopathological characteristics similar to breast cancers. Serial transplantation of the primary cultured cells into mammary fat pads evoked the same features of breast cancer, while this result was perturbed following subcutaneous transplantation. The tumors formed in the mammary fat pads exhibited immune reactivities to prolactin receptor, progesterone receptor, green florescent protein, Ki67, CD44, estrogen receptor α/β and cytokeratin 8, while all of the tumors and their derived primary cells exhibited immunoreactivity to estrogen receptor α/β and cytokeratin 8. Cancer stem cells can be developed from pluripotent stem cells via the secretory factors of cancer-derived cells with the capacity to inherit tissue specificity. However, cancer stem cells should be plastic enough to be affected by the microenvironment of specific tissues. In summary, we successfully established a breast cancer tumor model using mouse induced pluripotent stem cells developed from normal fibroblasts without genetic manipulation.

{Summary Background 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]

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BACKGROUND: Recognition of viral nucleic acids is one of the primary triggers for a type I interferon-mediated antiviral immune response. Inborn errors of type I interferon immunity can be associated with increased inflammation and/or increased susceptibility to viral infections as a result of dysbalanced interferon production. NFX1-type zinc finger-containing 1 (ZNFX1) is an interferon-stimulated double-stranded RNA sensor that restricts the replication of RNA viruses in mice. The role of ZNFX1 in the human immune response is not known.

OBJECTIVE: We studied 15 patients from 8 families with an autosomal recessive immunodeficiency characterized by severe infections by both RNA and DNA viruses and virally triggered inflammatory episodes with hemophagocytic lymphohistiocytosis-like disease, early-onset seizures, and renal and lung disease.

METHODS: Whole exome sequencing was performed on 13 patients from 8 families. We investigated the transcriptome, posttranscriptional regulation of interferon-stimulated genes (ISGs) and predisposition to viral infections in primary cells from patients and controls stimulated with synthetic double-stranded nucleic acids.

RESULTS: Deleterious homozygous and compound heterozygous ZNFX1 variants were identified in all 13 patients. Stimulation of patient-derived primary cells with synthetic double-stranded nucleic acids was associated with a deregulated pattern of expression of ISGs and alterations in the half-life of the mRNA of ISGs and also associated with poorer clearance of viral infections by monocytes.

CONCLUSION: ZNFX1 is an important regulator of the response to double-stranded nucleic acids stimuli following viral infections. ZNFX1 deficiency predisposes to severe viral infections and a multisystem inflammatory disease.

BACKGROUND: Galloway-Mowat syndrome (GAMOS) is characterized by neurodevelopmental defects and a progressive nephropathy, which typically manifests as steroid-resistant nephrotic syndrome. The prognosis of GAMOS is poor, and the majority of children progress to renal failure. The discovery of monogenic causes of GAMOS has uncovered molecular pathways involved in the pathogenesis of disease.

METHODS: Homozygosity mapping, whole-exome sequencing, and linkage analysis were used to identify mutations in four families with a GAMOS-like phenotype, and high-throughput PCR technology was applied to 91 individuals with GAMOS and 816 individuals with isolated nephrotic syndrome. and studies determined the functional significance of the mutations identified.

RESULTS: Three biallelic variants of the transcriptional regulator were detected in six families with proteinuric kidney disease. Four families with a variant in the protein's zinc-finger (ZNF) domain have additional GAMOS-like features, including brain anomalies, cardiac defects, and skeletal defects. All variants destabilize the PRDM15 protein, and the ZNF variant additionally interferes with transcriptional activation. Morpholino oligonucleotide-mediated knockdown of Prdm15 in embryos disrupted pronephric development. Human wild-type RNA rescued the disruption, but the three variants did not. Finally, CRISPR-mediated knockout of in human podocytes led to dysregulation of several renal developmental genes.

CONCLUSIONS: Variants in can cause either isolated nephrotic syndrome or a GAMOS-type syndrome on an allelic basis. PRDM15 regulates multiple developmental kidney genes, and is likely to play an essential role in renal development in humans.

The high demand for sufficient and safe food, and continuous damage of environment by conventional agriculture are major challenges facing the globe. The necessity of smart alternatives and more sustainable practices in food production is crucial to confront the steady increase in human population and careless depletion of global resources. Nanotechnology implementation in agriculture offers smart delivery systems of nutrients, pesticides, and genetic materials for enhanced soil fertility and protection, along with improved traits for better stress tolerance. Additionally, nano-based sensors are the ideal approach towards precision farming for monitoring all factors that impact on agricultural productivity. Furthermore, nanotechnology can play a significant role in post-harvest food processing and packaging to reduce food contamination and wastage. In this review, nanotechnology applications in the agriculture and food sector are reviewed. Implementations of nanotechnology in agriculture have included nano- remediation of wastewater for land irrigation, nanofertilizers, nanopesticides, and nanosensors, while the beneficial effects of nanomaterials (NMs) in promoting genetic traits, germination, and stress tolerance of plants are discussed. Furthermore, the article highlights the efficiency of nanoparticles (NPs) and nanozymes in food processing and packaging. To this end, the potential risks and impacts of NMs on soil, plants, and human tissues and organs are emphasized in order to unravel the complex bio-nano interactions. Finally, the strengths, weaknesses, opportunities, and threats of nanotechnology are evaluated and discussed to provide a broad and clear view of the nanotechnology potentials, as well as future directions for nano-based agri-food applications towards sustainability.

Africa has many untreated neurosurgical cases due to limited access to safe, affordable, and timely care. In this study, we surveyed young African neurosurgeons and trainees to identify challenges to training and practice. African trainees and residents were surveyed online by the Young Neurosurgeons Forum from April 25th to November 30th, 2018. The survey link was distributed via social media platforms and through professional society mailing lists. Univariate and bivariate data analyses were run and a -value < 0.05 was considered to be statistically significant. 112 respondents from 20 countries participated in this study. 98 (87.5%) were male, 63 (56.3%) were from sub-Saharan Africa, and 52 (46.4%) were residents. 39 (34.8%) had regular journal club sessions at their hospital, 100 (89.3%) did not have access to cadaver dissection labs, and 62 (55.4%) had never attended a WFNS-endorsed conference. 67.0% of respondents reported limited research opportunities and 58.9% reported limited education opportunities. Lack of mentorship ( = 0.023, Phi = 0.26), lack of access to journals ( = 0.002, Phi = 0.332), and limited access to conferences ( = 0.019, Phi = 0.369) were associated with the country income category. This survey identified barriers to education, research, and practice among African trainees and young neurosurgeons. The findings of this study should inform future initiatives aimed at reducing the barriers faced by this group.