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Abstract Gene editing has great potential in treating diseases caused by well-characterized molecular alterations. The introduction of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)–based gene-editing tools has substantially improved the precision and efficiency of gene editing. The CRISPR/Cas9 system offers several advantages over the existing gene-editing approaches, such as its ability to target practically any genomic sequence, enabling the rapid development and deployment of novel CRISPR-mediated knock-out/knock-in methods. CRISPR/Cas9 has been widely used to develop cancer models, validate essential genes as druggable targets, study drug-resistance mechanisms, explore gene non-coding areas, and develop biomarkers. CRISPR gene editing can create more-effective chimeric antigen receptor (CAR)-T cells that are durable, cost-effective, and more readily available. However, further research is needed to define the CRISPR/Cas9 system’s pros and cons, establish best practices, and determine social and ethical implications. This review summarizes recent CRISPR/Cas9 developments, particularly in cancer research and immunotherapy, and the potential of CRISPR/Cas9-based screening in developing cancer precision medicine and engineering models for targeted cancer therapy, highlighting the existing challenges and future directions. Lastly, we highlight the role of artificial intelligence in refining the CRISPR system's on-target and off-target effects, a critical factor for the broader application in cancer therapeutics.

Virus reassortment drives genetic diversity and evolution and is governed by intra-host dynamics that are less well understood. Here, the authors characterise the within-host dynamics of influenza A virus reassortment in swine, ferrets and guinea pigs, considering their spatial distribution.

AbstractGiven a graph G with at least one edge, the line graph L(G) is that graph whose vertices are the edges of G, with two of these vertices being adjacent if the corresponding edges are adjacent in G. The line graph transformation is one of the most extensively studied, and the concept extends naturally to digraphs. The authors have recently published a book Line Graphs and Line Digraphs that covers many properties and generalizations of both types of structure. In this paper we discuss some recent progress in this area. We include a discussion of several recognition algorithms related to line graphs, and some new results on the line completion numbers. We also present some open problems and directions for further research.

Rupesh Raina,1– 3 Ahmad Houry,1,3 Pratik Rath,1 Guneive Mangat,1 Davinder Pandher,1,4 Muhammad Islam,3 Ala’a Grace Khattab,3 Joseph K Kalout,1 Sumedha Bagga5 1Akron Nephrology Associates/Cleveland Clinic Akron General Medical Center, Akron, OH, USA; 2Department of Nephrology, Akron Children’s Hospital, Akron, OH, USA; 3College of Medicine, Northeast Ohio Medical University, Rootstown, OH, USA; 4Mount Sinai South Nassau, Oceanside, NY, 11570, USA; 5Questrom School of Business, Boston University, Boston, MA, USACorrespondence: Rupesh Raina, Consultant Nephrologist, Adult-Pediatric Kidney Disease/Hypertension, Akron Nephrology Associates/Cleveland Clinic Akron General Medical Center, Akron, OH, USA, Tel +1 330-543-8950, Fax +1 330-543-3980, Email rraina@akronchildrens.org; raina@akronnephrology.comAbstract: Autosomal dominant polycystic kidney disease, also known as ADPKD, is the most common hereditary kidney disease, affecting different age groups. ADPKD can eventually lead to end-stage renal disease. The etiology of ADPKD is genetic, resulting in the formation of cysts containing fluids on the kidneys. Patients with ADPKD present a range of symptoms following a decline in kidney function. Pain, stones, proteinuria and osteoporosis are few of the many symptoms, resulting from decreased kidney function. Tolvaptan, a selective V2 receptor antagonist, is the etiological treatment used for ADPKD. In this paper, we conducted a systematic review of the literature between 2011 and 2021 to gather data regarding the tolerability and efficacy of tolvaptan use in ADPKD. A total of 22 trials were reviewed. Tolvaptan efficacy in the trials was measured using changes in eGFR or changes in total kidney volume. Results showed that tolvaptan use in ADPKD was associated with a slower decline in kidney function and a decrease in total kidney volume. Side effects of this drug include polyuria, nocturia and polydipsia along with hepatotoxicity. The two biggest trials, TEMPO and REPRISE, change in eGFR from pre-treatment baseline to post-treatment was 1.3 mL/min/1.73 for REPRISE and 1 mL/min/1.73 for TEMPO 3:4. A mean decrease of 49% in total kidney volume from baseline to post-treatment was found in the TEMPO 3:4 study.Keywords: ADPKD, tolvaptan

Abstract Introduction Acanthamoeba is an emerging pathogen, infamous for its resilience against antiprotozoal compounds, disinfectants and harsh environments. It is known to cause keratitis, a sight-threatening, painful and difficult to treat corneal infection which is often reported among contact lens wearers and patients with ocular trauma. Acanthamoeba comprises over 24 species and currently 23 genotypes (T1-T23) have been identified. Aims This retrospective study was designed to examine the Acanthamoeba species and genotypes recovered from patients with Acanthamoeba keratitis (AK), determine the presence of endosymbionts in ocular isolates of Acanthamoeba and review the clinical presentations. Methodology Thirteen culture-confirmed AK patients treated in a tertiary eye care facility in Hyderabad, India from February to October 2020 were included in this study. The clinical manifestations, medications and visual outcomes of all patients were obtained from medical records. The Acanthamoeba isolates were identified by sequencing the ribosomal nuclear subunit (rns) gene. Acanthamoeba isolates were assessed for the presence of bacterial or fungal endosymbionts using molecular assays, PCR and fluorescence in situ hybridization (FISH). Results The mean age of the patients was 33 years (SD ± 17.4; 95% CI 22.5 to 43.5 years). Six (46.2%) cases had AK associated risk factors; four patients had ocular trauma and two were contact lens wearers. A. culbertsoni (6/13, 46.2%) was the most common species, followed by A. polyphaga and A. triangularis. Most of the isolates (12/13) belonged to genotype T4 and one was a T12; three sub-clusters T4A, T4B, and T4F were identified within the T4 genotype. There was no significant association between Acanthamoeba types and clinical outcomes. Eight (61.5%) isolates harboured intracellular bacteria and one contained Malassezia restricta. The presence of intracellular microbes was associated with a higher proportion of stromal infiltrates (88.9%, 8/9), epithelial defect (55.6%, 5/9) and hypopyon (55.6%, 5/9) compared to 50% (2/4), 25% (1/4) and 25% (1/4) AK cases without intracellular microbes, respectively. Conclusions Genotype T4 was the predominant isolate in southern India. This is the second report of T12 genotype identified from AK patient in India, which is rarely reported worldwide. The majority of the Acanthamoeba clinical isolates in this study harboured intracellular microbes, which may impact clinical characteristics of AK.

All education in Sweden, or the Swedish eduscape, is permeated by discourses of compensation and inclusion, conceptualized in this study as a one-school-for-all ethos or perspective. This ethos contributes to a social-ecological framing, wherein the intentions are a society where everyone can participate as active members. This study scrutinizes the governmental strategy of 2017 to digitalize the Swedish educational system based on a one-school-for-all perspective. The study is framed by SWaSP (Second Wave of Southern Perspective) theoretical ideas, with a special focus on positionings, languaging, timespaces, and epistemological-methodological dimensions, including ethics based on the entangled tenets of sociocultural, integrationist, and southern perspectives. Furthermore, this study is anchored in three research projects and one societal developmental project. Materials - e.g., video recordings, audio recordings, photos, artifacts, fieldnotes – from these projects have been generated through (n)ethnographic methods from different institutions in the Swedish educational landscape i.e., eduscape. These span across compulsory schools to Swedish for Immigrants (SFI), within Municipal Adult Education. Three themes have emerged in the multi-scalar data analysis from across settings: (i) intended inclusion, (ii) unintended exclusion, and (iii) intended exclusion. The first theme highlights how digital tools (DTs) create inclusion for students with special needs, or those who are new to the named-language Swedish, in the classroom community, thus contributing to social-ecological sustainability. The second theme illustrates how DTs intended for inclusion in classroom practices morph into tools of exclusion for individuals in mainstream classrooms. The third theme highlights how students in the Swedish eduscape are intentionally excluded from mainstream classrooms. We argue that a social-ecological sustainable stance troubles the division of eduscapes into “mainstream” and “other” settings in contemporary societies, calling for the inclusion of all students irrespective of their positionalities. Our findings highlight that multimodal use of DTs potentially can facilitate inclusion, by providing tools where individual students can participate in and contribute to teaching and learning—what we frame as a third position of classroom organization.

Purpose: To validate Grobman’s nomogram for prediction of trial of labour after caesarean section (TOLAC) success in the Indian population. Methods: A prospective observational study of women with previous lower segment caesarean sections (LSCS) who were admitted for TOLAC between January 2019 and June 2020 at a tertiary care hospital We compared the Grobman’s predicted VBAC success probability to the observed VBAC rate in the study population and devised a receiver-operator characteristics (ROC) curve for the nomogram. Results: Among the 124 women with prior LSCS who chose TOLAC and were included in the study, 68 (54.8%) had a successful VBAC and 56 (45.2%) had a failed TOLAC. The mean Grobman’s predicted success probability for the cohort was 76.7%, significantly higher in VBAC women versus CS women (80.6% vs. 72.1%; p 0.001). The VBAC rate was 69.1% with a predicted probability of > 75% and only 42.9% with a probability of 50%. Women in the > 75% probability group had a nearly similar observed and predicted VBAC rate (69.1% vs. 86.3%; p = 0.002), and a greater number of women in the 50% probability group had successful VBAC than predicted (42.9% vs. 39.5%; p = 0.018). The area under the ROC curve for the study was 0.703 (95% CI 0.609–0.797; p 0.001). Grobman’s nomogram had a sensitivity of 57.35%, a specificity of 82.14%, a positive predictive value (PPV) of 79.59%, and a negative predictive value (NPV) of 61.33% at a predicted probability cut-off of 82.5%. Conclusions: Women who had a higher Grobman’s predicted probability had greater VBAC success rates than those with low predicted probability scores. The prediction ability of the nomogram was highly accurate at higher predicted probabilities, and even at lower predicted probabilities, women did have good odds of delivering vaginally.

Since 2004, the processing of the iron oxide–copper–gold (IOCG) ore of Guelb Moghrein, Akjoujt, Mauritania, has resulted in the generation of approximately 40 million tons of mine tailings. The storage of these tailings poses significant environmental challenges particularly to surface and underground water resources. To address this issue, we propose an approach involving both mineralurgical and environmental characterization. Our mineralogical analysis reveals that the TSF tailings consist of sulfides and iron oxides associated with a silico-carbonated matrix. This mineralogical analysis also shows that the TSF tailings consist of secondary minerals, resulting from sulfides oxidation. Furthermore, our findings indicate that the chemical analysis of the TSF tailings contains potential toxic elements (PTEs) such as Cu, As, Co, Ni, Sb, and Se. Regarding the environmental characterization of the tailings, conducted through acid-based accounting (ABA) static tests, we demonstrate that leaching from the tailings generates a contaminated neutral drainage (CND).

BACKGROUND: One of the major objectives of orthodontic treatment is to improve facial attractiveness. To orthodontists, this means that the nose, lips, and chin form an attractive outline when the faces are viewed from one side. The aim of the study is to evaluate the influence of lip inclination on perceived attractiveness using North Indian observer ratings on profile silhouettes. MATERIALS AND METHODS: A profile photograph of an Indian male and female were converted to silhouettes for the study using computer software. The lip inclination of the idealized profile image was altered in two-degree increments to create a series of profiles with different upper lip inclination angles and rated by laypersons on a Likert scale. RESULTS: An angle of 79° was deemed to be neither attractive nor unattractive. Therefore, within the range of 65°–75°, the pictures were deemed acceptable. Angles above or below this range, up to 91° were perceived as slightly unattractive, and anything outside the range of 93°–105° was deemed very unattractive. LIMITATIONS: The study is not generalizable to ethnic groups other than the North Indian population. Another limitation is the inability to visualize the entire face for a complete facial analysis. CONCLUSION: An upper lip inclination of 75°–85° in the male profile was associated with perceived attractiveness in all three groups whereas it was in the range of 65°–75° for a female profile. An upper lip inclination angle ranging from 95° to 105° was associated with unattractiveness in all three groups of observers and requires correctional intervention.