Customised pre-operative cranioplasty to achieve maximal surgical resection of tumours with osseous involvement-a case series.

PURPOSE: Surgical resection with bony margins would be the treatment of choice for tumours with osseous involvement such as meningiomas and metastasis. By developing and designing pre-operative customised 3D modelled implants, the patient can undergo resection of meningioma and repair of bone defect in the same operation. We present a generalisable method for designing pre-operative cranioplasty in patients to repair the bone defect after the resection of tumours. MATERIALS AND METHODS: We included six patients who presented with a tumour that was associated with overlying bone involvement. They underwent placement of customised cranioplasty in the same setting. A customised implant using a pre-operative imaging was designed with a 2-cm margin to allow for any intra-operative requirements for extending the craniectomy. RESULTS: Six patients were evaluated in this case series. Four patients had meningiomas, 1 patient had metastatic breast cancer on final histology, and 1 patient was found to have an intra-osseous arteriovenous malformation. Craniectomy based on margins provided by a cutting guide was fashioned. After tumour removal and haemostasis, the cranioplasty was then placed. All patients recovered well post-operatively with satisfactory cosmetic results. No wound infection was reported in our series. CONCLUSION: Our series demonstrate the feasibility of utilising pre-designed cranioplasty for meningiomas and other tumours with osseous involvement. Following strict infection protocols, minimal intra-operative handling/modification of the implant, and close follow-up has resulted in good cosmetic outcomes with no implant-related infections.

Nivolumab plus ipilimumab in advanced salivary gland cancer: a phase 2 trial.

Salivary gland cancers (SGCs) are rare, aggressive cancers without effective treatments when metastasized. We conducted a phase 2 trial evaluating nivolumab (nivo, anti-PD-1) and ipilimumab (ipi, anti-CTLA-4) in 64 patients with metastatic SGC enrolled in two histology-based cohorts (32 patients each): adenoid cystic carcinoma (ACC; cohort 1) and other SGCs (cohort 2). The primary efficacy endpoint (≥4 objective responses) was met in cohort 2 (5/32, 16%) but not in cohort 1 (2/32, 6%). Treatment safety/tolerability and progression-free survival (PFS) were secondary endpoints. Treatment-related adverse events grade ≥3 occurred in 24 of 64 (38%) patients across both cohorts, and median PFS was 4.4 months (95% confidence interval (CI): 2.4, 8.3) and 2.2 months (95% CI: 1.8, 5.3) for cohorts 1 and 2, respectively. We present whole-exome, RNA and T cell receptor (TCR) sequencing data from pre-treatment and on-treatment tumors and immune cell flow cytometry and TCR sequencing from peripheral blood at serial timepoints. Responding tumors universally demonstrated clonal expansion of pre-existing T cells and mutational contraction. Responding ACCs harbored neoantigens, including fusion-derived neoepitopes, that induced T cell responses ex vivo. This study shows that nivo+ipi has limited efficacy in ACC, albeit with infrequent, exceptional responses, and that it could be promising for non-ACC SGCs, particularly salivary duct carcinomas. ClinicalTrials.gov identifier: NCT03172624 .

Diagnostic dilemma in acute neurological presentation of spinal arachnoid cysts: A case report.

Background: Spinal arachnoid cysts are relatively uncommon, cerebrospinal fluid-filled sacs formed by arachnoid membranes that can be either idiopathic or acquired. The neurological presentation of these cysts is varied. Advances in imaging techniques have allowed an improved characterization of these entities and excluded other possible causes of clinical manifestation. Their presentation remains varied, ranging from pain to progressive neurological deficits. Here, we present two cases of patients with thoracic arachnoid cysts that posed a diagnostic dilemma at initial presentation because of their acute neurological deficit, and their eventual recovery after surgical intervention. Case description: The first case is of a patient with end-stage renal failure, which prevented the administration of contrast during the workup. The differential diagnosis ranged from intradural abscess to arachnoid cyst. The second patient presented with non-remitting back pain that progressed to an acute neurological deficit. Both patients recovered well after decompression of the cyst. Conclusion: The decision to intervene is still patient-dependent and based on the extent of neurological deterioration at the time of presentation due to the relatively benign nature and lack of understanding of the temporal presentation of neurological symptoms, which are rapidly and almost completely reversed after surgery. However, further studies need to be done to understand the acute presentation of these cysts, which are apparently long-standing.

Postsurgical outcomes of nonfunctioning pituitary adenomas: a patient-level meta-analysis.

BACKGROUND: Surgical resection is the main treatment for symptomatic nonfunctioning pituitary adenomas (NFPA). We aimed to analyze the impact of surgical approach, completeness of resection, and postoperative radiotherapy on long-term progression-free survival (PFS) of NFPA, using individual patient data (IPD) meta-analysis. METHODS: An electronic literature searched was conducted on PubMed, EMBASE, and Web of Science from database inception to 6 November 2022. Studies describing the natural history of surgically resected NFPA, with provision of Kaplan-Meier curves, were included. These were digitized to obtain IPD, which was pooled in one-stage and two-stage meta-analysis to determine hazard ratios (HRs) and 95%CIs of gross total resection (GTR) versus subtotal resection (STR), and postoperative radiotherapy versus none. An indirect analysis of single-arm data between endoscopic endonasal (EES) and microscopic transsphenoidal (MTS) surgical technique was also performed. RESULTS: Altogether, eleven studies (3941 patients) were retrieved. PFS was significantly lower in STR than GTR (shared-frailty HR 0.32, 95%CI 0.27-0.39, p < 0.001). Postoperative radiotherapy significantly improved PFS compared to no radiotherapy (shared-frailty HR 0.20, 95%CI 0.15-0.26, p < 0.001), including in the subgroup of patients with STR (shared-frailty HR 0.12, 95%CI 0.08-0.18, p < 0.001). Similar PFS was observed between EES and MTS (indirect HR 1.09, 95%CI 0.92-1.30, p = 0.301). CONCLUSIONS: This systematic review and patient-level meta-analysis provides a robust prognostication of surgically treated NFPA. We reinforce current guidelines stating that GTR should be the standard of surgical resection. Postoperative radiotherapy is of considerable benefit, especially for patients with STR. Surgical approach does not significantly affect long-term prognosis. REGISTRATION: PROSPERO CRD42022374034.

Use of Mixed Reality in Neurosurgery Training: A Single Centre Experience.

BACKGROUND: Mixed reality (MR) technology has opened new avenues for planning, visualization, and education in surgery. Neurosurgical pathologies require a very clear understanding of the relationships between pathology and critical neurovascular structures. The decline in cadaveric dissections and resource constraints has pushed the educators to find newer ways of rendering the same knowledge. The aim of this study was to determine the feasibility of employing a MR device in a high-volume center for neurosurgical teaching. The study also evaluated the results of the trainee experience in using the MR platform. METHODS: Three neurosurgical consultants who are part of the teaching faculty were asked to facilitate the session. No prior training on utilizing the MR device was given to the trainees. HoloLens 2 was used as the MR device. Two questionnaires were used to understand the experience of the trainees. RESULTS: Eight active neurosurgical trainees who are currently training at our institution were recruited for the purposes of this study. Despite having no prior training on a MR platform, the learning curve was short for most of the trainees. Whether MR replace current traditional methods of teaching neuroanatomy, the response was divided across the trainees. The results of the User Experience Questionnaire were positive with the trainees finding the device as attractive, dependable, novel, and user-friendly. CONCLUSION: This study demonstrates the feasibility of using MR platform in neurosurgery training without significant preparation requirements. These data are required to justify the future investment in this technology for training institutions.

Comparison of C-MAC Miller blade video laryngoscope with conventional Miller blade in infants undergoing elective surgery- A prospective randomised trial.

Background and Aims: Endotracheal intubation (ET) in infants is considered a challenging task over the decades. Infants have short safe apnoea time, and this difficulty has been vanquished to some extent by using the videolaryngoscopes (VLs), but there exists a dearth of research particularly in this vulnerable subset. Therefore, this trial was conducted to evaluate intubation times obtained with C-MAC VL and conventional Miller laryngoscopes in infants. Methods: A total of 80 infants aged between 1 month and 1 year with American Society of Anesthesiologists physical status I-II requiring ET were randomised in two groups; the C-MAC VL or Miller laryngoscope ML. Anaesthesia was induced with sevoflurane 1-8% and atracurium 0.5 mg/kg IV. The primary outcome was evaluated as the total time taken to intubate. Secondary outcomes were time to achieve best glottic view (TBGV), tube insertion time (TIT), percentage of glottic opening (POGO) score, number of attempts and intubation difficulty score (IDS). Results: The median (interquartile range) of time taken for ET was less in VL; 22.5 (20.75-26) compared to ML; 26 (21.75-31). TBGV was achieved early in VL group than the ML group (6.03 ± 1.33s/7.88 ± 2.44) respectively (P-value < 0.001). POGO was better in VL (99.12 ± 4.795s) compared to ML (85.50 ± 31.13s). IDS was less in the VL group (0.07 ± 0.27) than in ML (0.70 ± 1.14). Other parameters, such as the number of attempts, bougie usage, adverse effects and TIT, were comparable across the two groups. Conclusion: When compared to the ML group, the C-MAC VL group exhibited a decreased intubation time, early TBGV, better POGO score, reduced IDS and subjective intubation difficulty. As a result, we consider VL to be a more efficacious device for intubating the trachea in infants.

Giant aneurysm arising from a cortical middle cerebral artery branch presenting as an extra-axial tumour: a case report.

The size and anatomical complexity make giant intracranial aneurysms challenging surgical lesions. There is limited literature available for those arising from distal branches. The cases that have been reported in the literature have all presented with symptoms from a rupture leading to an intracranial haemorrhage. In this case report, the authors present a case of a giant aneurysm arising from a cortical branch of the middle cerebral artery presenting as an extra-axial tumour. A 76-year-old gentleman presented with a 2-day history of subjective left arm numbness. Imaging revealed a large conical right-sided parietal lesion. Intraoperatively, it was found that the lesion was being supplied by a single vascular pedicle. Histology was consistent with an aneurysm. In this case, that patient did not have any evidence of a rupture unlike all reported cases of cortical giant aneurysms. This case highlights the myriad location and presentation of giant intracranial aneurysms.

Use of Mixed Reality in Neuro-Oncology: A Single Centre Experience.

(1) Background: Intra-operative neuronavigation is currently an essential component to most neurosurgical operations. Recent progress in mixed reality (MR) technology has attempted to overcome the disadvantages of the neuronavigation systems. We present our experience using the HoloLens 2 in neuro-oncology for both intra- and extra-axial tumours. (2) Results: We describe our experience with three patients who underwent tumour resection. We evaluated surgeon experience, accuracy of superimposed 3D image in tumour localisation with standard neuronavigation both pre- and intra-operatively. Surgeon training and usage for HoloLens 2 was short and easy. The process of image overlay was relatively straightforward for the three cases. Registration in prone position with a conventional neuronavigation system is often difficult, which was easily overcome during use of HoloLens 2. (3) Conclusion: Although certain limitations were identified, the authors feel that this system is a feasible alternative device for intra-operative visualization of neurosurgical pathology. Further studies are being planned to assess its accuracy and suitability across various surgical disciplines.

Awake craniotomy for brain tumor resection: Patient experience and acceptance in an Asian population.

INTRODUCTION: Awake craniotomy is well-established for resection of brain tumor in the eloquent areas. Previous studies from Western countries have reported good level of patient tolerance and acceptance. However, its acceptability in non-Western populations, with different ethnic, social, cultural, religious, and linguistic backgrounds, has not been studied systematically. This study aims to evaluate the experience of patients from an Asian population who underwent awake craniotomy for tumor resection. METHODS: Data on patient experience were collected by interviewing patients using a structured questionnaire at follow-up appointment. Data on patient demographics and diagnosis were collected from medical records. RESULTS: Eighteen patients (age 16-68 years) who underwent 20 awake craniotomies were recruited. Preoperatively, all (100%) patients understood the indication for awake craniotomy. Almost all felt fully counseled by the neurosurgeon (90%), anesthetist (100%), and neuropsychologist (95%). Ninety-five percent reported their family to be supportive of awake craniotomy. Seventy-five percent felt adequately prepared on operation day. Intraoperatively, most patients did not experience pain/discomfort (55%) or anxiety (65%). Nearly all found intraoperative motor and language testing to be easy (100% and 90%, respectively). Postoperatively, 100% were satisfied with their care. One hundred percent rated their overall experience as good or excellent. Eighty percent were willing to undergo awake craniotomy again if indicated. CONCLUSION: Awake craniotomy is well-accepted in an Asian population. All patients had good-to-excellent overall experience, with most willing to undergo awake craniotomy again. Our findings underscore the generalizability of awake craniotomy across different socio-cultural backgrounds and support its utilization in countries with a significant Asian population.

A Bacteriophage-Based, Highly Efficacious, Needle- and Adjuvant-Free, Mucosal COVID-19 Vaccine.

The U.S. Food and Drug Administration-authorized mRNA- and adenovirus-based SARS-CoV-2 vaccines are intramuscularly injected in two doses and effective in preventing COVID-19, but they do not induce efficient mucosal immunity or prevent viral transmission. Here, we report the first noninfectious, bacteriophage T4-based, multicomponent, needle- and adjuvant-free, mucosal vaccine harboring engineered Spike trimers on capsid exterior and nucleocapsid protein in the interior. Intranasal administration of two doses of this T4 SARS-CoV-2 vaccine 21 days apart induced robust mucosal immunity, in addition to strong systemic humoral and cellular immune responses. The intranasal vaccine induced broad virus neutralization antibody titers against multiple variants, Th1-biased cytokine responses, strong CD4+ and CD8+ T cell immunity, and high secretory IgA titers in sera and bronchoalveolar lavage specimens from vaccinated mice. All of these responses were much stronger in intranasally vaccinated mice than those induced by the injected vaccine. Furthermore, the nasal vaccine provided complete protection and sterilizing immunity against the mouse-adapted SARS-CoV-2 MA10 strain, the ancestral WA-1/2020 strain, and the most lethal Delta variant in both BALB/c and human angiotensin converting enzyme (hACE2) knock-in transgenic mouse models. In addition, the vaccine elicited virus-neutralizing antibodies against SARS-CoV-2 variants in bronchoalveolar lavage specimens, did not affect the gut microbiota, exhibited minimal lung lesions in vaccinated and challenged mice, and is completely stable at ambient temperature. This modular, needle-free, phage T4 mucosal vaccine delivery platform is therefore an excellent candidate for designing efficacious mucosal vaccines against other respiratory infections and for emergency preparedness against emerging epidemic and pandemic pathogens. IMPORTANCE According to the World Health Organization, COVID-19 may have caused ~15-million deaths across the globe and is still ravaging the world. Another wave of ~100 million infections is predicted in the United States due to the emergence of highly transmissible immune-escaped Omicron variants. The authorized vaccines would not prevent these transmissions since they do not trigger mucosal immunity. We circumvented this limitation by developing a needle-free, bacteriophage T4-based, mucosal vaccine. This intranasally administered vaccine generates superior mucosal immunity in mice, in addition to inducing robust humoral and cell-mediated immune responses, and provides complete protection and sterilizing immunity against SARS-CoV-2 variants. The vaccine is stable, adjuvant-free, and cost-effectively manufactured and distributed, making it a strategically important next-generation COVID vaccine for ending this pandemic.

Length-dependent motions of SARS-CoV-2 frameshifting RNA pseudoknot and alternative conformations suggest avenues for frameshifting suppression.

The SARS-CoV-2 frameshifting element (FSE), a highly conserved mRNA region required for correct translation of viral polyproteins, defines an excellent therapeutic target against Covid-19. As discovered by our prior graph-theory analysis with SHAPE experiments, the FSE adopts a heterogeneous, length-dependent conformational landscape consisting of an assumed 3-stem H-type pseudoknot (graph motif 3_6), and two alternative motifs (3_3 and 3_5). Here, for the first time, we build and simulate, by microsecond molecular dynamics, 30 models for all three motifs plus motif-stabilizing mutants at different lengths. Our 3_6 pseudoknot systems, which agree with experimental structures, reveal interconvertible L and linear conformations likely related to ribosomal pausing and frameshifting. The 3_6 mutant inhibits this transformation and could hamper frameshifting. Our 3_3 systems exhibit length-dependent stem interactions that point to a potential transition pathway connecting the three motifs during ribosomal elongation. Together, our observations provide new insights into frameshifting mechanisms and anti-viral strategies.

Length-dependent motions of SARS-CoV-2 frameshifting RNA pseudoknot and alternative conformations suggest avenues for frameshifting suppression.

Conserved SARS-CoV-2 RNA regions of critical biological functions define excellent targets for anti-viral therapeutics against Covid-19 variants. One such region is the frameshifting element (FSE), responsible for correct translation of viral polyproteins. Here, we analyze molecular-dynamics motions of three FSE conformations, discovered by graph-theory analysis, and associated mutants designed by graph-based inverse folding: two distinct 3-stem H-type pseudoknots and a 3-way junction. We find that the prevalent H-type pseudoknot in literature adopts ring-like conformations, which in combination with 5' end threading could promote ribosomal pausing. An inherent shape switch from "L" to linear that may help trigger the frameshifting is suppressed in our designed mutant. The alternative conformation trajectories suggest a stable intermediate structure with mixed stem interactions of all three conformations, pointing to a possible transition pathway during ribosomal translation. These observations provide new insights into anti-viral strategies and frameshifting mechanisms.

CRISPR Engineering of Bacteriophage T4 to Design Vaccines Against SARS-CoV-2 and Emerging Pathogens.

The COVID-19 pandemic brought to the fore the urgent need for vaccine design and delivery platforms that can be rapidly deployed for manufacture and distribution. Though the mRNA and adenoviral vector platforms have been enormously successful to control SARS-CoV-2 viral infections, it is unclear if this could be replicated against more complex pathogens or the emerging variants. Recently, we described a "universal" platform that can incorporate multiple vaccine targets into the same nanoparticle scaffold by CRISPR engineering of bacteriophage T4. A T4-COVID vaccine designed with this technology elicited broad immunogenicity and complete protection against virus challenge in a mouse model. Here, we describe the detailed methodology to generate recombinant bacteriophage T4 backbones using CRISPR that can also be broadly applicable to other bacteriophages that abundantly pervade the Earth.

Perceptions regarding tobacco control strategies amongst female youth in Delhi, India - a qualitative study.

Tobacco-related cancer is one of the commonest causes of cancer-related mortality in low- and middle-income countries. As per Global Youth Tobacco Survey-4, India; nearly one-fifth of students aged 13-15 used any form of the tobacco product. Tobacco related challenges have been countered through various tobacco control strategies; however, ignorance and non-compliance to tobacco control strategies to combat the tobacco epidemic shield the tobacco industry in India as well. There is limited literature on perception of tobacco use and tobacco control strategies amongst female youth. Hence, the present study aimed to assess tobacco control perception and perceived challenges through a qualitative approach amongst the youth of Delhi, India. Thematic analysis design of qualitative research was used amongst students of the Senior Secondary (Class XII) at a Government School of Delhi. One-to-one in-depth interviews were carried out for 6-7 individual participants in a day depending upon their availability. A summative content analysis was conducted of all the responses obtained by a data coder who was blinded to the identity of the respondent. A total of 82 school children participated in the study. The majority (82.9%, N = 68) of the participants felt that 'Tobacco is dangerous to health' and 41.5% (N = 34) of the participants were aware of some of the existing tobacco control laws in the country. Around 53.7% (N = 44) of the study respondents considered existing tobacco related laws to be ineffective. Regarding the perceived challenges; 31.7% (N = 26) of the respondents considered the lack of strict tobacco control laws and punishment strategies as the main factors. The findings from this study substantiated the focus on school based tobacco control strategies. The participants were well appraised regarding the impending danger of tobacco use and dynamic involvement of youth in tobacco control policies is the need of the hour.

To Knot or Not to Knot: Multiple Conformations of the SARS-CoV-2 Frameshifting RNA Element.

The SARS-CoV-2 frameshifting RNA element (FSE) is an excellent target for therapeutic intervention against Covid-19. This small gene element employs a shifting mechanism to pause and backtrack the ribosome during translation between Open Reading Frames 1a and 1b, which code for viral polyproteins. Any interference with this process has a profound effect on viral replication and propagation. Pinpointing the structures adapted by the FSE and associated structural transformations involved in frameshifting has been a challenge. Using our graph-theory-based modeling tools for representing RNA secondary structures, "RAG" (RNA-As-Graphs), and chemical structure probing experiments, we show that the 3-stem H-type pseudoknot (3_6 dual graph), long assumed to be the dominant structure, has a viable alternative, an HL-type 3-stem pseudoknot (3_3) for longer constructs. In addition, an unknotted 3-way junction RNA (3_5) emerges as a minor conformation. These three conformations share Stems 1 and 3, while the different Stem 2 may be involved in a conformational switch and possibly associations with the ribosome during translation. For full-length genomes, a stem-loop motif (2_2) may compete with these forms. These structural and mechanistic insights advance our understanding of the SARS-CoV-2 frameshifting process and concomitant virus life cycle, and point to three avenues of therapeutic intervention.

To knot or not to knot: Multiple conformations of the SARS-CoV-2 frameshifting RNA element.

The SARS-CoV-2 frameshifting RNA element (FSE) is an excellent target for therapeutic intervention against Covid-19. This small gene element employs a shifting mechanism to pause and backtrack the ribosome during translation between Open Reading Frames 1a and 1b, which code for viral polyproteins. Any interference with this process has profound effect on viral replication and propagation. Pinpointing the structures adapted by the FSE and associated structural transformations involved in frameshifting has been a challenge. Using our graph-theory-based modeling tools for representing RNA secondary structures, "RAG" (RNA-As-Graphs), and chemical structure probing experiments, we show that the 3-stem H-type pseudoknot (3_6 dual graph), long assumed to be the dominant structure has a viable alternative, an HL-type 3-stem pseudoknot (3_3) for longer constructs. In addition, an unknotted 3-way junction RNA (3_5) emerges as a minor conformation. These three conformations share Stems 1 and 3, while the different Stem 2 may be involved in a conformational switch and possibly associations with the ribosome during translation. For full-length genomes, a stem-loop motif (2_2) may compete with these forms. These structural and mechanistic insights advance our understanding of the SARS-CoV-2 frameshifting process and concomitant virus life cycle, and point to three avenues of therapeutic intervention.

Performing Awake Surgeries in Times of COVID-19 - A Singapore Experience.

INTRODUCTION: It has been 17 years since the severe acute respiratory syndrome outbreak and Singapore is facing yet another daunting pandemic - the novel coronavirus (COVID-19). To date, there are 57,607 cases and 27 casualties. This deadly pandemic requires significant changes especially in the field of awake surgeries for intra-axial tumors that routinely involve long clinic consults, significant interactions between patient and multiple other team members pre, intra, and postoperatively. MATERIALS AND METHODS: A retrospective review of all awake cases done during the COVID-19 pandemic from February to June 2020 was done. In this article, we outline the rigorous measures adopted during the COVID-19 pandemic that has allowed us to proceed with awake surgeries and intraoperative mapping at our institution. RESULTS AND DISCUSSION: We have divided the protocol into various phases of care of patients planned for an awake craniotomy. Preoperatively, teleconsults have been used where possible thereby limiting multiple hospital visits and interaction. Intraoperatively, safety nets have been established during asleep-awake-asleep phases of awake craniotomy for all the team members. Postoperatively, early discharge and teleconsult are being employed for rehabilitation and follow-ups. CONCLUSIONS: Multiple studies have shown that with intraoperative mapping, we can improve neurological outcomes. As the future of the pandemic remains unknown, the authors believe that surgical treatment should not be delayed for intracranial tumors. Awake craniotomies and intraoperative mapping can be safely carried out by adopting the described protocols with combination of multiple checkpoints and usage of telecommunication.

Structure-altering mutations of the SARS-CoV-2 frameshifting RNA element.

With the rapid rate of COVID-19 infections and deaths, treatments and cures besides hand washing, social distancing, masks, isolation, and quarantines are urgently needed. The treatments and vaccines rely on the basic biophysics of the complex viral apparatus. Although proteins are serving as main drug and vaccine targets, therapeutic approaches targeting the 30,000 nucleotide RNA viral genome form important complementary approaches. Indeed, the high conservation of the viral genome, its close evolutionary relationship to other viruses, and the rise of gene editing and RNA-based vaccines all argue for a focus on the RNA agent itself. One of the key steps in the viral replication cycle inside host cells is the ribosomal frameshifting required for translation of overlapping open reading frames. The RNA frameshifting element (FSE), one of three highly conserved regions of coronaviruses, is believed to include a pseudoknot considered essential for this ribosomal switching. In this work, we apply our graph-theory-based framework for representing RNA secondary structures, "RAG (or RNA-As-Graphs)," to alter key structural features of the FSE of the SARS-CoV-2 virus. Specifically, using RAG machinery of genetic algorithms for inverse folding adapted for RNA structures with pseudoknots, we computationally predict minimal mutations that destroy a structurally important stem and/or the pseudoknot of the FSE, potentially dismantling the virus against translation of the polyproteins. Our microsecond molecular dynamics simulations of mutant structures indicate relatively stable secondary structures. These findings not only advance our computational design of RNAs containing pseudoknots, they pinpoint key residues of the SARS-CoV-2 virus as targets for antiviral drugs and gene editing approaches.

"YES it's the Perfect Time to Quit": Fueling Tobacco Cessation in India during COVID-19 Pandemic.

Entire world is battling the Novel Coronavirus Disease (COVID-19) pandemic. India too, has undertaken stringent containment measures to combat this disease. The country is in a state of national lockdown, which has inadvertently led more than a quarter of the Indian population to not use tobacco. This paper discusses the opportunity that surfaces with unavailability of tobacco products, and advocates the need for escalation of tobacco cessation services as well as strategic management of stress to stay tobacco-free.