Prostate tissue ablation and drug delivery by an image-guided injectable ionic liquid in ex vivo and in vivo models.

Benign prostatic hyperplasia and prostate cancer are often associated with lower urinary tract symptoms, which can severely affect patient quality of life. To address this challenge, we developed and optimized an injectable compound, prostate ablation and drug delivery agent (PADA), for percutaneous prostate tissue ablation and concurrently delivered therapeutic agents. PADA is an ionic liquid composed of choline and geranic acid mixed with anticancer therapeutics and a contrast agent. The PADA formulation was optimized for mechanical properties compatible with hand injection, diffusion capability, cytotoxicity against prostate cells, and visibility of an x-ray contrast agent. PADA also exhibited antibacterial properties against highly resistant clinically isolated bacteria in vitro. Ultrasound-guided injection, dispersion of PADA in the tissue, and tissue ablation were tested ex vivo in healthy porcine, canine, and human prostates and in freshly resected human tumors. In vivo testing was conducted in a murine subcutaneous tumor model and in the canine prostate. In all models, PADA decreased the number of viable cells in the region of dispersion and supported the delivery of nivolumab throughout a portion of the tissue. In canine survival experiments, there were no adverse events and no impact on urination. The injection approach was easy to perform under ultrasound guidance and produced a localized effect with a favorable safety profile. These findings suggest that PADA is a promising therapeutic prostate ablation strategy to treat lower urinary tract symptoms.

Calculated Fracture Risk among Hypertensive and Non-hypertensive Osteoporotic Women.

Vertebral and Hip fractures are the commonly encountered in low bone mass condition termed as osteoporosis. Bone mass and structure also affected by hypertension leading to increased susceptibility to fractures. This comparative cross-sectional study was conducted at two tertiary care centers in Dhaka metropolis from 1st January 2017 to 31st December 2017 under the department of Community Medicine, National Institute of Preventive and Social Medicine (NIPSOM) to assess whether HTN is linked with higher OP fracture risk. In this study 54 hypertensive and 34 non-hypertensive osteoporotic female patients were involved. After face to face interview data were collected by using semi-structured questionnaire and checklist. Online assessment of fracture risk probability was done among the two groups by Fracture Risk Assessment Tool (FRAX) and statistical analysis was performed by Statistical Packages for Social Sciences (SPSS-23.0). In this study it is found that the mean ages were 61.94±9.362 years and 59.18±11.269 years for hypertensive and non-hypertensive patients respectively. Most of the patients with hypertensive (96.3%) and non-hypertensive (82.4%) were housewives. Mean duration of hypertension in osteoporotic women was 6.41±4.049 years while mean duration of osteoporosis was 8.80±5.022 years and 7.53±5.920 years in hypertensive and non-hypertensive patients respectively. The difference in risk of major osteoporotic fractures (MOF) by age was significantly (Χ², p<0.05) higher among patients aged 60-79 years and remarkably higher in hypertensive patients. In hypertensive patients though the risk of MOF by hypertension was relatively higher but it was not significant statistically (Χ², p>0.05). However the risk of hip fracture (HF) by hypertension was relatively higher among hypertensive patients and it was significant statistically (Χ², p<0.05). This reflects that the risk of hip fracture is higher significantly in hypertensive patients.

Delayed management of acute type A aortic dissection with concomitant coronary artery bypass graft.

BACKGROUND: Pre-operative coronary angiography and concomitant, planned coronary artery bypass are infrequently performed with type A aortic dissection repair. We present a case in which pre-operative coronary computed tomography angiography was appropriate, and subsequent dissection repair and concomitant coronary artery bypass were successfully performed. CASE PRESENTATION: The patient is a 58-year-old male with heart failure with preserved ejection fraction, renal insufficiency, hypertension, obesity, and smoking history, who presented with a three-to-four-day history of persistent back pain, worsening exertional dyspnea, and orthopnea, as well as a two-to-three month history of dyspnea, lower extremity edema, and intermittent angina. He was diagnosed with an acute type A aortic dissection and anti-impulse control was initiated. However, repair was delayed in order to allow apixaban to metabolize and decrease the risk of bleeding, as the patient was approximately six days post-dissection, without malperfusion, with a well-controlled blood pressure on anti-impulse therapy, and had received five days of anticoagulation. During this time, coronary computed tomography angiography was performed to assess the need for concomitant revascularization and showed coronary artery disease. Ascending aorta hemiarch replacement with aortic valve resuspension, two-vessel coronary artery bypass grafting, and left atrial appendage clipping were performed successfully. CONCLUSIONS: Pre-operative imaging can be considered in a select group of acute type A aortic dissections that present without malperfusion, and with well-controlled blood pressure on anti-impulse/negative inotropic therapy.

Tissue Ablation: Applications and Perspectives.

Tissue ablation techniques have emerged as a critical component of modern medical practice and biomedical research, offering versatile solutions for treating various diseases and disorders. Percutaneous ablation is minimally invasive and offers numerous advantages over traditional surgery, such as shorter recovery times, reduced hospital stays, and decreased healthcare costs. Intra-procedural imaging during ablation also allows precise visualization of the treated tissue while minimizing injury to the surrounding normal tissues, reducing the risk of complications. Here, the mechanisms of tissue ablation and innovative energy delivery systems are explored, highlighting recent advancements that have reshaped the landscape of clinical practice. Current clinical challenges related to tissue ablation are also discussed, underlining unmet clinical needs for more advanced material-based approaches to improve the delivery of energy and pharmacology-based therapeutics.

Genome-wide CRISPR/Cas9 screen shows that loss of GET4 increases mitochondria-endoplasmic reticulum contact sites and is neuroprotective.

Organelles form membrane contact sites between each other, allowing for the transfer of molecules and signals. Mitochondria-endoplasmic reticulum (ER) contact sites (MERCS) are cellular subdomains characterized by close apposition of mitochondria and ER membranes. They have been implicated in many diseases, including neurodegenerative, metabolic, and cardiac diseases. Although MERCS have been extensively studied, much remains to be explored. To uncover novel regulators of MERCS, we conducted a genome-wide, flow cytometry-based screen using an engineered MERCS reporter cell line. We found 410 genes whose downregulation promotes MERCS and 230 genes whose downregulation decreases MERCS. From these, 29 genes were selected from each population for arrayed screening and 25 were validated from the high population and 13 from the low population. GET4 and BAG6 were highlighted as the top 2 genes that upon suppression increased MERCS from both the pooled and arrayed screens, and these were subjected to further investigation. Multiple microscopy analyses confirmed that loss of GET4 or BAG6 increased MERCS. GET4 and BAG6 were also observed to interact with the known MERCS proteins, inositol 1,4,5-trisphosphate receptors (IP3R) and glucose-regulated protein 75 (GRP75). In addition, we found that loss of GET4 increased mitochondrial calcium uptake upon ER-Ca2+ release and mitochondrial respiration. Finally, we show that loss of GET4 rescues motor ability, improves lifespan and prevents neurodegeneration in a Drosophila model of Alzheimer's disease (Aß42Arc). Together, these results suggest that GET4 is involved in decreasing MERCS and that its loss is neuroprotective.

Designed mosaic nanoparticles enhance cross-reactive immune responses in mice.

1Using computational methods, we designed 60-mer nanoparticles displaying SARS-like betacoronavirus (sarbecovirus) receptor-binding domains (RBDs) by (i) creating RBD sequences with 6 mutations in the SARS-COV-2 WA1 RBD that were predicted to retain proper folding and abrogate antibody responses to variable epitopes (mosaic-2COMs; mosaic-5COM), and (ii) selecting 7 natural sarbecovirus RBDs (mosaic-7COM). These antigens were compared with mosaic-8b, which elicits cross-reactive antibodies and protects from sarbecovirus challenges in animals. Immunizations in naïve and COVID-19 pre-vaccinated mice revealed that mosaic-7COM elicited higher binding and neutralization titers than mosaic-8b and related antigens. Deep mutational scanning showed that mosaic-7COM targeted conserved RBD epitopes. Mosaic-2COMs and mosaic-5COM elicited higher titers than homotypic SARS-CoV-2 Beta RBD-nanoparticles and increased potencies against some SARS-CoV-2 variants than mosaic-7COM. However, mosaic-7COM elicited more potent responses against zoonotic sarbecoviruses and highly mutated Omicrons. These results support using mosaic-7COM to protect against highly mutated SARS-CoV-2 variants and zoonotic sarbecoviruses with spillover potential.

A new modified biased estimator for Zero inflated Poisson regression model.

Zero-inflated Poisson (ZIP) model is widely used for counting data with excessive zeroes. The multicollinearity is the common factor in the explanatory variables of the count data. In this context, typically, maximum likelihood estimation (MLE) generates unsatisfactory results due to inflation of mean square error (MSE). In the solution of this problem usually, ridge parameters are used. In this study, we proposed a new modified zero-inflated Poisson ridge regression model to reduce the problem of multicollinearity. We experimented within the context of a specified simulation strategy and recorded the behavior of proposed estimators. We also apply our proposed estimator to the real-life data set and explore how our proposed estimators perform well in the presence of multicollinearity with the help of ZIP model for count data.

COVID-19 vaccine hesitancy among healthcare workers in Arab Countries: A systematic review and meta-analysis.

BACKGROUND: Vaccine hesitancy is a major obstacle to the large efforts made by governments and health organizations toward achieving successful COVID-19 vaccination programs. Healthcare worker's (HCWs) acceptance or refusal of the vaccine is an influencing factor to the attitudes of their patients and general population. This study aimed to report the acceptance rates for COVID-19 vaccines among HCWs in Arab countries and identify key factors driving the attitudes of HCWs in the Arab world toward vaccines. METHODS: This systematic review and meta-analysis followed the PRISMA guidelines. PubMed and Scopus databases were searched using pre-specified keywords. All cross-sectional studies that assessed COVID-19 vaccine hesitancy and/or acceptance among HCWs in Arab countries until July 2022, were included. The quality of the included studies and the risk of bias was assessed using the JBI critical appraisal tool. The pooled acceptance rate of the COVID-19 vaccine was assessed using a random-effects model with a 95% confidence interval. RESULTS: A total of 861 articles were identified, of which, 43 were included in the study. All the studies were cross-sectional and survey-based. The total sample size was 57,250 HCWs and the acceptance rate of the COVID-19 vaccine was 60.4% (95% CI, 53.8% to 66.6%; I2, 41.9%). In addition, the COVID-19 vaccine acceptance rate among males was 65.4% (95% CI, 55.9% to 73.9%; I2, 0%) while among females was 48.2% (95% CI, 37.8% to 58.6%; I2, 0%). The most frequently reported factors associated with COVID-19 vaccine acceptance were being male, higher risk perception of contracting COVID-19, positive attitude toward the influenza vaccine, and higher educational level. Predictors of vaccine hesitancy most frequently included concerns about COVID-19 vaccine safety, living in rural areas, low monthly income, and fewer years of practice experience. CONCLUSION: A moderate acceptance rate of COVID-19 vaccines was reported among HCWs in the Arab World. Considering potential future pandemics, regulatory bodies should raise awareness regarding vaccine safety and efficacy and tailor their efforts to target HCWs who would consequently influence the public with their attitude towards vaccines.

Predictors of early peritoneal dialysis initiation in newborns and young infants following cardiac surgery.

OBJECTIVE: This single-centre, retrospective cohort study was conducted to investigate the predictors of early peritoneal dialysis initiation in newborns and young infants undergoing cardiac surgery. METHODS: There were fifty-seven newborns and young infants. All subjects received peritoneal dialysis catheter after completion of the cardiopulmonary bypass. Worsening post-operative (post-op) positive fluid balance and oliguria (<1 ml/kg/hour) despite furosemide were the clinical indications to start early peritoneal dialysis (peritoneal dialysis +). Demographic, clinical, and laboratory data were collected from the pre-operative, intra-operative, and immediately post-operative periods. RESULTS: Baseline demographic data were indifferent except that peritoneal dialysis + group had more newborns. Pre-operative serum creatinine was higher for peritoneal dialysis + group (p = 0.025). Peritoneal dialysis + group had longer cardiopulmonary bypass time (p = 0.044), longer aorta cross-clamp time (p = 0.044), and less urine output during post-op 24 hours (p = 0.008). In the univariate logistic regression model, pre-op serum creatinine was significantly associated with higher odds of being in peritoneal dialysis + (p = 0.021) and post-op systolic blood pressure (p = 0.018) and post-op mean arterial pressure (p=0.001) were significantly associated with reduced odds of being in peritoneal dialysis + (p = 0.018 and p = 0.001, respectively). Post-op mean arterial pressure showed a statistically significant association adjusted odds ratio = 0.89, 95% confidence interval [0.81, 0.96], p = 0.004) with peritoneal dialysis + in multivariate analysis after adjusting for age at surgery. CONCLUSIONS: In our single-centre cohort, pre-op serum creatinine, post-op systolic blood pressure, and mean arterial pressure demonstrated statistically significant association with peritoneal dialysis +. This finding may help to better risk stratify newborns and young infants for early peritoneal dialysis start following cardiac surgery.

Advances and Challenges in Interventional Immuno-Oncology Locoregional Therapies.

Interventional immuno-oncology is making strides in locoregional therapies to address complex tumor microenvironments. Long-standing interventional radiology cancer therapies, such as tumor ablation and embolization, are being recharacterized in the context of immunotherapy. Intratumoral injections, such as those of genetically engineered or unaltered viruses, and the delivery of immune cells, antibodies, proteins, or cytokines into targeted tumors, along with advancements in delivery techniques, have produced promising results in preliminary studies, indicating their antitumor effectiveness. Emerging strategies using DNA scaffolding, polysaccharides, glycan, chitosan, and natural products are also showing promise in targeted cancer therapy. The future of interventional immuno-oncology lies in personalized immunotherapies that capitalize on individual immune profiles and tumor characteristics, along with the exploration of combination therapies. This study will review various interventional immuno-oncology strategies and emerging technologies to enhance delivery of therapeutics and response to immunotherapy.

Interpreting Lower Trapezius Musculocutaneous Flap Skin Paddle Perfusion with Indocyanine Green Angiography.

Background: The lower trapezius myocutaneous flap (LTF) is a pedicled flap with clinically significant variability of distal skin flap perfusion. Objective: To compare the incidence of partial flap necrosis before and after the institution of routine intraoperative laser-assisted indocyanine green (ICG) angiography. Methods: This is a retrospective review of all LTF performed between November 2021 and July 2022. The outcomes measured in this study are the distance distal to the inferior border of the trapezius muscle with adequate perfusion, and incidence and degree of partial flap necrosis. Results: Sixteen patients met inclusion criteria with a median age of 64.5 years, and a median defect size of 147 cm2. Most patients (11/16) had undergone previous treatment for malignancy. Before utilizing ICG angiography, 40% (2/5) had partial flap necrosis, whereas after utilizing ICG angiography, 9% (1/11) of patients had partial flap necrosis. Seventy-three percent (8/11) of cases who underwent ICG angiography demonstrated a portion of the skin paddle with inadequate perfusion. The range of skin perfusion distal to the inferior border of the trapezius muscle was 0-7 cm (median, 4). Conclusions: The incidence of partial flap necrosis decreased after institution of routine ICG angiography.

Enhancing mean estimators in median ranked set sampling with dual auxiliary information.

When measuring the research variable is complicated, expensive, or problematic, median ranked set sampling (MRSS) is often utilized since it is straightforward to rank the components using a low-cost sorting criterion. Using this sampling scheme, many authors considered the problem of population mean estimation with a single auxiliary variable in order to obtain more precised estimators than the traditional ratio type regression estimators. In this article, we extend their ideas based on regression approach using two auxiliary variables and introduce a new regression-type estimator along with its theoretical expression of minimum mean square error (MSE). The suggested estimator's applicability is demonstrated using both simulated and real-world data sets.

A novel proposed class of estimators under ranked set sampling: Simulation and diverse applications.

This study presents a novel enhanced exponential class of estimators for population mean under RSS by employing data on an auxiliary variable. The suggested estimators' mean square error (MSE) is calculated approximately at order one. The efficiency conditions that make the suggested enhanced exponential class of estimators superior to the traditional estimators are found. A simulation study using hypothetically drawn normal and exponential populations evaluates the execution of the suggested estimators. The findings demonstrate that the suggested estimators outperform their traditional equivalents. In addition, real data examples are examined to show how the proposed estimators can be implemented in various real life problems.

One-Pot Formal Carboradiofluorination of Alkenes: A Toolkit for Positron Emission Tomography Imaging Probe Development.

We report the first one-pot formal alkene carboradiofluorination reaction employing easily accessible alkenes as both prosthetic group precursors and coupling partners. The methodology features rapid sequential Markovnikov-selective iodofluorination and photoinduced Pd(0/I/II)-catalyzed alkyl Heck reaction as a mild and robust fluorine-18 (18F) radiochemical approach for positron emission tomography (PET) imaging probe development. A new class of prosthetic groups for PET imaging probe synthesis was isolated as iodofluorinated intermediates in moderate to excellent yields. The one-pot formal alkenylfluorination reaction was carried out to produce over 30 analogues of a wide range of bioactive molecules. Further application of the Pd(0/I/II) manifold in PET probe development was illustrated by the direct carbo(radio)fluorination of electron-rich alkenes. The methods were successfully translated to radiolabel a broad scope of medicinally relevant small molecules in generally good radiochemical conversion. The protocol was further optimized to accommodate no-carrier-added conditions with similar efficiency for future (pre)clinical translation. Moreover, the radiosynthesis of prosthetic groups was automated in a radiochemistry module to facilitate its practical use in multistep radiochemical reactions.

Knowledge and Awareness of Systemic Lupus Erythematosus Among the Population of Makkah, Saudi Arabia: A Cross-Sectional Study.

Background Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that affects mostly females of childbearing age. The exact cause is still unknown, but hormonal and immunological features and genetic predisposition are considered likely etiological factors. Disease presentation is variable but is usually characterized by phases of remission and relapse. Objective This study was conducted to assess the knowledge and awareness of SLE among the general population of Makkah, Saudi Arabia. Methods Data were collected using an online survey created with Google Forms that was distributed to the residents of Makkah aged 18 years and older. The survey was disseminated between November 2022 and January 2023. Results A total of 488 participants were included in the study, and the mean age of the participants was 29.1 years; the majority were female (54%). Only 18.6% of the participants knew someone with SLE, while 52.3% had heard about SLE. Additionally, 79.9% of participants had below-average awareness of SLE. Moreover, 72.1% believed that awareness of SLE should be promoted; 65.5% knew about SLE from the Internet or e-resources. Finally, only 5.5% of the participants had heard about SLE from physicians. Conclusion This study showed an insufficient level of knowledge and awareness of SLE in the general population of Makkah. We recommend conducting physical and virtual disease awareness campaigns and activities to enhance the knowledge and awareness of SLE among the general population of Makkah and other parts of Saudi Arabia.

Association of transcription factor 7-like 2 rs12255372 polymorphism with susceptibility of type 2 diabetes mellitus in Bangladeshi population.

Polymorphism of transcription factor 7-like 2 (TCF7L2) has a link with type 2 diabetes mellitus (T2DM) through ß cell dysfunction that causes defect in blood glucose homeostasis. This case-control study recruited 67 T2DM as cases and 65 age-matched healthy individuals as controls to determine whether the polymorphism rs12255372 (G > T) in the TCF7L2 gene have an association with T2DM in Bangladeshi population. Genomic DNA was purified from peripheral whole blood sample and direct Sanger sequencing was done for genotyping of SNP. Bivariate logistic regression was done to find out the association between genetic variant and T2DM. In our study, the minor T allele frequency was significantly more frequent in T2DM group than healthy controls (29.1% vs. 16.9%). After adjusting with confounding factors, heterozygous-genotype GT had higher odds of developing T2DM (OR 2.4; 95% CI: 1.0-5.5; p value = 0.04) and in dominant model, having SNP in TCF7L2 increased the risk of T2DM 2.3 times (95% CI: 1.0-5.2; p value = 0.04). In interaction model, genetic susceptible SNP cases interacted significantly with increasing age and BMI, female gender, and having family history of diabetes mellitus to develop T2DM (pinteraction < 0.001). Having minor T allele either in heterozygous or homozygous variant form of rs12255372 (G > T) TCF7L2 had significant association with T2DM. In conclusion, TCF7L2 gene variant increases risk of developing T2DM among the Bangladeshi population.

Evaluation of quantitative point-of-care test for measurement of glucose-6-phosphate dehydrogenase enzyme activity in Malaysia.

INTRODUCTION: The treatment of Plasmodium vivax malaria with 8-aminoquinolines is contraindicated in glucose-6-phosphate dehydrogenase (G6PD) deficient individuals due to the risk of acute haemolytic anaemia. Effective G6PD screening is paramount to avoid adverse drug reactions. This study aimed to evaluate the performance of novel quantitative point-of-care (POC) tests as a new screening method for G6PD deficiency in Malaysia. MATERIALS AND METHODS: A total of 153 neonatal cord blood, 99 peripheral blood of older children aged between 1 month to 12-years old, and 62 peripheral adult blood were screened for G6PD deficiency using two quantitative POC tests, CareStartTM biosensor (Carestart) and CareStartTM Biosensor 1 (S1). The results were compared with OSMMR2000D kit as a reference assay. Two statistical analyses were performed in this study to evaluate the POC test performances, the Spearman's correlation test and the Cohen's kappa method. RESULTS: Both Carestart and S1 tests showed significant positive correlations to OSMMRS000D with r2 = 0.7916 and r2 = 0.7467. Their measurement of agreement showed a kappa (κ) value of 0.805 (p<0.001, 95% CI), and 0.795 (p<0.001, 95% CI), respectively. Analysis of the area under the Receiver Operating Curve (ROC) at 60% cut-off illustrated that the Carestart had 90.2% sensitivity, 98.9% specificity, 98.3% positive predictive value (PPV), and 93.8% negative predictive value (NPV). The corresponding values for the S1 were 95.2%, 100%, 100%, and 96.8%, respectively. CONCLUSION: This study showed that the Carestart and S1 biosensors have high-performance reliability for screening of G6PD deficiency, which can guide safe prescriptions of anti-malaria medications and hence, eradication of Plasmodium vivax malaria.

Examination of Non-Infected Operatively-Excised Bioprostheses in the Aortic Valve Position to Determine the Reason for their Dysfunction.

Described herein are findings in 55 non-infected bioprostheses that had been in the aortic valve position from 2 to 276 months (mean 107). The major purpose of this study was to illustrate the variable causes prompting excision of the bioprostheses. Fifty-three (96%) patients survived ≥ 30 days following the bioprosthetic excision and 50 (91%) patients lived ≥1 year postoperatively. The techniques used to explant the bioprostheses appear to vary considerably among the operating surgeons.

Effectiveness of antimicrobial stewardship interventions on early switch from intravenous-to-oral antimicrobials in hospitalized adults: A systematic review.

BACKGROUND: This review aimed to summarize the available evidence on the effectiveness and safety of antimicrobial stewardship interventions to improve the practice of IV-to-PO antimicrobial switch therapy in hospitalized adults. METHODS: Following the PRISMA guidelines, we searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE/PubMed, and Scopus from inception to September 1, 2020, for original articles investigating any interventions aimed to improve the practice of IV-to-PO antimicrobial switch therapy in hospitalized adults with infectious diseases. We included randomized controlled trials (RCTs) and quasi-experimental studies. Studies were excluded if they evaluated drugs other than antimicrobials, head-to-head comparison of interventions, included pediatrics or oncology patients. RESULTS: Of 506 unique citations identified, 36 studies met the inclusion criteria. The 36 included studies reported 92 interventions as a single (n = 10) or a bundle of interventions (n = 26). The most common interventions used were guideline/protocol/pathway (n = 25), audit and feedback (n = 20), and education (n = 17). CONCLUSIONS: This review provides health care providers with a comprehensive summary on the interventions to promote IV-to-PO antimicrobial switch. While no one intervention could be identified as the safest and most effective as most of the included studies used a bundle of interventions, all interventions resulted in optimizing antibiotic use and reducing health care expenditures without compromising the clinical outcomes. As such, each hospital should design and utilize interventions that are applicable based on available resources and expertise.

Hyperactivation of p53 using CRISPRa kills human papillomavirus-driven cervical cancer cells.

Clinical and pre-clinical work for a number of cancer types has demonstrated relatively positive outcomes and effective tumour regression when the level and function of p53, a well-established tumour suppressor, is restored. Human papillomavirus (HPV)-driven cancers encode the E6 oncoprotein, which leads to p53 degradation, to allow the carcinogenic process to proceed. Indeed, there have been several attempts to revive p53 function in HPV-driven cancers by both pharmacological and genetic means to increase p53 bioavailability. Here, we employed a CRISPR activation (CRISPRa) approach to overcome HPV-mediated silencing of p53 by hyperexpressing the p53 gene promoter. Our data show that CRISPRa-mediated hyperexpression of p53 leads to HPV+ cervical cancer cell killing and the reduction of cell proliferation. This proof-of-concept data suggest that increasing p53 bioavailability may potentially be a promising therapeutic approach for the treatment of HPV-driven cancers.