Optimising craniospinal irradiation for medulloblastoma: a dosimetric comparison of two VMAT planning methods.

Background: Craniospinal irradiation (CSI) poses a challenging planning process because of the complex target volume. Traditional 3D conformal CSI does not spare any critical organs, resulting in toxicity in patients. Here the dosimetric advantages of volumetric-modulated arc therapy (VMAT) using partial arc and avoidance sectors are compared with each other in planning in adult patients undergoing CSI to develop a clinically feasible technique that is both effective and efficient. Patient and methods: Eight adult patients treated with CSI were retrospectively identified. In total 16 plans were made. We generated two plans for each patient: 1. VMAT plan using partial arc, namely VMAT_pa. 2. VMAT plan using avoidance sectors, namely VMAT_as. The dose prescribed was 36 Gy in 20 fractions. The dose-volume histogram for planning target volume (PTV) and organs at risk (OAR) (lens, eye, heart, thyroid, lungs, liver, gonads and kidneys) were analysed and compared. Dose parameters of mean dose, V95%, and V107% for the PTV were evaluated. Results: The median length of PTV is 65.58 cm (45.8-79.5). The volume of PTV receiving 95% of the dose (V95%) in both the plans are 97.51% (VMAT_as) and 97.99% (VMAT_pa) (p = 0.121) while V107% are 0.733 and 0.742 for VMAT_as and VMAT_pa, respectively (p = 0.969). The doses of OARs such as lens, eye, liver and gonads were comparable. The mean heart dose was 10.4 and 9.0 Gy in VMAT_as and VMAT_pa plans, respectively (p = 0.005). Significant lower doses to the thyroid, kidneys and lungs were seen in VMAT plans using avoidance sectors. Conclusion: This study provides a practically useful VMAT planning method for the treatment of CSI and illustrates the ability of VMAT using avoidance sectors to generate highly conformal and homogeneous treatment plans for CSI, while limiting the dose to the relevant OARs.

Retinal Dystrophies Associated With Peripherin-2: Genetic Spectrum and Novel Clinical Observations in 241 Patients.

Purpose: To describe the clinical, electrophysiological and genetic spectrum of inherited retinal diseases associated with variants in the PRPH2 gene. Methods: A total of 241 patients from 168 families across 15 sites in 9 countries with pathogenic or likely pathogenic variants in PRPH2 were included. Records were reviewed for age at symptom onset, visual acuity, full-field ERG, fundus colour photography, fundus autofluorescence (FAF), and SD-OCT. Images were graded into six phenotypes. Statistical analyses were performed to determine genotype-phenotype correlations. Results: The median age at symptom onset was 40 years (range, 4-78 years). FAF phenotypes included normal (5%), butterfly pattern dystrophy, or vitelliform macular dystrophy (11%), central areolar choroidal dystrophy (28%), pseudo-Stargardt pattern dystrophy (41%), and retinitis pigmentosa (25%). Symptom onset was earlier in retinitis pigmentosa as compared with pseudo-Stargardt pattern dystrophy (34 vs 44 years; P = 0.004). The median visual acuity was 0.18 logMAR (interquartile range, 0-0.54 logMAR) and 0.18 logMAR (interquartile range 0-0.42 logMAR) in the right and left eyes, respectively. ERG showed a significantly reduced amplitude across all components (P < 0.001) and a peak time delay in the light-adapted 30-Hz flicker and single-flash b-wave (P < 0.001). Twenty-two variants were novel. The central areolar choroidal dystrophy phenotype was associated with 13 missense variants. The remaining variants showed marked phenotypic variability. Conclusions: We described six distinct FAF phenotypes associated with variants in the PRPH2 gene. One FAF phenotype may have multiple ERG phenotypes, demonstrating a discordance between structure and function. Given the vast spectrum of PRPH2 disease our findings are useful for future clinical trials.

Investigating and Quantifying Molecular Complexity Using Assembly Theory and Spectroscopy.

Current approaches to evaluate molecular complexity use algorithmic complexity, rooted in computer science, and thus are not experimentally measurable. Directly evaluating molecular complexity could be used to study directed vs undirected processes in the creation of molecules, with potential applications in drug discovery, the origin of life, and artificial life. Assembly theory has been developed to quantify the complexity of a molecule by finding the shortest path to construct the molecule from building blocks, revealing its molecular assembly index (MA). In this study, we present an approach to rapidly infer the MA of molecules from spectroscopic measurements. We demonstrate that the MA can be experimentally measured by using three independent techniques: nuclear magnetic resonance (NMR), tandem mass spectrometry (MS/MS), and infrared spectroscopy (IR). By identifying and analyzing the number of absorbances in IR spectra, carbon resonances in NMR, or molecular fragments in tandem MS, the MA of an unknown molecule can be reliably estimated. This represents the first experimentally quantifiable approach to determining molecular assembly. This paves the way to use experimental techniques to explore the evolution of complex molecules as well as a unique marker of where an evolutionary process has been operating.

Understanding genetic risks: Computational exploration of human ß-Synuclein nsSNPs and their potential impact on structural alteration.

Synucleins are pivotal in neurodegenerative conditions. Beta-synuclein (ß-synuclein) is part of the synuclein protein family alongside alpha-synuclein (α-synuclein) and gamma-synuclein (γ-synuclein). These proteins, found mainly in brain tissue and cancers, are soluble and unstructured. ß-synuclein shares significant similarity with α-synuclein, especially in their N-terminus, with a 90% match. However, their aggregation tendencies differ significantly. While α-synuclein aggregation is believed to be counteracted by ß-synuclein, which occurs in conditions like Parkinson's disease, ß-synuclein may counteract α-synuclein's toxic effects on the nervous system, offering potential treatment for neurodegenerative diseases. Under normal circumstances, ß-synuclein may guard against disease by interacting with α-synuclein. Yet, in pathological environments with heightened levels or toxic substances, it might contribute to disease. Our research aims to explore potential harmful mutations in the ß-synuclein using computational tools to predict their destabilizing impact on protein structure. Consensus analysis revealed rs1207608813 (A63P), rs1340051870 (S72F), and rs1581178262 (G36C) as deleterious. These findings highlight the intricate relationship between nsSNPs and protein function, shedding light on their potential implications in disease pathways. Understanding the structural consequences of nsSNPs is crucial for elucidating their role in pathogenesis and developing targeted therapeutic interventions. Our results offer a robust computational framework for identifying neurodegenerative disorder-related mutations from SNP datasets, potentially reducing the costs associated with experimental characterization.

Control strategy for current limitation and maximum capacity utilization of grid connected PV inverter under unbalanced grid conditions.

Under grid voltage sags, over current protection and exploiting the maximum capacity of the inverter are the two main goals of grid-connected PV inverters. To facilitate low-voltage ride-through (LVRT), it is imperative to ensure that inverter currents are sinusoidal and remain within permissible limits throughout the inverter operation. An improved LVRT control strategy for a two-stage three-phase grid-connected PV system is presented here to address these challenges. To provide over current limitation as well as to ensure maximum exploitation of the inverter capacity, a control strategy is proposed, and performance the strategy is evaluated based on the three generation scenarios on a 2-kW grid connected PV system. An active power curtailment (APC) loop is activated only in high power generation scenario to limit the current's amplitude below the inverter's rated current. The superior performance of the proposed strategy is established by comparison with two recent LVRT control strategies. The proposed method not only injects necessary active and reactive power but also minimizes overcurrent with increased exploitation of the inverter's capacity under unbalanced grid voltage sag.

Impact of Virtual Reality on Pain, ROM, Muscle Strength and Quality of Life among Breast Cancer Patients: An Integrative Review of Literature.

BACKGROUND: Breast cancer is the most commonly diagnosed cancer among women globally, with significant impacts on physical, emotional, and functional well-being. Traditional rehabilitation methods may not fully address the multifaceted challenges faced by breast cancer survivors (BCSs), prompting exploration into innovative approaches such as Virtual Reality (VR) technology. OBJECTIVE: The present review aims to assess the effectiveness of VR in alleviating pain, improving Range of Motion (ROM), enhancing muscle strength, and augmenting the overall quality of life in patients undergoing breast cancer rehabilitation. METHODS: A comprehensive review of existing literature was conducted, focusing on studies investigating the use of VR in breast cancer rehabilitation. PubMed, Scopus, PEDro and Google scholar were searched for articles addressing VR interventions targeting pain management, ROM improvement, muscle strength enhancement, and quality of life enhancement in breast cancer patients. RESULTS: Findings yielded total 12 articles matching the selection criteria. VR technology has shown promising results in addressing the multifaceted needs of breast cancer patients. VR also serves as a distraction tool, positively impacting psychological well-being and mitigating negative psychological symptoms associated with the disease. CONCLUSION: VR represents a non-pharmacological approach to pain management and rehabilitation in breast cancer patients. Its ability to engage emotional, cognitive, and attention processes contributes to its effectiveness in enhancing overall quality of life. Further research is warranted to elucidate the long-term benefits and optimal utilization of VR technology in breast cancer rehabilitation programs.

Hypoxia delays steroid-induced developmental maturation in Drosophila by suppressing EGF signaling.

Animals often grow and develop in unpredictable environments where factors like food availability, temperature, and oxygen levels can fluctuate dramatically. To ensure proper sexual maturation into adulthood, juvenile animals need to adapt their growth and developmental rates to these fluctuating environmental conditions. Failure to do so can result in impaired maturation and incorrect body size. Here we describe a mechanism by which Drosophila larvae adapt their development in low oxygen (hypoxia). During normal development, larvae grow and increase in mass until they reach critical weight (CW), after which point a neuroendocrine circuit triggers the production of the steroid hormone ecdysone from the prothoracic gland (PG), which promotes maturation to the pupal stage. However, when raised in hypoxia (5% oxygen), larvae slow their growth and delay their maturation to the pupal stage. We find that, although hypoxia delays the attainment of CW, the maturation delay occurs mainly because of hypoxia acting late in development to suppress ecdysone production. This suppression operates through a distinct mechanism from nutrient deprivation, occurs independently of HIF-1 alpha and does not involve dilp8 or modulation of Ptth, the main neuropeptide that initiates ecdysone production in the PG. Instead, we find that hypoxia lowers the expression of the EGF ligand, spitz, and that the delay in maturation occurs due to reduced EGFR/ERK signaling in the PG. Our study sheds light on how animals can adjust their development rate in response to changing oxygen levels in their environment. Given that hypoxia is a feature of both normal physiology and many diseases, our findings have important implications for understanding how low oxygen levels may impact animal development in both normal and pathological situations.

Calcium signaling induces partial EMT and renal fibrosis in a Wnt4mCherry knock-in mouse model.

The renal tubular epithelial cells (TEC) have a strong capacity for repair after acute injury, but when this mechanism becomes uncontrollable, it leads to chronic kidney diseases (CKD). Indeed, in progress toward CKDs, the TECs may dedifferentiate, undergo epithelial-to-mesenchyme transition (EMT), and promote inflammation and fibrosis. Given the critical role of Wnt4 signaling in kidney ontogenesis, we addressed whether changes in this signaling are connected to renal inflammation and fibrosis by taking advantage of a knock-in Wnt4mCh/mCh mouse. While the Wnt4mCh/mCh embryos appeared normal, the corresponding mice, within one month, developed CKD-related phenotypes, such as pro-inflammatory responses including T-cell/macrophage influx, expression of fibrotic markers, and epithelial cell damage with a partial EMT. The Wnt signal transduction component ß-catenin remained unchanged, while calcium signaling is induced in the injured TECs involving Nfat and Tfeb transcription factors. We propose that the Wnt4 signaling pathway is involved in repairing the renal injury, and when the signal is overdriven, CKD is established.

Dengue dynamics: Prognostic and disease monitoring through molecular and serological profiling of clinical isolates.

BACKGROUND OBJECTIVES: Dengue fever is a mosquito-borne illness that affects millions of people worldwide every year. With no vaccination available, early detection and treatment is critical. One-hundred-twelve countries in the world pose a risk to travelers, particularly in metropolitan areas. Laboratory diagnoses vary according to objectives, resources, and schedule, with sensitivity and specificity must be balanced for effective testing. METHODS: The current work is a cross-sectional diagnostic study and samples from suspected patients of dengue was collected from May 15 to November 15 2023 and transported to laboratory, and RT-PCR and Dengue Duo Rapid test diagnosis techniques were used on 48 clinical samples included in this study. RESULTS: Blood was collected from suspected cases of dengue and subjected further to different molecular and serological parameters. Serum was separated from all 48 blood samples. RNA was isolated by silica column extraction method which is further utilized as a template for amplification and detection of dengue serotyping. Master Mix was prepared for the amplification and detection of dengue virus by Rotor-Gene Q Real-Time PCR Machine and further serological profiling of positive dengue cases was studied by conventional PCR. INTERPRETATION CONCLUSION: Our laboratory effectively standardized an RT-PCR-based approach for molecular identification of dengue virus in clinical specimens. This adaptive technique which used numerous primer sets displayed good specificity and sensitivity in serotype detection. The technology provides for quick and reliable identification of dengue virus infections, allowing for targeted treatment and preventative actions for successful disease management in highly populated regions.

Fine-tuning covalent organic frameworks for structure-activity correlation via adsorption and catalytic studies.

In applications utilizing Covalent Organic Frameworks (COFs) for adsorption, the interplay between crystallinity (vis-à-vis surface area) and active sites still remains ambiguous. To address this, the present study introduces three isoreticular COFs-COP-N18 (covalent organic polymer with short-range order), COF-N18 (COF having long-range order), and COF-N27 (semicrystalline COF with pyridyl heteroatoms)-to explore this duality. Through systematic variations in structural order, pore volume, and pore-wall nitrogen content, we aim to establish a structure-activity relationship (SAR) for these COFs via adsorption and catalysis, using CO2 and I2 as probes. Our investigation highlights the positive influence of crystallinity, surface area, and pore volume in adsorption as well as catalysis. However, the presence of heteroatoms manifests complex behavior in CO2 adsorption and CO2 cycloaddition reactions with epoxides. COF-N18 and COF-N27 showed comparable CO2 uptake capacities at different temperatures (273, 293, and 313 K) and ∼1 bar pressure. Additionally, CO2 cycloaddition reactions were performed with substrates possessing different polarities (epichlorohydrin, 1,2-epoxydodecane) to elucidate the role of COF surface polarity. Further investigation into iodine adsorption was performed to understand the impact of COF structural features on the modes of adsorption and adsorption kinetics. Improvements in COF-crystallinity results in faster average iodine uptake rate at 80% (K80% = 1.79 g/h) by COF-N18. Whereas, heteroatom doping slows down iodine adsorption kinetics (0.35 g/h) by prolonging the adsorption process up to 72 h. Overall, this study advances our understanding of COFs as adsorbents and catalysts, providing key insights into their SAR while emphasizing structural fine-tuning as a key factor for impactful environmental applications.

Reconstruction of Partial Defect of Ear in a Tertiary Care Institute.

Auricle is the outward visible part of ear and composed of skin and cartilage. Auricle due to its standout and projected position is more vulnerable to get injured and cause distortion of the facial aesthetics. Reconstruction of the ear defect should be individualized depending on the defect size, location, nearby skin, patient requirement and surgeon experience. To present the results of various reconstructive options for partial ear defect which will aid in decision making among reconstructive options available. Reconstruction was individualized considering the defect size, depth, location, surrounding skin. In upper 1/3 defect reconstructive options include Antia-Buch chondrocutaneous advancement flap, autogenous cartilage with temporoparietal fascial flap, for middle 1/3 defect options include retroauricular soft tissue tube flap, diefenbach procedure, Autogenous cartilage graft and temporoparietal fascial flap, for lower 1/3 defect reconstructive options include pre auricular flap, triangular repair method, Zenteno Alanis technique. Reconstruction with various techniques results in aesthetically good outcomes. There is no major complication seen in any patient. Reconstruction of ear defect with various options available has good outcome. Planning is important part in reconstruction process. Reconstructive option chosen for a ear defect should be individualized depending on patient characteristics, surgeon experience.

Chest wall perforator flap partial breast reconstruction: a retrospective analysis of surgical, cosmetic and survival outcome.

Introduction: Oncoplastic breast surgery includes volume replacement as well as volume displacement. Autologous tissue is the preferred approach for volume replacement and includes chest wall perforator flaps (CWPF). Although described more than a decade ago, CWPFs have not been adopted widely in clinical practice till recently. We report the largest single-centre institutional data on CWPFs. Patients and methods: The study includes all patients who underwent breast conservation surgery (BCS) using CWPFs from January 2015 to December 2022. Data were retrieved from the institutional electronic record and Redcap database. The analysis was done using SPSS 23 and STATA 14. Results: 150 patients were included in the study. The mean age was 48.8 years (SD 10.4), and the body mass index was (26.6 kg/m2, SD 4.3). >50% of patients had breasts with small cup sizes (A&B) and mild ptosis (Non-ptotic and Grade 1 ptosis). 44.7% of patients underwent lateral intercostal artery perforator flap (LICAP), anterior intercostal artery perforator flap in 31.3%, lateral thoracic perforator flap (LTAP) in 12%, LICAP + LTAP in 11.3% and thoracodorsal artery perforator flap in 1%. Post-operatively, haematoma was seen in 1.3%, complete flap necrosis in 1.3%, seroma in 7%, wound dehiscence in 12%, and positive margin in 6.7%. 92 patients responded to the satisfaction assessment, of which >90% were happy with the surgical scars, comfortable going out in a public place, satisfied with the symmetry of the breast, and no one chose mastectomy in hindsight. The 5-year predicted disease free survival and overall survival were 86.4% and 94.7%, respectively. Conclusion: BCS with CWPF is an excellent option for reconstruction in small to medium-sized breasts. It is associated with minimal morbidity and comparable patient-reported cosmetic and survival outcomes.

Synergistic Influence of Melatonin-Hydrocolloid Coating on Decay and Senescence of Nectarine (Prunus persica var. nucipersica) during Supermarket Storage Conditions.

Nectarines have remarkable nutritional value, low caloric content, and are rich in antioxidants. However, despite substantial local and global demand, their susceptibility to rapid spoilage during peak summer harvest is limited. To address this issue, the current study investigated the potential benefits of using melatonin (MLT), an antioxidant biomolecule, in combination with edible hydrocolloid coatings like carboxymethylcellulose (CMC) and gum Arabic (G.A.) on 'Snow Queen' nectarine fruits. The nectarines were treated with various combinations of coatings, including 1% and 1.5% CMC, 8% and 10% G.A., and 0.1 mM melatonin. These coated and non-coated samples were stored under standard supermarket conditions (18 ± 1 °C, 85-90% R.H.) for 16 days. The outcomes demonstrated that the most effective treatment was the combination of 1% CMC with 0.1 mM melatonin. This treatment significantly (p ≤ 0.05) reduced the rate of respiration, curbed fruit decay by approximately 95%, minimized weight loss by around 42%, and maintained approximately 39% higher levels of total phenol content and roughly 30% greater antioxidant (AOX) activity. These positive effects were accompanied by preserved firmness and overall quality attributes. Moreover, the treatment extended the shelf life to 16 days through retarding senescence and suppressing the activities of lipoxygenase (LOX) and pectin methylesterase (PME), all without compromising the functional qualities of the nectarine.

Understanding Female and Male Insights in Psychology: Who Thinks What?

Evolutionary psychology is the study of human psychological behavior. During childhood, men and women behave similarly; however, as a child approaches puberty, new physical and behavioral changes emerge. Behavioral psychology focuses on understanding the functioning and thought processes of the human mind. The general population lacks knowledge of basic behavioral differences between men and women, leaving them unaware of their role, limitations, societal responsibilities, resulting in an underestimation of their own natural talents and biology. Thus, people tend to follow societal norms rather than exploring and utilizing their natural talents. The current review was designed and conducted to enforce compression on behavioral psychology in both genders as well as to identify variations in hormonal activity and sexual preferences.

Evading Musculoskeletal Conditions Using Qigong as a Rescue Technique.

Classically, Qigong is a Chinese technique that has been practiced in China for the past 3,000 years for healing the inner self. Qigong, wherein "Qi" means body energy and "Gong" denotes cultivation, regulates the energy flow in the body. The Qigong technique comprises a package of deep breathing training, gentle and rhythmic movement, and muscle-strengthening exercises that heal the body to activate one's internal soul energy. It has demonstrated its efficacy by inducing relaxation, building up stamina, strengthening immunity, appreciating muscle conditioning, and minimizing anxiety and depression. Furthermore, it has been beneficial in improving awareness of joint and movement senses. Specifically, Qigong brings healing by regulating energy flow in the whole-body systems. Moreover, it has exhibited a variety of regenerating effects by inducing emotional and mental relaxation. In today's world, Qigong exercises are being used for treating musculoskeletal disorders that are work- and stress-related by nature. Qigong is practiced globally as deep breathing exercises, and meditation is practiced for peace of mind and spirituality, whereas vigorous practice includes martial arts.

Highly efficient photonic radar by incorporating MDM-WDM and machine learning classifiers under adverse weather conditions.

Photonic radar, a cornerstone in the innovative applications of microwave photonics, emerges as a pivotal technology for future Intelligent Transportation Systems (ITS). Offering enhanced accuracy and reliability, it stands at the forefront of target detection and recognition across varying weather conditions. Recent advancements have concentrated on augmenting radar performance through high-speed, wide-band signal processing-a direct benefit of modern photonics' attributes such as EMI immunity, minimal transmission loss, and wide bandwidth. Our work introduces a cutting-edge photonic radar system that employs Frequency Modulated Continuous Wave (FMCW) signals, synergized with Mode Division and Wavelength Division Multiplexing (MDM-WDM). This fusion not only enhances target detection and recognition capabilities across diverse weather scenarios, including various intensities of fog and solar scintillations, but also demonstrates substantial resilience against solar noise. Furthermore, we have integrated machine learning techniques, including Decision Tree, Extremely Randomized Trees (ERT), and Random Forest classifiers, to substantially enhance target recognition accuracy. The results are telling: an accuracy of 91.51%, high sensitivity (91.47%), specificity (97.17%), and an F1 Score of 91.46%. These metrics underscore the efficacy of our approach in refining ITS radar systems, illustrating how advancements in microwave photonics can revolutionize traditional methodologies and systems.

Identifying data-driven subtypes of major depressive disorder with electronic health records.

BACKGROUND: Efforts to reduce the heterogeneity of major depressive disorder (MDD) by identifying subtypes have not yet facilitated treatment personalization or investigation of biology, so novel approaches merit consideration. METHODS: We utilized electronic health records drawn from 2 academic medical centers and affiliated health systems in Massachusetts to identify data-driven subtypes of MDD, characterizing sociodemographic features, comorbid diagnoses, and treatment patterns. We applied Latent Dirichlet Allocation (LDA) to summarize diagnostic codes followed by agglomerative clustering to define patient subgroups. RESULTS: Among 136,371 patients (95,034 women [70 %]; 41,337 men [30 %]; mean [SD] age, 47.0 [14.0] years), the 15 putative MDD subtypes were characterized by comorbidities and distinct patterns in medication use. There was substantial variation in rates of selective serotonin reuptake inhibitor (SSRI) use (from a low of 62 % to a high of 78 %) and selective norepinephrine reuptake inhibitor (SNRI) use (from 4 % to 21 %). LIMITATIONS: Electronic health records lack reliable symptom-level data, so we cannot examine the extent to which subtypes might differ in clinical presentation or symptom dimensions. CONCLUSION: These data-driven subtypes, drawing on representative clinical cohorts, merit further investigation for their utility in identifying more homogeneous patient populations for basic as well as clinical investigation.

SARS-CoV-2 virulence factor ORF3a blocks lysosome function by modulating TBC1D5-dependent Rab7 GTPase cycle.

SARS-CoV-2, the causative agent of COVID-19, uses the host endolysosomal system for entry, replication, and egress. Previous studies have shown that the SARS-CoV-2 virulence factor ORF3a interacts with the lysosomal tethering factor HOPS complex and blocks HOPS-mediated late endosome and autophagosome fusion with lysosomes. Here, we report that SARS-CoV-2 infection leads to hyperactivation of the late endosomal and lysosomal small GTP-binding protein Rab7, which is dependent on ORF3a expression. We also observed Rab7 hyperactivation in naturally occurring ORF3a variants encoded by distinct SARS-CoV-2 variants. We found that ORF3a, in complex with Vps39, sequesters the Rab7 GAP TBC1D5 and displaces Rab7 from this complex. Thus, ORF3a disrupts the GTP hydrolysis cycle of Rab7, which is beneficial for viral production, whereas the Rab7 GDP-locked mutant strongly reduces viral replication. Hyperactivation of Rab7 in ORF3a-expressing cells impaired CI-M6PR retrieval from late endosomes to the trans-Golgi network, disrupting the biosynthetic transport of newly synthesized hydrolases to lysosomes. Furthermore, the tethering of the Rab7- and Arl8b-positive compartments was strikingly reduced upon ORF3a expression. As SARS-CoV-2 egress requires Arl8b, these findings suggest that ORF3a-mediated hyperactivation of Rab7 serves a multitude of functions, including blocking endolysosome formation, interrupting the transport of lysosomal hydrolases, and promoting viral egress.