Protein Disulfide Isomerase 4 Is an Essential Regulator of Endothelial Function and Survival.

Endothelial autophagy plays an important role in the regulation of endothelial function. The inhibition of endothelial autophagy is associated with the reduced expression of protein disulfide isomerase 4 (PDIA-4); however, its role in endothelial cells is not known. Here, we report that endothelial cell-specific loss of PDIA-4 leads to impaired autophagic flux accompanied by loss of endothelial function and apoptosis. Endothelial cell-specific loss of PDIA-4 also induced marked changes in endothelial cell architecture, accompanied by the loss of endothelial markers and the gain of mesenchymal markers consistent with endothelial-to-mesenchymal transition (EndMT). The loss of PDIA-4 activated TGFß-signaling, and inhibition of TGFß-signaling suppressed EndMT in PDIA-4-silenced endothelial cells in vitro. Our findings help elucidate the role of PDIA-4 in endothelial autophagy and endothelial function and provide a potential target to modulate endothelial function and/or limit autophagy and EndMT in (patho-)physiological conditions.

Multipronged effects of increased screen time on the nutritional imbalance: A cross-sectional study of students of Amritsar aged 6-16 years.

Background: Intense marketing of fast-food items impacts the eating habits among children and adolescents. Various studies suggest that increased screen time leads to increased fast-food consumption and decreased sleep duration, both of which are linked to obesity in growing age. Objectives: To assess screen time and dietary habits among the study group and to estimate their effect on sleep deprivation and obesity. Methods: This cross-sectional study was conducted from January 2019 to December 2019 in three schools in Amritsar selected by lottery method of simple random sampling. Out of 4,226 students, 355 overweight and obese students were interviewed regarding their dietary habits. An informed written assent was taken from the mothers. The information was collected on a semi-structured, pre-designed questionnaire by interviewing the mothers of students between 6 and 11 years of age and the students of 12-16 years. Results: 94.4% of students preferred fast foods to regular meals and 58.3% were in the habit of skipping breakfast. 59.4% had a history of daily intake of fast foods while 76.1% had a habit of consuming fast foods while watching television. Only 31.7% had an adequate sleeping pattern of 9-11 hours and 79.7% of the students had a screen time of over 3 hours. Conclusions: More the screen time, the more the chances of missing meals. Being awake for a long odd time leads to increased consumption of foods/snacks furthermore. Regarding the harmful effects of fast foods, the source of information was from schools, but only 41.4% were aware about these effects.

Prevalence, Characteristics, and Trends in Retracted Spine Literature: 2000 - 2023.

BACKGROUND: Retraction of scientific publications is an important check on scientific misconduct and serves to maintain the integrity of the scientific literature. The present study aims to examine the prevalence, trends, and characteristics of retracted spine literature across basic science and clinical spine literature. METHODS: Multiple databases were queried for retracted papers relating to spine or spine surgery, between January 2000 and May 2023. Of 112,668 publications initially identified, 125 were ultimately included in the present study following screening by two independent reviewers. Journal of origin, reasons for retraction, date of publication, date of retraction, impact factor of journal, countries of research origin, and study design were collected for each included publication. RESULTS: Clinical studies were the most frequent type of retracted publication (n=70). The most common reason for retraction was fraud (n=58), followed by plagiarism (n=22) and peer review process manipulation (n=16). Impact factors ranged from 0.3 to 11.1 with a median of 3.75. Average months from publication to retraction across all studies was 37.5 months. The higher the journal impact factor, the longer the amount of time between publication and retraction (p = 0.01). China (n=63) was the country of origin of more than half of all retracted spine publications. CONCLUSIONS: The rate of retractions has been increasing over the past 23 years, and clinical studies have been the most frequently retracted publication type. Clinicians treating disorders of the spine should be aware of these trends when relying on the clinical literature to inform their practice.

The Effect of Concomitant Spinal Cord Injury on Postoperative Health-related Quality of Life After Traumatic Subaxial Cervical Spine Injuries: A Nationwide Registry Study.

OBJECTIVE: To evaluate the effect of spinal cord injury (SCI) on the health-related quality of life (HRQoL) in patients surgically treated for traumatic subaxial cervical spine injuries and investigate the agreement between objective neurologic outcomes and patient reported outcome measures (PROMs) in that context. STUDY DESIGN: Observational study on prospectively collected multi-institutional registry data. SETTING: Sweden. PARTICIPANTS: Patients with traumatic subaxial spine injuries identified in the Swedish Spine Registry (Swespine) between 2006 and 2016. INTERVENTIONS: Anterior, posterior, or anteroposterior cervical fixation surgery. MAIN OUTCOMES: Patient-reported outcome measures (PROMs) consisting of EQ-5D-3Lindex and Neck Disability Index (NDI). RESULTS: Among the 418 identified patients, 93 (22%) had a concomitant SCI. In this group, 30 (32%) had a complete SCI (Frankel A), and the remainder had incomplete SCIs (17%) Frankel B; 25 (27%) Frankel C; 22 (24%) Frankel D. PROMs significantly correlated with the Frankel grade (P<.001). However, post hoc analysis revealed that the differences between adjacent Frankel grades failed to reach both statistical and clinical significance. On univariable linear regression, the Frankel grade was a significant predictor of a specific index derived from the EQ-5D-3L questionnaire (EQ-5D-3Lindex) at 1, 2, and 5 years postoperatively as well as the NDI at 1 and 2 years postoperatively (P<.001). Changes of PROMs over time from 1, to 2, and 5 years postoperatively did not reach statistical significance, regardless of the presence and degree of SCI (P>.05). CONCLUSION: Overall, the Frankel grade significantly correlated with the EQ-5D-3Lindex and NDI and was a significant predictor of PROMs at 1, 2, and 5 years. PROMs were stable beyond 1 year postoperatively regardless of the severity of the SCI.

Long-Term Functional Outcomes Following Surgical Treatment of Spinal Schwannomas: A Population-Based Cohort Study.

Spinal schwannomas are the second most common form of primary intradural spinal tumor. Despite being benign, they may cause spinal cord compression and subsequently acute or chronic neurological dysfunction. The primary treatment is surgical resection. The aim of this study was to identify pre- and postoperative predictors of favorable outcomes after surgical treatment for spinal schwannoma. All adult patients surgically treated for spinal schwannoma between 2006 and 2020 were eligible for inclusion. Medical records and imaging data were retrospectively reviewed. The primary outcome measures were neurological improvement according to the modified McCormick Scale (mMC) and changes in motor deficit, sensory deficit, gait disturbance, bladder dysfunction, and pain at long-term follow-up. In total, 180 patients with a median follow-up time of 4.4 years were included. Pain was the most common presenting symptom (87%). The median time between symptom presentation and surgery was 12 months, while the median time between diagnosis (first MRI) and surgery was 3 months. Gross total resection (GTR) was achieved in 150 (83%) patients and the nerve root could be preserved in 133 (74%) patients. A postoperative complication occurred in 10 patients (5.6%). There were significant postoperative improvements in terms of motor, sensory, gait, and bladder functions, as well as pain (p < 0.001). Of these symptoms, bladder dysfunction was the one most often improved, with complete symptom resolution in all cases. However, no other predictors of improvement could be identified. There were three cases of recurrence after GTR and nine cases of regrowth after STR. Reoperation was performed in six (3.3%) cases. GTR was associated with a significant improvement in neurological status at long-term follow-up and increased the chance of progression-free survival.

Dysphagia, health-related quality of life, and return to work after occipitocervical fixation.

PURPOSE: The purpose of this study was to evaluate patient-reported outcome measures (PROMS) on dysphagia, health-related quality of life (HRQoL) and return to work after occipitocervical fixation (OCF). Postoperative radiographic measurements were evaluated to identify possible predictors of dysphagia. METHODS: All individuals (≥ 18 years) who underwent an OCF at the study center or were registered in the Swedish spine registry (Swespine) between 2005 and 2019, and were still alive when the study was conducted, were eligible for inclusion. There was no overlap between the cohorts. Prospectively collected data on dysphagia (Dysphagia Short Questionnaire DSQ), HRQoL (EQ5D-3L) and return to work were used. Radiological and baseline patient data were retrospectively collected. In addition, HRQoL data of a matched sample of individuals was elicited from the Stockholm Public Health Survey 2006. RESULTS: In total, 54 individuals were included. At long-term follow-up, 26 individuals (51%) had no dysphagia, and 25 (49%) reported some degree of dysphagia: 11 (22%) had mild dysphagia, and 14 (27%) had moderate to severe dysphagia. On a group level, the OCF sample scored significantly lower EQVAS and EQ-5Dindex values compared to the general population (60.0 vs. 80.0, p = 0.016; 0.43 vs. 0.80, p < 0.001). Individuals working preoperatively returned to work after surgery. Of those responding, 88% stated that they would undergo the OCF operation if it was offered today. No predictors of dysphagia based on radiographic measurements were identified. CONCLUSION: Occipitocervical fixation results in a high frequency of long-term dysphagia. The HRQoL of OCF patients is significantly reduced compared to matched controls. However, most patients are satisfied with their surgery. No radiographic predictors of long-term dysphagia could be identified. Future prospective and systematic studies with larger samples and more objective outcome measures are needed to elucidate the causes of dysphagia in OCF.

Borane-Pyridine: An Efficient Catalyst for Direct Amidation.

Borane-pyridine acts as an efficient (5 mol%) liquid catalyst, providing improved solubility for the direct amidation of a wide range of aromatic and aliphatic carboxylic acids and amines to form secondary and tertiary carboxamides. Tolerance of potentially incompatible halo, nitro, and alkene functionalities has been demonstrated.

Conservative or surgical management of orbital schwannomas: a population-based case series.

INTRODUCTION: Orbital schwannomas (OS) are rare occurrences with no more than 500 cases reported in the literature. The tumor's potential to compromise the delicate neuro-ophthalmic structures within the orbit prompts surgical removal. Tumor removal is performed by ophthalmologists, often requiring a multidisciplinary surgical approach. The literature contains a very limited number of cases managed non-surgically. However, the inherent risks of orbital surgery warrant a comparison of the outcomes of conservative and surgical management strategies. AIMS: To review the national Swedish experience with the management of orbital schwannomas. METHODS: The study center is the primary Swedish referral center for the multidisciplinary management of orbital tumors, including schwannomas. During the period of 2005 to 2021, 16 patients with an OS diagnosis were managed at the center. RESULTS: Four patients initially underwent surgery where gross total resection (GTR) was achieved in three (75%) and subtotal resection (STR) in one (25%) case. The remaining 12 patients, who had a low risk of neuro-ophthalmic impairment, were managed conservatively with radiological and clinical examinations at regular intervals. After an average follow-up of 17 months, surgery was performed in three of these cases (25%). No recurrences or tumor growths were detected on radiological follow-ups (mean 50 months), and all patients experienced postoperative improvement at clinical follow-up (mean 65 months). The remainder of the conservatively treated patients (n=9) experienced no clinical progression (mean 30 months). A slight radiological tumor progression was detected in one patient after 17 months. CONCLUSION: There were no differences in long-term outcome between patients who had been managed with early surgery and those operated later after an initially conservative management. Conservatively treated patients had minimal to no symptoms and remained clinically stable throughout the follow-up period. Based on these findings, conservative management may successfully be adopted in cases with mild symptoms, no signs of compressive optic neuropathy and low risk of neuro-ophthalmic impairment. Conversion to surgical management is indicated upon clinical deterioration or tumor growth. Based on the findings of this study a decision tree for the management of orbital schwannomas is suggested.

Dural arteriovenous fistula embolisation with venous remodelling following venous sinus stenting.

We report a case of the formation of a dural arteriovenous fistula (dAVF) of the transverse-sigmoid sinus following venous sinus stenting (VSS), treated with trans-arterial embolisation and venous remodelling. An obese woman in her 30s presented with persistent daily headaches after undergoing endoscopic repair of a skull base cerebrospinal fluid leak. Angiography demonstrated a focal right transverse-sigmoid sinus stenosis, and she underwent VSS of the right transverse sinus. She developed progressive pulsatile tinnitus within 3 months, and angiography demonstrated the formation of a Borden type 1 dAVF along the stent. Trans-arterial embolisation of the dAVF was performed with venous remodelling using a Copernic RC balloon. While VSS has become a promising treatment for venous sinus stenosis and idiopathic intracranial hypertension, dAVF formation is a rare but significant potential complication. Embolisation with venous remodelling can be performed to treat these lesions.

HIV-1 Vpr induces ciTRAN to prevent transcriptional repression of the provirus.

The functional consequences of circular RNA (circRNA) expression on HIV-1 replication are largely unknown. Using a customized protocol involving direct RNA nanopore sequencing, here, we captured circRNAs from HIV-1-infected T cells and identified ciTRAN, a circRNA that modulates HIV-1 transcription. We found that HIV-1 infection induces ciTRAN expression in a Vpr-dependent manner and that ciTRAN interacts with SRSF1, a protein known to repress HIV-1 transcription. Our results suggest that HIV-1 hijacks ciTRAN to exclude serine/arginine-rich splicing factor 1 (SRSF1) from the viral transcriptional complex, thereby promoting efficient viral transcription. In addition, we demonstrate that an SRSF1-inspired mimic can inhibit viral transcription regardless of ciTRAN induction. The hijacking of a host circRNA thus represents a previously unknown facet of primate lentiviruses in overcoming transmission bottlenecks.

Long-term outcomes following surgical treatment of spinal arachnoid cysts: a population-based consecutive cohort study.

BACKGROUND CONTEXT: Spinal arachnoid cysts (SACs) are rare, cerebrospinal fluid-filled sacs lined by an arachnoid membrane in the spinal canal. Symptoms can develop due to pressure on the spinal cord or adjacent spinal nerves by the cyst itself or by interrupted flow of cerebrospinal fluid. If noninvasive management fails or neurological deterioration occurs, surgical treatment is recommended. However, data is lacking on long-term outcomes after surgery. PURPOSE: To determine long-term outcomes in patients surgically treated for SACs. STUDY DESIGN: Population-based cohort-study. PATIENT SAMPLE: All consecutive patients treated for either intra- or extradural SACs with surgery between 2005 and 2020 at the author's institution were included. OUTCOME MEASURES: American Spinal Injury Association Impairment Scale (AIS) and modified Japanese Orthopedic Association score (mJOA). METHODS: Data was primarily extracted from electronic patient medical notes. Telephone interviews were performed to assess long-term postoperative outcomes. All analyses were conducted using the statistical software program R version 4.0.5. Statistical significance was set at p<.05. RESULTS: Thirty-four patients were included. Cyst excision was performed in 11 (32%) cases, and fenestration in the remaining 23 (68%). The median follow-up time was 8.0 years. Surgery resulted in a significant long-term improvement in both AIS (p=.012) and mJOA (p=.005). Sensory deficit was the symptom that most often improved (81%), followed by pain (74%) and motor function (64%). AIS deteriorated in two patients, of which one case was attributed to a surgical complication. Local cyst recurrence requiring reoperation was seen in 4 (12%) cases, all of them following cyst fenestration. One patient (3%) required reoperation for progression of the cyst progression at a different level. CONCLUSION: This study reports outcomes of surgically treated SACs with the longest follow-up time to date. Microsurgical cyst excision or fenestration were safe treatment options, and the neurological improvements seen in the immediate postoperative phase were maintained at long-term follow-up.

Cervical extradural arteriovenous fistula with radiculopathy managed endovascularly.

Background: Extradural arteriovenous fistulas (AVFs) of the cervical spine are extremely rare, and typically manifest as slowly progressive myelopathy caused by mass effect. This is a unique case of extradural AVF of the cervical spine manifesting with purely radicular symptoms and treated endovascularly with coil and liquid embolization. Case Description: A 55-year-old woman presented with neck pain and right upper extremity radiculopathy persisting for 9 months. Imaging studies demonstrated an AVF spanning from C4-C6 with extension into the C5-C6 foramen supplied primarily from the deep cervical branch of the costocervical trunk. The patient underwent successful coil and liquid (Onyx) embolization. Six-week postoperatively, the patient's symptoms completely resolved and magnetic resonance imaging and angiographic imaging confirmed complete obliteration of the fistula. Conclusion: While extradural AVFs typically present with myelopathic symptoms, they may present with solely radicular symptoms and can be successfully treated endovascularly.

Identification of new modulator of DNA repairing pathways based on natural product (±)-peharmaline A.

The complex heterogenic environment of tumour mass often leads to drug resistance and facilitate chemo insensitivity triggering more malignant phenotypes among cancer patients. Major DNA-damaging cancer drugs have been consistently proven unsuccessful in terms of elevating chemo-resistance. (±)-peharmaline A, a hybrid natural product isolated from seeds of Peganum harmala L. possesses significant cytotoxic activities. Herein, we have described the design, and synthesis of a novel library of close and simplified analogues around the anticancer natural product (±)-peharmaline A and investigated their cytotoxic activities, which led to the identification of three structurally simplified lead compounds exhibiting better potency than parent natural product. Among them, demethoxy analogue of peharmaline A was further investigated for its anticancer potential eliciting demethoxy analogue as potent DNA-damage inducing agent attenuating the expression of the proteins responsible for the DNA damage repair. Therefore, this demethoxy analogue warrants detailed investigations for the confirmations of the molecular mechanism-based studies responsible for its anticancer activity. ______________________________________________________________________________.

Development of a multiscale mechanistic modeling framework integrating differential cellular kinetics of CAR T-cell subsets and immunophenotypes in cancer patients.

Chimeric antigen receptor (CAR) T-cell subsets and immunophenotypic composition of the pre-infusion product, as well as their longitudinal changes following infusion, are expected to affect CAR T-cell expansion, persistence, and clinical outcomes. Herein, we sequentially evolved our previously described cellular kinetic-pharmacodynamic (CK-PD) model to incorporate CAR T-cell product-associated attributes by utilizing published preclinical and clinical datasets from two affinity variants (FMC63 and CAT19 scFv) anti-CD19 CAR T-cells. In step 1, a unified cell-level PD model was used to simultaneously characterize the in vitro killing datasets of two CAR T-cells against CD19+ cell lines at varying effector:target ratios. In step 2, an augmented CK-PD model for anti-CD19 CAR T-cells was developed, by integrating CK dataset(s) from two bioanalytical measurements (quantitative polymerase chain reaction and flow cytometry) in patients with cancer. The model described the differential in vivo expansion properties of CAR T-cell subsets. The estimated expansion rate constant was ~1.12-fold higher for CAR+CD8+ cells in comparison to CAR+CD4+ T-cells. In step 3, the model was extended to characterize the disposition of four immunophenotypic populations of CAR T-cells, including stem-cell memory, central memory, effector memory, and effector cells. The model adequately characterized the longitudinal changes in immunophenotypes post anti-CD19 CAR T-cell infusion in pediatric patients with acute lymphocytic leukemia. Polyclonality in the pre-infusion product was identified as a categorical covariate influencing differentiation of immunophenotypes. In the future, this model could be leveraged a priori toward optimizing the composition of CAR T-cell infusion product, and further understand the CK-PD relationship in patients.

Awareness and Hesitancy of COVID-19 and other Vaccines among People Living with HIV/AIDS Attending Antiretroviral Therapy (ART) Center in North India.

Introduction: Approximately 40 years have passed since we first learned about the human immunodeficiency virus (HIV), but several people living with HIV (PLHIV) in developing countries such as India cannot avail treatments. This makes preventive measures, such as vaccinations, critical in these persons to avoid vaccine preventable diseases (VPDs). However, little is known about the willingness and perceptions of PLHIV regarding these vaccines. Therefore, we explored vaccine awareness and hesitancy, especially during the recent COVID-19 pandemic. Objectives: The primary objective was to determine the uptake of the Covid-19 vaccine and other VPD's among PLHIV and factors affecting the same in Antiretroviral therapy (ART) centers in a tertiary care hospital in North India. Research Design and Methods: This was a cross-sectional study of HIV patients who attended our Antiretroviral Therapy center (ART). Clinical data were collected using a questionnaire on general profile, disease information, knowledge, attitude, and practice (KAP) regarding vaccinations, and vaccination status for different VPDs. Results/Findings: We enrolled 300 subjects and found that 82% of the patients attending our ART center were aware of vaccinations, most of whom were aware of the polio vaccine (n=91, 30.33%), followed by tuberculosis (n=61, 20.33%), and the majority of them were not aware of vaccines indicated in PLHIV. We also found that the majority (n= 240, 80.23%) of patients had vaccine hesitancy, especially regarding the new COVID-19 vaccine. Conclusion: There is a need to create awareness among people about the benefits and uses of vaccination to achieve the greater goal of reduced morbidity and mortality among PLHIV. There is a need for free vaccination programs for VPDs in PLHIV patients.

Comparing 30-Day Outcomes After Emergent Spine Procedures Performed "During Hours" vs "After Hours".

BACKGROUND: Spinal injuries, whether mechanical or neurological, frequently require urgent intervention. Superior outcomes are associated with earlier intervention, which often requires operating overnight and on weekends. However, operating after hours has been associated with increased risks of complications in selected studies. The authors sought to determine whether there are differences in outcomes for "after hours" surgery compared with "during hours" surgery for spinal emergencies. METHODS: This is a single-center retrospective cohort study of spine surgery patients who underwent urgent surgery within 6 hours, from January 2015 through December 2019. Surgery was considered during hours if it started between 8 am and 5 pm Monday through Friday. After hours was defined as from 5 pm through 8 am on a weekday or Saturday or Sunday. We assessed 30-day outcome measures for differences between operations performed during hours or after hours. RESULTS: There were 241 spine procedures performed (49 during hours and 192 after hours). There was no significant difference between the length of operation (145.3 vs 129.8 minutes, P = 0.29), estimated blood loss (303.9 vs 274.4 mL, P = 0.61), improvement in American Spinal Injury Association scale (0.26 vs 0.24 grade, P = 0.85), 30-day return to the operating room (OR; 14.3% vs 6.8%, P = 0.09), 30-day readmission (2.0% vs 6.3% P = 0.24), intensive care unit length of stay (4.6 vs 6.3 days, P = 0.27), hospital length of stay (13.5 days vs 14.2 days, P = 0.72), or 30-day mortality (4.1% vs 7.3%, P = 0.42) for cases performed during hours compared with those after hours, respectively. On multivariate analysis, prior malignancy (P = 0.008) and blue immediate status (P = 0.004) were predictors of 30-day mortality. However, "after hours" surgery was not a predictor of 30-day return to the OR, readmission, or mortality in either univariate or multivariate analysis. CONCLUSIONS: Spine surgery must often be performed after hours. However, the time of day does not significantly impact the 30-day outcomes for emergent spine surgery.

Titanium-Mediated Reduction of Carboxamides to Amines with Borane-Ammonia.

In this study, the successful titanium tetrachloride-catalyzed reduction of aldehydes, ketones, carboxylic acids, and nitriles with borane-ammonia was extended to the reduction (deoxygenation) of a variety of aromatic and aliphatic pri-, sec- and tert-carboxamides, by changing the stoichiometry of the catalyst and reductant. The corresponding amines were isolated in good to excellent yields, following a simple acid-base workup.

Efficacy of Alexa, Google Assistant, and Siri for Supporting Informed Prostate Cancer Screening Decisions for African-American Men.

Prostate cancer is the most prevalent non-skin cancer among all men, but African-Americans have morbidity and mortality at significantly higher rates than White men. To reduce this burden, authorities such as the American Cancer Society recommend that men make informed/shared screening decisions with a healthcare provider. Informed/shared screening decisions require that men have adequate prostate cancer knowledge. Virtual assistants are interactive communication technologies that have become popular for seeking health information, though information quality has been mixed. No prior research has investigated the quality of prostate cancer information disseminated by virtual assistants. The purpose of this study was to determine the response rates, accuracy, breadth, and credibility of three popular virtual assistants (Alexa, Google Assistant, and Siri) for supporting informed/shared prostate cancer screening decisions for African-American men. Each virtual assistant was evaluated on a tablet, cell phone, and smart speaker using 12 frequently asked screening questions. Responses were rated dichotomously (i.e., yes/no), and analyses were conducted using SPSS. Alexa on a phone or tablet and Google Assistant on a smart speaker had the best overall performance based on a combination of response, accuracy, and credibility scores. All other assistants scored below 75% in one or more areas. Additionally, all virtual assistants lacked the breadth to support an informed/shared prostate cancer screening decision. African-American men may be especially disadvantaged by using virtual assistants for prostate cancer information because of the lack of emphasis on their greater disease risk, higher mortality rates, and appropriate ages at which they should begin screening conversations.

Current perspectives on Vaxinia virus: an immuno-oncolytic vector in cancer therapy.

Viruses are being researched as cutting-edge therapeutic agents in cancer due to their selective oncolytic action against malignancies. Immuno-oncolytic viruses are a potential category of anticancer treatments because they have natural features that allow viruses to efficiently infect, replicate, and destroy cancer cells. Oncolytic viruses may be genetically modified; engineers can use them as a platform to develop additional therapy modalities that overcome the limitations of current treatment approaches. In recent years, researchers have made great strides in the understanding relationship between cancer and the immune system. An increasing corpus of research is functioning on the immunomodulatory functions of oncolytic virus (OVs). Several clinical studies are currently underway to determine the efficacy of these immuno-oncolytic viruses. These studies are exploring the design of these platforms to elicit the desired immune response and to supplement the available immunotherapeutic modalities to render immune-resistant malignancies amenable to treatment. This review will discuss current research and clinical developments on Vaxinia immuno-oncolytic virus.

A Novel Deep Learning-Based Classification Framework for COVID-19 Assisted with Weighted Average Ensemble Modeling.

COVID-19 is an infectious disease caused by the deadly virus SARS-CoV-2 that affects the lung of the patient. Different symptoms, including fever, muscle pain and respiratory syndrome, can be identified in COVID-19-affected patients. The disease needs to be diagnosed in a timely manner, otherwise the lung infection can turn into a severe form and the patient's life may be in danger. In this work, an ensemble deep learning-based technique is proposed for COVID-19 detection that can classify the disease with high accuracy, efficiency, and reliability. A weighted average ensemble (WAE) prediction was performed by combining three CNN models, namely Xception, VGG19 and ResNet50V2, where 97.25% and 94.10% accuracy was achieved for binary and multiclass classification, respectively. To accurately detect the disease, different test methods have been proposed and developed, some of which are even being used in real-time situations. RT-PCR is one of the most successful COVID-19 detection methods, and is being used worldwide with high accuracy and sensitivity. However, complexity and time-consuming manual processes are limitations of this method. To make the detection process automated, researchers across the world have started to use deep learning to detect COVID-19 applied on medical imaging. Although most of the existing systems offer high accuracy, different limitations, including high variance, overfitting and generalization errors, can be found that can degrade the system performance. Some of the reasons behind those limitations are a lack of reliable data resources, missing preprocessing techniques, a lack of proper model selection, etc., which eventually create reliability issues. Reliability is an important factor for any healthcare system. Here, transfer learning with better preprocessing techniques applied on two benchmark datasets makes the work more reliable. The weighted average ensemble technique with hyperparameter tuning ensures better accuracy than using a randomly selected single CNN model.