Objective quantification of nerves in immunohistochemistry specimens of thyroid cancer utilising deep learning.

Accurate quantification of nerves in cancer specimens is important to understand cancer behaviour. Typically, nerves are manually detected and counted in digitised images of thin tissue sections from excised tumours using immunohistochemistry. However the images are of a large size with nerves having substantial variation in morphology that renders accurate and objective quantification difficult using existing manual and automated counting techniques. Manual counting is precise, but time-consuming, susceptible to inconsistency and has a high rate of false negatives. Existing automated techniques using digitised tissue sections and colour filters are sensitive, however, have a high rate of false positives. In this paper we develop a new automated nerve detection approach, based on a deep learning model with an augmented classification structure. This approach involves pre-processing to extract the image patches for the deep learning model, followed by pixel-level nerve detection utilising the proposed deep learning model. Outcomes assessed were a) sensitivity of the model in detecting manually identified nerves (expert annotations), and b) the precision of additional model-detected nerves. The proposed deep learning model based approach results in a sensitivity of 89% and a precision of 75%. The code and pre-trained model are publicly available at https://github.com/IA92/Automated_Nerves_Quantification.

Immunogenicity and Safety of the Inactivated SARS-CoV-2 Vaccine (BBIBP-CorV) in Patients with Malignancy.

OBJECTIVE: To evaluate the safety and immunogenicity of the inactivated SARS-CoV-2 vaccine in cancer patients. MATERIAL AND METHOD: 364 cancer patients who received two doses of vaccine were enrolled. The presence of SARS-CoV-2 anti-Spike protein IgG and neutralizing antibody 2 months following vaccination were measured by ELIZA. RESULTS: Injection site pain and fever were the most common local and systemic side effects. The overall seroconversion rate was 86.9% that was lower in older age, those with hematological malignancies and chemotherapy receivers. CONCLUSION: The result of study confirmed the safety and short-term efficacy of inactivated vaccine in patients with malignancies.

Multicenter Study of Antibody Seroprevalence against COVID-19 in Patients Presenting to Iranian Cancer Centers after One Year of the COVID-19 Pandemic.

Patients with cancer are at significantly greater risk of COVID-19 and its complications than the general population. Since IgG antibodies remain detectable well after infection with the SARS-CoV-2 virus, seroprevalence can be used to estimate the proportion of the cancer population previously infected and potentially immune to SARS-CoV-2. The current study is a multi-center, prospective observational study to assess the seroprevalence of SARS-CoV-2 IgG antibody in a cancer population referred for vaccination between April and June 2021. Of a total of 270 adult patients with cancer accrued, 16% reported a history of COVID-19 more than four weeks previously confirmed by PCR. At the same time, serologic positivity for SARSCoV2 IgG was found in 29% of patients prior to vaccination including nearly 20% of patients without a history of confirmed COVID-19. Seropositivity was significantly greater in females consistent with higher rates in patients with breast cancer and gynecologic cancers. A seroconversion rate of 79.5% was observed in cancer patients with a history of PCR confirmed COVID-19, less than observed in the general population. In multivariable analysis, gender and prior history of COVID-19 were both independently associated with seropositivity prior to vaccination. Follow-up is continuing of this cohort of patients with cancer following vaccination to assess antibody and clinical outcomes.

Low-dose radiation therapy (LDRT) for COVID-19 and its deadlier variants.

Coronavirus variants are gaining strongholds throughout the globe. Despite early signals that SARS-CoV-2 coronavirus case numbers are easing up in the United States and during the middle of a (not so easy) vaccination roll out, the country has passed a grim landmark of 600,000 deaths. We contend that these numbers would have been much lower if the medical community undertook serious investigations into the potential of low doses of radiation (LDRT) as a mainstream treatment modality for COVID-19 pneumonia. LDRT has been posited to manifest anti-infectious and anti-inflammatory properties at doses of 0.3-1.0 Gy via the activation of the Nrf-2 pathway. Although some researchers are conducting well-designed clinical trials on the potential of LDRT, the deep-rooted, blind, and flawed acceptance of the Linear No-Threshold (LNT) model for ionizing radiation has led to sidelining of this promising therapy and thus unimaginable numbers of deaths in the United States.

Extended dosing (12 cycles) vs conventional dosing (6 cycles) of adjuvant temozolomide in adults with newly diagnosed high-grade gliomas: a randomized, single-blind, two-arm, parallel-group controlled trial.

Purpose: Maximum safe surgical resection followed by adjuvant chemoradiation and temozolomide chemotherapy is the current standard of care in the management of newly diagnosed high grade glioma. However, there are controversies about the optimal number of adjuvant temozolomide cycles. This study aimed to compare the survival benefits of 12 cycles against 6 cycles of adjuvant temozolomide adults with newly diagnosed high grade gliomas. Methods: Adult patients with newly diagnosed high grade gliomas, and a Karnofsky performance status>60%, were randomized to receive either 6 cycles or 12 cycles of adjuvant temozolomide. Patients were followed-up for assessment of overall survival (OS) and progression-free survival (PFS) by brain MRI every 3 months within the first year after treatment and then every six months. Results: A total of 100 patients (6 cycles, 50; 12 cycles, 50) were entered. The rate of treatment completion in 6 cycles and 12 cycles groups were 91.3% and 55.1%, respectively. With a median follow-up of 26 months, the 12-, 24-, 36-, and 48-month OS rates in 6 cycles and 12 cycles groups were 81.3% vs 78.8%, 58.3% vs 49.8%, 47.6% vs 34.1%, and 47.6% vs 31.5%, respectively (p-value=.19). Median OS of 6 cycles and 12 cycles groups were 35 months (95% confidence interval (CI), 11.0 to 58.9) and 23 months (95%CI, 16.9 to 29.0). The 12-, 24-, 36-, and 48- month PFS rates in 6 cycles and 12 cycles groups were 70.8% vs 56.9%, 39.5% and 32.7%, 27.1% vs 28.8%, and 21.1% vs 28.8%, respectively (p=.88). The Median PFS of 6 cycles and 12 cycles groups was 18 months (95% CI, 14.8 to 21.1) and 16 (95% CI, 11.0 to 20.9) months. Conclusion: Patients with newly diagnosed high grade gliomas treated with adjuvant temozolomide after maximum safe surgical resection and adjuvant chemoradiation do not benefit from extended adjuvant temozolomide beyond 6 cycles. Trial registration: Prospectively registered with the Iranian Registry of Clinical Trials: IRCT20160706028815N3. Date registered: 18/03/14.

Bombarding Oligoprogression: Oncologic Outcomes After Radiation to Patients With Oligoprogressive Non-Small Cell Lung Cancer on Maintenance Systemic Therapy.

OBJECTIVES: This study aims to evaluate the efficacy and toxicity of radiotherapy (RT) to oligoprogressive metastatic non-small cell lung cancer (NSCLC). METHODS: This is a retrospective analysis of 23 patients with metastatic NSCLC on maintenance systemic therapy, developed oligoprogression (1 to 5 sites), and all oligoprogressive sites amenable to and treated with RT. The primary endpoints included progression-free survival (PFS) and median time to start next-line therapy (MTT). Kaplan-Meier survival analysis and log-rank testing were performed using R-Studio software. RESULTS: Twenty-three patients met the inclusion criteria. The median overall survival for the entire cohort was 31.3 months (interquartile range [IQR]: 17.86 to 45.4). The median event-free survival for the entire cohort was 8.3 months (IQR: 2.7 to 12). Patients with no prior radiation had longer median event-free survival of 11.9 months (IQR: 8.4 to 18.2) compared with patients with a history of prior radiation at 4.1 months (IQR: 2.7 to 12; P = 0.041). The local control rate for the treated lesions was 97.5%. At 12 months follow-up, 6 (43%) of 14 living patients maintained systemic therapy without initiating next-line therapy. The median PFS for the entire cohort was 8.4 months (IQR: 4.1 to 17.5). Patients who did not receive prior radiation had longer median PFS of 11.9 months (IQR: 8.4 to 18.2) compared with patients who received prior radiation 6.2 months (IQR: 2.7 to 8.5; P = 0.018). Two patients (9%) had grade 3 chronic toxicity related to RT and were medically managed. CONCLUSION: We identified that in patients with oligoprogressive metastatic NSCLC, targeted RT to all progressive sites yielded high LC and favorable rates of PFS and MTT.

Microbiome and Abdominopelvic Radiotherapy Related Chronic Enteritis: A Microbiome-based Mechanistic Role of Probiotics and Antibiotics.

Chronic diarrhea and abdominal pain after radiotherapy continue to be a problem in cancer survivors. Gut microbiomes are essential for preventing intestinal inflammation, maintaining intestinal integrity, maintaining enterohepatic circulation, regulating bile acid metabolism, and absorption of nutrients, including fat-soluble vitamins. Gut microbiome dysbiosis is expected to cause inflammation, bile acid malabsorption, malnutrition, and associated symptoms. Postradiotherapy, Firmicutes and Bacteroidetes phylum are significantly decreased while Fusobacteria and other unclassified bacteria are increased. Available evidence suggests harmful bacteria Veillonella, Erysipelotrichaceae, and Ruminococcus are sensitive to Metronidazole or Ciprofloxacin. Beneficial bacteria lactobacillus and Bifidobacterium are relatively resistant to metronidazole. We hypothesize and provide an evidence-based review that short-course targeted antibiotics followed by specific probiotics may lead to alleviation of radiation enteritis.

Digital Screen Time and the Risk of Female Breast Cancer: A Retrospective Matched Case-Control Study.

Background: As the use of electronic devices such as mobile phones, tablets, and computers continues to rise globally, concerns have been raised about their potential impact on human health. Exposure to high energy visible (HEV) blue light, emitted from digital screens, particularly the so-called artificial light at night (ALAN), has been associated with adverse health effects, ranging from disruption of circadian rhythms to cancer. Breast cancer incidence rates are also increasing worldwide. Objective: This study aimed at finding a correlation between breast cancer and exposure to blue light from mobile phone. Material and Methods: In this retrospective matched case-control study, we aimed to investigate whether exposure to blue light from mobile phone screens is associated with an increased risk of female breast cancer. We interviewed 301 breast cancer patients (cases) and 294 controls using a standard questionnaire and performed multivariate analysis, chi-square, and Fisher's exact tests for data analysis. Results: Although heavy users in the case group of our study had a statistically significant higher mean 10-year cumulative exposure to digital screens compared to the control group (7089±14985 vs 4052±12515 hours, respectively, P=0.038), our study did not find a strong relationship between exposure to HEV and development of breast cancer. Conclusion: Our findings suggest that heavy exposure to HEV blue light emitted from mobile phone screens at night might constitute a risk factor for promoting the development of breast cancer, but further large-scale cohort studies are warranted.

A Systematic Review of Clinical Trials Comparing Radiation Therapy Versus Radical Prostatectomy in Prostate Cancer.

The treatment landscape for localized and regional prostate cancer includes active surveillance, radiation therapy (RT), and radical prostatectomy (RP). Population-based studies comparing RP to radiation reveal conflicting results due to methodological flaws. This systematic review and pooled analysis of studies aim to compare cause-specific survival (CSS), overall survival (OS), disease-free survival (DFS) and toxicity outcomes, comparing RP to RT in the management of prostate cancer. This systematic review search included the PubMed, Embase, and Cochrane libraries according to the PRISMA statement with the inception of each database up to June 24, 2023. Randomized phase 2 or 3 clinical trials that compared RP to RT in prostate cancer were included. The forest plot for the Odds ratio (OR) was plotted using the Mantel-Haenszel method, and the Z test was used to assess significance. A fixed effects model was used for meta-analysis. The search yielded seven completed randomized clinical trials and four ongoing trials. The majority of complete trials had low to intermediate-risk patient populations. OR for OS was 1.00 with 95% CI, 0.71-1.41 (P-value: 0.98), CSS OR was 0.99 with 95% CI, 0.45-2.18 (P-value 0.11), OR for DFS was 1.26 with 95% CI, 0.89-1.78 (P-value 0.19) when comparing RP to RT. The rate of distant metastatic disease was 2.3% in the RP versus 2.9% in the RT at 10 years. The rate of second malignant neoplasms was 4.5% in the RP compared to 4.2% in the RT arm at 10 years. RP caused more urinary symptoms, with a predominance of the need for urinary pads and a higher incidence of sexual dysfunction, and RT caused a higher incidence of bowel symptoms, such as blood in stools and fecal incontinence. This study provides evidence that the treatment-related outcomes are similar in patients with low to intermediate-risk prostate cancer when comparing RP to RT. Multidisciplinary treatment approaches and factoring patients' values and preferences should form the cornerstone of the ideal treatment option for each patient with localized prostate cancer. Patients with prostate cancer have an equal chance of being cancer-free and alive at 10 years with either RP or RT. In terms of side effects, RP causes more urine leakage and loss of erections, whereas RT tends to cause more bowel side effects, such as blood in stools and fecal leakage.

Computationally Efficient Simulation of Calcium Signaling in Cardiomyocytes.

The objective of this paper is to develop a computationally efficient simulation model of Calcium signalling in cardiomyocytes. The model considered here consists of more than two million stiff, nonlinear, and stochastic systems, each of which is composed of 62 state equations. The size of the model, combined with the broad numerical scale, non-continuous stochastic state-transitions, and underlying physiological constraints, presents a significant implementation challenge. The method involves development of specialised algorithms for parallelisation, which include fully-implicit Runge-Kutta integration with both L-stability and step-size control, Newton's root finding method with exception handling, and Conjugate Residual Squared for solving linear systems not of full-rank within available computational precision. Parallelisation of the problem across the systems is employed to allow for practical scaling with computing resources. The results produce sparks and waves akin to those observed in actual laboratory experiments within an acceptable timeframe. Performance measures of the simulation model with respect to accuracy and computation time are also given. The conclusion is that the methodologies utilised in this work are can simulate cardiomyocyte's calcium signalling in a computationally efficient manner with the results produced replicating those in the laboratory. The significance of this paper is that computational models such as the one developed here provide a way to simulate and understand the complex biological interactions operating in organisms. Accurate simulations are extremely computationally intensive and this pursuit is considered as the grand challenge for computational science into the 21st century.

Outcome of Second Line Treatment of Recurrent High- Grade Glioma by re-Irradiation or Bevacizumab-based Chemotherapy: A Cross Sectional Study.

INTRODUCTION: Currently, there is no standard of treatment for the management of the recurrent high-grade glioma. Re-resection, re-irradiation, and chemotherapy are among main treatment options without any proven efficacy. AIM: To compare the outcome of second line treatment of recurrent high-grade glioma by re-irradiation or bevacizumab-based chemotherapy. METHODS: Retrospectively, patients with the recurrent high-grade glioma treated by re-irradiation (ReRT group) (34 patients) or bevacizumab-based chemotherapy (Bev group) (40 patients) as the first-file after the first recurrence were compared in term of first-line progression free survival (PFS), second-line PFS, and overall survival (OS). RESULTS: Both groups were similar in term of gender (p=0.859), age (=0.071), type of first-line treatment (p=0.227), and performance status (p=0.150). With a median follow-up of 31 months (m), mortality rate was 41.2% and 70% in the ReRT and Bev groups, respectively. In the Bev and ReRT groups, median OS was 27 m (95% confidence interval (CI) 20-33.9 m) vs. 132 m (95% CI 52.9-211 m) (p<0.0001), median first-line PFS was 11 m (95% CI 7.14-28.7 m) vs. 37 m (95% CI 8.42-65.75 m) (p<0.0001), and median second-line PFS was 7 m (95% CI 3.9-10 m) vs. 9 m (95% CI 5.5-12.4 m) (p=0.564), respectively. CONCLUSION: The PFS is similar after the second line treatment of recurrent primary central nervous system malignancies either by re-irradiation or bevacizumab-based chemotherapy.

How Reactivation of SARS-CoV-2 in Astronauts with Dysregulated Immune Systems Can Negatively Affect the Odds of Success in Future Space Missions.

We have previously reported that during future space missions the risk of severe COVID-19 infection will be a cardinal issue that needs careful attention. Our studies show that even with the most reliable pre-mission screening and quarantine strategies, astronauts with a latent (hidden, inactive, or dormant) SARS-CoV-2 infection might be sent to space. Given this consideration, an asymptomatic individual with dormant SARS-CoV-2 infection may successfully pass all the pre-launch medical tests. Then during a space mission such as a journey to Mars or beyond, when the immune system of these astronauts starts to weaken, the dormant infection may progress to a severe infection that possibly affects the chance of the mission's success. The effects of microgravity and the elevated space radiation are two key factors that should be evaluated. Furthermore, the limited size of the spacecraft, the proximity of crew members during flight operations, spacecraft atmospheric composition, limited exercise capability, effects of viral response to space radiation, and uncertainty in the likelihood of the virus to mutate and evolve during a space mission merit additional study.

The Rationale for Radiation Therapy in Alzheimer's Disease.

Alzheimer's Disease (AD) represents a major health problem without effective treatments. As the incidence of the disease will continue to rise, it is imperative to find new treatment options to halt or slow disease progression. In recent years, several groups have begun to study the utility of low total dose radiation therapy (LTDRT) to inhibit some of the pathological features of AD and improve cognition in a variety of animal models. These preclinical studies have led to Phase 1 and 2 trials in different centers around the world. In this review, we present and interpret the pre-clinical evidence report some preliminary clinical data from a Phase 2 trial in early-stage AD patients.

Multi-institutional Development and Validation of Contouring Guidelines for Para-aortic Elective Nodal Irradiation in Prostate Cancer Based on Patterns of Involvement on Targeted Molecular Imaging Positron Emission Tomography/Computed Tomography.

PURPOSE: Molecular imaging better identifies anatomic regions of metastatic spread of prostate cancer compared with conventional imaging, resulting in para-aortic (PA) nodal metastases being increasingly identified. Consequently, some radiation oncologists electively treat the PA lymph node region in patients with gross or high risk of PA nodal involvement. The anatomic locations of at-risk PA lymph nodes for prostate cancer are unknown. Our objective was to use molecular imaging to develop guidelines for the optimal delineation of the PA clinical target volume (CTV) in patients with prostate cancer. METHODS AND MATERIALS: We conducted a multi-institutional retrospective cohort study of patients with prostate cancer undergoing 18F-fluciclovine or 18F-DCFPyL prostate-specific membrane antigen positron emission tomography (PET)/computed tomography (CT). Images of patients with PET-positive PA nodes were imported into the treatment planning system, avid nodes were contoured, and measurements were taken in relation to anatomic landmarks. A contouring guideline that encompassed the location of ≥95% of PET-positive PA nodes was created using descriptive statistics and then validated in an independent data set. RESULTS: Five hundred fifty-nine patients had molecular PET/CT imaging in the development data set (78% 18F-fluciclovine, 22% prostate-specific membrane antigen). Seventy-six patients (14%) had evidence of PA nodal metastasis. We determined that expanding the CTV to 1.8 cm left of the aorta, 1.4 cm right of the inferior vena cava (IVC), 7 mm posterior to the aorta/IVC or to the vertebral body, and superiorly to the T11/T12 vertebral interface, with the anterior border 4 mm anterior to the aorta/IVC and inferior border at the bifurcation of the aorta/IVC, resulted in coverage of ≥95% of PET-positive PA nodes. When the guideline was used in the independent validation data set (246 patients with molecular PET/CT imaging, of whom 31 had PA nodal metastasis), 97% of nodes were encompassed, thereby validating our guideline. CONCLUSIONS: We used molecular PET/CT imaging to determine the anatomic locations of PA metastases to develop contouring guidelines for creating a prostate cancer PA CTV. Although the optimal patient selection and clinical benefits of PA radiation therapy remain uncertain, our results will aid in delineating the optimal target when PA radiation therapy is pursued.

Case series on patients with primary central nervous system lymphoma: From clinical presentations to outcomes.

Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin lymphoma. In this report, we present 11 cases of PCNSL which were treated with high-dose MTX and WBI with a localized radiation boost to the tumor bed.

Ramsar, Iran, as a Natural Radiobiological Surrogate for Mars.

ABSTRACT: Terrestrial experiments involving acute exposures of low-LET radiation on inbred lab animals are quick, simple, and inexpensive but are relatively uninformative about the real radiobiological hazards of planned manned space missions. A more predictive model could involve human beings chronically exposed to "space-like" high-LET radiation. Such radiation exposure has been ongoing for thousands of years in Ramsar, Iran, and some other high-LET high background radiation regions on Earth. Examining the health of Ramsar residents can be illuminating and potentially relevant to space missions.

The Paradoxical Role of far-Ultraviolet C (far-UVC) in Inactivation of SARS-CoV-2: The Issue of Droplet Size.

The Omicron variant is spreading at a rate we have never observed with any previous variant. A lot of efforts have been taken to inactivate SARS-CoV-2, especially the omicron variant. Specific wavelength ranges of electromagnetic radiation can be exploited to inactivate coronaviruses. Previous studies show that 222-nm far-Ultraviolet C (far-UVC) light inactivates airborne influenza virus efficiently. Considering the similar genomic sizes of all human coronaviruses, other human coronaviruses, such as SARS-CoV-2, would be expected to be inactivated by far-UVC with a similar efficacy. Taking this into account, it is concluded that exposure to far-UVC can be introduced as a safe method that significantly reduces the ambient level of airborne coronaviruses in crowded places. Biomolecules, particularly proteins, strongly absorb ultraviolet radiation at a wavelength of around 200 nm. Given this consideration, far-UVC has a limited ability to permeate biological materials. Thus, for example, in only around 0.3 mm of tissue, the intensity of 200-nm UV radiation is decreased by half, compared to tissue penetration of about 3 mm at 250 nm. This paper aims to answer the key question of whether far-UVC can penetrate SARS-CoV-2 inside inhalable respiratory droplets (with diameters up to 100 µm).