Recent Advances in the Therapeutic Potential of Carotenoids in Preventing and Managing Metabolic Disorders.

Carotenoids constitute compounds of significant biological interest due to their multiple biological activities, such as antimicrobial, anticancer, antiadipogenic, antidiabetic, and antioxidant properties. Metabolic syndrome (MetS) comprehends a series of metabolic abnormalities (e.g., hypertension, obesity, and atherogenic dyslipidemia) that can affect children, adolescents, and the elderly. The treatment of MetS involves numerous medications, which, despite their efficacy, pose challenges due to prolonged use, high costs, and various side effects. Carotenoids and their derivatives have been proposed as alternative treatments to MetS because they reduce serum triglyceride concentrations, promote insulin response, inhibit adipogenesis, and downregulate angiotensin-converting enzyme activity. However, carotenoids are notably sensitive to pH, light exposure, and temperature. This review addresses the activity of carotenoids such as lycopene, lutein, fucoxanthin, astaxanthin, crocin, and ß-carotene towards MetS. It includes a discussion of sources, extraction methods, and characterization techniques for analyzing carotenoids. Encapsulation approaches are critically reviewed as alternatives to prevent degradation and improve the biological performance of carotenoids. A brief overview of the physiopathology and epidemiology of the diseases, including MetS, is also provided.

The secretome from human-derived mesenchymal stem cells augments the activity of antitumor plant extracts in vitro.

Cancer is understood as a multifactorial disease that involve multiple cell types and phenotypes in the tumor microenvironment (TME). The components of the TME can interact directly or via soluble factors (cytokines, chemokines, growth factors, extracellular vesicles, etc.). Among the cells composing the TME, mesenchymal stem cells (MSCs) appear as a population with debated properties since it has been seen that they can both promote or attenuate tumor progression. For various authors, the main mechanism of interaction of MSCs is through their secretome, the set of molecules secreted into the extracellular milieu, recruiting, and influencing the behavior of other cells in inflammatory environments where they normally reside, such as wounds and tumors. Natural products have been studied as possible cancer treatments, appealing to synergisms between the molecules in their composition; thus, extracts obtained from Petiveria alliacea (Anamu-SC) and Caesalpinia spinosa (P2Et) have been produced and studied previously on different models, showing promising results. The effect of plant extracts on the MSC secretome has been poorly studied, especially in the context of the TME. Here, we studied the effect of Anamu-SC and P2Et extracts in the human adipose-derived MSC (hAMSC)-tumor cell interaction as a TME model. We also investigated the influence of the hAMSC secretome, in combination with these natural products, on tumor cell hallmarks such as viability, clonogenicity, and migration. In addition, hAMSC gene expression and protein synthesis were evaluated for some key factors in tumor progression in the presence of the extracts by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Multiplex, respectively. It was found that the presence of the hAMSC secretome did not affect the cytotoxic or clonogenicity-reducing activities of the natural extracts on cancer cells, and even this secretome can inhibit the migration of these tumor cells, in addition to the fact that the profile of molecules can be modified by natural products. Overall, our findings demonstrate that hAMSC secretome participation in TME interactions can favor the antitumor activities of natural products.

Inference of tobacco and alcohol consumption habits from DNA methylation analysis of blood.

DNA methylation has become a biomarker of great interest in the forensic and clinical fields. In criminal investigations, the study of this epigenetic marker has allowed the development of DNA intelligence tools providing information that can be useful for investigators, such as age prediction. Following a similar trend, when the origin of a sample in a criminal scenario is unknown, the inference of an individual's lifestyle such as tobacco use and alcohol consumption could provide relevant information to help in the identification of DNA donors at the crime scene. At the same time, in the clinical domain, prediction of these trends of consumption could allow the identification of people at risk or better identification of the causes of different pathologies. In the present study, DNA methylation data from the UK AIRWAVE study was used to build two binomial logistic models for the inference of smoking and drinking status. A total of 348 individuals (116 non-smokers, 116 former smokers and 116 smokers) plus a total of 237 individuals (79 non-drinkers, 79 moderate drinkers and 79 drinkers) were used for development of tobacco and alcohol consumption prediction models, respectively. The tobacco prediction model was composed of two CpGs (cg05575921 in AHRR and cg01940273) and the alcohol prediction model three CpGs (cg06690548 in SLC7A11, cg0886875 and cg21294714 in MIR4435-2HG), providing correct classifications of 86.49% and 74.26%, respectively. Validation of the models was performed using leave-one-out cross-validation. Additionally, two independent testing sets were also assessed for tobacco and alcohol consumption. Considering that the consumption of these substances could underlie accelerated epigenetic ageing patterns, the effect of these lifestyles on the prediction of age was evaluated. To do that, a quantile regression model based on previous studies was generated, and the potential effect of tobacco and alcohol consumption with the epigenetic age was assessed. The Wilcoxon test was used to evaluate the residuals generated by the model and no significant differences were observed between the categories analyzed.

Coordination and Bioorganometallic Chemistry: Exploring the Potential Applications of Metal Coordination and Organometallic Complexes in Medical and Microbiological Advancements.

In the field of coordination and bioorganometallic chemistry, a notable shift is occurring. This mini-review explores a new generation of carefully 3D-crafted coordination and organometallic complexes that differ from conventional structures. Emphasizing disease intervention and microbial control, these compounds, incorporate noble and transition metals, and aim to enhance therapeutic efficacy while minimizing potential health risks. The mini-review covers diverse applications, showcasing their effectiveness against bacteria, viruses, fungi, and as potential tools in cancer treatment. Additionally, it sheds light on the inventive aspects of these complexes within biological systems. By highlighting advancements in bioorganometallic chemistry, the review offers insights and guidance for future developments in safer and more effective therapeutics.

Time Trends in Causes of Death in People with HIV: Insights from the Swiss HIV Cohort Study.

BACKGROUND: Advancements in access to antiretroviral therapy (ART) and human immunodeficiency virus (HIV) care have led to a decline in acquired immunodeficiency syndrome (AIDS)-related deaths among people with HIV (PWH) in Switzerland. However, data on the ongoing changes in causes of death among PWH over the past 15 years is scarce. METHODS: We investigated all reported deaths in the Swiss HIV Cohort Study between 2005-2022. Causes of death were categorized using the Coding Causes of Death in HIV protocol. The statistical analysis included demographic stratification to identify time trends and logistic regression models to determine associated factors for the underlying cause of death. RESULTS: In total, 1630 deaths were reported, with 23.7% of individuals assigned female at birth. Out of these deaths, 147 (9.0%) were HIV/AIDS-related, 373 (22.9%) due to non-AIDS, non-hepatic (NANH) cancers, 166 (10.2%) liver-related, and 158 (9.7%) cardiovascular-related. The median age at death increased from 45.0 [40.0,53.0] years in 2005-2007 to 61.0 [56.0,69.5] years in 2020-2022. HIV/AIDS and liver-related causes of death decreased, whereas deaths from NANH cancers increased, and cardiovascular-related deaths remained relatively stable. CONCLUSION: The proportionally decreasing HIV/AIDS and liver-related deaths showcase the effectiveness of ART, comprehensive HIV patient care, and interventions targeting hepatitis C virus co-infection. Future research should focus on managing cancer and cardiovascular-related conditions as the new leading causes of death among PWH. Comprehensive healthcare strategies focusing on non-AIDS-related comorbidities, cancer management, and sustaining liver and cardiovascular health are needed to bridge the ongoing health disparities between PWH and the general population.

Diagnosis and treatment of primary thyroid lymphoma from a surgical perspective: a multi-institutional study.

PURPOSE: Surgery of primary thyroid lymphoma (PTL) has been mostly limited to diagnostic work-up. This study aimed to further study its potential role. METHODS: This was a retrospective study from a multi-institutional registry of PTL patients. Clinical, diagnostic work-up (fine needle aspiration, FNA; core needle biopsy, CoreNB), contribution of surgery (open surgical biopsy, OpenSB; thyroidectomy), histology subtype, and outcome data were evaluated. RESULTS: Some 54 patients were studied. Diagnostic work-up included FNA in 47 patients, CoreNB in 11, and OpenSB in 21. CoreNB yielded the best sensitivity (90.9%). Thyroidectomy was performed in 14 patients with other diagnosis (incidental PTL), in 4 for diagnosis and in 4 for elective treatment of PTL. Incidental PTL was associated with not performed FNA nor CoreNB (OR 52.5; P = 0.008), mucosa-associated lymphoid tissue (MALT) subtype (OR 24.3; P = 0.012), and Hashimoto's thyroiditis (OR 11.1; P = 0.032). Lymphoma-related death (10 cases) mostly occurred within the first year after diagnosis and was associated with diffuse large B-cell (DLBC) subtype (OR 10.3; P = 0.018) and older patients (OR 1.08 for every 1-year increase; P = 0.010). There was a trend towards lower mortality rate in patients receiving thyroidectomy (2/22 versus 8/32, P = 0.172). CONCLUSION: Incidental PTL accounts for most of thyroid surgery cases and are associated with incomplete diagnostic work-up, Hashimoto's thyroiditis and MALT subtype. CoreNB appears to be the best tool for diagnosis. Most of PTL deaths occurred during the first year after diagnosis and mostly related to systemic treatment. Age and DLBC subtype are poor prognostic factors.

Epoxide of diosgenin acetate synthesis: DoE for diastereoselective yield optimization, antimicroibial, antioxidant and antiproliferative effects.

Diosgenin and its derivatives have proved a huge importance in diverse biological activities. The optimized production of the diastereoisomers of the epoxide of diosgenin acetate by means of mCPBA is reported herein. This transformation had a previous design of experiments using the application of a statistical factorial DoE of 4 parameters (nk), where one variable is varied at a time, while others stay constant. The temperature showed the greatest effect on the reaction yield; so, at 298 K the diastereomeric ratio 3:1 of α and ß-epoxides, normally found, was raised to 1:1. Time was the second significant variable, but due to its high correlation with temperature, 30 min were required for a global 90% conversion at least. These diastereoisomers were characterized both isolated and in the mixtures obtained, to determine their antioxidant, antimicrobial and antiproliferative activity, finding a low antioxidant capacity by DPPH, but antimicrobial activity at the level of penicillin in gram negative bacteria by 1ß better to 1α. The antiproliferative capacity was higher for diastereoisomer ß, agreeing with the proportion of the mixture obtained by different conditions, increasing this in relation to the amount of this diastereoisomer present in hormone-dependent cancer cell lines such as Hela, PC-3 and MCF-7, with 10.0 µM obtained values of viability at 21.8 %, 35.8 % and 12.3 % respectively. DoE optimization allows to manipulate the ratio between diastereoisomers with the minimum number of experiments, extending the analysis of the effect of the ratio between diastereoisomers and the in silico potential as well as the biological activity.

Active immunization with a structurally aggregated PD-L1 antigen breaks T and B immune tolerance in non-human primates and exhibits in vivo anti-tumoral effects in immunocompetent mouse tumor models.

Despite the clinical success of the programmed death ligand 1 (PD-L1) blocking therapy in cancer treatment, only a subset of patients exhibits durable responses, therefore further exploration of other immunotherapeutic alternatives are needed. This paper reported the development of the PKPD-L1Vac vaccine, a new protein vaccine candidate that uses aluminum phosphate as an adjuvant and as an antigen the extracellular domain of human PD-L1 fused to a 47 amino-terminal portion of the LpdA protein from N. meningitides (PKPD-L1). The PKPD-L1 antigen has different physical and biological characteristics than those found in the natural molecule and in others PD-L1 vaccine candidates. The quimeric protein has a reduced binding capacity to the PD-1 and CD80 receptors to decrease their pro-tumoral activity. Besides, the distinctive feature of the PKPD-L1 polypeptide to be structurally aggregated could be desirable for its immunogenic properties. PKPD-L1Vac elicited anti-PD-L1-specific IgG antibodies and T lymphocyte-mediated immunity in mice and non-human primates. The vaccine administration demonstrated antitumor activity on CT-26 and B16-F10 primary tumor models in mice. Moreover, the immunization with PKPD-L1Vac increased the tumor-infiltrating lymphocytes and decreased the proportion of CD3+CD8+PD1+high anergic T cells in CT-26 tumor tissues, suggesting that the vaccine may remodel the tumor microenvironment. In summary, the PKPD-L1Vac vaccine exhibits very promising preclinical results and deserves to move forward to a phase I clinical trial.

Use of audiovisual devices in transnasal endoscopy without sedation to improve tolerance. A prospective clinical trial.

INTRODUCTION AND AIM: Transnasal endoscopy (TNE) has proven its diagnostic utility, but it has not been widely accepted given that it is performed without sedation. There are no previous studies on the use of methods to improve its tolerability. Our aim was to evaluate the tolerability of TNE, when simultaneously performed with an audiovisual device as a distractor. METHODS: We evaluated 50 patients, 10 of whom did not agree to participate. The performance of the procedure was explained, using an audiovisual device. Before randomization, we applied anxiety and depression scores. Patients were divided into 2 groups: Group I (using an audiovisual device during the procedure) and Group II (without a device). Anxiety and numeric pain rating scales were used, and vital signs were monitored and recorded before, during, and after the endoscopy. An overall procedure satisfaction score was applied at the end of the study and 24 h later. RESULTS: Mean age was 41.6 years and 35 of the patients were women (87.5%). The most frequent indication for TNE was refractory gastroesophageal reflux disease. There were no severe comorbidities, and none of the patients had a significant anxiety or depression score. One patient in Group II did not tolerate TNE due to nasal pain. There was no statistically significant difference between groups, regarding anxiety, pain, vital signs, and satisfaction scale. CONCLUSION: Our study showed that TNE was well tolerated and had a high acceptance rate in our patients. The use of distracting audiovisual devices did not increase tolerance to the endoscopic procedure.

Soft Tissue Sarcomas in Octogenarian Patients: Are Treatment Options and Oncological Outcomes Different? A SEER Retrospective Study.

AIMS: As the US population continues to age, oncological strategies and outcomes for soft tissue sarcomas (STSs) should continue to be examined for varying age groups. The aim of this study was analyse and compare treatment strategies and oncological outcomes for octogenarian patients with STSs. MATERIALS AND METHODS: Data from the Surveillance, Epidemiology and End Results (SEER) national database were used. Varying treatment modalities were studied when utilised for specific tumour staging with respect to the eighth edition of the American Joint Committee on Cancer. RESULTS: In total, 24 666 patients were included for analysis, where 3341 (14%) were 80 years old or older. The octogenarian group was diagnosed with more advanced disease (stages II-IV), relative to their younger counterparts (85% versus 75%, P < 0.001). However, a smaller proportion of the older patients underwent surgical resection (74% versus 86%, P < 0.001). Likewise, the octogenarians received less chemotherapy (4% versus 21%, P < 0.001) and radiotherapy (29% versus 42%, P = 0.010). Surgical resection and chemotherapy significantly improved overall survival for those older patients with stage II STS, whereas surgical resection and radiotherapy improved mortality in this cohort with both stage III and IV STS. Overall survival at 1 and 5 years of follow-up was lower within the octogenarian group compared with the younger group (1 year: 68% versus 88%, P < 0.001 and 5 years: 7% versus 58%, P < 0.001). CONCLUSIONS: Octogenarian patients, in most cases, are diagnosed with stage III or metastatic disease. Surgical resection of the primary tumour was beneficial in both age cohorts, with radiotherapy correlating to better overall survival when used in those patients with higher stage STS. Chemotherapy was associated with better mortality in the younger cohort with respect to tumour stage. The octogenarian overall survival at 1 and 5 years was lower than for younger patients.

Transanal full-thickness excision for rectal neoplasm: is it advisable to leave the defect open?

PURPOSE: After a full-thickness total wall excision of a rectal tumor, suturing the defect is generally recommended. Recently, due to various contradictory studies, there is a trend to leave the defects open. Therefore, this study aimed to determine whether leaving the defect open is an adequate management strategy compared with suturing it closed based on postoperative outcomes and recurrences. METHODS: A retrospective review of our prospectively maintained database was conducted. Adult patients who underwent transanal surgery for rectal neoplasm in our institution from 1997 to 2019 were analyzed. Patients were divided into two groups: sutured (group A) or unsutured (group B) rectal defect. The primary outcomes were morbidity (early and late) and recurrence. RESULTS: In total, 404 (239 men) patients were analyzed, 143 (35.4%) from group A and 261 (64.6%) from group B. No differences were observed in tumor size, distance from the anal verge or operation time. The overall incidence of complications was significantly higher in patients from group B, which nearly double the rate of group A. With a mean follow-up of 58 (range, 12-96) months, seven patients presented with a rectal stricture, all of them from group B. CONCLUSIONS: We acknowledge the occasional impossibility of closing the defect in patients who undergo local excision; however, when it is possible, the present data suggest that there may be advantages to suturing the defect closed.

Combined transposition of internal obturator and superficial gluteal muscles for perineal hernia treatment in dogs: 17 cases (2017-2020).

OBJECTIVES: To report the results of the combined transposition of the internal obturator muscle and superficial gluteal muscle for perineal hernia treatment in dogs. MATERIALS AND METHODS: Retrospective case series of dogs treated with this technique from November 2017 to May 2020, including pre- and post-operative clinical findings, outcome and complications. RESULTS: Seventeen dogs were included in the study. Twelve dogs were presented with unilateral perineal hernia and five dogs with bilateral perineal hernias. Mean duration of clinical signs before presentation was 9 months. All perineal hernias were successfully repaired using a transposition of the internal obturator muscle to cover the ventral aspect of the perineal hernia and the superficial gluteal muscle to cover the dorsal aspect of the hernia with minimal tension. All dogs regained normal defecation within 24 hours post-surgery. Average follow-up time was 16 months. No recurrence of clinical signs or rectal deviation was observed. Five dogs developed a superficial minor partial necrosis of the T-shaped incision and two had surgical site infections. CLINICAL SIGNIFICANCE: Perineal herniorrhaphy using a combined transposition of the internal obturator and the superficial gluteal muscles is feasible and offered excellent results in this cohort of dogs. It may be considered as a technique for repairing chronic and extensive unilateral and bilateral perineal hernias.

Síntomas depresivos, ansiosos e insomnio, y posibles factores asociados en personal de salud, en un Hospital General en Suramérica, durante la pandemia por COVID-19 en 2020 / Depressive and anxious symptoms and insomnia, and possible associated factors in health workers, in a General Hospital in South America, during the COVID-19 pandemic in 2020

La pandemia por el nuevo coronavirus COVID- 19 ha tenido impacto en la salud mental del personal médico y de enfermería en todo el mundo. Objetivo: identificar la frecuencia de síntomas depresivos, ansiosos e insomnio y los factores posiblemente relacionados con estos desenlaces en el personal sanitario de un hospital de Suramérica durante el primer pico de la pandemia. Materiales y métodos: se aplicaron las escalas PHQ-9 para depresión, GAD- 7 para ansiedad, ISI - 7 para insomnio en 876 trabajadores de la salud del Hospital Pablo Tobón Uribe en la ciudad de Medellín. Resultados: de los 876 participantes (29,2% médicos, 21.2% profesionales de enfermería y 49,5% auxiliares de enfermería), 357 (40.8%) presentaron síntomas depresivos, 300 (34.2%) síntomas ansiosos y 317 (36.2%) insomnio. Se observaron síntomas de depresión, ansiedad e insomnio, con mayor frecuencia en quienes no tenían las necesidades básicas satisfechas y en quienes se sentían estigmatizados por ser personal de salud. Además, la depresión se presentó con más frecuencia en mujeres, la ansiedad en menores de 44 años y el insomnio en personas separadas. Conclusiones: la frecuencia de problemas de salud mental en el personal de salud es considerable. Estos hallazgos demuestran la necesidad de atención en la salud mental de los profesionales médicos y de enfermería durante la pandemia por COVID-19 y la búsqueda de estrategias para mitigar el riesgo en esta población.

Background: pandemic due to novel coronavirus COVID-19 has impacted on the mental health of health care workers all around the world. Material and Methods: this is a cross sectional study in which questionnaires PHQ-9 for depression, GAD-7 for anxiety, ISI-7 for insomnia were virtually and self administered by 876 health care workers laboring in hospital Pablo Tobón Uribe in Medellin city. Results: from 876 participants (29.2% physicians, 21.2% nurses and 49.5% technical nurses), 357 (40.8%) developed depressive symptoms, 300 (34.2%) anxious symptoms and 317 (36.2%) insomnia. Symptoms of depression, anxiety and insomnia were more frequently found in those who did not have basic needs satisfied and in those who felt stigmatized due to being health personal. Besides, depressive symptoms were more frequent in women, anxious symptoms in people younger than 44 years old and insomnia in divorced people. Conclusions: the frequency of mental health problems in health care workers is significant, these findings bring to light the needs for mental health attention in nurses and doctors during COVID-19 pandemic and the research of strategies to mitigate the risk on this population. Feeling stigmatized and not having basic needs satisfied were associated with symptoms of anxiety, depression and insomnia.

Biocatalyst developed with recovered iron-rich minerals enhances the biotransformation of SARS-CoV-2 antiviral drugs in anaerobic bioreactors.

The biotransformation of the SARS-CoV-2 antiviral drugs, ribavirin and tenofovir, was studied in methanogenic bioreactors. The role of iron-rich minerals, recovered from a metallurgic effluent, on the biotransformation process was also assessed. Enrichment of anaerobic sludge with recovered minerals promoted superior removal efficiency for both antivirals (97.4 % and 94.7 % for ribavirin and tenofovir, respectively) as compared to the control bioreactor lacking minerals, which achieved 58.5 % and 37.9 % removal for the same drugs, respectively. Further analysis conducted by liquid chromatography coupled to mass spectroscopy revealed several metabolites derived from the biotransformation of both antivirals. Interestingly, tracer analysis with 13CH4 revealed that anaerobic methane oxidation coupled to Fe(III) reduction occurred in the enriched bioreactor, which was reflected in a lower content of methane in the biogas produced from this system, as compared to the control bioreactor. This treatment proposal is suitable within the circular economy concept, in which recovered metals from an industrial wastewater are applied in bioreactors to create a biocatalyst for promoting the biotransformation of emerging pollutants. This strategy may be appropriate for the anaerobic treatment of wastewaters originated from hospitals, as well as from the pharmaceutical and chemical sectors.

Epigenetic age estimation in saliva and in buccal cells.

Age estimation based on epigenetic markers is a DNA intelligence tool with the potential to provide relevant information for criminal investigations, as well as to improve the inference of age-dependent physical characteristics such as male pattern baldness or hair color. Age prediction models have been developed based on different tissues, including saliva and buccal cells, which show different methylation patterns as they are composed of different cell populations. On many occasions in a criminal investigation, the origin of a sample or the proportion of tissues is not known with certainty, for example the provenance of cigarette butts, so use of combined models can provide lower prediction errors. In the present study, two tissue-specific and seven age-correlated CpG sites were selected from publicly available data from the Illumina HumanMethylation 450 BeadChip and bibliographic searches, to help build a tissue-dependent, and an age-prediction model, respectively. For the development of both models, a total of 184 samples (N = 91 saliva and N = 93 buccal cells) ranging from 21 to 86 years old were used. Validation of the models was performed using either k-fold cross-validation and an additional set of 184 samples (N = 93 saliva and N = 91 buccal cells, 21-86 years old). The tissue prediction model was developed using two CpG sites (HUNK and RUNX1) based on logistic regression that produced a correct classification rate for saliva and buccal swab samples of 88.59 % for the training set, and 83.69 % for the testing set. Despite these high success rates, a combined age prediction model was developed covering both saliva and buccal cells, using seven CpG sites (cg10501210, LHFPL4, ELOVL2, PDE4C, HOXC4, OTUD7A and EDARADD) based on multivariate quantile regression giving a median absolute error (MAE): ± 3.54 years and a correct classification rate ( %CP±PI) of 76.08 % for the training set, and an MAE of ± 3.66 years and a %CP±PI of 71.19 % for the testing set. The addition of tissue-of origin as a co-variate to the model was assessed, but no improvement was detected in age predictions. Finally, considering the limitations usually faced by forensic DNA analyses, the robustness of the model and the minimum recommended amount of input DNA for bisulfite conversion were evaluated, considering up to 10 ng of genomic DNA for reproducible results. The final multivariate quantile regression age predictor based on the models we developed has been placed in the open-access Snipper forensic classification website.

Low-dose radiotherapy to the lungs using an interventional radiology C-arm fluoroscope: Monte Carlo treatment planning and dose measurements in a postmortem subject.

Objective.The goal of this study was to use Monte Carlo (MC) simulations and measurements to investigate the dosimetric suitability of an interventional radiology (IR) c-arm fluoroscope to deliver low-dose radiotherapy to the lungs.Approach.A previously-validated MC model of an IR fluoroscope was used to calculate the dose distributions in a COVID-19-infected patient, 20 non-infected patients of varying sizes, and a postmortem subject. Dose distributions for PA, AP/PA, 3-field and 4-field treatments irradiating 95% of the lungs to a 0.5 Gy dose were calculated. An algorithm was created to calculate skin entrance dose as a function of patient thickness for treatment planning purposes. Treatments were experimentally validated in a postmortem subject by using implanted dosimeters to capture organ doses.Main results.Mean doses to the left/right lungs for the COVID-19 CT data were 1.2/1.3 Gy, 0.8/0.9 Gy, 0.8/0.8 Gy and 0.6/0.6 Gy for the PA, AP/PA, 3-field, and 4-field configurations, respectively. Skin dose toxicity was the highest probability for the PA and lowest for the 4-field configuration. Dose to the heart slightly exceeded the ICRP tolerance; all other organ doses were below published tolerances. The AP/PA configuration provided the best fit for entrance skin dose as a function of patient thickness (R2 = 0.8). The average dose difference between simulation and measurement in the postmortem subject was 5%.Significance.An IR fluoroscope should be capable of delivering low-dose radiotherapy to the lungs with tolerable collateral dose to nearby organs.

A singular value decomposition entropy approach to assess the impact of Covid-19 on the informational efficiency of the WTI crude oil market.

This work investigates the impact of the Covid-19 outbreak on crude oil market efficiency. The approach is based on the singular value decomposition (SVD) entropy. Iso-distributional surrogate data test was used to contrast the results against random patterns, and phase randomization based on Fourier transform was used to assess nonlinearities. The analysis considered the WTI market and focused on the Covid-19 pandemic period January 2020-November 2021 and contrasted with the long preceding period from January 2000 to date. It was found that the crude oil market was informationally efficient most of the time with small sporadic deviations from efficiency in the pre-Covid-19 years. The Covid-19 period exhibited the largest deviations from efficiency, mainly in the first months of the outbreak, accompanied by a marked reduction of nonlinear components. The analysis was conducted for different scales, and the results showed that the deviations from efficiency were more pronounced for quarterly scales. For the sake of comparison, the analysis was also carried out on the trading volume dynamics and the results showed that the market activity is not fully random. The dynamics of the trading volume exhibited significant deviations from the randomness behavior when the crude oil market was efficient, and a behavior that was consistent with nonlinear patterns. The opposite behavior was noted for stages when the crude oil market showed strong deviations from efficiency. Overall, the findings of this study suggest an increasing opportunity for crude oil price predictions and abnormal returns during the Covid-19 pandemic.