Rapid response petrology for the opening eruptive phase of the 2021 Cumbre Vieja eruption, La Palma, Canary Islands

How and why magmatic systems reactivate and evolve is a critical question for monitoring and hazard mitigation efforts during initial response and ongoing volcanic crisis management. Here we report the first integrated petrological results and interpretation provided to monitoring authorities during the ongoing eruption of Cumbre Vieja, La Palma, Canary Islands, Spain. The first eruptive products comprised simultaneous Strombolian fountain-fed lava flows and tephra fall from near-continuous eruption plumes. From combined field, petrographic and geochemical analyses conducted in the 10 days following sample collection, we infer low percentage mantle melts with a variably equilibrated multimineralic crystal-cargo and compositional fractionation by winnowing during eruptive processes. Hence ‘rapid response’ petrology can untangle complex magmatic and volcanic processes for this eruption, which combined with further study and methodological improvement can increasingly assist in active decision making.

PCOS: a Chronic Disease That Fails to Produce Adequately Specialized Pro-resolving Lipid Mediators (SPMs).

Introduction: Polycystic Ovary Syndrome (PCOS) is an endocrinologic disorder that affects 5-15 % of women of their reproductive age and is a frequent cause of infertility. Major symptoms include hyperandrogenism, ovulatory dysfunction, and often obesity and/or insulin resistance. PCOS also represents a state of chronic low-grade inflammation that is closely interlinked with the metabolic features. "Classical" pro-inflammatory lipid mediators like prostaglandins (PG), leukotrienes (LT), or thromboxanes (TX) are derived from arachidonic acid (AA) and are crucial for the initial response. Resolution processes are driven by four families of so-called specialized pro-resolving mediators (SPMs): resolvins, maresins, lipoxins, and protectins. The study aimed to establish lipid mediator profiles of PCOS patients compared to healthy women to identify differences in their resolutive and pro-inflammatory lipid parameters. Material and Methods: Fifteen female patients (18-45 years) were diagnosed with PCOS according to Rotterdam criteria, and five healthy women, as comparator group, were recruited for the study. The main outcome measures were: Pro-inflammatory lipid mediators (PG, LT, TX) and their precursor AA; SPMs (Resolvins, Maresins, Protectins, Lipoxins), their precursors EPA, DHA, DPA, and their active biosynthesis pathway intermediates (18-HEPE, 17-HDHA, 14-HDHA).Results: The level of pro-inflammatory parameters in serum was significantly higher in PCOS-affected women. The ratio [(sum of pro-inflammatory molecules) / (sum of SPMs plus hydroxylated intermediates)] reflecting the inflammatory state was significantly lower in the group of healthy women.Conclusion: There is a strong pro-inflammatory state in PCOS patients. Further research will clarify whether supplementation with SPMs or their precursors may improve this state.

The Activation of Mesenchymal Stem Cells by Glioblastoma Microvesicles Alters Their Exosomal Secretion of miR-100-5p, miR-9-5p and let-7d-5p

Glioblastoma (GBM) is the most aggressive brain tumor, and despite initial response to chemo- and radio-therapy, the persistence of glioblastoma stem cells (GSCs) unfortunately always results in tumor recurrence. It is now largely admitted that tumor cells recruit normal cells, including mesenchymal stem cells (MSCs), and components of their environment, to participate in tumor progression, building up what is called the tumor microenvironment (TME). While growth factors and cytokines constitute essential messengers to pass on signals between tumor and TME, recent uncovering of extracellular vesicles (EVs), composed of microvesicles (MVs) and exosomes, opened new perspectives to define the modalities of this communication. In the GBM context particularly, we investigated what could be the nature of the EV exchange between GSCs and MSCs. We show that GSCs MVs can activate MSCs into cancer-associated fibroblasts (CAFs)-like cells, that subsequently increase their secretion of exosomes. Moreover, a significant decrease in anti-tumoral miR-100-5p, miR-9-5p and let-7d-5p was observed in these exosomes. This clearly suggests a miRNA-mediated GBM tumor promotion by MSCs exosomes, after their activation by GBM MVs.

Integrative time-scale and multi-omic analysis of host-responses to Hop stunt viroid infection

Constricted by an extreme biological simplicity, viroids are compelled to subvert host regulatory networks in order to accomplish their infectious process. Most of the studies focused on the response to viroid infection have only addressed a specific host regulatory level and considered a unique infection time. Thus, much remains to be done if we want to understand the temporal evolution and complex nature of viroid-host interactions. Here we present an integrative analysis of the timing and intensity of the genome-wide alterations in cucumber plants infected with Hop stunt viroid (HSVd). Differential host transcriptome, sRNAnome and methylome were integrated to determine the temporal response to viroid-infection. Our results support that HSVd promotes a dynamic redesign of the cucumber regulatory pathways predominantly affecting specific regulatory layers at different infection phases. Remarkably, the initial response was characterized by a reconfiguration of the host transcriptome by differential exon usage, followed by a predominant down-regulation of the transcriptional activity possibly modulated by the host epigenetic changes associated to infection and characterized by an increased hypermethylation. The silencing of at least three cucumber transcripts potential targets of vd-sRNAs was also observed. The alteration in host sRNA and miRNA metabolism was marginal. We expect that these data constituting the first comprehensive map of the cucumber-response to HSVd could contribute to elucidate the molecular basis of the host alterations triggered by viroid infection.

Initial response of young people with thyrotoxicosis to block and replace or dose titration thionamide

Objective Patients with thyrotoxicosis are treated with anti-thyroid drug (ATD) using block and replace (BR) or a smaller, titrated dose of ATD (dose titration, DT). Design A multi-centre, phase III, open-label trial of newly diagnosed paediatric thyrotoxicosis patients randomised to BR/DT. We compared the biochemical response to BR/DT in the first 6 months of therapy. Methods Patients commenced 0.75 mg/kg carbimazole (CBZ) daily with randomisation to BR/DT. We examined baseline patient characteristics, CBZ dose, time to serum thyroid-stimulating hormone (TSH)/free thyroxine (FT4) normalisation and BMI Z-score change. Results There were 80 patients (baseline) and 78 patients (61 female) at 6 months. Mean CBZ dose was 0.9 mg/kg/day (BR) and 0.5 mg/kg/day (DT). There was no difference in time to non-suppressed TSH concentration; 16 of 39 patients (BR) and 11 of 39 (DT) had suppressed TSH at 6 months. Patients with suppressed TSH had higher mean baseline FT4 levels (72.7 vs 51.7 pmol/L; 95% CI for difference 1.73, 31.7; P = 0.029). Time to normalise FT4 levels was reduced in DT (log-rank test, P = 0.049) with 50% attaining normal FT4 at 28 days (95% CI 25, 32) vs 35 days in BR (95% CI 28, 58). Mean BMI Z-score increased from 0.10 to 0.81 at 6 months (95% CI for difference 0.57, 0.86; P < 0.001) and was greatest in patients with higher baseline FT4 concentrations. Conclusions DT-treated patients normalised FT4 concentrations more quickly than BR. Overall, 94% of patients have normal FT4 levels after 6 months, but 33% still have TSH suppression. Excessive weight gain occurs with both BR and DT therapy.

A Review of COVID-19 Initial Response Systems and A Proposal to Adjust the Operation of Residential treatment centers

Objective: The COVID-19 pandemic has caused a periodic shortage of quarantine beds, medical personnel, and medical equipment in South Korea. Asthe pandemic is expected to continue, a need existsto readjust the capacities of residentialtreatment centersfor asymptomatic ormild cases. Thisstudy aimed to identify howother countriestreat asymptomatic or have mild COVID-19 patients, and suggest a effective operation plan of residential treatment centers.Methods: A literature review was conducted to examine how policies on asymptomatic or mild COVID-19 cases have changed at different phases of the pandemic in different countries. A reviewwas also conducted on the epidemiological characteristics of Korean patients, including clinicalstatus and treatment period, and public opinion on residential treatment centers. A plan to improve how residential treatment centers operate during the pandemic was derived based on expert advice, and discussion within the research team.Results: Home care is being recommended for asymptomatic or mild cases of COVID-19 in many countries. In Korea, despite the increase in the number of newly confirmed cases, fatality rate of COVID-19 shows a decreasing and vaccination rate an increasing trend. Three-fourths of the public recognized that home care may be more appropriate for asymptomatic or mild cases. Assuch,we recommend a reduction in length ofstay in residential treatment centers, from 10 to 3 or 5 days, and ensuring patient’s participation in decision‒making of hospitalization.Conclusions: A need existsto prepare a systematic response system, including patient education, virtual treatment and transfersystem in orderto shorten patients’ admission period in residential treatment centers and expand home care. A functioning emergency response system should also be prepared concurrently.

Periocular capillary hemangioma treated with low dose oral propranolol - presentation and outcome of 30 patients

Purpose: To evaluate the presentation and outcome of periocular capillary hemangioma treated with low-dose oral propranolol. Method: Thirty cases of periocular capillary hemangioma prospectively studied from 1st June 2015 to 31st May 2017 who received oral propranolol on an outpatient basis. Hemangioma causing any threat to vision or disfigurement was included and age below 3 months and multiple lesions were excluded. Starting dose of propranolol was 1 mg/kg and increased to 2 mg/kg after 2 weeks as a maintenance dose. The tapering dose was 1 mg/kg of body weight before discontinuing the medication. Treatment was continued till the child is 1 year of age or no further change in color or size of the lesion in two successive follow-ups. Results: Presenting age was 6.36 ± 3.36 months (ranged 3–24 months) with female predominance (70%). In 86.6% of cases, the vision was Central Steady and Maintained and cycloplegic refraction showed marked astigmatism in 3 children which resolved after treatment. Forty-six percent of children showed color change as an initial response to treatment. Most children (33.3%) responded completely within 5 months after starting the treatment. One third patients (33.3%) showed 100% resolution, 50% showed 90% to 70% resolution. Pretreatment and post-treatment lesion size was1.60 ± 0.86 cm2 and 0.30 ± 0.40 cm2 respectively (p - value < 0.0005). None showed any significant adverse effect of oral propranolol. Conclusion: Low-dose oral propranolol is an effective and cost-effective treatment modality for periocular capillary hemangioma and is safe as an outpatient basis.

Prediction of Flooded Compartment Damage Locations in Ships by Using Spectrum Analysis of Ship Motions in Waves

Considering the nature of marine accidents, even a single accident can result in significant damage to the environment and property, as well as loss of life. Therefore, the initial response should be rapid and accurate, and various decision support systems have been developed to achieve this. Research on simulating progressive flooding on board immediately after an accident is being actively conducted, but this requires high levels of computing power. In this study, a methodology for converting simulated ship motion data into a ship motion database is presented. The model of a training ship from the Korea Institute of Maritime and Fisheries Technology and KRISO in-house code SMTP was used for ship motion computations. The short-time Fourier transform was used to convert time-series motion data into a spectrogram motion database. A methodology for deriving a predicted location of the damage center is presented. The candidate locations of the damage centers were obtained by comparing the root mean square error values of the ship motion database from the simulation and real-time ship motion data. Finally, a probability function was suggested to confirm the predicted location of the damage center. Using 100 randomly selected test cases, our method showed 95% accuracy.

Multigene Profiling of Circulating Tumor Cells (CTCs) for Prognostic Assessment in Treatment-Naïve Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)

The substantial biological heterogeneity of metastatic prostate cancer has hindered the development of personalized therapeutic approaches. Therefore, it is difficult to predict the course of metastatic hormone-sensitive prostate cancer (mHSPC), with some men remaining on first-line androgen deprivation therapy (ADT) for several years while others progress more rapidly. Improving our ability to risk-stratify patients would allow for the optimization of systemic therapies and support the development of stratified prospective clinical trials focused on patients likely to have the greatest potential benefit. Here, we applied a liquid biopsy approach to identify clinically relevant, blood-based prognostic biomarkers in patients with mHSPC. Gene expression indicating the presence of CTCs was greater in CHAARTED high-volume (HV) patients (52% CTChigh) than in low-volume (LV) patients (23% CTChigh; * p = 0.03). HV disease (p = 0.005, q = 0.033) and CTC presence at baseline prior to treatment initiation (p = 0.008, q = 0.033) were found to be independently associated with the risk of nonresponse at 7 months. The pooled gene expression from CTCs of pre-ADT samples found AR, DSG2, KLK3, MDK, and PCA3 as genes predictive of nonresponse. These observations support the utility of liquid biomarker approaches to identify patients with poor initial response. This approach could facilitate more precise treatment intensification in the highest risk patients.

Increased Plasma Soluble PD-1 Concentration Correlates with Disease Progression in Patients with Cancer Treated with Anti-PD-1 Antibodies

Immune checkpoint inhibitors (ICIs) confer remarkable therapeutic benefits to patients with various cancers. However, many patients are non-responders or develop resistance following an initial response to ICIs. There are no reliable biomarkers to predict the therapeutic effect of ICIs. Therefore, this study investigated the clinical implications of plasma levels of soluble anti-programmed death-1 (sPD-1) in patients with cancer treated with ICIs. In total, 22 patients (13 with non-small-cell lung carcinoma, 8 with gastric cancer, and 1 with bladder cancer) were evaluated for sPD-1 concentration using enzyme-linked immunosorbent assays for diagnostic and anti-PD-1 antibody analyses. sPD-1 levels were low before the administration of anti-PD-1 antibodies. After two and four cycles of anti-PD-1 antibody therapy, sPD-1 levels significantly increased compared with pretreatment levels (p = 0.0348 vs. 0.0232). We observed an increased rate of change in plasma sPD-1 concentrations after two and four cycles of anti-PD-1 antibody therapy that significantly correlated with tumor size progression (p = 0.024). sPD-1 may be involved in resistance to anti-PD-1 antibody therapy, suggesting that changes in sPD-1 levels can identify primary ICI non-responders early in treatment. Detailed analysis of each cancer type revealed the potential of sPD-1 as a predictive biomarker of response to ICI treatment in patients with cancer.