High resolution seafloor thermometry for internal wave and upwelling monitoring using Distributed Acoustic Sensing.

Temperature is an essential oceanographic variable (EOV) that still today remains coarsely resolved below the surface and near the seafloor. Here, we gather evidence to confirm that Distributed Acoustic Sensing (DAS) technology can convert tens of kilometer-long seafloor fiber-optic telecommunication cables into dense arrays of temperature anomaly sensors having millikelvin (mK) sensitivity, thus allowing to monitor oceanic processes such as internal waves and upwelling with unprecedented detail. Notably, we report high-resolution observations of highly coherent near-inertial and super-inertial internal waves in the NW Mediterranean sea, offshore of Toulon, France, having spatial extents of a few kilometers and producing maximum thermal anomalies of more than 5 K at maximum absolute rates of more than 1 K/h. We validate our observations with in-situ oceanographic sensors and an alternative optical fiber sensing technology. Currently, DAS only provides temperature changes estimates, however practical solutions are outlined to obtain continuous absolute temperature measurements with DAS at the seafloor. Our observations grant key advantages to DAS over established temperature sensors, showing its transformative potential for the description of seafloor temperature fluctuations over an extended range of spatial and temporal scales, as well as for the understanding of the evolution of the ocean in a broad sense (e.g. physical and ecological). Diverse ocean-oriented fields could benefit from the potential applications of this fast-developing technology.

Domain-based mRNA vaccines encoding spike protein N-terminal and receptor binding domains confer protection against SARS-CoV-2.

With the success of messenger RNA (mRNA) vaccines against coronavirus disease 2019, strategies can now focus on improving vaccine potency, breadth, and stability. We designed and evaluated domain-based mRNA vaccines encoding the wild-type spike protein receptor binding domain (RBD) or N-terminal domain (NTD) alone or in combination. An NTD-RBD-linked candidate vaccine, mRNA-1283, showed improved antigen expression, antibody responses, and stability at refrigerated temperatures (2° to 8°C) compared with the clinically available mRNA-1273, which encodes the full-length spike protein. In BALB/c mice administered mRNA-1283 as a primary series, booster, or variant-specific booster, similar or greater immune responses from viral challenge were observed against wild-type, beta, delta, or omicron (BA.1) viruses compared with mRNA-1273-immunized mice, especially at lower vaccine dosages. K18-hACE2 mice immunized with mRNA-1283 or mRNA-1273 as a primary series demonstrated similar degrees of protection from challenge with SARS-CoV-2 Delta and Omicron variants at all vaccine dosages. These results support clinical assessment of mRNA-1283, which has now entered clinical trials (NCT05137236).

Development of SARS-CoV-2 mRNA vaccines encoding spike N-terminal and receptor binding domains.

With the success of mRNA vaccines against coronavirus disease 2019 (COVID-19), strategies can now focus on improving vaccine potency, breadth, and stability. We present the design and preclinical evaluation of domain-based mRNA vaccines encoding the wild-type spike-protein receptor-binding (RBD) and/or N-terminal domains (NTD). An NTD-RBD linked candidate vaccine, mRNA-1283, showed improved antigen expression, antibody responses, and stability at refrigerated temperatures (2-8°C) compared with the clinically available mRNA-1273, which encodes the full-length spike protein. In mice administered mRNA-1283 as a primary series, booster, or variant-specific booster, similar or greater immune responses and protection from viral challenge were observed against wild-type, beta, delta, or omicron (BA. 1) compared with mRNA-1273 immunized mice, especially at lower vaccine dosages. These results support clinical assessment of mRNA-1283 ( NCT05137236 ). One Sentence Summary: A domain-based mRNA vaccine, mRNA-1283, is immunogenic and protective against SARS-CoV-2 and emerging variants in mice.

Variant SARS-CoV-2 mRNA vaccines confer broad neutralization as primary or booster series in mice.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of a global pandemic. Safe and effective COVID-19 vaccines are now available, including mRNA-1273, which has shown 94% efficacy in prevention of symptomatic COVID-19 disease. However, the emergence of SARS-CoV-2 variants has led to concerns of viral escape from vaccine-induced immunity. Several variants have shown decreased susceptibility to neutralization by vaccine-induced immunity, most notably B.1.351 (Beta), although the overall impact on vaccine efficacy remains to be determined. Here, we present the initial evaluation in mice of 2 updated mRNA vaccines designed to target SARS-CoV-2 variants: (1) monovalent mRNA-1273.351 encodes for the spike protein found in B.1.351 and (2) mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. Both vaccines were evaluated as a 2-dose primary series in mice; mRNA-1273.351 was also evaluated as a booster dose in animals previously vaccinated with mRNA-1273. The results demonstrated that a primary vaccination series of mRNA-1273.351 was effective at increasing neutralizing antibody titers against B.1.351, while mRNA-1273.211 was effective at providing broad cross-variant neutralization. A third (booster) dose of mRNA-1273.351 significantly increased both wild-type and B.1.351-specific neutralization titers. Both mRNA-1273.351 and mRNA-1273.211 are being evaluated in pre-clinical challenge and clinical studies.

Variant SARS-CoV-2 mRNA vaccines confer broad neutralization as primary or booster series in mice.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of a global pandemic. Safe and effective COVID-19 vaccines are now available, including mRNA-1273, which has shown 94% efficacy in prevention of symptomatic COVID-19 disease. However, the emergence of SARS-CoV-2 variants has led to concerns of viral escape from vaccine-induced immunity. Several variants have shown decreased susceptibility to neutralization by vaccine-induced immunity, most notably B.1.351 (Beta), although the overall impact on vaccine efficacy remains to be determined. Here, we present the initial evaluation in mice of 2 updated mRNA vaccines designed to target SARS-CoV-2 variants: (1) monovalent mRNA-1273.351 encodes for the spike protein found in B.1.351 and (2) mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. Both vaccines were evaluated as a 2-dose primary series in mice; mRNA-1273.351 was also evaluated as a booster dose in animals previously vaccinated with mRNA-1273. The results demonstrated that a primary vaccination series of mRNA-1273.351 was effective at increasing neutralizing antibody titers against B.1.351, while mRNA-1273.211 was effective at providing broad cross-variant neutralization. A third (booster) dose of mRNA-1273.351 significantly increased both wild-type and B.1.351-specific neutralization titers. Both mRNA-1273.351 and mRNA-1273.211 are being evaluated in pre-clinical challenge and clinical studies.

CT-Based Hepatic Residual Volume and Predictors of Outcomes of Patients with Hepatocellular Carcinoma Unsuitable for Surgical Therapy Undergoing Transarterial Chemoembolization.

RATIONALE AND OBJECTIVES: To assess the association between baseline CT-based volumetric parameters and biochemical hepatic evaluations, such as, Child-Pugh, MELD score, and modified MELD-Na score, on the prediction of outcomes of patients with HCC undergoing transarterial chemoembolization (TACE). MATERIALS AND METHODS: A retrospective of a prospectively maintained database, single arm, and single center study was performed including 41 patients with diagnosis of hepatocellular carcinoma treated with TACE. Study endpoints included liver dysfunction (new events of ascites, encephalopathy, and/or death) and overall survival rate. Multi-phase CT-based volumetric analysis was performed to calculate total liver volume and tumor volume using portal and late arterial phases, respectively. Residual volume was calculated subtracting the tumor volume minus the total liver volume. Child-Pugh, MELD score, and MELD-Na score were measured during the baseline evaluation. RESULTS: At a median follow-up time of 8 months (IQR, 5-14), 16 patients (39%) were diagnosed with hepatic dysfunction. In patients with hepatic dysfunction, the median residual hepatic volume was 1002.1 cc (IQR, 633-1077.1 cc) compared to patients with normal liver function post-TACE with a median residual volume of 1233 cc (IQR, 1018.7-1437.6 cc) (p = 0.02). Survival analysis demonstrated an overall survival rate of 95%, 90%, 85% at 30 days, 12 months, and 24 months, respectively. The overall survival rate in patients with Child-Pugh A was 100%, 97%, and 97% at 6, 12, and 24 months, respectively; compared to patients with Child Pugh B with an overall survival of rate of 86%, 78%, and 78% at 6, 12, and 24 months, respectively (p = 0.07). Median baseline MELD-Na score was higher in patients that died during the study period compared to patients that survived (6.7 [IQR, 5-14.2] versus 4.1 [IQR, 2.14-6.85]) (p = 0.09). CONCLUSION: Low baseline CT-based residual volume is associated with the occurrence of hepatic dysfunction at a median time of 8 months. Baseline Child-Pugh A patients were found to have higher survival rate than Child-Pugh B. Interestingly, higher baseline MELD-Na score was associated with mortality.