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Background and Objectives: Data on HIV drug resistance in Madagascar are rare and outdated. In this study, we assessed the prevalence of HIV drug resistance mutations to antiretrovirals (ARVs) and genetic diversity of circulating strains in treatment-naive people living with HIV (PLHIV) in Madagascar., Materials and Methods: We amplified the protease (PR), fragments of the Reverse Transcriptase (RT) and Integrase (IN) genes according to the French ANRS protocol. The amplicons were sequenced using next-generation sequencing technology on an Illumina platform (MiSeq). We determined HIV-1 subtypes through phylogenetic analysis using maximum likelihood in PhyML. Resistance interpretation was performed using the Stanford algorithm (version 9.5.1)., Results: We included 239 HIV-infected adults and children, sampled between January 2019 and November 2023, with a median age of 30 years and a mean plasma HIV viral load of 6.3 Log copies/mL. We sequenced at least one genomic fragment (PR or RT or IN) of the 239 samples, but 9 were excluded from analysis (mean depth < 10,000×). Phylogenetic analysis of 230 sequences revealed the presence of subtype C (33.91 %), A1 (11.30 %), B (11.30 %), CRF02&#95;AG (9.56 %), subtype G (3.04 %), subtype D (0.43 %), CRF01&#95;AE (0.43 %), and a significant proportion of unique recombinant forms (URFs) (30.30 %). The prevalence of transmitted drug resistance (TDR) was 4.95 % (10/202) among patients aged 15 years and older. When stratified by ARV class, this prevalence was 4.79 % for non-nucleoside reverse transcriptase inhibitors (NNRTIs), 0.59 % for Nucleoside Reverse Transcriptase inhibitors (NRTIs), and 0.50 % for integrase strand transfer inhibitors (INSTIs). Among children under 15 years old (n = 28), the prevalence of TDR was 14.28 % (4/28), with all mutations conferring resistance to NNRTIs. No mutation conferring resistance to protease inhibitors was found, neither in children nor in adults., Conclusion: Our results show a low prevalence of ARV resistance mutations among adult treatment-naive PLHIV in Madagascar. In children under 15 years old, 92 % were infants under two years old, the high resistance rate is likely related to mother-to-child transmission. No resistance mutation to dolutegravir was detected. We also observed high frequencies of subtypes C, B, A1 and a high proportion of URFs, highlighting an ongoing dynamic epidemic., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Recent reports raise concerns on the changing epidemiology of mpox in the Democratic Republic of the Congo (DRC). High-quality genomes were generated for 337 patients from 14/26 provinces to document whether the increase in number of cases is due to zoonotic spillover events or viral evolution, with enrichment of APOBEC3 mutations linked to human adaptation. Our study highlights two patterns of transmission contributing to the source of human cases. All new sequences from the eastern South Kivu province (n = 17; 4.8%) corresponded to the recently described clade Ib, associated with sexual contact and sustained human-to-human transmission. By contrast, all other genomes are clade Ia, which exhibits high genetic diversity with low numbers of APOBEC3 mutations compared with clade Ib, suggesting multiple zoonotic introductions. The presence of multiple clade I variants in urban areas highlights the need for coordinated international response efforts and more studies on the transmission and the reservoir of mpox., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Rationale: Immune checkpoint inhibitor (ICI)-related pneumonitis is a serious autoimmune event affecting as many as 20% of patients with non-small-cell lung cancer (NSCLC), yet the factors underpinning its development in some patients and not others are poorly understood. Objectives: To investigate the role of autoantibodies and autoreactive T cells against surfactant-related proteins in the development of pneumonitis. Methods: The study cohort consisted of patients with NSCLC who provided blood samples before and during ICI treatment. Serum was used for proteomics analyses and to detect autoantibodies present during pneumonitis. T-cell stimulation assays and single-cell RNA sequencing were performed to investigate the specificity and functionality of peripheral autoreactive T cells. The findings were confirmed in a validation cohort comprising patients with NSCLC and patients with melanoma. Measurements and Main Results: Across both cohorts, patients in whom pneumonitis developed had higher pretreatment levels of immunoglobulin G autoantibodies targeting surfactant protein (SP)-B. At the onset of pneumonitis, these patients also exhibited higher frequencies of CD4 + IFN-γ-positive SP-B-specific T cells and expanding T-cell clonotypes recognizing this protein, accompanied by a proinflammatory serum proteomic profile. Conclusions: Our data suggest that the cooccurrence of SP-B-specific immunoglobulin G autoantibodies and CD4 + T cells is associated with the development of pneumonitis during ICI therapy. Pretreatment levels of these antibodies may represent a potential biomarker for an increased risk of developing pneumonitis, and on-treatment levels may provide a diagnostic aid.

The abundance of potentially habitable hypersaline environments in our solar system compels us to understand the impacts of high-salt matrices and brine dynamics on biosignature detection efforts. We identified and quantified organic compounds in brines from South Bay Salt Works (SBSW), where evapoconcentration of ocean water enables exploration of the impact of NaCl- and MgCl 2 -dominated brines on the detection of potential biosignature molecules. In SBSW, organic biosignature abundance and distribution are likely influenced by evapoconcentration, osmolyte accumulation, and preservation effects. Bioluminescence assays show that adenosine triphosphate (ATP) concentrations are higher in NaCl-rich, low water activity ( a w ) samples (<0.85) from SBSW. This is consistent with the accumulation and preservation of ATP at low a w as described in past laboratory studies. The water-soluble small organic molecule inventory was determined by using microchip capillary electrophoresis paired with high-resolution mass spectrometry (µCE-HRMS). We analyzed the relative distribution of proteinogenic amino acids with a recently developed quantitative method using CE-separation and laser-induced fluorescence (LIF) detection of amino acids in hypersaline brines. Salinity trends for dissolved free amino acids were consistent with amino acid residue abundance determined from the proteome of the microbial community predicted from metagenomic data. This highlights a tangible connection up and down the "-omics" ladder across changing geochemical conditions. The detection of water-soluble organic compounds, specifically proteinogenic amino acids at high abundance (>7 mM) in concentrated brines, demonstrates that potential organic biomarkers accumulate at hypersaline sites and suggests the possibility of long-term preservation. The detection of such molecules in high abundance when using diverse analytical tools appropriate for spacecraft suggests that life detection within hypersaline environments, such as evaporates on Mars and the surface or subsurface brines of ocean world Europa, is plausible and argues such environments should be a high priority for future exploration. Key Words: Salts-Analytical chemistry-Amino acids-Biosignatures-Capillary electrophoresis-Preservation. Astrobiology 24, 795-812.

Bluetooth Low Energy (BLE) is a prominent short-range wireless communication protocol widely extended for communications and sensor systems in consumer electronics and industrial applications, ranging from manufacturing to retail and healthcare. The BLE protocol provides four generic access profile (GAP) roles when it is used in its low-energy version, i.e., ver. 4 and beyond. GAP roles control connections and allow BLE devices to interoperate each other. They are defined by the Bluetooth special interest group (SIG) and are primarily oriented to connect peripherals wirelessly to smartphones, laptops, and desktops. Consequently, the existing GAP roles have characteristics that do not fit well with vehicular communications in cooperative intelligent transport systems (C-ITS), where low-latency communications in high-density environments with stringent security demands are required. This work addresses this gap by developing two new GAP roles, defined at the application layer to meet the specific requirements of vehicular communications, and by providing a service application programming interface (API) for developers of vehicle-to-everything (V2X) applications. We have named this new approach ITS-BLE. These GAP roles are intended to facilitate BLE-based solutions for real-world scenarios on roads, such as detecting road traffic signs or exchanging information at toll booths. We have developed a prototype able to work indistinctly as a unidirectional or bidirectional communication device, depending on the use case. To solve security risks in the exchange of personal data, BLE data packets, here called packet data units (PDU), are encrypted or signed to guarantee either privacy when sharing sensitive data or authenticity when avoiding spoofing, respectively. Measurements taken and their later evaluation demonstrated the feasibility of a V2X BLE network consisting of picocells with a radius of about 200 m.

Introduction: Radium-223 dichloride (Ra-223) is recommended as a treatment option for metastatic castration-resistant prostate cancer (mCRPC) patients with symptomatic bone metastases and no visceral disease, after docetaxel failure, or in patients who are not candidates to receive it. In this study, we aimed to ambispectively analyze overall survival (OS) and prognostic features in mCRPC in patients receiving Ra-223 as per clinical routine practice and identify the most suitable treatment sequence., Patients and Methods: This study is observational, multicentric, and ambispective. Eligibility criteria included mCRPC patients treated with Ra-223, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, without visceral metastases, and no more than three cm involved lymph nodes., Results: A total of 145 patients were included; the median age was 73.97 years, and a Gleason score of more than or equal to 7 in 61 (48%) patients; 73 (81%) had previously received docetaxel. The most important benefit was reached by those patients who received Ra-223 in the second-line setting, with a median OS of 17 months (95% CI, 12-21), and by patients who received six cycles of treatment, with a median OS of 19 months (95% CI, 14-21). An alkaline phosphatase (ALP) decrease was also identified as a prognosis marker. When performing the multivariate analysis, the time to develop castration-resistant disease longer than 24 months was the most important prognostic factor to predict the evolution of the patients receiving Ra-223. Ra-223 was well tolerated, with thrombocytopenia, anemia, and diarrhea being the main adverse events., Conclusion: There is a benefit for those patients who received Ra-223 in the second-line setting, regardless of prior use of docetaxel. In addition, a survival benefit for patients presenting with a decline in ALP was observed., Competing Interests: UA-H — Consultant or advisory board: Advanced Accelerator Applications, Ipsen, Astra Zeneca, Merck, Pfizer, Astellas, Bayer, MSD, BMS; travel support: Ipsen, Bayer, Merck, Pfizer, GSK, Roche, Sanofi, Advanced Accelerator Applications; honoraria: Advanced Accelerator Applications, Ipsen, Astra Zeneca, Merck, Eisai, BMS, Rovi, Grünenthal Pharma, Leo Pharma an inmediate family member. JC-N — Consultant: Janssen, BMS; honoraria as speaker: Astellas, Bayer, Janssen. OF-C — Consultant or Advisory role: Astellas, BMS, Ipsen, Merck, Eisai; Honoraria as speaker: Novartis, BMS, Ipsen, Roche, Astellas, Bayer. NF-N — Advisory board: Pfizer; speaking honoraria: Ipsen, Roche, Bayer. AG-C — Scientific advice to Astellas, AstraZeneca, Bayer, Ipsen, Janssen; honoraria and consulting from Astellas, AstraZeneca, Bayer, Ipsen, Janssen; travel and lodging support from Astellas, AstraZeneca, Bayer, Ipsen, Janssen. ML — Consultant or AdvisoryRole: BMS, MSD, Takeda, Pfizer, Roche, Ipsen, Astra–Zéneca, Merck, Boehringer, Bayer, Novartis, AAA; speaking: Roche, Ipsen, MSD, Lilly, Astellas, Janssen, Novartis, Boehringer; grant or travel support: MSD, Ipsen, Roche, Janssen, Pfizer, Astellas, Pierre–Fabré; participation in clinical trials: Merck, Astellas, Pfizer, Ipsen, Roche, AstraZeneca, Mirati, PharmaMar. SM-B — Advisory role: Bayer, AstraZeneca, Astellas; Honoraria as speaker: Bayer, AstraZeneca, Novartis, Astellas, Janssen, Amgen. AM-D — Honoraria: Eisai, Grünenthal Pharma, Kyowa Kirin, Pharmamar, Merck, BMS, Roche, Ipsen; travel, accommodation, and congress: Pfizer, BMS, MSD, Eisai, Kyowa Kirin, Merck, Pharmamar, AstraZeneca, Lilly, Sanofi, Takeda, Astellas, Roche, Pierre Fabre; advisory board: Bayer, Eisai, Pierre Fabre, Pharmamar, Pfizer, Merck, Astellas, BMS. DP-F — Honoraria as consultant: Astellas, Bayer, Janssen; honoraria as speaker: Astellas, Bayer, Janssen, Ipsen; travel, accomodations and expenses: Astellas, Bayer, Janssen, Ipsen. JR-B — Travel, accommodations, and expenses: Merck, Pierre–Fabre, Sanofi, and Seagen; honoraria for educational activities: Ipsen; institutional research funding: Nouscom, Pfizer, and Roche. SV-E — Honoraria as consultant and advisory boards: Pfizer, Astellas, Janssen, MSD, Bayer, Roche, BMS, AztraZeneca, Ipsen, Organon and Merck; honoraria as speaker: Lilly, Astellas, Bayer, Roche, Ipsen, Janssen, Takeda, Merck, Organon and AstraZeneca; Travel grants: Pfizer, Roche, Ipsen and AstraZeneca. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Anido-Herranz, Fernandez-Calvo, Ruiz-Bañobre, Martinez-Breijo, Fernandez-Nuñez, Nogareda-Seoane, Garrido-Pumar, Casas-Nebra, Muñiz-Garcia, Portela-Pereira, Gomez-Caamaño, Perez-Fentes, Santome-Couto, Lázaro, Molina-Diaz, Medina-Colmenero and Vazquez-Estevez.)

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

In September 2022, deaths of pigs manifesting pox-like lesions caused by swinepox virus were reported in Tshuapa Province, Democratic Republic of the Congo. Two human mpox cases were found concurrently in the surrounding community. Specific diagnostics and robust sequencing are needed to characterize multiple poxviruses and prevent potential poxvirus transmission.