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The DArk Matter In CCDs at Modane (DAMIC-M) experiment is designed to search for light dark matter (m\\(_\\)<10\\,GeV/c\\(^2\\)) at the Laboratoire Souterrain de Modane (LSM) in France. DAMIC-M will use skipper charge-coupled devices (CCDs) as a kg-scale active detector target. Its single-electron resolution will enable eV-scale energy thresholds and thus world-leading sensitivity to a range of hidden sector dark matter candidates. A DAMIC-M prototype, the Low Background Chamber (LBC), has been taking data at LSM since 2022. The LBC provides a low-background environment, which has been used to characterize skipper CCDs, study dark current, and measure radiopurity of materials planned for DAMIC-M. It also allows testing of various subsystems like readout electronics, data acquisition software, and slow control. This paper describes the technical design and performance of the LBC.

The DAMIC-M experiment will search for sub-GeV dark matter particles with a large array of silicon skipper charge-coupled devices (CCDs) at the Modane Underground Laboratory (LSM) in France. After five years of development, we recently completed the production of 28 CCD modules at the University of Washington, each consisting of four 9-megapixel skipper CCDs. Material screening and background controls were implemented to meet stringent radio-purity targets, while extensive testing was employed to select science-grade CCDs for the modules and confirm their excellent performance after fabrication. Further testing at LSM will select 26 of these modules (\\({\\sim}\\)350 g active mass) to be installed and operated in the DAMIC-M detector in early 2026.

The DAMIC-M (DArk Matter In CCDs at Modane) experiment employs thick, fully depleted silicon charged-coupled devices (CCDs) to search for dark matter particles with a target exposure of 1 kg-year. A novel skipper readout implemented in the CCDs provides single electron resolution through multiple non-destructive measurements of the individual pixel charge, pushing the detection threshold to the eV-scale. DAMIC-M will advance by several orders of magnitude the exploration of the dark matter particle hypothesis, in particular of candidates pertaining to the so-called \"hidden sector.\" A prototype, the Low Background Chamber (LBC), with 20g of low background Skipper CCDs, has been recently installed at Laboratoire Souterrain de Modane and is currently taking data. We will report the status of the DAMIC-M experiment and first results obtained with LBC commissioning data.

• Chitosan is a partially deacetylated linear polysaccharide composed of β-1,4-linked units of D-glucosamine and N-acetyl glucosamine. As well as a structural component of fungal cell walls, chitosan is a potent antifungal agent. However, the mode of action of chitosan is poorly understood. • Here, we report that chitosan is effective for control of rice blast disease. Chitosan application impairs growth of the blast fungus Magnaporthe oryzae and has a pronounced effect on appressorium-mediated plant infection. Chitosan inhibits septin-mediated F-actin remodelling at the appressorium pore, thereby preventing repolarization of the infection cell. • Chitosan causes plasma membrane permeabilization of M. oryzae and affects NADPH oxidase-dependent synthesis of reactive oxygen species, essential for septin ring formation and fungal pathogenicity. We further show that toxicity of chitosan to M. oryzae requires the protein kinase C-dependent cell wall integrity pathway, the Mps1 mitogen-activated protein kinase and the Nox1 NADPH oxidase. A conditionally lethal, analogue (PP1)-sensitive mutant of Pkc1 is partially remediated for growth in the presence of chitosan, while Δnox1 mutants increase their glucan : chitin cell wall ratio, rendering them resistant to chitosan. • Taken together, our data show that chitosan is a potent fungicide which requires the cell integrity pathway, disrupts plasma membrane function and inhibits septin-mediated plant infection.

The vaginal microbiota plays a critical role in maintaining reproductive health. Although Lactobacillus species often dominate the vaginal environment in healthy individuals, recent studies have shown that healthy microbiota compositions can also include Lactobacillus -depleted states, as described by the Community State Types (CSTs) framework. However, disruptions in the microbiota composition, such as those caused by sexually transmitted infections (STIs), can lead to increased diversity and instability, compromising host protection. This study investigates the association between vaginal microbiota composition and the prevalence of STIs in a cohort of incarcerated women in Chile. Using metataxonomic approaches targeting 16S and 18S rRNA genes, we characterized prokaryotic and eukaryotic components of the vaginal microbiota across healthy, dysbiotic, and pathogen-dominated subjects. Alpha diversity analysis using the Shannon index indicated that Lactobacillus -dominant communities were associated with lower microbial diversity correlates with reduced variability. Whereas communities dominated by pathogens including Trichomonas vaginalis , Gardnerella vaginalis , Treponema pallidum , and HIV, tended to exhibit higher diversity. The pathogen-dominated group displayed an increased prevalence of opportunistic microorganisms and reduced Lactobacillus abundance, which may reflect an imbalance in the microbial ecosystem, often interpreted as reduced stability. This study provides novel insights into the intricate dynamics between normal and altered vaginal microbiomes and their association with STIs. Understanding these community-level patterns and associations is crucial for designing targeted interventions aimed at restoring microbial balance and preventing infections.

The recent revision of the Acidithiobacillia class using genomic taxonomy methods has shown that, in addition to the existence of previously unrecognized genera and species, some species of the class harbor levels of divergence that are congruent with ongoing differentiation processes. In this study, we have performed a subspecies-level analysis of sequenced strains of Acidithiobacillus ferrooxidans to prove the existence of distinct sublineages and identify the discriminant genomic/genetic characteristics linked to these sublineages, and to shed light on the processes driving such differentiation. Differences in the genomic relatedness metrics, levels of synteny, gene content, and both integrated and episomal mobile genetic elements (MGE) repertoires support the existence of two subspecies-level taxa within A. ferrooxidans . While sublineage 2A harbors a small plasmid related to pTF5, this episomal MGE is absent in sublineage 2B strains. Likewise, clear differences in the occurrence, coverage and conservation of integrated MGEs are apparent between sublineages. Differential MGE-associated gene cargo pertained to the functional categories of energy metabolism, ion transport, cell surface modification, and defense mechanisms. Inferred functional differences have the potential to impact long-term adaptive processes and may underpin the basis of the subspecies-level differentiation uncovered within A. ferrooxidans . Genome resequencing of iron- and sulfur-adapted cultures of a selected 2A sublineage strain (CCM 4253) showed that both episomal and large integrated MGEs are conserved over twenty generations in either growth condition. In turn, active insertion sequences profoundly impact short-term adaptive processes. The ISAfe1 element was found to be highly active in sublineage 2A strain CCM 4253. Phenotypic mutations caused by the transposition of ISAfe1 into the pstC2 encoding phosphate-transport system permease protein were detected in sulfur-adapted cultures and shown to impair growth on ferrous iron upon the switch of electron donor. The phenotypic manifestation of the △ pstC2 mutation, such as a loss of the ability to oxidize ferrous iron, is likely related to the inability of the mutant to secure the phosphorous availability for electron transport-linked phosphorylation coupled to iron oxidation. Depletion of the transpositional △ pstC2 mutation occurred concomitantly with a shortening of the iron-oxidation lag phase at later transfers on a ferrous iron-containing medium. Therefore, the pstII operon appears to play an essential role in A. ferrooxidans when cells oxidize ferrous iron. Results highlight the influence of insertion sequences and both integrated and episomal mobile genetic elements in the short- and long-term adaptive processes of A. ferrooxidans strains under changing growth conditions.

The emergence of large-scale cooperation during the Holocene remains a central problem in the evolutionary literature. One hypothesis points to culturally evolved beliefs in punishing, interventionist gods that facilitate the extension of cooperative behaviour toward geographically distant co-religionists. Furthermore, another hypothesis points to such mechanisms being constrained to the religious ingroup, possibly at the expense of religious outgroups. To test these hypotheses, we administered two behavioural experiments and a set of interviews to a sample of 2228 participants from 15 diverse populations. These populations included foragers, pastoralists, horticulturalists, and wage labourers, practicing Buddhism, Christianity, and Hinduism, but also forms of animism and ancestor worship. Using the Random Allocation Game (RAG) and the Dictator Game (DG) in which individuals allocated money between themselves, local and geographically distant co-religionists, and religious outgroups, we found that higher ratings of gods as monitoring and punishing predicted decreased local favouritism (RAGs) and increased resource-sharing with distant co-religionists (DGs). The effects of punishing and monitoring gods on outgroup allocations revealed between-site variability, suggesting that in the absence of intergroup hostility, moralizing gods may be implicated in cooperative behaviour toward outgroups. These results provide support for the hypothesis that beliefs in monitoring and punitive gods help expand the circle of sustainable social interaction, and open questions about the treatment of religious outgroups.

Total knee arthroplasty is a consistently successful, cost-efficient, and highly effective surgical procedure for treating severe knee osteoarthritis. The success and longevity of total knee arthroplasty depend significantly on the fixation method used to secure the prosthetic components. This comprehensive review examines the primary fixation methods (cemented, cementless, and hybrid fixation), analysing their biomechanics, clinical outcomes, advantages, and disadvantages, focusing on recent advances and trends in total knee arthroplasty fixation.

Anaemia affects 46% of pregnancies in Africa; oral iron is recommended by WHO but uptake and adherence are suboptimal. We tested a single dose of a modern intravenous iron formulation, ferric carboxymaltose, for anaemia treatment in Malawian pregnant women. In this open-label, individually randomised controlled trial, we enrolled women with a singleton pregnancy of 13–26 weeks' gestation in primary care and outpatient settings across two regions in southern Malawi. Women were eligible if they had capillary haemoglobin of less than 10·0 g/dL and negative malaria rapid diagnostic test. Participants were randomised by sealed envelope 1:1. Assessors for efficacy outcomes (laboratory parameters and birthweight) were masked to intervention; participants and study nurses were not masked. Participants were given ferric carboxymaltose up to 1000 mg (given once at enrolment in an outpatient primary care setting), or standard of care (60 mg elemental iron twice daily for 90 days), along with intermittent preventive malaria treatment. The primary maternal outcome was anaemia at 36 weeks' gestation. The primary neonatal outcome was birthweight. Analyses were performed in the intention-to-treat population for mothers and liveborn neonates, according to their randomisation group. Safety outcomes included incidence of adverse events during infusion and all adverse events from randomisation to 4 weeks' post partum. The trial is registered with ANZCTR, ACTRN12618001268235. The trial has completed follow-up. Between Nov 12, 2018, and March 2, 2021, 21 258 women were screened, and 862 randomly assigned to ferric carboxymaltose (n=430) or standard of care (n=432). Ferric carboxymaltose did not reduce anaemia prevalence at 36 weeks' gestation compared with standard of care (179 [52%] of 341 in the ferric carboxymaltose group vs 189 [57%] of 333 in the standard of care group; prevalence ratio [PR] 0·92, 95% CI 0·81 to 1·06; p=0·27). Anaemia prevalence was numerically lower in mothers randomly assigned to ferric carboxymaltose compared with standard of care at all timepoints, although significance was only observed at 4 weeks' post-treatment (PR 0·91 [0·85 to 0·97]). Birthweight did not differ between groups (mean difference –3·1 g [–75·0 to 68·9, p=0·93). There were no infusion-related serious adverse events or differences in adverse events by any organ class (including malaria; ≥1 adverse event: ferric carboxymaltose 183 [43%] of 430 vs standard of care 170 [39%] of 432; risk ratio 1·08 [0·92 to 1·27]; p=0·34). In this malaria-endemic sub-Saharan African setting, treatment of anaemic pregnant women with ferric carboxymaltose was safe but did not reduce anaemia prevalence at 36 weeks' gestation or increase birthweight. Bill & Melinda Gates Foundation (INV-010612).

Background: An inadequate response to initial empirical treatment of community acquired pneumonia (CAP) represents a challenge for clinicians and requires early identification and intervention. A study was undertaken to quantify the incidence of failure of empirical treatment in CAP, to identify risk factors for treatment failure, and to determine the implications of treatment failure on the outcome. Methods: A prospective multicentre cohort study was performed in 1424 hospitalised patients from 15 hospitals. Early treatment failure (<72 hours), late treatment failure, and in-hospital mortality were recorded. Results: Treatment failure occurred in 215 patients (15.1%): 134 early failure (62.3%) and 81 late failure (37.7%). The causes were infectious in 86 patients (40%), non-infectious in 34 (15.8%), and undetermined in 95. The independent risk factors associated with treatment failure in a stepwise logistic regression analysis were liver disease, pneumonia risk class, leucopenia, multilobar CAP, pleural effusion, and radiological signs of cavitation. Independent factors associated with a lower risk of treatment failure were influenza vaccination, initial treatment with fluoroquinolones, and chronic obstructive pulmonary disease (COPD). Mortality was significantly higher in patients with treatment failure (25% v 2%). Failure of empirical treatment increased the mortality of CAP 11-fold after adjustment for risk class. Conclusions: Although these findings need to be confirmed by randomised studies, they suggest possible interventions to decrease mortality due to CAP.