Structure-Based Optimization of Pyridone α-Ketoamides as Inhibitors of the SARS-CoV-2 Main Protease.

The main protease M is a clinically validated target to treat infections by the coronavirus SARS-CoV-2. Among the first reported M inhibitors was the peptidomimetic α-ketoamide , whose cocrystal structure with M paved the way for multiple lead-finding studies. We established structure-activity relationships for the series by modifying residues at the P1', P3, and P4 sites.

Positive association between chronic hepatitis B virus infection and anemia in pregnancy in Southern China.

This observational investigation aimed to explore potential risk factors for anemia in pregnancy. Firstly, a cross-sectional study was conducted, encompassing a review of clinical data of 43,201 pregnant women admitted to the Hainan Women and Children's Medical Center between January 2017 and December 2020. Comparison between women with and without anemia in pregnancy revealed significant differences between the two groups concerning age, gestational diabetes, hypothyroidism, hyperthyroidism, chronic hepatitis B virus infection, syphilis infection, and human immunodeficiency virus infection.

HSPG-binding peptide Pep19-2.5 is a potent inhibitor of HPV16 infection.

Peptide-based therapeutics are gaining attention for their potential to target various viral and host cell factors. One notable example is Pep19-2.5 (Aspidasept), a synthetic anti-lipopolysaccharide peptide that binds to heparan sulfate proteoglycans (HSPGs) and has demonstrated inhibitory effects against certain bacteria and enveloped viruses.

Dysregulated autoantibodies targeting AGTR1 are associated with the accumulation of COVID-19 symptoms.

Coronavirus disease 2019 (COVID-19) presents a wide spectrum of symptoms, the causes of which remain poorly understood. This study explored the associations between autoantibodies (AABs), particularly those targeting G protein-coupled receptors (GPCRs) and renin‒angiotensin system (RAS) molecules, and the clinical manifestations of COVID-19. Using a cross-sectional analysis of 244 individuals, we applied multivariate analysis of variance, principal component analysis, and multinomial regression to examine the relationships between AAB levels and key symptoms.

Clinical epidemiology, genetic diversity, and drug susceptibility patterns by whole genome sequencing of complex isolates in Gabon from 2012 to 2022.

Objectives: This study aimed to investigate genotypic characteristics and drug resistance profiles of complex (Mtbc) strains isolated from patients with suspected tuberculosis (TB) in Gabon.

Methods: We performed whole genome sequencing of 430 Mtbc strains cultured between 2012 and 2022. Phylogenetic strain classification, genomic resistance prediction, and cluster analysis were also performed.

Optimizing vaccine uptake in sub-Saharan Africa: a collaborative COVID-19 vaccination campaign in Madagascar using an adaptive approach.

Background: The COVID-19 pandemic has highlighted the need for more effective immunization programs, including in limited resource settings. This paper presents outcomes and lessons learnt from a COVID-19 vaccination campaign (VC), which used a tailored adaptive strategy to optimise vaccine uptake in the Boeny region of Madagascar.

Methods: Guided by the Dynamic Sustainability Framework (DSF), the VC implementation was regularly reviewed through multi-sectoral stakeholder feedback, key informant interviews, problem-solving meetings, and weekly monitoring of outcome indicators to identify and apply key adaptations.

Prediction of cccDNA dynamics in hepatitis B patients by a combination of serum surrogate markers.

Quantification of intrahepatic covalently closed circular DNA (cccDNA) is a key for evaluating an elimination of hepatitis B virus (HBV) in infected patients. However, quantifying cccDNA requires invasive methods such as a liver biopsy, which makes it impractical to access the dynamics of cccDNA in patients. Although HBV RNA and HBV core-related antigens (HBcrAg) have been proposed as surrogate markers for evaluating cccDNA activity, they do not necessarily estimate the amount of cccDNA.

Awareness and knowledge regarding female genital schistosomiasis among European healthcare workers: a cross-sectional online survey.

Background: Adequate knowledge and awareness regarding diseases are essential for appropriate, high-quality healthcare. Female Genital Schistosomiasis (FGS) is a non-sexually transmitted gynaecological disease that is caused by the presence of Schistosoma haematobium eggs in the female genital tract and the resulting immune response that causes tissue damage. It is estimated to affect 56 million women, mostly in sub-Saharan Africa (SSA), where healthcare workers (HCWs) have limited awareness and knowledge of FGS.

Immune Response to SARS-CoV-2 XBB.1.5 and JN.1 Variants Following XBB.1.5 Booster Vaccination in Liver Transplant Recipients.

Background/objectives: The efficacy of monovalent BNT162b2 Omicron XBB.1.5 booster vaccination in liver transplant recipients (LTRs) has yet to be described, particularly regarding the immune response to emerging variants like JN.

Strategies to Enhance Diagnostic Capabilities for the New Drug-Resistant Tuberculosis (DR-TB) Drugs.

The global burden of drug-resistant tuberculosis (DR-TB) continues to challenge healthcare systems worldwide. There is a critical need to tackle DR-TB by enhancing diagnostics and drug susceptibility testing (DST) capabilities, particularly for emerging DR-TB drugs. This endeavor is crucial to optimize the efficacy of new therapeutic regimens and prevent the resistance and overuse of these invaluable weapons.

House Mice in the Atlantic Region: Genetic Signals of Their Human Transport.

Background/objectives: The colonization history of house mice reflects the maritime history of humans that passively transported them worldwide. We investigated western house mouse colonization in the Atlantic region through studies of mitochondrial D-loop DNA sequences from modern specimens.

Methods: We assembled a dataset of 758 haplotypes derived from 2765 mice from 47 countries/oceanic archipelagos (a combination of new and published data).

Phylodynamic analysis reveals disparate transmission dynamics of -complex lineages in Botswana.

Tuberculosis epidemics have traditionally been conceptualized as arising from a single uniform pathogen. However, -complex (Mtbc), the pathogen causing tuberculosis in humans, encompasses multiple lineages exhibiting genetic and phenotypic diversity that may be responsible for heterogeneity in TB transmission. We analysed a population-based dataset of 1,354 Mtbc whole-genome sequences collected over four years in Botswana, a country with high HIV and tuberculosis burden.

MVA-based SARS-CoV-2 vaccine candidates encoding different spike protein conformations induce distinct early transcriptional responses which may impact subsequent adaptive immunity.

Introduction: Vaccine platforms such as viral vectors and mRNA can accelerate vaccine development in response to newly emerging pathogens, as demonstrated during the COVID-19 pandemic. However, the differential effects of platform and antigen insert on vaccine immunogenicity remain incompletely understood. Innate immune responses induced by viral vector vaccines are suggested to have an adjuvant effect for subsequent adaptive immunity.

Blood levels of Mycobacterium tuberculosis (Mtb)antigen-triggered immune markers in people exposed to tuberculosis with regard to Mtb infection status and receipt of tuberculosis preventive therapy.

Background: Interferon-γ release assays (IGRAs) for tuberculosis infection (TBI) cannot distinguish different stages of the TBI spectrum (including spontaneously cleared infection). We investigated patterns of Mtb-specific blood mediators in people with and without TBI during tuberculosis preventive therapy (TPT).

Methods: Individuals with likelihood of recent Mtb exposure, aged 15-25 years, with valid IGRA results, in whom tuberculosis (TB) had been excluded, were included.

C3 deficiency promotes pulmonary inflammation in AT1R-induced mouse model for systemic sclerosis.

Introduction: Autoantibody-mediated complement activation plays an essential role in a variety of autoimmune disorders. However, the role of complement in systemic sclerosis (SSc) remains largely unknown. In this study, we aimed to determine the role of complement C3 in the development of a recently described SSc mouse model based on autoimmunity to angiotensin II receptor type 1 (AT1R).

The molecular bacterial load assay predicts treatment responses in patients with pre-XDR/XDR-tuberculosis more accurately than GeneXpert Ultra MTB/Rif.

Objectives: Early detection of treatment failure is essential to improve the management of drug-resistant tuberculosis (DR-TB). We evaluated the molecular bacterial load assay (MBLA) in comparison to standard diagnostic tests for monitoring therapy of patients affected by drug-resistant TB.

Methods: The performance of MBLA in tracking treatment response in a prospective cohort of patients with pulmonary MDR/RR- and pre-XDR/XDR-TB was compared with mycobacterial culture, mycobacterial DNA detection using GeneXpert (Xpert) and microscopy detection of sputum acid-fast-bacilli.

Long-Term Self-Administered Outpatient Parenteral Antimicrobial Therapy in the Treatment of Tuberculosis.

Objectives: To investigate the safety profiles and clinical outcomes in a continuous cohort of tuberculosis (TB) patients from a clinical referral centre in Germany receiving self-administered outpatient parenteral antimicrobial therapy (sOPAT).

Methods: We conducted a retrospective observational cohort study of patients receiving sOPAT after discharge from the Research Center Borstel in Germany between January 2015 and December 2020. Data were extracted from medical records.

Impact of drug-resistant tuberculosis on socio-economic status, quality of life and psychological well-being of patients in Bucharest, Romania: a prospective cohort study.

Background: Tuberculosis (TB) remains a global health challenge, with 1.3 million deaths in 2022. Ten countries in the European Union (EU) and European Economic Area (EEA) accounted for 88.

Effectiveness of the primary Bacillus Calmette-Guérin vaccine against the risk of Mycobacterium tuberculosis infection and tuberculosis disease: a meta-analysis of individual participant data.

Background: Tuberculosis vaccine trials using disease as the primary endpoint are large, time consuming, and expensive. An earlier immunological measure of the protection against disease would accelerate tuberculosis vaccine development. We aimed to assess whether the effectiveness of the Bacillus Calmette-Guérin (BCG) vaccine for prevention of Mycobacterium tuberculosis infection was consistent with that for prevention of tuberculosis disease.

A Comparative Pharmacokinetics Study of Orally and Intranasally Administered 8-Nitro-1,3-benzothiazin-4-one (BTZ043) Amorphous Drug Nanoparticles.

BTZ043 is an 8-nitro-1,3-benzothiazin-4-one with potency against multidrug-resistant . Low solubility and hepatic metabolism are linked to poor oral bioavailability. Amorphous drug nanoparticles (ADN) were formulated to improve the bioavailability.

The mediating role of behavioural and socio-structural factors on the association between household wealth and childhood malaria in Ghana.

Background: Children under five continue to bear a disproportionate burden of malaria morbidity and mortality in endemic countries. While the link between socioeconomic position (SEP) and malaria is well established, the causal pathways remain poorly understood, hindering the design and implementation of more targeted structural interventions. This study examines the association between SEP and malaria among children in Ghana and explores the potential mediating role of behavioural and socio-structural factors.