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BACKGROUND: For decades, poor treatment options and low-quality evidence plagued care for patients with rifampin-resistant tuberculosis. The advent of new drugs to treat tuberculosis and enhanced funding now permit randomized, controlled trials of shortened-duration, all-oral treatments for rifampin-resistant tuberculosis. METHODS: We conducted a phase 3, multinational, open-label, randomized, controlled noninferiority trial to compare standard therapy for treatment of fluoroquinolone-susceptible, rifampin-resistant tuberculosis with five 9-month oral regimens that included various combinations of bedaquiline (B), delamanid (D), linezolid (L), levofloxacin (Lfx) or moxifloxacin (M), clofazimine (C), and pyrazinamide (Z). Participants were randomly assigned (with the use of Bayesian response-adaptive randomization) to receive one of five combinations or standard therapy. The primary end point was a favorable outcome at week 73, defined by two negative sputum culture results or favorable bacteriologic, clinical, and radiologic evolution. The noninferiority margin was -12 percentage points. RESULTS: Among the 754 participants who underwent randomization, 699 were included in the modified intention-to-treat analysis, and 562 in the per-protocol analysis. In the modified intention-to-treat analysis, 80.7% of the patients in the standard-therapy group had favorable outcomes. The risk difference between standard therapy and each of the four new regimens that were found to be noninferior in the modified intention-to-treat population was as follows: BCLLfxZ, 9.8 percentage points (95% confidence interval [CI], 0.9 to 18.7); BLMZ, 8.3 percentage points (95% CI, -0.8 to 17.4); BDLLfxZ, 4.6 percentage points (95% CI, -4.9 to 14.1); and DCMZ, 2.5 percentage points (95% CI, -7.5 to 12.5). Differences were similar in the per-protocol population, with the exception of DCMZ, which was not noninferior in that population. The proportion of participants with grade 3 or higher adverse events was similar across the regimens. Grade 3 or higher hepatotoxic events occurred in 11.7% of participants overall and in 7.1% of those receiving standard therapy. CONCLUSIONS: Consistent results across all the analyses support the noninferior efficacy of three all-oral shortened regimens for the treatment of rifampin-resistant tuberculosis. (Funded by Unitaid and others; endTB ClinicalTrials.gov number, NCT02754765.).

Rationale: C-reactive protein (CRP)-based tuberculosis (TB) screening is recommended for people with HIV. However, its performance among people without HIV and in diverse settings is unknown. Objectives: In a multicountry study, we aimed to determine whether CRP meets the minimum accuracy targets (sensitivity ⩾ 90%, specificity ⩾ 70%) for an effective TB screening test. Methods: Consecutive outpatient adults with cough ⩾2 weeks from five TB endemic countries in Africa and Asia had baseline blood collected for point-of-care CRP testing and HIV and diabetes screening. Sputum samples were collected for Xpert MTB/RIF Ultra (Xpert) testing and culture. CRP sensitivity and specificity (5 mg/L cut-point) was determined in reference to sputum test results and compared by country, sex, and HIV and diabetes status. Variables affecting CRP performance were identified using a multivariate receiver operating curve regression model. Measurements and Main Results: Among 2,904 participants, of whom 613 (21%) had microbiologically confirmed TB, CRP sensitivity was 84% (95% confidence interval [CI], 81–87%) and specificity was 61% (95% CI, 59–63%). CRP accuracy varied geographically, with higher sensitivity in African countries (⩾91%) than Asian countries (64–82%). Sensitivity was higher among men than women (86% vs. 78%; difference, +8%; 95% CI, 1–15%) and specificity was lower among people with HIV than people without HIV (64% vs. 45%; difference, +19%; 95% CI, 13–25%). Receiver operating curve regression identified country and measures of TB disease severity as predictors of CRP performance. Conclusions: Overall, CRP did not achieve the minimum accuracy targets, and its performance varied by setting and in some subgroups, likely reflecting population differences in mycobacterial load. [ABSTRACT FROM AUTHOR]

With within-species genetic diversity estimates that span the gamut of that seen across the entirety of animals, the Caenorhabditis genus of nematodes holds unique potential to provide insights into how population size and reproductive strategies influence gene and genome organization and evolution. Our study focuses on Caenorhabditis brenneri, currently known as one of the most genetically diverse nematodes within its genus and, notably, across Metazoa. Here, we present a high-quality, gapless genome assembly and annotation for C. brenneri, revealing a common nematode chromosome arrangement characterized by gene-dense central regions and repeat-rich arms. Comparison of C. brenneri with other nematodes from the 'Elegans' group revealed conserved macrosynteny but a lack of microsynteny, characterized by frequent rearrangements and low correlation of orthogroup size, indicative of high rates of gene turnover, consistent with previous studies. We also assessed genome organization within corresponding syntenic blocks in selfing and outcrossing species, affirming that selfing species predominantly experience loss of both genes and intergenic DNA. Comparison of gene structures revealed a strikingly small number of shared introns across species, yet consistent distributions of intron number and length, regardless of population size or reproductive mode, suggesting that their evolutionary dynamics are primarily reflective of functional constraints. Our study provides valuable insights into genome evolution and expands the nematode genome resources with the highly genetically diverse C. brenneri, facilitating research into various aspects of nematode biology and evolutionary processes., (© The Author(s) 2025. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

A previous study demonstrated noninferior efficacy of 4-month rifapentine/moxifloxacin regimen for tuberculosis (TB) treatment compared with the standard regimen. We explored results among study participants with diabetes. Among 2,516 randomized participants, 181 (7.2%) had diabetes. Of 166 participants with diabetes in the microbiologically eligible analysis group, 26.3% (15/57) had unfavorable outcomes in the control regimen, 13.8% (8/58) in the rifapentine/moxifloxacin regimen, and 29.4% (15/51) in the rifapentine regimen. The difference in proportion of unfavorable outcomes between the control and rifapentine/moxifloxacin arms in the microbiologically eligible analysis group was -12.5% (95% CI -27.0% to 1.9%); the difference between the control and rifapentine arms was 3.1% (95% CI -13.8% to 20.0%). Safety outcomes were similar in the rifapentine/moxifloxacin regimen and control arms. Among participants with TB and diabetes, the rifapentine/moxifloxacin arm had fewest unfavorable outcomes and was safe. Our findings indicate that the rifapentine/moxifloxacin regimen can be used in persons with TB and diabetes.

The Caenorhabditis Intervention Testing Program recently characterized the longevity-promoting effects of the vitamin A derivative all-trans retinoic acid (atRA). Here, we test two atRA-related compounds, tamibarotene and bakuchiol, for longevity effects in three strains of Caenorhabditis species. Both tamibarotene, a potent RAR agonist, and bakuchiol, a meroterpene derived from Psoralea corylifolia , showed no significant increase in lifespan across a dosage range of six concentrations. Additionally, bakuchiol was broadly toxic at higher doses. These findings highlight the specificity of atRA's longevity effects and suggest that compounds related to atRA may not universally promote lifespan extension., Competing Interests: The authors declare that there are no conflicts of interest present., (Copyright: © 2025 by the authors.)