The Mesosoma of Protanilla (Leptanillinae) and the Groundplan of the Formicidae (Hymenoptera).

The study of ant morphology is advancing through parallel insights provided by phylogenomics-which provides a statistically robust basis for comparison and evolutionary inference-and phenomics via the application of microcomputed tomography (µ-CT) for the efficient and precise documentation of anatomy. The information provided by µ-CT is complex and rich, allowing for the quantification of geometry and biomechanically relevant variables, as well as comparative morphology via 3D rendering. Recently, the complete musculature of the thorax, propodeum, and legs was documented for the first time in an ant (Formica rufa L.

Comparative risk of incident malignancies in rheumatoid arthritis patients treated with Janus kinase inhibitors or bDMARDs: observational data from the German RABBIT register.

Objectives: To estimate the effects of Janus kinase inhibitors (JAKis) vs biologic disease-modifying antirheumatic drugs (bDMARDs) on the risk of incident malignancies (excluding nonmelanoma skin cancer) in patients and patient subgroups with rheumatoid arthritis.

Methods: Episodes of disease-modifying antirheumatic drug (DMARD) treatment initiated between January 2017 and December 2020 and followed up to June 2024 in RABBIT, the German register for the long-term observation of therapy with biologics and targeted disease-modifying antirheumatic drugs in adult patients with rheumatoid arthritis, were analysed. Incidence rates (IRs) per 1000 patient-years with 95% CIs were calculated, and incident malignancy risk was estimated as hazard ratios (HRs) by inverse probability weighted adjusted Cox models.

Next-generation rifamycins for the treatment of mycobacterial infections.

is a rapidly growing nontuberculous causing severe pulmonary infections, especially in immunocompromised individuals and patients with underlying lung conditions like cystic fibrosis (CF). While rifamycins are the pillar of tuberculosis treatment, their efficacy against lung disease is severely compromised by intrabacterial ADP-ribosylation. Additionally, rifamycins induce cytochrome P450 3A4 (CYP3A4), a major human drug-metabolizing enzyme, further limiting their use in patients with comorbidities that require treatment with CYP3A4 substrates such as CF and HIV coinfection.

A fossil-informed pattern of body size increase and local extinction in dirt ants (Hymenoptera: Formicidae).

dirt ants are morphologically distinct and widely distributed members of Neotropical communities. These ants possess features that aid in leaf litter camouflage and are larger than other closely related lineages with similar cryptic adaptations. Here, we report the first fossil of this genus group, sp.

A Simple In Vitro Method to Determine Bactericidal Activity Against Under Hypoxic Conditions.

: Non-replicating persisters (NRPs) of are a bacterial subpopulation that can survive in the host under unfavorable conditions, such as hypoxia or nutrient starvation. The eradication of these bacteria is difficult, which is one reason for the long treatment duration and treatment failure. The drug discovery process should therefore contain methods to screen activity against NRPs.

Identifying relevant intersections in relation to motivation and attempt to stop smoking by using a combination of methods to develop robust predictive models and resampling techniques: A cross-sectional study of the German population.

Aims: To illustrate robust intersections of co-occurring factors for two predictors of smoking cessation, motivation to stop smoking (MTSS) and past year-quit attempts (QA), by using means to develop robust predictive models such as bootstrap resampling, scoring rules to evaluate the predictive accuracy and spline functions.

Design, Setting And Participants: Cross-sectional data from the German Study on Tobacco Use (DEBRA). Past-years smokers (≥18 years, n = 13 245) from 22 survey waves (2016-2020) were included.

Nearly complete late Eocene skull from the North Pacific elucidates the cranial morphology and affinities of the penguin-like Plotopteridae.

The extinct Plotopteridae were penguin-like, wing-propelled diving birds of the North Pacific. Recently, the oldest and most complete plotopterid skull has been discovered in the late Eocene lower part of the Lincoln Creek Formation, southern Olympic Peninsula (Washington State, USA), and informs the poorly known cranial morphology of these birds. This skull is somewhat larger than previously described partial skulls from the Oligocene Pysht Formation of the northern Olympic Peninsula, from which it also differs in the shape of the nostrils.

Synthesis and Antimycobacterial Assays of Some New Ethambutol Analogs.

Ethambutol (EMB) is a first-line anti-tuberculosis drug that is also considered in treatment regimens for infections caused by non-tuberculous mycobacteria (NTM). EMB targets the arabinosyl transferases EmbCAB, which are important for the synthesis of cell wall constituents. To further explore and narrow down the structural variability of EMB, we synthesized three series of new EMB analogs.

Glycogen synthase kinase 3 inhibition controls infection.

Compounds targeting host control of infectious diseases provide an attractive alternative to antimicrobials. A phenotypic screen of a kinase library identified compounds targeting glycogen synthase kinase 3 as potent inhibitors of (Mtb) intracellular growth in the human THP-1 cell line and primary human monocytes-derived macrophages (hMDM). CRISPR knockouts and siRNA silencing showed that GSK3 isoforms are needed for the growth of Mtb and that a selected compound, P-4423632 targets GSK3β.

Determination of bactericidal activity against 3HC-2-Tre-labelled Mycobacterium abscessus (Mycobacteroides abscessus) by automated fluorescence microscopy.

The minimum bactericidal concentration (MBC) of antibiotics is an important parameter for the potency of a drug in eradicating a bacterium as well as an important measure of the potential of a drug candidate in research and development. We have established a fluorescence-based microscopy method for the determination of MBCs against the non-tuberculous mycobacterium Mycobacterium abscessus (Mycobacteroides abscessus) to simplify and accelerate the performance of MBC determination compared to counting colony forming units on agar. Bacteria are labelled with the trehalose-coupled dye 3HC-2-Tre and analysed in a 96-well plate.

3-[(Benzo-1,3-dioxol-5-yl)amino]-4-methoxycyclobut-3-ene-1,2-dione: polymorphism and twinning of a precursor to an antimycobacterial squaramide.

The title compound, 3-[(benzo-1,3-dioxol-5-yl)amino]-4-methoxycyclobut-3-ene-1,2-dione, CHNO (3), is a precursor to an antimycobacterial squaramide. Block-shaped crystals of a monoclinic form (3-I, space group P2/c, Z = 8, Z' = 2) and needle-shaped crystals of a triclinic form (3-II, space group P-1, Z = 4, Z' = 2) were found to crystallize concomitantly. In both crystal forms, R(10) dimers assemble through N-H.

Broad-Spectrum In Vitro Activity of α-Aroyl--Aryl-Phenylalanine Amides against Non-Tuberculous Mycobacteria and Comparative Analysis of RNA Polymerases.

This study investigates the in vitro activity of α-aroyl--aryl-phenylalanine amides (AAPs), previously identified as antimycobacterial RNA polymerase (RNAP) inhibitors, against a panel of 25 non-tuberculous mycobacteria (NTM). The compounds, including the hit compound MMV688845, were selected based on their structural diversity and previously described activity against mycobacteria. Bacterial strains, including the complex, complex, and other clinically relevant NTM, were cultured and subjected to growth inhibition assays.

Categorization of continuous covariates and complex regression models-friends or foes in intersectionality research.

Objectives: To reduce health inequities, it is important to identify intersections in characteristics of individuals subject to privilege or disadvantage. Different proposals for that have recently been published. One approach (1) considers models specified with first- and all second-order effects and another (2) the stratification based on multiple covariates; both categorize continuous covariates.

Nα-Aroyl-N-Aryl-Phenylalanine Amides: A Promising Class of Antimycobacterial Agents Targeting the RNA Polymerase.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains the leading cause of death from a bacterium in the world. The global prevalence of clinically relevant infections with opportunistically pathogenic non-tuberculous mycobacteria (NTM) has also been on the rise. Pharmacological treatment of both TB and NTM infections usually requires prolonged regimens of drug combinations, and is often challenging because of developed or inherent resistance to common antibiotic drugs.

Prednisolone Versus Colchicine for Acute Gout in Primary Care: statistical analysis plan for the pragmatic, multicenter, randomized, and double-blinded COPAGO non-inferiority trial.

Background: To date, colchicine and prednisolone are two effective therapies for the treatment of acute gout but have never been compared directly in a randomized clinical trial. In addition, in previous trials of treating acute gout patients with concomitant comorbidities were often excluded due to contraindications to naproxen.

Study Design: This pragmatic, prospective, double-blind, double-dummy, parallel-group, randomized, non-inferiority trial compares prednisolone with colchicine in terms of non-inferiority in patients with acute gout.

Synthesis and in vitro Metabolic Stability of Sterically Shielded Antimycobacterial Phenylalanine Amides.

Nα-aroyl-N-aryl-phenylalanine amides (AAPs) are RNA polymerase inhibitors with activity against Mycobacterium tuberculosis and non-tuberculous mycobacteria. We observed that AAPs rapidly degrade in microsomal suspensions, suggesting that avoiding hepatic metabolism is critical for their effectiveness in vivo. As both amide bonds are potential metabolic weak points of the molecule, we synthesized 16 novel AAP analogs in which the amide bonds are shielded by methyl or fluoro substituents in close proximity.

Crystal structure and anti-mycobacterial evaluation of 2-(cyclo-hexyl-meth-yl)-7-nitro-5-(tri-fluoro-meth-yl)benzo[]iso-thia-zol-3(2)-one.

The title compound, CHFNOS, crystallizes in the monoclinic system, space group 2/, with = 8. As expected, the nine-membered heterobicyclic system is virtually planar and the cyclo-hexyl group adopts a chair conformation. There is structural evidence for intra-molecular N-S⋯O chalcogen bonding between the benziso-thia-zolinone S atom and one O atom of the nitro group, approximately aligned along the extension of the covalent N-S bond [N-S⋯O = 162.

The feeding apparatus of ants: an overview of structure and function.

Ants are a dominant family of eusocial terrestrial insects with a diversity of ecologies, lifestyles and morphologies. Ant diet preferences range from strict carnivory through omnivory to almost complete herbivory in species feeding on seeds or exudates of plant-sucking insects. While several studies have investigated ant feeding performance on different substrates, comparatively little is known about the functional morphology of the structures involved in food uptake or their diversification across the ants.

Prednisolone Versus Colchicine for Acute Gout in Primary Care (COPAGO): protocol for a two-arm multicentre, pragmatic, prospective, randomized, double-blind, controlled clinical trial of prednisolone and colchicine for non-inferiority with a parallel group design.

Background: Gout is the most common form of rheumatic disease in which monosodium urate crystals are deposited in the joints followed by acute inflammatory reactions. There are various approved drugs that can be prescribed for pain relief during an acute gout attack. However, to date, no direct comparison of efficacy of colchicine and prednisolone for the treatment of acute gout attacks has been investigated.

Mechanism of mycobacterial ATP synthase inhibition by squaramides and second generation diarylquinolines.

Mycobacteria, such as Mycobacterium tuberculosis, depend on the activity of adenosine triphosphate (ATP) synthase for growth. The diarylquinoline bedaquiline (BDQ), a mycobacterial ATP synthase inhibitor, is an important medication for treatment of drug-resistant tuberculosis but suffers from off-target effects and is susceptible to resistance mutations. Consequently, both new and improved mycobacterial ATP synthase inhibitors are needed.

Imidazopyridine Amides: Synthesis, CIIICIV Supercomplex Binding, and In Vitro Antimycobacterial Activity.

Q203 (telacebec) is an imidazopyridine amide (IPA) targeting the respiratory CIIICIV supercomplex of the mycobacterial electron transport chain (ETC). Aiming for a better understanding of the molecular mechanism of action of IPA, 27 analogues were prepared through a seven-step synthetic scheme. Oxygen consumption assay was designed to test the inhibition of purified CIIICIV by these compounds.

Conducting an Epidemiologic Study and Making It FAIR: Reusable Tools and Procedures from a Population-Based Cohort Study.

Conducting large-scale epidemiologic studies requires powerful software for electronic data capture, data management, data quality assessments, and participant management. There is also an increasing need to make studies and the data collected findable, accessible, interoperable, and reusable (FAIR). However, reusable software tools from major studies, underlying such needs, are not necessarily known to other researchers.

Synthesis and Characterization of Phenylalanine Amides Active against and Other Mycobacteria.

α-2-thiophenoyl-d-phenylalanine-2-morpholinoanilide [MMV688845, Pathogen Box; Medicines for Malaria Venture; IUPAC: (2)--(1-((2-morpholinophenyl)amino)-1-oxo-3-phenylpropan-2-yl)thiophene-2-carboxamide)] is a hit compound, which shows activity against (MIC 6.25-12.5 μM) and other mycobacteria.

Synthesis, structures, reactivity and medicinal chemistry of antitubercular benzothiazinones.

Tuberculosis is the leading bacterial killer worldwide. 8-Nitro-4-benzo[][1,3]thiazin-4-ones are a potent class of antitubercular agents with a new mechanism of action. BTZ043 and PBTZ169 (macozinone) have progressed to clinical studies.

Methyl 1-[(6-meth-oxy-5-methyl-pyrimidin-4-yl)meth-yl]-1-benzo[]imidazole-7-carboxyl-ate: a combined X-ray and DFT study.

The title compound, CHNO, was obtained as a side product during the synthesis of the previously reported anti-tubercular agent -(2-fluoro-eth-yl)-1-[(6-meth-oxy-5-methyl-pyrimidin-4-yl)meth-yl]-1-benzo[]imidazole-4-carboxamide and structurally characterized by X-ray crystallography and computational methods. In the crystal (space group 2/, = 4), the title compound adopts a twisted conformation with a dihedral angle between the benzimidazole and pyrimidine mean planes of 84.11 (3)°.