Browse Articles

Correction: Predicting hypertension and identifying most important factors among married women in Bangladesh using machine learning approach

Prothrombinase again, but different this time

An ancient recombination desert is a speciation supergene in placental mammals

GHz dynamic holographic VCSEL chip via current-addressed modes multiplexing

Cardiovascular disease prevention by personalized health promotion considering educational attainment

Risk of ciguatoxins is shaped by Gambierdiscus community structure

Ciguatoxins (CTXs) are produced by marine microbial eukaryotes ( Gambierdiscus/Fukuyoa , Dinophyta: Alveolata) that live epiphytically on macroalgae and other substrates. When CTXs accumulate in seafood they cause Ciguatera Poisoning (CP), which affects ca. 20–50,000 people p.a. and is likely worsened by climate change. CTXs in fish are highly variable with diet, ecology, size, age and phylogeny. Chemical identification of CTXs is difficult, and while detection of Gambierdiscus is simple, often no clearly CTX-producing Gambierdiscus are known from CP sites. Here, we coupled custom deep metabarcoding with quantitative PCR, CTXs in both Gambierdiscus and a sentinel fish ( Ctenochaetus striatus ) with limited home range, in the Cook Islands, an endemic CP area. Using neuroblastoma cell assays and liquid chromatography-tandem mass spectrometry, CTXs were present in fish species from six families. Dinoflagellate α-diversity was dominated by nine Gambierdiscus/Fukuyoa spp., the highest diversity yet reported from a single location. Sites where the rare species, G. polynesiensis, were detected on artificial substrates and macroalgae were more closely aligned with concentrations of P-CTX3B in C. striatus , unrelated to fish age or size, than with overall Gambierdiscus abundance. Of newly isolated Gambierdiscus strains, only the three G. polynesiensis produced P-CTXs. We show rare Gambierdiscus spp. and sentinel fish can map site-specific CP risk to address a growing climate change-related public health threat.

A myeloma identity crisis yields daratumumab resistance

ALKB-1-dependent tRNA methylation is required for efficient paternal mitochondrial elimination

Structural elucidation, biological significance and computational approach of Copper(ii), Nickel(ii) and Cobalt(ii) with bidentate schiff base of N-(Napthalene-1-ylmethylene)isonicotinohydrazide

Abstract The increasing prevalence of antibiotic-resistant bacteria and oxidative stress-related diseases underscores the need for novel therapeutic agents with potential dual functionality. In this research, a schiff base ligand, N-(Napthalene-1-ylmethylene)isonicotinohydrazide, was synthesized and complexed with Copper(II), Nickel(II), and Cobalt(II) ions. Characterization of the compounds using various spectroscopic and analytical techniques confirmed successful complex formation and structural stability. Antibacterial testing through the disc diffusion method revealed that the Ni(II) complex exhibited the highest antibacterial activity, with significant inhibition against Staphylococcus aureus , Bacillus subtilis , Escherichia coli , and Shigella flexneri . The antioxidant activity, evaluated via DPPH radical scavenging, showed that the Cu(II) complex was the most effective with an IC 50 value of 187.81 ± 1.42 µg/mL. Molecular docking studies against DNA gyrase (PDB ID: 7P2M) predicted the Ni(II) complex as the best binder (–9.9 kcal/mol), suggesting strong initial affinity. Complementary molecular dynamic simulations further demonstrated that Cu(II) and Co(II) complexes maintained the most stable protein-ligand interactions under dynamic conditions, highlighting their potential as robust inhibitors. ADMET predictions indicated favorable pharmacokinetic and toxicity profiles, though recognized as preliminary. DFT calculations confirmed stable geometries and showed a reduction of the HOMO–LUMO energy gap from 4.21 eV (ligand) to 2.85 eV (Ni complex), consistent with enhanced reactivity and biological activity. Mapping of electron density and atomic charge analysis identified potential nucleophilic attack sites, reinforcing the complexes’ therapeutic potential in combating bacterial infections and oxidative stress.

Knowledge, attitudes and practices relating to HIV self-testing following its introduction in the Bas-Sassandra region of Côte d’Ivoire: the case of the ATLAS project

Background Awareness of HIV status is crucial for accessing HIV care and prevention but remains suboptimal in West Africa. The ATLAS initiative, launched in Côte d’Ivoire, Mali, and Senegal, addressed this gap by distributing approximately 380,000 HIV self-testing (HIVST) kits from 2019 to 2021, primarily to key populations and their social networks. This study assessed levels and correlates of Knowledge, Attitudes, and Practices (KAP) related to HIVST in the Bas-Sassandra region of Côte d’Ivoire following ATLAS’s introduction. Method A cross-sectional population-based survey was conducted in the Bas-Sassandra region in 2021 among individuals aged 15–49. A total of 6,271 people (3,203 men and 3,068 women) were interviewed. They were selected using a three-stage stratified sampling approach in the Bas-Sassandra region. Bivariate statistics and multivariable logistic regressions were used to assess KAP levels and the associated factors. Results Although few participants reported having heard about HIVST (11%) or having used it (3%), most of them reported that if it were freely available, they would be interested/very interested in using it for themselves (76%), as well as for their sexual partners (75%). Education and wealth were positively associated with knowledge and positive attitudes towards HIVST among both men and women, whereas age was positively correlated to knowledge and use of HIVST among men only. The number of sexual partners over the last 12 months was positively associated with knowledge of HIVST and willingness to use HIVST for themselves or their sexual partners among both sexes. We also found that high HIV-related knowledge and low levels of negative attitude were positively associated with positive attitudes towards HIVST, while exposure to the media appeared to be correlated to knowledge of HIVST. Conclusion The high level of positive attitudes towards HIVST calls for a scaling up of access to HIVST in the region. Specific attention to groups with the worst KAP, such as the less educated, the poor or those with more HIV-related negative attitude, could enhance the success of such initiatives.

The proteasome: a gatekeeper stabilizing BCMA expression

Accurate determination of the 3D atomic structure of amorphous materials

Pantropical moist forests are converging towards a middle leaf longevity

Adaptive fuzzy cluster-guided simple, fast, and efficient feature selection for high-dimensional and highly imbalanced binary-class bioinformatics microarray data

Impact of physical exercise on sleep quality in college students: A Chain mediating role of self-efficacy and emotional control

Objective The study aims to examine the impact of physical exercise on sleep quality among college students and elucidate the mediating roles of self-efficacy and emotional control in this relationship. Methods Data were obtained from the 2024 China College Students’ Physical Activity and Health Tracking Survey (CPAHLS-CS). A sample of 10,970 college students was included. Physical exercise levels were measured using the Physical Activity Rating Scale-3 (PARS-3), sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI), self-efficacy was measured using the General Self-Efficacy Scale (GSES), and emotional control was assessed using the Adolescent Psychological Resilience Scale. Regression analysis and Bootstrap mediation analysis were employed to test the hypothesised relationships. Results (1) The direct effect of physical exercise on sleep quality was not significant (β = 0.011, P > 0.05). However, the total effect was negative (β = −0.056, P < 0.001), indicating that indirect effects comprised the predominant mechanism. (2) Self-efficacy (effect size = −0.024) and emotional control (effect size = −0.022) each independently mediated the relationship between physical exercise and sleep quality. (3) In the pathway through which physical exercise influences sleep quality, self-efficacy, and emotional control functioned as independent mediating variables. Specifically, physical exercise indirectly improved sleep quality by enhancing self-efficacy while positively impacting sleep quality through a distinct mediating mechanism involving strengthening emotional control. Conclusions This study demonstrates the influence of physical exercise, self-efficacy, and emotional control on sleep quality. The findings suggest that physical exercise indirectly optimises sleep quality through a dynamic and synergistic mechanism involving the enhancement of self-efficacy and emotional control. This study provides theoretical support and practical pathways for sleep quality interventions in college students.

Target antigen and plasma cell phenotype are critical factors for sensitivity to response-adapted daratumumab therapy

Abstract In this response-adapted clinic trial with daratumumab monotherapy for older patients with newly diagnosed multiple myeloma (MM), we identified target antigen expression, a plasma cell phenotype, and an activated immune tumor microenvironment (iTME) as critical features associated with response to CD38 monoclonal antibody therapy. Here, patients achieving a partial response after 2 cycles continued daratumumab, otherwise lenalidomide or bortezomib was added. This strategy resulted in an overall response rate of 97% and low rates of adverse events, with 37% of patients able to continue daratumumab monotherapy. Importantly, we found that higher CD38 expression, plasma cell gene expression programming, and an activated iTME were associated with patients who were able to continue daratumumab therapy alone. In contrast, patients requiring the addition of lenalidomide or bortezomib had increased expression of adhesion, tumor necrosis factor signaling, KRAS signaling, and B-cell programs, as well as an immunosuppressed iTME. Tracking of clonal dynamics illustrated the selection of subclones enriched for de novo resistance gene expression programs after only 2 cycles of daratumumab monotherapy. Upon relapse, daratumumab refractory MM cells were characterized by the expansion of preexisting minor subclones with mixed transcriptomic programs containing the plasma cell phenotype with decreased CD38 expression and maintenance of resistance programs, suggesting development of acquired resistance involves an uncoupling of transcriptional programs present in therapy-naïve tumors. To our knowledge, this is the first study to demonstrate the effectiveness of response-adapted daratumumab treatment and describe critical biomarkers of single-agent daratumumab sensitivity in vulnerable patients with therapy-naïve MM. This trial was registered at www.ClinicalTrials.gov as #NCT04151667.

A molecularly defined basalo-prefrontal-thalamic circuit regulates sensory and affective dimensions of pain in male mice

Abstract Both the medial prefrontal cortex (mPFC) and thalamus have been implicated in pain regulation. However, the roles of the mPFC-thalamus connection in pain and how the mPFC modulates nociceptive processing remain unclear. Here, we show that the mPFC neurons projecting to thalamus, marked by Foxp2 expression, are deactivated in both acute and chronic pain in male mice. Persistent inactivation of the mPFC Foxp2 + neurons enhances nociceptive sensitivity, while their activation alleviates multiple aspects of pain. Circuit-specific manipulations revealed that the projections to parataenial nucleus, mediodorsal and ventromedial thalamus differentially modulate sensory and affective pain. Additionally, the mPFC Foxp2 + neurons receive cholinergic input from the basal forebrain, particularly the horizontal diagonal band (HDB). Notably, activation of the α4β2-containing nicotinic acetylcholine receptor in mPFC exerts antinociceptive effects in Foxp2 + neuron-dependent manner. Together, our study defines an HDB→mPFC Foxp2 →thalamus circuit essential for sensory and affective pain modulation and underscores the therapeutic potential of targeting mPFC cholinergic signaling in chronic pain management.

Accuracy of DentalMonitoring’s artificial intelligence in detecting common orthodontic braces treatment related emergencies

Abstract This study aimed to evaluate the diagnostic performance of DentalMonitoring™ (DM) (Dental Monitoring SAS, Paris, France), an FDA-cleared AI-powered orthodontic remote monitoring software, in detecting three common orthodontic appliance issues: bracket debonding, open self-ligating clips, and tie loss. Datasets from 1,014 US-based patients were analyzed. Each DM image set was assessed by the AI algorithm and independently reviewed by a panel of three orthodontic experts, whose consensus served as the reference standard. A total of 659 evaluations were included for bracket debonding, 647 for self-ligating clip status, and 653 for tie presence. Sensitivity and specificity along with their 95% confidence intervals were calculated using a two-level evaluation basis (positive vs. negative) across the three clinical parameters. DM’s AI demonstrated high diagnostic performance, with sensitivity of 98.4% for bracket debonding, 91.1% for open self-ligating clips, and 93.3% for tie loss. Corresponding specificity values were 99.6%, 88.3%, and 96.5%, respectively. Current results indicate that DM’s AI analysis system has high accuracy in detecting bracket debonding, open self-ligating clips, and tie loss. DM can help significantly reduce the rate of these undetected clinical incidents, providing a better approach to managing emergencies and maintaining clinical control in orthodontic treatment.

Phyllosphere microbial communities are modulated by pathogen coinfection, but not a plant defense hormone

Phyllosphere microbial communities play important roles in plant health, yet the roles of plant defense hormones and coinfections in shaping these communities remain unclear. This study investigated how exogenous application of the plant defense hormone salicylic acid and fungal coinfection influenced microbial communities on leaves of tall fescue. In a factorial experiment, we treated leaves with salicylic acid (at 100 mg/L) or a control solution and inoculated them with one of four inoculation treatments: Rhizoctonia solani alone, mock inoculation, co-inoculation with both R. solani and Colletotrichum cereale , or mock co-inoculation. We characterized the fungal and bacterial communities using ITS and 16S rRNA gene sequencing, respectively. Salicylic acid application did not significantly alter the diversity, composition, or taxa abundances of either fungal or bacterial communities. In contrast, co-inoculation significantly shifted fungal community composition and increased fungal diversity compared to inoculation with R. solani alone. Bacterial communities were not significantly impacted by either inoculation treatment. These results suggest that in this system, coinfection has a stronger influence on phyllosphere fungal communities than exogenous salicylic acid application. Our findings highlight the potential for pathogen coinfections to shape plant-associated microbial communities, particularly fungi, and emphasize the need for further research on the effects of salicylic acid across different host species and experimental approaches.

Dynamic rRNA methylation regulates translation in the hematopoietic system and is essential for stem cell fitness

Abstract Self-renewal and differentiation are at the basis of hematopoiesis. Although it is known that tight regulation of translation is vital for hematopoietic stem cells’ (HSC) biology, the mechanisms underlying translation regulation across the hematopoietic system remain obscure. Here, we reveal a novel mechanism of translation regulation in the hematopoietic hierarchy, which is mediated by rRNA methylation dynamics. Using ultralow-input ribosome profiling, we characterized cell-type–specific translation capacity during erythroid differentiation. We found that translation efficiency (TE) changes progressively with differentiation and can distinguish between discrete cell populations, as well as define differentiation trajectories. To reveal the underlying mechanism, we performed comprehensive mapping of the most abundant rRNA modification, 2ʹ-O-methyl (2ʹOMe). We found that, such as TE, 2ʹOMe dynamics followed a distinct trajectory during erythroid differentiation. Genetic perturbation of individual 2ʹOMe sites demonstrated their distinct roles in modulating proliferation and differentiation. By combining CRISPR screening, molecular, and functional analyses, we identified a specific methylation site, 28S-Gm4588, which is progressively lost during differentiation, as a key regulator of HSC self-renewal. We showed that low methylation at this site led to translational skewing, mediated mainly by codon frequency, which promoted differentiation. Functionally, HSC with diminished 28S-Gm4588 methylation exhibited impaired self-renewal capacity ex vivo, and loss of fitness in vivo in bone marrow transplants. Extending our findings beyond the hematopoietic system, we also found distinct dynamics of 2ʹOMe profiles during differentiation of non-HSC. Our findings reveal rRNA methylation dynamics as a general mechanism for cell-type–specific translation, required for cell function and differentiation.