Browse Articles
Discover research articles across all indexed journals
Criterion-related validity of self-screening using the KOJI AWARENESS™ test for range of motion and strength in healthy participants
Objective This study aimed to establish the validity of the KOJI AWARENESS™ sub-components by determining whether there is a connection between the sub-component scores and joint range of motion, muscle strength, and balance. Methods Fifty healthy adults (17 females and 33 males) participated in the study, completing the KOJI AWARENESS™ assessments and measurements of joint range of motion, muscle strength, and balance. The range of motion of the upper and lower extremities and trunk was measured using either a goniometer or an inclinometer. A handheld dynamometer was used to measure muscle strength. Balance ability was assessed using a modified balance error scoring system. Using the Mann–Whitney U test or the Jonckheere–Terpstra test, we compared KOJI AWARENESS™ scores with the corresponding body segments at a significance level of P ≤ 0.05. Results Our results indicated associations between external references and many items; however, no associations were found for flexion, extension, and rotation of neck mobility, extension and external rotation of hip mobility, and mid-section stability strength in KOJI AWARENESS™. Conclusion Overall, the KOJI AWARENESS™ sub-component scores demonstrated good validity, except for the items related to neck and hip flexibility and trunk muscle strength. Future analyses should include a wider range of age groups, such as middle-aged and older adults.
A broad-spectrum antibiotic targets multiple-drug-resistant bacteria with dual binding targets and no detectable resistance
Unmasking the rising global burden of depression: A 32-year GBD analysis of gender disparities and regional hotspots in Sub-Saharan Africa
Aims Depression, a leading contributor to the global disease burden, exhibits alarming increases in incidence and prevalence, with pronounced disparities across regions and genders. This study provides the first comprehensive analysis of depression burden from 1990 to 2021, integrating the latest Global Burden of Disease (GBD) 2021 data to identify critical hotspots and policy-relevant trends. Methods Estimated global, regional, and national burden of disease for depression from 1990–2021 by extracting incidence, prevalence, and DALYS from the Global Burden of Disease(GBD) database 2021. Results From 1990 to 2021, the global incidence of depression surged by 15.6% (3,749–4,334 per 100,000), with Sub-Saharan Africa emerging as an unexpected epicenter. Uganda and The Gambia recorded the highest incidence rates globally (9,644 and 7,624 per 100,000, respectively), likely linked to civil instability and healthcare deficits. Women bore a disproportionate burden, with adolescent females (15–19 years) showing 64% higher incidence than males (5,584 vs. 3,401 per 100,000). High-income regions paradoxically exhibited steeper annual percentage increases (EAPC: 1.0 in North America), suggesting improved detection or escalating stressors. Conclusions This study highlights urgent priorities: (1) integrating mental health services into primary care in conflict-affected African nations. (2) gender-sensitive interventions targeting adolescent females. (3) global equity in mental health resource allocation.
RIFINs displayed on malaria-infected erythrocytes bind KIR2DL1 and KIR2DS1
Abstract Natural killer (NK) cells use inhibitory and activating immune receptors to differentiate between human cells and pathogens. Signalling by these receptors determines whether an NK cell becomes activated and destroys a target cell. In some cases, such as killer immunoglobulin-like receptors, immune receptors are found in pairs, with inhibitory and activating receptors containing nearly identical extracellular ligand-binding domains coupled to different intracellular signalling domains 1 . Previous studies showed that repetitive interspersed family (RIFIN) proteins, displayed on the surfaces of Plasmodium falciparum -infected erythrocytes, can bind to inhibitory immune receptors and dampen NK cell activation 2,3 , reducing parasite killing. However, no pathogen-derived ligand has been identified for any human activating receptor. Here we identified a clade of RIFINs that bind to inhibitory immune receptor KIR2DL1 more strongly than KIR2DL1 binds to the human ligand (MHC class I). This interaction mediates inhibitory signalling and suppresses the activation of KIR2DL1-expressing NK cells. We show that KIR2DL1-binding RIFINs are abundant in field-isolated strains from both Africa and Asia and reveal how the two RIFINs bind to KIR2DL1. The RIFIN binding surface of KIR2DL1 is conserved in the cognate activating immune receptor KIR2DS1. We find that KIR2DL1-binding RIFINs can also bind to KIR2DS1, resulting in the activation of KIR2DS1-expressing NK cells. This study demonstrates that activating killer immunoglobulin-like receptors can recruit NK cells to target a pathogen and reveals a potential role for activating immune receptors in controlling malaria infection.
RSGPT: a generative transformer model for retrosynthesis planning pre-trained on ten billion datapoints
Cryo-EM reveals an extrahelical allosteric binding site at the M5 mAChR
Abstract The M5 muscarinic acetylcholine receptor (M5 mAChR) represents a promising therapeutic target for neurological disorders. However, the high conservation of its orthosteric binding site poses significant challenges for drug development. While selective positive allosteric modulators (PAMs) offer a potential solution, a structural understanding of the M5 mAChR and its allosteric binding sites remains limited. Here, we present a 2.8 Å cryo-electron microscopy structure of the M5 mAChR complexed with heterotrimeric Gq protein and the agonist iperoxo, completing the active-state structural characterization of the mAChR family. To identify the binding site of M5-selective PAMs, we implement an integrated approach combining mutagenesis, pharmacological assays, structural biology, and molecular dynamics simulations. Our mutagenesis studies reveal that selective M5 PAMs bind outside previously characterized M5 mAChR allosteric sites. Subsequently, we obtain a 2.1 Å structure of M5 mAChR co-bound with acetylcholine and the selective PAM VU6007678, revealing an allosteric pocket at the extrahelical interface between transmembrane domains 3 and 4 that is confirmed through mutagenesis and simulations. These findings demonstrate the diverse mechanisms of allosteric regulation in mAChRs and highlight the value of integrating pharmacological and structural approaches to identify allosteric binding sites.
Dynamic and structural insights into allosteric regulation on MKP5 a dual-specificity phosphatase
Fe3O4 nanoparticles and IAA auxin affect secondary metabolism over time without altering genetic stability in chrysanthemum
Author Correction: Genetic fusions favor tumorigenesis through degron loss in oncogenes
Preoperative neutrophil percentage-to-albumin ratio as a postoperative AKI predictor in non-cardiac surgery: a retrospective cohort secondary analysis
Abstract Acute kidney injury (AKI) is a critical postoperative complication in non-cardiac surgery patients, significantly impacting patient outcomes. The neutrophil percentage-to-albumin ratio (NPAR) is a promising inflammatory biomarker for predicting AKI. However, it is still unclear whether NPAR could be used as a predictor of postoperative AKI in Non-Cardiac Surgical Patients. Univariate and multivariable logistic regression analyses were conducted to assess the predictive value of NPAR for postoperative AKI, controlling for potential confounders. A total of 3041 patients were considered for the analysis after excluding those with preoperative infections and chronic kidney disease. The area under the receiver operating characteristic (ROC) curve for NPAR was 0.723, indicating moderate predictive capability for postoperative AKI. The optimal threshold for NPAR was 5.310, with a specificity of 0.640 and a sensitivity of 0.729. Multivariable regression analysis revealed that NPAR was significantly associated with postoperative AKI risk (adjusted odds ratio 1.093, 95% CI 1.072–1.116, P < 0.001), independent of other clinical factors. Preoperative NPAR is a significant predictor of postoperative AKI in non-cardiac surgical patients under general anesthesia and could be a valuable biomarker for identifying non-cardiac surgical patients at high-risk of AKI.
Mogat1 drives metabolic adaptations to evade immune surveillance
Pediatric adenoidectomy is safe surgery with a low complication rate: a population-based study
Abstract Population-based data on incidence of complications after pediatric adenoidectomy are sparse. Therefore, a retrospective population-based study of all 2105 pediatric adenoidectomies (59.9% male, median age: 4 years) in the year 2019 in all otolaryngology departments in one federal state, Thuringia, in Germany, was performed. Patients’ and treatment characteristics, and complications were analyzed. The highest surgery rate was seen at the age of 3 years (2747.4 per 100,000 children). Adenoidectomy was combined with tonsillotomy or tonsillectomy in 29.2% and 1.5% of the cases. Postoperative bleeding needing re-surgery occurred in 1.1% of all cases. The revision surgery for bleeding rate after solitary adenoidectomy was 0.7%. A wound infection was seen in 1.0%. Complications classified according to the Clavien-Dindo classification (CDC) occurred in 2.6% of cases. The overall complication rate was 20.3/100,000 population. Additional tonsillectomy was independently associated to bleeding > 24 h after surgery (Odds ratio [OR] = 52.141; confidence interval [CI] = 7.772-349.818; p < 0.0001). There was no independent associative factor to enhanced risk of wound infection. CDC complications occurred more frequently in comorbid patients (OR = 4.175; CI = 1.222–14.271; p = 0.023), underweight children (OR = 2.430; CI = 1.198–6.571; p = 0.040), when additional tonsillectomy was performed (OR = 11.177; CI = 2.098–59.548; p < 0.0001), and when perioperative antibiotics were applied (OR = 13.251; CI = 5.695–30.834; p < 0.001). Adenoidectomy is very safe surgery. Main risk factor for bleeding complications is additional tonsillectomy, not adenoidectomy itself.
SP140–RESIST pathway regulates interferon mRNA stability and antiviral immunity
Abstract Type I interferons are essential for antiviral immunity 1 but must be tightly regulated 2 . The conserved transcriptional repressor SP140 inhibits interferon-β ( Ifnb1 ) expression through an unknown mechanism 3,4 . Here we report that SP140 does not directly repress Ifnb1 transcription. Instead, SP140 negatively regulates Ifnb1 mRNA stability by directly repressing the expression of a previously uncharacterized regulator that we call RESIST (regulated stimulator of interferon via stabilization of transcript; previously annotated as annexin 2 receptor). RESIST promotes Ifnb1 mRNA stability by counteracting Ifnb1 mRNA destabilization mediated by the tristetraprolin (TTP) family of RNA-binding proteins and the CCR4–NOT deadenylase complex. SP140 localizes within punctate structures called nuclear bodies that have important roles in silencing DNA-virus gene expression in the nucleus 3 . Consistent with this observation, we find that SP140 inhibits replication of the gammaherpesvirus MHV68. The antiviral activity of SP140 is independent of its ability to regulate Ifnb1 . Our results establish dual antiviral and interferon regulatory functions for SP140. We propose that SP140 and RESIST participate in antiviral effector-triggered immunity 5,6 .
A role for the thalamus in danger evoked awakening during sleep
Development of a novel deep learning method that transforms tabular input variables into images for the prediction of SLD
‘Immortal’ stars have an elixir of youth: dark matter
Artificial intelligence-integrated video analysis of vessel area changes and instrument motion for microsurgical skill assessment
Abstract Mastering microsurgical skills is essential for neurosurgical trainees. Video-based analysis of target tissue changes and surgical instrument motion provides an objective, quantitative method for assessing microsurgical proficiency, potentially enhancing training and patient safety. This study evaluates the effectiveness of an artificial intelligence (AI)-based video analysis model in assessing microsurgical performance and examines the correlation between AI-derived parameters and specific surgical skill components. A dual AI framework was developed, integrating a semantic segmentation model for artificial blood vessel analysis with an instrument tip-tracking algorithm. These models quantified dynamic vessel area fluctuation, tissue deformation error count, instrument path distance, and normalized jerk index during a single-stitch end-to-side anastomosis task performed by 14 surgeons with varying experience levels. The AI-derived parameters were validated against traditional criteria-based rating scales assessing instrument handling, tissue respect, efficiency, suture handling, suturing technique, operation flow, and overall performance. Rating scale scores correlated with microsurgical experience, exhibiting a bimodal distribution that classified performance into good and poor groups. Video-based parameters showed strong correlations with various skill categories. Receiver operating characteristic analysis demonstrated that combining these parameters improved the discrimination of microsurgical performance. The proposed method effectively captures technical microsurgical skills and can assess performance.