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PubMed2026

Can host genetics transform the sustainable control of tropical theileriosis? Insights from the Tick-Theileria interface.

Tropical theileriosis, caused by the tick-transmitted apicomplexan parasite Theileria annulata, remains a major constraint on cattle production across North Africa, the Mediterranean basin, the Middle East and South Asia. Current control depends on acaricides, the theilericidal drug buparvaquone and live attenuated schizont vaccines, but acaricide resistance, buparvaquone-resistance mutations and the logistical demands of vaccination are eroding the sustainability of these tools. Host genetics offers a complementary and durable alternative. Indigenous Bos indicus breeds are consistently more resistant to ticks and tolerate T. annulata infection better than exotic Bos taurus cattle, and this advantage has a measurable heritable component. Unlike previous reviews, which treat tick resistance, T. annulata immunobiology and livestock genomic selection as separate subjects, we integrate all three and assess host genetics specifically against the failure modes of current control. We review the tick, parasite and host interface, the evidence for natural resistance, and the genetic and immunological mechanisms involved, including signal-regulatory protein, bovine major histocompatibility complex class II and inflammatory pathway genes. We then assess whether genomic selection, multi-omics, machine learning and gene editing can translate these mechanisms into resistant cattle, and we weigh the biological, economic and infrastructural barriers to implementation. The evidence indicates that host genetics will not replace existing control but could reduce reliance on acaricides and chemotherapy. That contribution remains prospective rather than demonstrated: no resistance marker for T. annulata has yet been validated, prediction accuracies are moderate and transfer poorly between breeds, and no endemic production system has implemented selection for resistance.

Animals↗

PubMed2026

Hydroxyl Radical Inactivation of Vesicle-Cloaked and Free Murine Norovirus: Linking Biomolecular Oxidation to Lifecycle Disruption and Infectivity Loss.

Hydroxyl radicals (•OH) play a central role in inactivating human viruses during advanced oxidation processes for water and wastewater treatment, solar disinfection, and natural attenuation in sunlit aquatic environments. Human norovirus, a leading cause of gastroenteritis, is efficiently transmitted through water and exhibits strong environmental persistence. The recent discovery of vesicle-cloaked virus clusters (viral vesicles) further challenges water treatment and reuse, particularly for norovirus elimination. We investigated •OH inactivation kinetics and mechanisms of murine norovirus 1 (MNV-1), a human norovirus surrogate, in free-virus and vesicle-cloaked forms. •OH rapidly inactivated both MNV-1 vesicles and free MNV-1 with second rate constants of ∼1010 M-1 s-1; however, the vesicle membrane provided a 2.24-fold protective effect to cloaked MNV-1, resulting in slower inactivation kinetics than those of free MNV-1. •OH oxidized viral capsid proteins and genomes together with vesicle proteins and lipids, resulting in impaired CD300lf receptor and cell-based binding, disrupted genome replication, and diminished viral assembly. Despite these biochemical and functional impairments, most vesicle structures remained largely intact following •OH exposure. This study establishes a quantitative framework linking biomolecular damage to viral infectivity loss through functional impairment and lifecycle disruption, providing mechanistic insights into advance water disinfection strategies and public health protection.

Norovirus↗

PubMed2026

Tranexamic acid protects human dermal fibroblasts from D-galactose-induced senescence via the GPR30/MAPK pathway.

BACKGROUND: Tranexamic acid (TXA) is widely used for pigmentary disorders, but its anti-ageing potential remains unclear. This study aimed to evaluate whether topical 3% TXA improves early periorbital wrinkles in women with facial melasma and to investigate whether TXA protects human dermal fibroblasts from D-galactose-induced senescence via the GPR30/MAPK pathway. METHODS: Fifty women with melasma were randomized to 3% TXA serum plus moisturizer or moisturizer alone for 8 weeks, with follow-up to week 12. Periorbital wrinkles were graded using a modified Fitzpatrick Wrinkle Scale (MFWS). Separately, D-gal-induced senescence in HDFs was assessed via viability, SA-β-gal activity, senescence markers, ROS, antioxidant enzymes, SASP/ECM gene expression, and MAPK activation. GPR30 involvement was examined using antagonist G15, shRNA knockdown, and molecular docking. RESULTS: Topical TXA produced significantly greater MFWS reductions versus moisturizer alone at weeks 4, 8, and 12, with benefit persisting post-treatment. In HDFs, TXA preserved viability, reduced SA-β-gal positivity, attenuated p21/p16, restored Lamin B1, decreased ROS, and rescued antioxidant activities. TXA downregulated IL-6, IL-8, MMP1, and MMP3, and suppressed D-gal-induced ERK, JNK, and p38 phosphorylation. These effects were weakened by G15 or GPR30 knockdown; docking supported a stable TXA-GPR30 interaction. CONCLUSIONS: TXA showed clinical anti-wrinkle activity in melasma patients and protected HDFs from D-gal-induced senescence, partly via GPR30-dependent modulation of oxidative stress, SASP/ECM expression, and MAPK signalling. TXA is a promising candidate for skin ageing intervention.

Humans↗

PubMed2026

Comparative Transcriptomics Reveals Shared Downstream Pathways in Craniofacial Pathology.

Treacher Collins syndrome and Nager syndrome are craniofacial developmental disorders caused by defects in ribosome biogenesis and RNA splicing, respectively, yet they exhibit overlapping abnormalities affecting neural crest cell-derived craniofacial structures. To investigate shared downstream pathogenic mechanisms, we performed a comparative transcriptomic analysis of zebrafish polr1c and sf3b4 mutant models from our previous studies. Comparative analysis identified 17 shared differentially expressed genes (DEGs) between polr1c and sf3b4 mutants, with the majority of shared genes dysregulated in the same direction, indicating a coordinated rather than random transcriptional response. Gene ontology analysis identified ATP-dependent protein folding chaperone activity as the only shared molecular function, driven in part by upregulation of hsp90aa1.2, indicating a common proteostasis response. Because chaperone activity is linked to extracellular matrix (ECM) protein processing, we cross-referenced DEGs from both mutants against the curated zebrafish matrisome. Three of the 17 shared DEGs (serpinh1b, il11a, and lepa) were matrisome-associated and upregulated in both mutants. Serpinh1b, a collagen-specific chaperone, was strongly expressed in craniofacial cartilage and mesenchymal populations during pharyngeal arch development and exhibited nearly identical fold changes in both mutants. Il11a is of particular interest because its receptor, IL11RA, is known to be associated with human craniosynostosis, suggesting potential relevance to craniofacial development. Together, it is possible to hypothesize that shared chaperone-associated transcriptional changes, together with altered ECM-related gene expression, may contribute to polr1c- and sf3b4-associated craniofacial disorders, warranting further functional validation.

Extracellular Matrix↗

PubMed2026

Adjuvant oxaliplatin with S-1 (SOX) versus S-1 for stage II-III gastric cancer (CAPITAL): A randomized, open-label, phase 3 trial.

BACKGROUND: Adjuvant chemotherapy following D2 gastrectomy constitutes the standard-of-care for resectable gastric or gastroesophageal junction (GEJ) carcinoma. The CAPITAL trial is a multicenter, randomized, phase 3 study, aiming to assess the efficacy and safety of adjuvant oxaliplatin plus S-1 (SOX) versus S-1 alone. METHODS: Patients with histologically confirmed pathological stage II-III gastric or GEJ adenocarcinoma after gastrectomy with D2 lymphadenectomy were randomly assigned (1:1) to receive either the SOX regimen (n = 362) or the S-1 regimen (n = 362). The primary endpoint was overall survival. This study is registered with ClinicalTrials.gov (NCT01795027). FINDINGS: The median follow-up was 74.0 months (interquartile range [IQR], 35.5-89.3). The 5-year overall survival rates were 70.9% (95% confidence interval [CI], 66.0-76.1) in the SOX group and 62.9% (95% CI, 57.8-68.5) in the S-1 group (hazard ratio [HR], 0.74; 95% CI, 0.58-0.95; p = 0.018). The 3- and 5-year disease-free survival rates were 71.2% (95% CI, 66.5-76.3) and 66.2% (95% CI, 61.2-71.6) in the SOX group, as compared with 65.1% (95% CI, 60.2-70.5) and 55.6% (95% CI, 50.4-61.3) in the S-1 group (HR, 0.76; 95% CI, 0.61-0.96). Treatment-related adverse events of grade 3-4 occurred in 87 (25%) of 349 patients in the SOX group and 45 (13%) of 347 patients in the S-1 group. The most common grade 3-4 adverse event was neutropenia, occurring in 44 (13%) of 349 patients in the SOX group and 23 (7%) of 347 patients in the S-1 group. CONCLUSIONS: The addition of adjuvant oxaliplatin to S-1 chemotherapy significantly improved overall survival and disease-free survival in patients with gastric cancer. FUNDING: This research was supported by the National Natural Science Foundation of China (82573092 and 82573387).

Humans↗

PubMed2026

Maternal transfer of nonylphenol drives oxidative, immune, and epigenetic dysregulation in zebrafish offspring.

Nonylphenol (NP), a widespread surfactant and endocrine-disrupting pollutant, poses significant ecological and public health risks globally; however, its transgenerational effects remain poorly understood. Using zebrafish (Danio rerio), we compared chronic maternal NP exposure (50 and 100 µg/L, 28 days) with acute embryonic exposure (0.22 µmol/L) during 0-3 days post-fertilization (dpf) to delineate mechanistic differences in toxicity. Maternal NP exposure produced severe developmental defects in offspring, including edema, axial curvature, impaired swim bladder inflation, reduced growth, cardiac dysfunction, and decreased viability. These phenotypes were accompanied by systemic molecular disruptions including oxidative stress, altered estrogen receptor (ER) expression, dysregulated mitogen-activated protein kinase (MAPK) signaling, and suppressed innate immune response characterized by attenuated neutrophil/macrophage density, reduced CD68 and complement protein C3 expression, diminished nitrite load, and downregulation of pro-inflammatory mediators at both transcript and protein levels. Maternal exposure further induced apoptosis and persistent epigenetic reprogramming (alterations in DNA methylation and histone-modifying enzymes), hallmarks of transgenerational toxicity. In contrast, direct embryonic NP exposure elicited morphological abnormalities without significant lethality, accompanied by induction of pro-inflammatory cytokines, nitric oxide (NO) synthesis, and MAPK activation, reflecting an augmented inflammatory response. These mechanistic contrasts reveal that maternal NP exposure is a potent driver of systemic, heritable molecular reprogramming, whereas embryonic exposure triggers acute inflammatory pathways. Together, our findings underscore the global relevance of NP as a transgenerational toxicant, advocating for its urgent inclusion in ecotoxicological risk assessments and regulatory frameworks.

Animals↗

PubMed2026

Adaptive proteomic remodeling and eNOS upregulation in luminal endothelium and perivascular adipose tissue of patent saphenous vein grafts after CABG.

OBJECTIVE: Long-term patency of saphenous vein grafts (SVGs) remains a significant challenge in coronary artery bypass grafting (CABG). The biological factors underlying successful human grafts are poorly understood. We aimed to characterize the structural and molecular features associated with successful graft function. METHODS: Patent and occluded SVG and internal thoracic artery (ITA) grafts were obtained from explanted hearts of CABG patients undergoing heart transplantation for end-stage heart failure not attributable to graft failure, along with freshly harvested ITA and SVG controls. Samples underwent histomorphological analysis, immunohistochemistry (IHC), and liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomics. RESULTS: Patent ITA (ITA-P) showed minimal intimal hyperplasia with medial reinforcement, whereas patent SVGs (SVG-P) had organized, α-smooth muscle actin (αSMA)-positive myofibroblast-rich neointima. Endothelial nitric oxide synthase (eNOS) was markedly upregulated in patent grafts at two sites-the luminal endothelium and adventitial microvessels within perivascular adipose tissue (PVAT)-and lost at both sites in occluded SVG (SVG-O). Adventitial CD31-positive microvessels were significantly increased in patent grafts. Proteomically, ITA-P and SVG-P shared a largely common adaptive proteome enriched in translation, RNA processing, and extracellular matrix (ECM) organization, with shared upstream activation of NR4A3, EGFR, and STAT1, and conduit-specific signatures (IGF-1/RUNX2 in ITA-P; RETN/SRC/PTGES in SVG-P). PTGES was strongly expressed in the adventitia of SVG-P. CONCLUSIONS: Patent arterial and venous bypass grafts exhibited a shared adaptive phenotype characterized by dual-site upregulation of eNOS in both the luminal endothelium and the perivascular microvessels/PVAT. In SVG-P, PTGES was co-upregulated alongside eNOS, indicating a mechanistic link between the proteomic and IHC findings. These findings highlight the perivascular compartment as a site of adaptive, eNOS-associated changes in patent vein grafts.

Humans↗

PubMed2026

Comparison of VCV and PCV-VG modes on diaphragmatic function in diabetic patients undergoing laparoscopic colorectal surgery: a prospective randomized controlled study.

BACKGROUND: Diabetic patients are prone to induce diaphragmatic weakness, which can lead to postoperative pulmonary complications (PPCs). The optimal mechanical ventilation mode may potentially improve postoperative diaphragmatic function. This study evaluates the effects of two ventilation modes under driving pressure-guided ventilation strategy on diaphragmatic function, as assessed by diaphragm thickening fraction (DTF) and diaphragm excursion (DE), in diabetic patients following laparoscopic colorectal surgery. METHODS: Eighty patients diagnosed with Type II diabetes scheduled for elective laparoscopic colorectal surgery, were randomly allocated to either the pressure-controlled volume-guaranteed ventilation (PCV-VG) group (Group P) or the volume-controlled ventilation (VCV) group (Group V) during surgery. The primary outcome was diaphragmatic function assessed during both tidal breathing and maximal inspiratory effort after surgery. Secondary outcomes included intraoperative mechanical power, PPCs, and other complications. RESULTS: A total of eighty patients were included in the final analysis. The averaged area under the curve (AUC) for mechanical power during ventilation was significantly lower in Group P than in Group V (p = 0.002). PCV-VG significantly improved both DE and DTF within the first two days post-surgery (AUCDEtidal: p = 0.088, AUCDTFtidal: p = 0.004, AUCDEmax: p = 0.029, AUCDTFmax: p = 0.017). Postoperative diaphragmatic weakness was less frequent in Group P than in Group V (p = 0.019). However, there was no difference in the incidence of PPCs between the two groups (p = 0.155). CONCLUSION: PCV-VG mode can reduce intraoperative mechanical power, better preserve postoperative diaphragmatic function. However, these improvements did not translate into clinical benefits, as evidenced by the lack of reduction in the incidence of PPCs.

Humans↗

PubMed2026

Whole genome sequencing of unusual Hepatitis C virus subtypes and drug resistance analysis during direct-acting antiviral therapy in India.

INTRODUCTION AND OBJECTIVES: Pangenotypic direct-acting antivirals (DAA) are effective against highly prevalent Hepatitis C virus (HCV) subtypes, but have been clinically validated almost exclusively in high-income countries. Unusual HCV subtypes may carry natural polymorphisms, potentially impacting DAA susceptibility. We conducted full-genome characterization and resistance analysis of unusual HCV subtypes in patients receiving DAA treatment. PATIENTS AND METHODS: In this prospective hospital-based study, eligible patients were screened for anti-HCV antibodies and active infection was confirmed by diagnostic 5'NCR-based HCV RNA detection. Genotyping was performed by core region sequencing, and viral load quantified by real-time PCR. For whole genome sequencing, multiplex primers were designed using alignments of global reference sequences. Sequencing was carried out using the Oxford Nanopore Technology platform. Phylogenetic analysis used multiple sequence alignment and the HCV-GLUE resource for resistance-associated substitution (RAS) analysis. RESULTS: Predominant genotype was genotype 3 in 64.3% (n = 45); genotype 6 in 21.4% (n = 15); and genotype 1 in 14.2% (n = 10). Unusual HCV subtype 6xa was detected in two patients and showed no NS5A resistance mutations. One genotype 3b patient relapsed at 24 weeks post-DAA treatment completion and carried NS5A resistance-associated substitutions 30 K and 31 M both at baseline and at relapse, conferring high-level resistance to NS5A inhibitors. CONCLUSION: This is the first report from India of whole genome sequencing of HCV subtype 6xa. The identification of NS5A resistance mutations in the 3b relapse case underscores challenges for global HCV elimination strategies.

Humans↗

PubMed2026

The effect of olfactory training and odor exposure on visual selective attention.

Olfactory training (OT) is a well-established, non-invasive intervention that improves olfactory function by repeated, structured exposure to odorants. Beyond sensory outcomes, it also influences multiple aspects of cognition. Yet, its influence on attention, a fundamental process underlying many cognitive domains, remains unclear. This study examined the impact of a 12-week OT program on visual selective attentional performance and the effect of on-task odor exposure. Ninety-four healthy participants were initially included, and randomized into OT or placebo groups. Participants completed the d2 Test of Attention simultaneously with and without odor exposure in a randomized sequence at baseline, post-training, and a follow-up four weeks after stopping the training. The d2 test measures commission errors, omission errors, and concentration performance. Ninety-three participants (OT=51, placebo=42) completed baseline measurement, 74 (OT=39, placebo=35) returned for post-training session, and 57 participants (OT=29, placebo=28) returned for the follow-up appointment. Results showed that OT did not significantly improve d2 test performance. In the primary model, on-task PEA exposure reduced commission errors compared to the odorless condition, suggesting a possible transient effect of olfactory input on the inhibitory control in the context of the d2 attentional test. This effect, however, was no longer significant once the follow-up data were included and should be regarded as preliminary. Overall, these findings raise the possibility of a distinction between relatively long-term OT and short-term odor exposure: while OT did not improve visual selective attention, brief on-task odor exposure may transiently enhance inhibitory control during attentional tasks, a possibility that remains to be confirmed.

Humans↗

PubMed2025

Coupling of spectroscopy and nitrogen-oxygen isotopes unveils the mechanisms of dissolved organic matter and nitrate pollution in lakes within the agro-pastoral transition zone.

Lakes in arid and semi-arid regions are subjected to severe ecological stress, such as organic pollution, eutrophication, and salinization, due to climate change and human activities. This study investigates Chagannur Lake, a typical arid-region lake that is representative and ecologically sensitive in Northern China's agro-pastoral ecotone, to uncover its pollution characteristics and mechanisms. We employed fluorescence spectroscopy and stable isotope analysis to trace dissolved organic matter (DOM) and nitrate sources. The DOM composition was dominated by microbial metabolic byproducts and protein-like substances, suggesting that microbial processes are key to organic matter transformation. Source apportionment revealed that pollutants primarily originated from livestock and poultry manure (37.6 %), agricultural fertilizers (35.6 %), and soil erosion (24.7 %), with agricultural fertilizers contributing most significantly in the Gogstai River (63.3 %). A structural equation model (SEM) coupling spectral and mass spectrometric data revealed that microbial transformation significantly impairs the lake's self-purification capacity, thereby promoting pollutant accumulation (path coefficient = 0.91,*p < 0.05). Moreover, microbial processes link endogenous and exogenous pollution, a mechanism effectively traced by isotopic and fluorescence indices (path coefficient = 0.55, ⁎⁎p < 0.01). These findings enhance the understanding of pollution sources and transformation mechanisms in arid-region lakes and offer foundational theoretical support for policymakers engaged in pollution control strategies.

Lakes↗

PubMed2026

Safety and immunogenicity of an mRNA COVID-19 vaccine administered to adults: A phase 2, randomized, active-controlled trial.

We conducted a phase 2, randomized, active-controlled, observer-blind study (NCT05960097) among healthy adults ≥18 y of age who completed a primary COVID-19 mRNA vaccination series, with or without a booster, ≥3 months earlier. Participants were randomized (1:1:1:1:1) to either receive an investigational bivalent mRNA COVID-19 vaccine encoding ancestral D614G and Omicron BA.4-5 spike proteins (CV0701 mRNA vaccine) at one of three dose levels, an investigational monovalent mRNA COVID-19 vaccine encoding the Omicron BA.4-5 spike protein (CV0601 mRNA vaccine), or a licensed Original Wuhan/Omicron BA.4-5 bivalent mRNA COVID-19 vaccine. The primary objectives were to evaluate reactogenicity, safety and immunogenicity post-vaccination. Secondary and tertiary objectives were to further evaluate humoral and cell-mediated immunity post-vaccination. In total, 425 participants were vaccinated and 381 were included in the Day 29 per-protocol immunogenicity analysis. Most solicited events were mild to moderate. No vaccine-related serious adverse events or myocarditis/pericarditis cases were reported. For the CV0701 mRNA vaccine, a dose-dependent increase in Day 29 neutralizing titers against ancestral D614G and Omicron BA.4-5 was observed. Neutralizing titers against ancestral D614G and Omicron BA.4-5 declined by Days 91 and 181, but remained above baseline. Similar immune responses were observed for the CV0601 mRNA vaccine. At Day 8, CD4+ T cells (Th1 profile) increased in all study groups and CD8+ T cells increased in all study groups, except the lowest CV0701 dose group. The CV0701 and CV0601 mRNA vaccines elicited robust humoral and cellular immunity with an acceptable safety profile, comparable to a licensed, bivalent mRNA vaccine. Clinical Trial Registration EU CT number: 2023-504596-25-00 ClinicalTrials.gov: NCT05960097.

Humans↗

PubMed2026

SET domain bifurcated histone lysine methyltransferase 1 regulates histone modification and DNA damage response during zygotic genome activation in pigs.

SET domain bifurcated histone lysine methyltransferase 1 (SETDB1) is a key epigenetic regulator that catalyzes histone H3 lysine 9 trimethylation (H3K9me3), a mark essential for transcriptional repression and heterochromatin formation. Here, we investigated the role of SETDB1 during zygotic genome activation (ZGA) in porcine embryos. SETDB1 knockdown (KD) was induced by microinjecting double-stranded RNA (dsRNA), and its impact on early embryonic development was evaluated. SETDB1 KD decreased H3K9me3 levels, markedly increased H3K9ac, and downregulated ZGA-associated genes. These epigenetic alterations were accompanied by impaired cleavage, reduced blastocyst formation, and a lower total cell number. Upon etoposide-induced DNA double-strand breaks, SETDB1 KD embryos showed reduced expression of key DNA repair proteins, failed to efficiently restore DNA integrity, and exhibited increased apoptosis, indicating a compromised DNA damage response and repair process. SETDB1 KD also reduced HDAC3 expression, suggesting that SETDB1 may regulate HDAC3 to maintain histone acetylation balance. Consistently, HDAC3 inhibition increased H3K9ac, decreased H3K9me3, and reduced SETDB1 protein levels, supporting a reciprocal regulatory relationship. Together, these findings indicate that SETDB1 is important for porcine embryonic development by coordinating histone modifications and safeguarding genomic integrity during ZGA, and they suggest that the interplay between SETDB1 and HDAC3 constitutes a potentially important epigenetic axis for proper histone modification dynamics and developmental competence.

Animals↗

PubMed2026

Challenges and future directions in AI-driven biomaterials for microbiome-associated oral infectious diseases: A systematic review.

Oral biofilm-induced antimicrobial resistance is the core pathogenic mechanism of microbiome-associated oral infectious diseases (dental caries, periodontitis, peri-implantitis, and endodontic infection). Traditional therapies and biomaterials are limited by poor biofilm penetration, drug resistance induction, single functionality, and inadequate adaptation to dynamic oral microenvironmental changes (e.g., pH fluctuations, salivary rinsing, masticatory stimulation). Artificial intelligence (AI) has transformed the field by integrating materials science, microbiology, and stomatology data. Via machine learning, deep learning, and multi-physics simulation, AI optimizes biomaterial physicochemical properties, decodes microenvironmental signals, constructs precise sensing-response loops, and supports the full chain of material design, performance prediction, and action simulation, advancing treatment from empirical intervention to precision regulation. This systematic review retrieved literature from PubMed, Embase, and Web of Science (January 2016-January 2026) using keywords across three dimensions: AI, biomaterials, and oral microbiome. Following inclusion/exclusion criteria, 99 articles were included. It elaborates on five core mechanisms of AI-driven oral biomaterials (precise oral microbiome analysis, targeted material design/optimization, performance prediction/simulation, targeted delivery/intervention, effect evaluation/dynamic regulation), analyzes their applications in microbiome-targeted biomaterial research and development (R&D) and clinical practice for the four major oral infectious diseases, addresses technical bottlenecks (insufficient targeting specificity and precision of biomaterials, poor stability and durability in complex oral microenvironments, inadequate biofilm disruption capacity, and clinical translation obstacles), and proposes future directions (multimodal design to enhance targeting specificity, structural and component optimization to improve stability/durability, development of multi-mechanism synergistic biofilm disruption strategies, strengthening translational research for clinical application, and deep integration of AI in the full chain of biomaterial R&D). This work provides comprehensive theoretical and practical support for the R&D, optimization, and clinical translation of AI-driven microbiome-targeted oral biomaterials.

Humans↗

PubMed2026

Educational interventions to improve medical students' bad news communication skills: A systematic review and meta-analysis.

OBJECTIVES: This systematic review aimed to both determine whether educational interventions improve medical students' ability and/or confidence in Bad News Communication (BNC), as well as assess the relative efficacy of instructional formats. METHODS: Performed according to the PRISMA guidelines, four databases were searched for articles describing education-based interventions to improve medical student's BNC ability and/or confidence, published in English between 2001 and 2024. Data on students' self-reported or observer-assessed level of competence/ability in BNC (primary outcome), and students' self-assessed confidence in BNC skills (secondary outcomes), were analysed. Meta regression explained the influence of several categorical moderators on heterogeneity in relation to intervention effects on competence/ability. RESULTS: 27 studies met the criteria for inclusion in the systematic review and 17 studies for the meta-analysis. Interventions described in controlled studies were associated with a moderate and significant increase in BNC ability (13 data sets; standardized mean difference [SMD] = 1.09, 95% CI = 0.52 - 1.66). Interventions detailed in pre-post design studies were associated with a significant increase in BNC ability (20 data sets; SMD = 0.92, 95% CI = 0.52 - 1.32), and student confidence/comfort in their BNC skills (12 data sets; SMD = 1.16, 95% CI = 0.57 - 1.75). Subgroup analysis demonstrated better skills/competence outcomes in studies that included simulation-based training (SBT). CONCLUSIONS: Educational interventions improve the BNC ability and confidence of medical students. Interventions should include an SBT element as this leads to greater improvements in BNC ability. Further research is needed to determine to what extent these interventions translate to positive patient outcomes. PRACTICE IMPLICATIONS: Diverse educational programme, especially those including simulation-based training, are effective in improving BNC skills, although the longetivity of these improvements is at present unclear. Therefore, we recommend that refresher courses or practice opportunities should be scheduled throughout students' medical education to ensure retention of BNC skills.

Humans↗

PubMed2026

Efficacy and safety of deucravacitinib, an oral, selective tyrosine kinase 2 inhibitor, in patients with active psoriatic arthritis: 52-week results from the randomised, double-blind, placebo-controlled phase 3 POETYK PsA-1 trial.

OBJECTIVES: The randomised, double-blind, placebo-controlled, phase 3 Program fOr Evaluation of TYK2 inhibitor Psoriatic Arthritis-1 (POETYK PsA-1) trial evaluated the efficacy, safety, and tolerability of deucravacitinib, an oral, selective tyrosine kinase 2 inhibitor, in patients with PsA naïve to biologic disease-modifying antirheumatic drugs. METHODS: Adults with active PsA, high-sensitivity C-reactive protein concentration ≥ 3 mg/L, and ≥ 1 PsA-related hand and/or foot erosion detectable via radiograph were randomised 1:1 to oral deucravacitinib 6 mg once daily or placebo through week (W) 16. At W16, patients continued receiving deucravacitinib or switched from placebo to deucravacitinib through W52. The primary endpoint was American College of Rheumatology 20% improvement in response (ACR20) at W16. Nonresponder imputation was used for missing data. Efficacy and safety were evaluated through W52. Post hoc rank analysis of covariance was used to evaluate structural damage with no missing data imputation. RESULTS: In 670 patients, a significantly greater proportion of those receiving deucravacitinib vs placebo achieved ACR20 at W16 (54.2% vs 34.1%, P < .001). Responses with deucravacitinib were increased at W52. Patients who switched from placebo to deucravacitinib achieved improvements similar to those in patients who received continuous deucravacitinib. Inhibition of structural damage was observed at W16 and W52. At W16, incidences of serious adverse events (AEs) (deucravacitinib, 1.8%; placebo, 2.4%) and discontinuations due to AEs (2.4%; 1.8%) were low and remained low through W52, without imbalances in cardiovascular events, malignancies, or opportunistic infections. No new safety signals were detected; no deaths occurred. CONCLUSIONS: Deucravacitinib demonstrated superiority vs placebo for clinical responses, patient-reported outcomes, and structural damage inhibition in patients with PsA, with favourable tolerability and safety.

Humans↗

PubMed2026

A framework for delivering real-time, instrument-relative navigation in transoral robotic surgery.

Transoral robotic surgery (TORS) is a minimally invasive, inside-out technique that, compared with traditional open approaches, provides fewer post-operative complications, shorter hospital stays, and improved survival for early-stage head and neck cancer. However, TORS is limited by its steep learning curve and poor visualization of deep tumor margins. This randomized crossover study evaluated a surgical navigation system's potential to enhance accuracy and user experience with real-time, instrument-relative feedback. Seven Teflon beads (d = 2.381 mm) were embedded at the tongue base of a porcine pharynx-and-larynx model. Tongue blade compression and retraction were applied to the model to mimic intraoperative tissue deformation, reproducing the anatomical shifts that occur relative to preoperative imaging. Eight participants used the da Vinci Surgical system to localize the beads by placing pins under two conditions: (a) preoperative computed tomography with no navigation; (b) model-based visual navigation with quantitative instrument-to-target metrics. Surgical accuracy was determined by calculating the target localization error (TLE, pin-to-bead Euclidean distance) and the angular error (AE, pin axis trajectory to bead). Accounting for training level and bead depth, surgical navigation reduced TLE by 5.44 mm (95% CI, 4.02-6.86 mm; p = 2.00e-11) and AE by 8.47 degrees (95% CI, 6.21-10.72 degrees; p = 5.17e-11). Impressions of the system were generally favorable using a 5-point Likert survey and task duration (p = 0.26) or cognitive workload via the NASA-Task Load Index (p = 0.22) were not significantly affected. The navigation system demonstrated translational promise, offering improved target localization accuracy and more consistent performance across experience levels, two critical determinants of surgical quality in TORS.

Robotic Surgical Procedures↗

PubMed2026

Ecological Restoration of the Soil-Like Function in the Bauxite Residue: Natural Microbiomes Mediated Molecular Transformation of Dissolved Organic Matter.

Soilization of bauxite residues offers a scalable route for long-term carbon management and ecological restoration. However, the microbial processes that transform exogenous organic inputs into stable soil-like carbon pools remain poorly resolved. Here, we combined cross-ecosystem meta-analysis, machine-learning prediction, native synthetic community (SynCom) construction, 13C-labeled straw microcosms, field validation, Fourier transform ion cyclotron resonance mass spectrometry, and genome-resolved metagenomics to unravel microbiome-mediated carbon transformation at the dissolved organic matter (DOM) molecular scale. Our meta-analysis revealed that alkaline industrial wastes retained soil-like DOM signatures but were enriched in microbial humic- and protein-like components, indicating active yet incomplete carbon processing. Guided by these patterns, native SynCom inoculation increased 13C incorporation into total organic carbon (TOC) and dissolved organic carbon (DOC), enlarged biodegradable and adsorbable DOC fractions, and shifted DOM from recalcitrant aromatic pools toward oxygenated carbohydrate-, tannin-, and phenolic-like molecular classes. Genome-resolved analyses linked this transformation to complementary polymer degradation and nutrient-cycling functions across fungal and bacterial guilds, including enriched carbohydrate-active enzymes in straw-carbon-utilizing metagenome-assembled genomes. Null model and thermodynamic analyses further showed that microbial communities were constrained by homogeneous selection, whereas DOM molecules were diversified through variable selection and redox-dependent transformation. Field-scale validation confirmed that SynCom promoted TOC and DOC accumulation and humic-like, high-density DOM fractions under alkaline conditions. Together, these findings establish a mechanistic framework in which functional microbiomes couple plant carbon depolymerization, DOM molecular diversification, and mineral-interactive carbon stabilization, providing a microbiome-guided strategy for carbon sequestration and soilization in the bauxite residue.

Soil↗