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PubMed2026

Plant cis-regulatory grammar: Decoding the multidimensional code of transcriptional regulation for programmable crop engineering.

Cis-regulatory elements (CREs) orchestrate the spatiotemporal precision of gene expression that underlies plant development, adaptation, and domestication. Decoding the cis-regulatory grammar of plant genomes remains a central challenge in modern biology, with profound implications for programmable crop engineering. Here, recent conceptual and technological advances are synthesized to reshape our understanding of plant CREs. This review first argues that CRE function is not only an intrinsic property of DNA sequence alone but also emerges from a multidimensional context, including chromatin accessibility, histone modifications, three-dimensional genome topology, and cell type-specific regulatory landscapes. Furthermore, the convergence of single-cell epigenomics, high-throughput functional assays, and CRISPR-based dissection has begun to unravel this contextual grammar, revealing the computational principles governing transcriptional regulation. Critically, we propose that artificial intelligence (AI) platforms are catalyzing an ongoing transition from descriptive discovery to predictive engineering, wherein these platforms outperform natural evolution in designing synthetic CREs. Finally, a roadmap is outlined toward a plant regulatory grammar foundation model, which will enable truly predictive engineering of gene expression when fine-tuned for specific tasks. Collectively, the integration of single-cell resolution maps, precise genome editing, AI-driven design, and regulatory-compliant delivery systems promises to transform our ability to reprogram plant gene regulation for next-generation agriculture, bridging the gap between foundational regulatory biology and tangible crop improvement.

artificial intelligence↗
PubMed2026

Uncovering hidden complexity in the Apis mellifera mitotranscriptome: a polyadenylation-centered perspective.

Mitochondrial transcription is gaining increasing attention as researchers seek to better understand the full coding potential of mitochondrial DNA (mtDNA). Emerging evidence suggests that mtDNA may encode additional elements beyond classical oxidative phosphorylation genes, pointing to a more complex transcriptional architecture than previously recognized. In this study, we explored the mitochondrial transcriptome of Apis mellifera (Insecta: Hymenoptera), with a particular focus on polyadenylation-associated features. Our analysis revealed that both sense and antisense transcripts undergo polyadenylation, although transcript abundance and poly(A) tail lengths varied markedly across mitochondrial genes. Several transcripts exhibited alternative isoforms, either extended or truncated, frequently including intergenic regions. These regions may represent functional non-coding elements or structural variants rather than conventional untranslated regions (UTRs). Interestingly, some transcripts also contained non-templated nucleotide additions particularly cytosine residues immediately upstream of the poly(A) tails. Monocistronic units that included portions of downstream intergenic regions were among the most abundantly represented, suggesting a possible regulatory role for these sequences. To experimentally validate our in silico findings, we performed RT-qPCR to assess relative gene expression and applied 3' RACE-PCR to define transcript boundaries. These approaches confirmed the presence of multiple transcript isoforms and supported the involvement of polyadenylation in shaping mitochondrial RNA diversity. Together, our findings reveal a previously underappreciated level of complexity in the A. mellifera mitochondrial transcriptome and highlight the potential regulatory significance of polyadenylation dynamics and intergenic region transcription.

Animals↗
PubMed2026

Dealcoholized muscadine wine improved skin elasticity and oxidative stress biomarkers without affecting gut microbiome in women over 40 in a randomized controlled trial.

Muscadine wine has a unique polyphenol profile distinct from that of common wine, and limited research exists on its health benefits. This study aimed to investigate the effects of intake of dealcoholized muscadine wine (DMW) on skin health, oxidative stress, inflammatory biomarkers, and the gut microbiome. Seventeen healthy women were randomly assigned to consume 300 mL of DMW or a placebo daily for 6 weeks, separated by a 3-week washout period, in a randomized, single-blinded, crossover design. Skin health parameters were measured on the face and forearm. Oxidative stress and inflammatory biomarkers were assessed in plasma. Fecal bacterial DNA was sequenced using shotgun sequencing. DMW did not affect UVB-induced erythema compared to placebo. However, it significantly decreased transepidermal water loss and increased facial gross elasticity. Skin elasticity significantly improved on the forearm, whereas other skin parameters were not affected. DMW significantly decreased plasma levels of matrix metalloproteinase-9 and advanced glycation end products compared with placebo. However, the abundance, diversity, and functions of the gut microbiome were not affected. Polyphenol-rich DMW administered for six weeks improved certain skin health parameters and reduced oxidative and inflammatory stress, without affecting the gut microbiome in healthy women.

Humans↗
PubMed2026

Fructophilic lactic acid bacteria as a window into multi-scale convergent evolution.

Fructophilic lactic acid bacteria (FLAB) are a group of lactic acid bacteria with unique growth characteristics, that is, poor growth on glucose. Their growth is enhanced in the presence of fructose or external electron acceptors. These organisms inhabit fructose-rich environments such as flowers, fruits, and pollinating insects, particularly honey bees. Apilactobacillus spp. and Fructobacillus spp. are representatives of FLAB, although they belong to phylogenetically distant clades. These organisms commonly possess markedly small genomes with a low number of coding DNA sequences. Furthermore, their genomes are characterized by a markedly reduced number of genes involved in carbohydrate transport and metabolism. Genome reduction in FLAB reflects convergent adaptation to fructose-rich environments rather than general genome streamlining. The two distinct FLAB genera, Fructobacillus and Apilactobacillus, independently lost more than 100 genes in statistically similar orders. In contrast, genes involved in carbohydrate and amino acid metabolism exhibited reversed orders of loss between the two genera. Furthermore, FLAB genomes lack an intact bifunctional alcohol/aldehyde dehydrogenase gene (adhE), which causes their poor growth on glucose. A comparative genomic study suggested the evolutionary process underlying adhE gene decay during adaptation to the fructose-rich environments, including pollinating insects. In conclusion, FLAB represent a unique example of habitat-driven convergent reductive evolution that can be investigated across multiple biological scales - from individual genes to whole genomes - in the diverse LAB group with a wide range of habitats, and partially share the fructophilic evolution with eukaryotic yeasts found in fructose-rich habitats.

Fructose↗
PubMed2026

Characterization of ZIC5 expression in esophageal squamous cell carcinoma and its association with patient survival.

Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy known for its aggressive nature and poor prognosis. The present study aimed to investigate the expression levels and clinical importance of the Zic family member 5 (ZIC5) gene in ESCC. Gene expression data and survival information obtained from The Cancer Genome Atlas and Gene Expression Omnibus were utilized. In 176 patients with surgically resected ESCC, immunohistochemical analysis was conducted to validate the expression of ZIC5 protein in cancerous and adjacent tissues. The findings of the present study revealed a significant upregulation of ZIC5 in ESCC compared with normal tissues (P<0.05), which was further corroborated by immunohistochemistry exhibiting a notable association between ZIC5 expression and clinical parameters such as tumor size, invasion depth, lymph node metastasis and TNM staging (P<0.05). Survival analysis further indicated that high ZIC5 expression was an independent prognostic factor for poor outcomes in patients with ESCC (hazard ratio=1.519; 95% CI: 1.017-2.269; P<0.05). In addition, bioinformatic analyses predicted that hsa-microRNA-212-5p may regulate ZIC5 mRNA and gene enrichment analysis suggested that ZIC5 may facilitate ESCC progression through involvement in the cell cycle and DNA repair pathways. In conclusion, ZIC5 is highly expressed in ESCC and associated with a poor prognosis, indicating its potential as a therapeutic target and biomarker for ESCC management. Further studies are warranted to elucidate the precise mechanisms underlying the role of ZIC5 in ESCC progression.

ESCC↗
PubMed2026

Genomic identification and functional characterization of the nuclear receptor gene family in relation to sex determination and gonad development in the Pacific oyster (Crassostrea gigas).

Nuclear receptors (NRs) are a large superfamily of transcription factors that control a wide range of physiological processes by modulating the expression of downstream target genes. Numerous studies have confirmed that NR family members play critical and conserved roles in sex determination and gonadal development across metazoans. However, in mollusks, systematic characterization of NRs and their potential functions in gonadal regulation remain largely unexplored. In this study, 46 NR gene family members in the Pacific oyster (Crassostrea gigas) were identified and assigned to eight subfamilies. All NR family members contain at least one of the two core domains (DNA-binding domain, DBD; ligand-binding domain, LBD), and conserved exon-intron structures were observed within the same subgroup, indicating their evolutionary conservation. Furthermore, expression profiling revealed high expression of CgNR2F, CgNR5A1-1, and CgNR0B1 in undifferentiated gonads, suggesting their potential involvement in sex determination. CgNR1A and CgNR2E5 were specifically expressed in female gonads and exhibited female-biased expression patterns, indicating a putative role in ovarian development. Moreover, CgNR3A and CgNR3B showed high expression levels during the undifferentiated stage and early male development stage, implying their possible participation in male gonadal development and gametogenesis. These results expand the understanding of the NR gene family in C. gigas and help elucidate the potential functions of NR genes in sex determination and gonadal development.

Animals↗
PubMed2026

Do wound protectors reduce contamination in total shoulder arthroplasty? A randomized controlled trial.

HYPOTHESIS: Cutibacterium acnes is the most frequent cause of shoulder prosthetic joint infection with skin edges as a source of wound contamination. The primary purpose of this study was to determine if the use of a wound protector device decreases the deep wound bacterial colonization in primary shoulder arthroplasty. The secondary purpose was to assess the effect of device usage on deltopectoral muscle and cephalic vein injury. METHODS: This was a prospective, randomized controlled trial. A total of 100 patients undergoing primary total shoulder arthroplasty were enrolled and randomized into 2 groups: a wound protector group and a control group. Five patients withdrew from the study, leaving 48 patients in the wound protector group and 47 controls. Three deep wound culture swabs were taken after final arthroplasty implantation. The surgeon also graded deltoid, pectoralis major, and cephalic vein injury on a 0-3 scale based on modification to the Tscherne classification of soft tissue injury. The primary outcome of this study was positive culture results for C acnes. Secondary outcomes included total bacterial culture positivity as well as soft tissue injury grades. A subanalysis removing likely contaminant positive cultures (growth >7 days and 1 colony only) was also performed. Comparisons between groups were made using Fisher exact test for categorical outcomes and t tests and Mann-Whitney U tests for continuous variables. RESULTS: The use of a wound protector did not result in any significant differences compared with controls in the rate of positive cultures for C acnes (15% vs. 21%, P = .593) or all bacteria (15% vs. 26%, P = .304). Removing likely contaminant positive cultures did not demonstrate any significant difference in culture positivity (9% vs. 17%, P = .355, for C acnes; 9% vs. 19%, P = .231, for all bacterial species). The wound protector group had better soft tissue injury scores for the deltoid muscle (P < .001) and pectoralis muscle (P < .001). No difference in cephalic vein injury was noted between the 2 groups (P > .05). No difference in surgical time was noted. CONCLUSION: The use of a surgical wound protector device in total shoulder arthroplasty did not significantly decrease bacterial colonization of the deep wound. However, soft tissue damage to the deltoid and pectoralis muscle was less severe in the wound protector group. These findings suggest that this device reduces iatrogenic soft tissue injury.

Humans↗
PubMed2026

Inhibitory mechanism of phloretin on the AgrA LytTR domain-agr operon complex formation and its application in beef.

Staphylococcus aureus (S. aureus) represents a major foodborne pathogen whose enterotoxin production poses significant challenges to food safety due to its high environmental resistance and limited efficacy of conventional sterilization. Since the expression of enterotoxins is predominantly governed by the agr quorum sensing system, targeting this regulatory pathway has become a strategic choice for virulence control. This study elucidated the mechanism by which phloretin, a potential quorum sensing inhibitor, interferes with the agr system to attenuate virulence. To achieve this, the recombinant AgrA LytTR domain was expressed and purified, and its interaction with phloretin was characterized using thermal shift assays (TSA), electrophoretic mobility shift assays (EMSA), and molecular dynamics (MD) simulations. The results showed that phloretin specifically binds to the AgrA LytTR domain, enhancing its thermal stability and disrupting AgrA LytTR-agr operon binding by reducing the free energy of interaction between them, without causing significant structural rearrangement. Mechanistic analysis indicated that phloretin sterically hinders key &#x3b2;-sheet turn residues (HIS169, ASN201, ARG233), thereby impairing DNA recognition, downregulating RNAIII transcription, and inhibiting agr signaling. In cooked beef, phloretin significantly inhibited the secretion of enterotoxins and &#x3b1;-hemolysin, while delaying lipid oxidation and protein degradation, and maintaining the meat texture. These findings suggested that phloretin is a multifunctional substance with anti-virulence, antioxidant, and preservative properties, demonstrating its potential as a natural food preservative.

Phloretin↗
PubMed2026

Characterization of the Immune Response after Oral Cholera Vaccination (OCV) and Effects of Mycophenolate Mofetil on Priming of this Immune Response-A Randomized, Placebo-Controlled Trial.

Mycophenolate mofetil (MMF) is an immunosuppressive drug widely used by solid organ transplant recipients. Although it is known that MMF suppresses immune responses, its exact effects on specific vaccinations have not been investigated yet. Mucosal vaccinations are increasingly used, such as a cholera vaccination consisting of two oral immunizations (oral cholera vaccination; OCV). This study aimed to investigate the specific immunosuppressive effects of MMF use during the first dose of OCV in a randomized, placebo-controlled trial in healthy volunteers. Moreover, the study aimed to characterize the immune response provoked by OCV in detail. This randomized, placebo-controlled, single-blind trial included 16 healthy volunteers, each receiving two doses of Dukoral&#xae; and an intranasal rechallenge. Outcome measures were serum antibody responses (IgA and IgG) and IgA levels in saliva. Additionally, peripheral blood mononuclear cells (PBMCs) of participants were investigated for ex&#xa0;vivo cytokine production and expression of tissue-specific homing markers after OCV. There were considerable serum IgA and IgG responses after vaccination. MMF-treated volunteers still showed a significant cholera antibody response, though data suggest a potential suppression by MMF without reaching statistical significance. There was no substantial IgA response in saliva. Investigation of PBMCs from OCV-treated participants showed a Th2 skewing with increased ex&#xa0;vivo production of TNF, IL-2, IL-5, IL-13, and IL-22 compared to the placebo group. Taken together, this study provides a framework for future clinical pharmacology studies building on OCV as a challenge model and for further investigation of specific effects of MMF on mucosal vaccination responses.

Humans↗
PubMed2026

Distinct molecular responses to acute cold exposure revealed by comparative transcriptomic and metabolomic profiling in the bay scallop Argopecten irradians.

Acute cold stress can elicit distinct molecular responses even when bay scallop populations show similar phenotypic outcomes. We compared a seventh-generation fast-growing bay scallop line (BS) with a commercial control population (CC) during a 72-h acute cold exposure at -1&#xa0;&#xb1;&#xa0;0.3&#xa0;&#xb0;C. RNA-seq was used as the discovery layer, representative BS cold-responsive genes were evaluated by qRT-PCR, and paired LC-MS profiles provided a comparative metabolic layer. At baseline, 138 genes differed between BS and CC; after cold exposure, 134 of these baseline differences disappeared and 61 of 65 cold-state differences newly emerged. BS showed a larger transcriptomic response magnitude than CC, with 1129 cold-responsive genes compared with 28 genes in CC, and this ordering remained robust across multiple sensitivity analyses. Survival after 72&#xa0;h was identical in BS and CC (83/90, 92.2% in each population). Biochemical responses were time-dependent and marker-specific: CAT, LZM, T-SOD and T-AOC showed population-by-time interactions, whereas GSH-Px and MDA did not, and the 72-h differences were not consistently favourable to BS. Metabolomic cold effects were strongly concordant between populations, and no feature showed a significant population-by-cold interaction. Features putatively assigned to arachidonic acid metabolism were enriched, but this provider-annotated pathway signal remains exploratory because authentic-standard confirmation was not performed. These findings indicate population-specific differences in molecular responsiveness but do not establish superior cold tolerance in BS.

Animals↗
PubMed2026

Haemodialysis Nurses' Self-Reported Cultural Competence and Responsiveness: A Cross-Sectional Survey.

BACKGROUND: People receiving in-centre haemodialysis have distinct cultural care needs and preferences, and nurses are expected to respond to these. However, haemodialysis nurses' cultural competence and responsiveness are unknown. OBJECTIVES: To examine nurses' cultural competence and responsiveness when caring for people with diverse cultural characteristics. DESIGN: An online cross-sectional survey. PARTICIPANTS: Haemodialysis nurses from Australia and New Zealand (n&#x2009;=&#x2009;123), recruited through the Renal Society of Australasia and professional networks. MEASUREMENTS: The 25-item Cultural Competence Assessment instrument measured cultural awareness and sensitivity, and culturally responsive behaviours. Demographic characteristics were also collected. RESULTS: Of 123 complete responses, overall cultural competence was high (M&#x2009;=&#x2009;5.09, SD&#x2009;=&#x2009;0.76), particularly awareness and sensitivity (M&#x2009;=&#x2009;5.76, SD&#x2009;=&#x2009;0.53), with significantly higher scores among those who had completed cultural awareness training (p&#x2009;=&#x2009;0.009). In contrast, culturally responsive behaviours were moderate (M&#x2009;=&#x2009;4.53, SD&#x2009;=&#x2009;1.23), highlighting the gap between cultural competence and responsiveness. The lowest scoring areas were documentation of patients' cultural needs (M&#x2009;=&#x2009;3.88, SD&#x2009;=&#x2009;2.02) and access to cultural learning resources (M&#x2009;=&#x2009;3.02, SD&#x2009;=&#x2009;1.75), indicating limited supports. Qualitative findings reflected practices of culture care preservation and accommodation, with themes of cultural awareness and language differences highlighting barriers related to language and resources. CONCLUSIONS: High cultural competence does not necessarily translate into culturally responsive behaviour. Organisational supports, including guidance for documenting cultural needs, cultural assessment tools and accessible learning resources, may help strengthen culturally responsive haemodialysis care.

Humans↗
PubMed2026

Transcriptomic responses to developmental temperature in two field-collected Spodoptera exigua populations from Korea.

The beet armyworm, Spodoptera exigua, is a polyphagous insect whose development and seasonal occurrence are strongly influenced by temperature. However, transcriptomic responses to developmental thermal regimes remain insufficiently characterized in field-collected populations. In this study, we compared two Korean field-collected populations of S. exigua: a Haenam population collected in May and initially maintained at 15&#xa0;&#xb1;&#xa0;1&#xa0;&#xb0;C (HN), and a Jeju population collected in July and initially maintained at 27&#xa0;&#xb1;&#xa0;1&#xa0;&#xb0;C (JJ). F1 larvae from each population were reared under three fluctuating developmental temperature regimes: low (15-21&#xa0;&#xb0;C), middle (21-27&#xa0;&#xb0;C), and high (27-33&#xa0;&#xb0;C), followed by RNA-seq analysis. Differential expression analysis revealed population-associated variation in transcriptomic responses across developmental temperatures. HN exhibited a larger number of differentially expressed genes under the high-temperature regime, suggesting stronger transcriptomic sensitivity to elevated developmental temperature. Functional enrichment analyses identified population-associated differences in pathways related to heat response, oxidative metabolism, cytoskeletal organization, cuticle-associated processes, lipid metabolism, and immune-related functions. In JJ, heat-response and cuticle-related expression patterns were more prominent under warmer developmental conditions, whereas HN showed broader changes in stress- and metabolism-associated pathways under high temperature. Overall, this study provides a comparative transcriptomic analysis of two field-collected S. exigua populations under different developmental temperature regimes and identifies RNA-seq-based molecular response patterns associated with population-specific thermal response profiles.

Animals↗
PubMed2026

Whole-Genome Deep Learning Predicts Chemotherapy Response in Colorectal Cancer.

Chemotherapy response in colorectal cancer (CRC) exhibits significant heterogeneity, with current clinical predictors failing to capture complex genomic determinants of resistance. We developed a hybrid deep learning framework integrating convolutional neural networks (CNNs) and bidirectional long short-term memory (BiLSTM) networks to analyze whole-genome somatic mutations, evolutionary conservation, chromatin accessibility, and 3D genome architecture in 2,546 TCGA patients. An attention mechanism identified predictive genomic regions. The model achieved an AUC of 0.92 (95% CI: 0.89-0.94) in cross-validation and 0.88 (95% CI: 0.85-0.91) in independent validation, outperforming clinical models (&#x394;AUC = +0.18, p < 0.001). Key predictors included non-coding variants in TP53, KRAS, and PIK3CA regulatory regions. Triple-positive patients (mutations in all 3 regions) had significantly worse progression-free survival (HR = 4.7, p < 0.001). Our framework enables accurate chemotherapy response prediction and reveals novel non-coding resistance mechanisms, advancing precision oncology in CRC.

Humans↗
PubMed2026

Oxygen-controlled gamma-irradiation and annealing enable terminal processing of collagen-based biomaterials.

Gamma irradiation is a widely adopted method for terminal sterilization of medical devices; however, its application to collagen-based extracellular matrix (ECM) materials remains limited due to radiation-induced degradation of structural integrity and mechanical performance. Here, we present an engineered terminal-processing strategy that combines oxygen controlled gamma irradiation (25-30&#xa0;kGy) with post-irradiation dry-heat annealing to preserve ECM functionality while achieving effective sterilization. By modulating oxygen availability during irradiation, this approach alters radical reaction pathways, suppresses oxygen-mediated oxidative degradation, and generates a metastable radical-containing intermediate, which is subsequently converted into a structurally stabilized collagen network through thermal annealing. As a result, the treated matrices preserved ECM integrity and recovered clinically relevant mechanical properties. Furthermore, the process achieved cumulative viral reductions exceeding 6 log10 across a representative panel including enveloped and non-enveloped DNA and RNA viruses, demonstrating compatibility with sterility assurance and viral safety requirements for biologically derived medical devices. Notably, preliminary observations indicate that mechanical integrity can be partially preserved even at elevated irradiation doses up to 50&#xa0;kGy, suggesting potential applicability to sterilization validation frameworks requiring higher assurance levels. Overall, this work establishes a mechanistically grounded terminal-processing paradigm that enables control of radical fate, decouples sterilization efficacy from material degradation, and integrates sterilization, viral safety, and functional preservation into a unified and scalable framework for collagen-based biomaterials. This concept repositions gamma-irradiation from a purely degradative process to a controllable tool for tuning collagen structure and performance.

Gamma Rays↗
PubMed2026

Understanding FDA's reasons for nonapproval: A systematic review of complete response letters in cell and gene therapy.

BACKGROUND AIMS: Cell and gene therapy products face unique regulatory challenges due to their biological complexity and the stringent expectations for manufacturing control, analytical testing, and clinical assessment. As the pipeline grows, understanding the drivers of FDA non&#x2011;approval is increasingly important for improving first&#x2011;cycle success and reducing development delays. In this study, we aimed to characterize the frequency and impact of refuse&#x2011;to&#x2011;file actions, major amendments, and complete response letters issued for biologics licensing applications; and to identify recurring patterns of deficiencies contributing to delayed approval. METHODS: Publicly available documents were extracted from the FDA website. Data from each approved cell and gene therapy product's regulatory history-including complete responses, major amendments, inspection timing, and cited deficiencies-were compiled and categorized across clinical, quality, and labeling domains. RESULTS: Analysis showed that informational deficiencies were common across modalities. Major amendments occurred in roughly half of applications, and complete responses had the most significant impact. Quality deficiencies appeared in all complete responses and were the predominant barrier, while clinical and labeling issues were less frequent but meaningful when present. CONCLUSION: Overall, these findings highlight the need for proactive FDA engagement, comprehensive readiness, and early inspection preparation to reduce regulatory risk and improve first cycle approval outcomes.

Humans↗
PubMed2025

Social Responsiveness as a Mediator in Adapted Cognitive Behavioral Therapy for Autistic Youth with Maladaptive and Interfering Anxiety.

Numerous adaptations to interventions have been included in cognitive behavioral therapy (CBT) for autistic youth. This study examines the degree to which CBT adapted to the social needs of autistic youth confers significant benefit by promoting social responsiveness. A secondary analysis was conducted on a multisite randomized clinical trial (Wood et al. in JAMA Psychiatry 77:474-483, 2020) comparing adapted CBT with standard-of-practice CBT and treatment-as-usual (TA). Autistic youth (N&#x2009;=&#x2009;167; aged 7-13) with maladaptive and interfering anxiety participated. The adapted CBT (BIACA) uses a modular format, with an emphasis on supplementing common CBT practice elements (reframing and graded exposure) with social skill supports. The primary outcome measure was the Pediatric Anxiety Rating Scale. Social responsiveness was assessed with the Social Responsiveness Scale, Second Edition. Participants' general mental health was assessed as a secondary outcome using the Brief Problem Checklist. Mediation was tested using the SPSS PROCESS macro. Analyses suggested that the effect of adapted CBT on anxiety was mediated by its effects on social responsiveness, with a statistically significant indirect effect. Youth randomly assigned to adapted CBT exhibited better overall mental health at posttreatment compared to those randomized to the other conditions, and this effect was also mediated by improved social responsiveness. CBT adapted to address some of the social needs of autistic youth may enhance mental health outcomes by supporting social responsiveness, perhaps increasing the ease and effectiveness with which some youth can navigate potentially stressful situations such as entering and participating in group activities.

Humans↗
PubMed2026

Response-adapted surgical de-escalation following neoadjuvant immunotherapy in resectable mucosal HNSCC A systematic review and meta-analysis.

INTRODUCTION: Recent encouraging outcomes with neoadjuvant immune checkpoint inhibitors (ICIs) in mucosal head and neck squamous cell carcinoma (HNSCC) have generated interest in surgical de-escalation. However, the oncologic safety of response-adapted surgery (RAS) and its ability to achieve survival outcomes comparable to baseline-planned surgery (BPS) remain uncertain. METHODS: A systematic search of the PubMed, EMBASE, Cochrane Library, and the Clinical Trials Registry for studies of neoadjuvant ICIs, with or without chemotherapy, in resectable mucosal HNSCC, that explicitly report surgical extent, between 2020-2025 was performed. Two independent reviewers extracted data following PRISMA guidelines. Main outcomes included major pathologic response (MPR), pathologic complete response (pCR), event-free survival (EFS), and overall survival (OS). Study-level proportions were pooled by random effects models. Heterogeneity was assessed by the I2 statistic. RESULTS: The comparative analysis consisted of 4 RAS studies (involving 202 patients) and 11 BPS studies (403 patients). The pooled overall EFS was 83.3% (76.9-88.2) for the former and 82% (75.2-87.2) for the latter (P=.751), and the respective pooled OS was 92.3% (87.5-95.3) and 91.4% (80.3-96.5) (P=.839). The pooled pCR rate was 41.7% (95% CI 5.4-48.4; I2=.0) for RAS and 19.8% (95%CI 13.3-29.6; I2=.62) for BPS (P=.001), while the MPR was not significantly different (59.6%, versus 48.5%, P=.245). RAS was associated with greater organ preservation and reduced need for mandibulectomy and free-flap reconstruction. CONCLUSIONS: RAS following neoadjuvant ICIs in mucosal HNSCC may enable surgical de-escalation with preserved oncologic outcomes and improved function in selected patients. Larger prospective studies are warranted.

Humans↗