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PubMed2026

Effects of H-coil TMS on suicidality in major depression: A secondary analysis of data from a multisite randomized trial comparing accelerated to once-a-day stimulation.

Suicide is the 10th leading cause of death in US adults. Standard once-daily repetitive transcranial magnetic stimulation (rTMS) can reduce suicidal ideation. Yet, antidepressant and anti-suicidal effects often take several weeks to emerge, while rapid improvement is often required. Accelerated TMS has been proposed as a strategy to hasten therapeutic response. A recent FDA-regulated multicenter trial evaluated accelerated intermittent theta burst Deep TMS with the H1-coil versus standard high-frequency Deep TMS in MDD. Both groups demonstrated high remission and response rates for depression, with the accelerated protocol showing non-inferiority and a shorter time to remission. The goal of this exploratory secondary analysis was to evaluate the impact of these two H-coil TMS dosing paradigms on suicidal ideation. The Scale for Suicide Ideation (SSI), as well as suicidality items of HDRS, MADRS and CUDOS were collected and analyzed. On all scales, both accelerated and standard Deep TMS protocols were associated with meaningful reductions in suicidality. The accelerated protocol achieved a faster onset of improvement. Comparison between the timeline of improvement in suicidality and in overall depressive symptoms found a trend for faster improvement in suicidality, especially with the accelerated protocol. These findings highlight the importance of treatment frequency in determining time to clinical benefit and support the use of scalable accelerated protocols for patients requiring more rapid symptom relief.

Humans↗
PubMed2026

Modulating sentence comprehension in people with aphasia through anodal tDCS: A double-blind randomized cross-over study.

This double-blind randomized cross-over study investigated the effects of perilesional anodal transcranial direct current stimulation (AtDCS) combined with speech-language therapy on sentence comprehension in eight individuals with chronic nonfluent agrammatic aphasia. The behavioral therapy consisted of an intensive comprehension treatment including drilling in sentence-to-picture matching and Mapping Therapy. Each participant underwent both the anodal tDCS and sham stimulation conditions (five received sham first followed by real stimulation, and the remaining three the reverse sequence), with each condition paired with the same behavioral treatment and separated by a four-month washout period. Stimulation was applied over the perilesional area (left BA6) for 20 min during daily 40-min therapy sessions over four consecutive weeks. Sentence comprehension was assessed with the RiComprendo battery and functional communication with the Communicative Effectiveness Index (CETI). Data were analyzed using paired t-tests, Bayesian analyses, and linear mixed-effects models to control for baseline performance and individual variability. Both stimulation conditions produced significant pre-to-post improvements in sentence comprehension, particularly for syntactically complex structures such as passives and center-embedded object relatives. However, gains were overall greater following AtDCS, as reflected in larger effect sizes, stronger Bayes factors, and a significant treatment effect in the mixed-effects models. Only the AtDCS condition yielded significant improvements in self-perceived comprehension abilities on the CETI. These findings suggest that AtDCS over perilesional cortical areas may boost the effects of traditional language therapy on sentence comprehension, supporting its feasibility and potential as an adjuvant intervention in post-stroke aphasia rehabilitation.

Humans↗
PubMed2026

Engineering copper ferrite (CuFe2O4) nanocomposites for enhanced eco-friendly photocatalysis: a systematic critical review on mechanisms, performance, and environmental applications.

Water pollution caused by organic and inorganic contaminants, particularly dyes and pharmaceuticals, represents a major environmental challenge. Advanced oxidation processes based on photocatalysts have emerged as efficient and sustainable approaches for water and wastewater treatment. Copper ferrite (CuFe2O4) is considered a promising photocatalyst owing to its narrow bandgap, visible-light activity, chemical stability, and magnetic properties. Despite extensive experimental investigations, a comprehensive systematic comparison of CuFe2O4-based photocatalysts under diverse operational conditions has remained limited. In this study, a systematic review following PRISMA guidelines was conducted using studies published between January 2014 and November 2025 indexed in Scopus, PubMed, Web of Science, and ScienceDirect. From an initial pool of 397 studies, 98 articles met the inclusion criteria. Key parameters - including pollutant type, pH, catalyst dosage, initial pollutant concentration, irradiation time, light source, and degradation efficiency - were quantitatively compared to identify performance trends and operational optima. The results demonstrate that CuFe2O4-based nanocomposites, particularly heterojunction, Z-scheme, and S-scheme architectures combined with TiO2, g-C3N4, graphene, and metal oxides, achieve high degradation efficiencies (often >90 %) for a wide range of organic pollutants and selected inorganic contaminants (e.g., Cr(VI)). Enhanced charge separation and suppressed electron-hole recombination were identified as the primary factors contributing to improved photocatalytic activity. In addition, the intrinsic magnetic properties of these nanocomposites enable facile catalyst recovery and reuse. In conclusion, CuFe2O4-based nanocomposites, especially those incorporating advanced heterojunction architectures, emerge as highly efficient and magnetically recoverable photocatalytic platforms for sustainable water and wastewater treatment, with strong potential for scalable implementation and real-wastewater applications.

Catalysis↗
PubMed2026

Diversity and population connectivity of members of the family Eunicidae inhabiting deep-water corals in the North Atlantic.

Eunicid polychaetes are often found in association with Cold Water Corals (CWCs), even establishing symbiotic relationships, such as those described between Desmophyllum pertusum and Eunice norvegica. While genetic connectivity of CWCs across the North Atlantic has been widely studied, little is known about their associated fauna in this regard. Here, we present a study combining a focused analysis of the genetic and genomic connectivity of E. norvegica with a regional assessment of the distribution and evolutionary relationships of three CWC-associated eunicid species from the Cantabrian Sea and the North of the United Kingdom (190-1,230 m depth). An integrative approach using genetic (16S, COI and 18S), morphological and ecological data allowed the identification of the eunicids studied, with new records of Eunice cf. nicidioformis and Leodice cf. antarctica in the Cantabrian Sea, as well as previously undocumented associations with CWC species. In addition, RADseq data contributed to the delimitation of the closely related species E. norvegica and Eunice philocorallia. Moreover, the genetic connectivity of E. norvegica was studied trough a RADseq (1,067 neutral SNPs) approach. Our results indicate a single panmictic population across approximately 2,000 km, suggesting that oceanographic currents facilitate passive dispersal of E. norvegica lecithotrophic larvae, aided by coral host stepping-stones. The connectivity patterns observed for E. norvegica mirror those of D. pertusum, on which the worm is ecologically dependent. Our study highlights the importance of using integrated genetic, morphological and ecological data to characterise and delineate understudied CWC-associated species and improve our understanding of their dispersal capabilities and genetic connectivity to inform future conservation recommendations.

Animals↗
PubMed2026

Expression profiles of miRNAs in ruminant intermediate hosts with cystic echinococcosis.

Cystic echinococcosis (CE), caused by the larval stage of Echinococcus granulosus sensu lato (s.l.), is a parasitic zoonotic disease recognized by the World Health Organization as a neglected tropical disease of significant public health concern. Despite ongoing control programs, CE remains endemic, underlining the need for integrated control strategies that involve new diagnostic and therapeutic tools. Recent investigations have spotlighted microRNAs (miRNAs) as key regulators in parasite development, immunomodulation, and as potential diagnostic and therapeutic targets. In the present research, a molecular study was conducted to investigate hydatid cyst samples (protoscoleces and germinal membranes) collected in southern Italy from different ruminant species (sheep, cattle, and water buffaloes), naturally infected with CE, with the ultimate goal of establishing a more comprehensive picture of miRNA expression patterns in these intermediate hosts. The bioinformatic analysis of hydatid cyst samples revealed 168 mature miRNAs. Among these, egr-miR-10-5p, egr-let-7-5p, and egr-miR-71-5p were the most abundant, with egr-miR-10-5p showing particularly high expression levels. No significant differences in miRNA abundance between host species were found. In contrast, when focusing on the comparison between protoscoleces and sterile germinal membranes, 24 miRNAs were found to be differentially expressed. Targeted qPCR of four selected miRNAs (egr-miR-71-5p, egr-let-7-5p, egr-miR-125-5p, and egr-miR-10-5p) showed clear overexpression in protoscoleces and in fertile germinal membranes compared with sterile ones. The differential miRNA expression patterns provide insight into the molecular mechanisms controlling the parasite's lifecycle and may guide the development of novel intervention methods to enhance CE control in endemic areas.

Animals↗
PubMed2026

Comparative analysis of lipopolysaccharide lipid A structure and its biosynthetic genes in the plant-associated bacteria Brucella cytisi and Brucella lupini.

The genus Brucella comprises important human and animal pathogens, as well as numerous environmental and symbiotic species. Lipopolysaccharide (LPS), a major component of the outer membrane of Gram-negative bacteria, plays a crucial role in bacterial physiology and host interactions. In this study, the structures of lipid A, the hydrophobic anchor of lipopolysaccharide, isolated from two plant-associated strains, Brucella cytisi ESC1ᵀ and Brucella lupini LUP21ᵀ, were presented. Lipid A preparations were structurally characterized using chemical methods, MALDI-TOF mass spectrometry, and nuclear magnetic resonance spectroscopy. The obtained results indicated that both lipid A molecules have almost identical structures. Their sugar backbones consist exclusively of 2,3-diamino-2,3-dideoxy-d-glucose (d-GlcpN3N). Phosphate residues were connected to distal and proximal GlcpN3N in approximately half of the lipid A molecules. Fatty acid analysis revealed the presence of C14:0 (3-OH), C16:0 (3-OH), and traces of C18:0 (3-OH). All of these were primary fatty substituents of the sugar backbone and were amide-linked residues. Lactobacillic acid C19:0cyc and 27-hydroxyoctacosanoic acid (C28:0 (27-OH)) were found as ester-linked secondary acyl residues. In turn, C28:0 (27-OH) was partly esterified by a 3-hydroxybutyroyl residue. Two unsubstituted 3-hydroxyfatty acids were linked exclusively to the proximal d-GlcpN3N residue. It was pointed out that sequences of putative genes encoding enzymes required for lipid A biosynthesis and genes encoding specific enzymes involved in structural modifications of lipid A occurring in the genomes of both bacterial species are almost identical. The high sequence similarity of these proteins reflects the observed similarities in the lipid A structures in both investigated Brucella species.

Brucella↗
PubMed2026

Risk prediction models for blood transfusion in patients undergoing total hip and knee arthroplasty: a systematic review and meta-analysis.

OBJECTIVE: To systematically review and evaluate published risk prediction models for perioperative blood transfusion in patients undergoing total hip or knee arthroplasty (THA/TKA). METHODS: We systematically searched PubMed, Web of Science, the Cochrane Library, and Embase from inception to May 31, 2025. Two researchers independently screened the literature, extracted data, and assessed the risk of bias and applicability using the Prediction model Risk Of Bias Assessment Tool (PROBAST). The area under the receiver operating characteristic curve (AUC) values were pooled via a meta-analysis using Stata 18.0. RESULTS: d Fourteen studies containing 36 prediction models were included. The incidence of blood transfusion among THA/TKA patients ranged from 3.2% to 30.8%. Preoperative hemoglobin (Hb) level, tranexamic acid (TXA) use, operative duration, intraoperative blood loss, and age were the most frequently incorporated predictors. Model sensitivity ranged from 58% to 94.5%, and specificity ranged from 71.3% to 94%. Meta-analysis showed that the pooled AUC value of the 13 validated models was 0.87 (95% CI: 0.85-0.90), suggesting good discriminatory performance. All models were rated as having a high risk of bias. The applicability of four studies was rated as unclear. CONCLUSION: Although the included studies demonstrated promising discriminative ability of prediction models for blood transfusion in THA/TKA, all were assessed as having a high risk of bias using the PROBAST tool. Therefore, future research should prioritize the development of models with larger sample sizes, rigorous study designs, and multicenter external validation.

Humans↗
PubMed2026

Stapled versus hand-sewn intestinal anastomosis in pediatric surgery: A systematic review and meta-analysis.

BACKGROUND: Intestinal anastomosis is a core procedure in pediatric gastrointestinal surgery, performed for conditions such as necrotizing enterocolitis, intestinal atresia, Hirschsprung's disease, and inflammatory bowel disease. Although stapled anastomosis (SA) may improve operative efficiency, its safety and effectiveness compared with hand-sewn anastomosis (HA) in children remain uncertain. This meta-analysis compared clinical outcomes of SA and HA in pediatric patients. METHODS: The study followed PRISMA guidelines and was prospectively registered in PROSPERO (CRD420251177257). A systematic search of PubMed, Dimensions, and the Cochrane Library was conducted through June 2025. Studies including children under 7 years undergoing intestinal SA or HA were eligible. Two reviewers independently performed study selection, data extraction, and risk-of-bias assessment using ROB 2 and ROBINS-I tools. Statistical analysis was conducted using Comprehensive Meta-Analysis software (v3) with a random-effects model. RESULTS: Eleven studies involving 903 patients met inclusion criteria, including two randomized controlled trials. Of these, 333 patients underwent SA and 570 underwent HA. SA was associated with significantly shorter operative time (mean difference [MD] = -19.26 min; 95% CI: -24.24 to -14.28; p < 0.001) and earlier initiation of oral feeding (MD = -2.32 days; 95% CI: -3.78 to -0.86; p = 0.002). No significant differences were found in anastomotic leakage, stricture formation, reoperation rate, or length of hospital stay. CONCLUSIONS: Stapled anastomosis appears as safe as hand-sewn techniques in pediatric intestinal surgery while offering shorter operative duration and faster postoperative feeding recovery. Selective use of stapled techniques is supported when anatomically feasible, though further multicenter randomized trials are needed.

Humans↗
PubMed2026

Quantifying the combined effects of semi-closed terrain and monsoon on PM2.5 and O3 pollution aggregation in the North China Plain.

The North China Plain (NCP) and its surrounding regions represent one of the key priority areas for air pollution control. As anthropogenic emissions decline significantly, the effect of terrain and meteorology on air pollution pattern has become increasingly prominent, particularly given the NCP's unique semi-closed terrain and East Asian monsoon dynamics. However, quantitative characterization of terrain-dominated blocking effects remains unexplored. Here we quantitatively assess the blocking effects of mountains and terrain-coupled meteorological factors on air pollutant dispersion. We find the NCP on the eastern side of the Taihang Mountains showed high PM2.5 and O3 pollution levels, with winter PM2.5 and summer O3 high-value zones showing opposite north-south aggregation patterns. PM2.5 and O3 concentrations were highest in plains, followed by platforms, hills, and finally mountains. Within the 120-km buffer zones of the typical mountains in the NCP and its surrounding regions, PM2.5 and O3 concentrations increased initially with altitude but then decreased markedly above a threshold altitude. Above the threshold altitude, mountain blocking effects became dominant. The effective blocking altitudes of typical mountains in the NCP and its surrounding regions ranged between 22 and 929 m for winter PM2.5 pollution, and between 19 and 1060 m for summer O3 pollution. The Terrain-Wind Close Index indicates that the terrain-coupled East Asian monsoon showed stronger blocking effects on PM2.5 dispersion in southern NCP during winter and on O3 diffusion in northern NCP during summer, matching observed high-pollution zones. This study offers key insights for regional joint air pollution mitigation strategies, as well as regional pollution assessment.

Particulate Matter↗
PubMed2026

Multidisciplinary mHealth Rehabilitation for Patients With Abdominal Cancer Who Are Receiving Chemoradiotherapy: Randomized Phase II Trial.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) for abdominal cancer frequently induces muscle loss, weight loss, and malnutrition. OBJECTIVE: This exploratory randomized phase II trial evaluated whether a multidisciplinary, mobile health (mHealth)-based multimodal rehabilitation program could preserve handgrip strength and muscle mass in patients with abdominal cancer undergoing CCRT. METHODS: In this prospective, multicenter, randomized, open-label phase II trial (NCT05325554), 111 eligible patients with abdominal malignancies scheduled for CCRT were randomly assigned (1:1) to receive either multidisciplinary mHealth rehabilitation care (MRC; n=57) or standard care (SC; n=54). The MRC program was delivered by a dedicated multidisciplinary team using the AiNST mHealth platform and wearable heart rate monitors. The primary end point was handgrip strength at the end of CCRT (analyzed with analysis of covariance adjusting for baseline). Secondary end points were exploratory and analyzed without multiplicity adjustment; sensitivity analysis using false discovery rate (FDR) correction was performed. RESULTS: Between February 2022 and April 2023, 111 patients were enrolled. Adherence was high (n=93, 83.9% achieved exercise targets). After adjusting for baseline handgrip strength, the MRC group had significantly higher handgrip strength at the end of CCRT than the SC group (adjusted mean difference 4.87 kg, 95% CI 3.36-6.38; P<.001). Exploratory analyses of secondary end points (without multiplicity adjustment) showed that the MRC group also had better preservation of body weight (P=.005), skeletal muscle mass (P<.001), serum albumin (P=.009), prealbumin (P=.02), and lower rates of hematological toxicity (P<.05), as well as improved psychological status (distress thermometer [DT] and Hospital Anxiety and Depression Scale [HADS]) and nutritional scores (Nutritional Risk Screening 2002 [NRS-2002] and Patient-Generated Subjective Global Assessment [PG-SGA]) at the end of CCRT (all P<.05). All nominally significant secondary end points remained significant after FDR correction (q<.05). These findings are preliminary and should be interpreted with caution due to the open-label design, population heterogeneity, and exploratory secondary analyses. CONCLUSIONS: In this exploratory phase II trial, a multidisciplinary, mHealth-based multimodal rehabilitation program was associated with better preservation of handgrip strength, muscle mass, and nutritional status, as well as lower rates of certain treatment toxicities, compared with SC. However, definitive conclusions are limited by the open-label design, heterogeneity of tumor types, and short follow-up. Larger, blinded phase III trials are needed to confirm these findings.

Humans↗
PubMed2026

A Sentiment-Based Comparison of AI- and Physician-Generated Empathic Statements in Palliative Care.

CONTEXT: Empathic communication promotes trust in patient-provider relationships. As healthcare integrates artificial intelligence (AI) into patient communication, we have yet to understand how these models' communication compares to that of physicians. OBJECTIVES: Our primary objectives were to examine patient preferences for AI-generated vs. palliative care physician-generated empathic statements addressing fear and anxiety around cancer treatment, and to analyze associations between linguistic features and patient preferences. METHODS: We conducted a secondary analysis of the PALL-AI trial, a randomized controlled survey comparing cancer patients' preferences of AI- to physician-generated empathic statements. Physicians and AI were provided the same prompt with a maximum sentence length. Patient preferences for each statement were measured in blinded surveys. We analyzed sentiment of the statements using the Valence Aware Dictionary and Sentiment Reasoner (VADER) and the National Research Council Canada (NRC) Emotion Lexicon. We evaluated associations between sentiment scores and patient preferences using Spearman's correlation coefficients. RESULTS: A total of 105 patients completed blinded surveys, preferring the AI-generated statement 72.4% of the time. VADER sentiment analysis showed all three AI statements displayed positive sentiment, while all three physician statements displayed negative sentiment. Controlling for statement length, AI statements used twice as many positive words as human statements. However, they contained a similar number of negative words. Of the eight NRC emotions, "trust" and "joy" demonstrated the strongest correlations with patient preference. CONCLUSION: Patients preferred AI-generated statements around cancer care over those from palliative care physicians when standardized for prompt and statement length. Analysis shows AI-generated statements contain more positive language which may be the factor driving patient preference toward AI.

Humans↗
PubMed2026

Wildlife forensic DNA evidence links a suspected vehicle to a fatal lowland tapir (Tapirus terrestris) collision in Misiones, Argentina.

Vehicle collisions are recognized as a major driver of biodiversity loss, particularly in road-dense landscapes, exceeding the impact of invasive species and wildlife trafficking. For large-bodied, slow-reproducing, and low-abundance species, such as the lowland tapir (Tapirus terrestris), this threat can have major impacts. Here, we present a wildlife forensic investigation in Misiones, Argentina, involving a tapir, a species afforded the highest level of legal protection as a Provincial Natural Monument. The fatal hit-by-vehicle (HBV) incident occurred in northern Misiones on 31 March 2019 along Provincial Route 19, in a portion that bisects Parque Provincial Urugua-&#xed;, with the driver involved in the collision leaving the scene. The suspect was later located and claimed that the damage to the vehicle resulted from a collision with a horse (Equus caballus) rather than a tapir. To legally resolve the incident, DNA (hair and blood) recovered from the suspected vehicle's bumper (evidence) was compared with tissue samples from the tapir carcass (reference). Genetic confirmation of species identity used a 110-bp region of the mitochondrial cytochrome b gene, and individual identity was assessed using 12 species-specific microsatellite loci. These analyses confirmed that all evidence matched the tapir carcass at both species and individual levels, strongly supporting the association between the suspected vehicle and the HBV tapir, and refuting the alternative explanation proposed by the driver. This case demonstrates the value of using wildlife forensic genetics to reconstruct wildlife-vehicle collisions, supporting environmental law enforcement, and strengthening conservation efforts in the Atlantic Forest of Misiones, Argentina.

Animals↗
PubMed2026

Natural products alleviate exercise-induced fatigue by modulating gut microbiota: a systematic review.

BACKGROUND: Exercise-induced fatigue critically impairs athletic performance and training quality. The gut microbiota, as a key regulator of the "gut-muscle axis," has emerged as a promising anti-fatigue target. Natural products - owing to their diverse sources, structural complexity, and favorable safety profiles - have attracted growing research interest. However, a systematic synthesis comparing their anti-fatigue effects via gut microbiota modulation across different sources is lacking. SCOPE AND APPROACH: We systematically searched PubMed, Web of Science, the Cochrane Library, and CNKI for original studies that administered natural products and concurrently assessed gut microbiota changes and anti-fatigue outcomes. Twenty-six studies (25 animal experiments and 1 human trial) were included and categorized into seven groups by source and chemical characteristics. A descriptive systematic review was conducted to identify common mechanisms and source-specific differentiations. KEY FINDINGS AND CONCLUSIONS: The enrichment of short-chain fatty acid (SCFA)-producing bacteria and the activation of the SCFA-AMPK/PGC-1&#x3b1; axis were shared core events across all product categories. However, source-dependent mechanistic divergences emerged: polysaccharides acted primarily as fermentable substrates with an optimal dose window; polyphenols and saponins exerted dual modulation on both microbiota and host signaling pathways; compound extracts achieved systemic synergy through functional complementation; marine- and animal-derived products exhibited unique targeting profiles and rapid action. Intestinal barrier maintenance and brain-gut axis regulation further extended the anti-fatigue repertoire. Collectively, natural products possess a solid mechanistic basis for alleviating exercise-induced fatigue via gut microbiota remodeling. The differentiated characteristics of these methods in targeting precision and pathway engagement provide a theoretical foundation for designing precision intervention strategies tailored to specific fatigue contexts.

Humans↗
PubMed2026

A therapeutic atlas of monogenic inflammatory bowel disease.

BACKGROUND AND AIMS: Evidence-based, mechanism-guided therapies are urgently needed for treating monogenic inflammatory bowel disease (mIBD). For such rare diseases, mechanistic insight is essential to guide treatment when conventional clinical trials are often not feasible. We aimed to summarize literature-based evidence and to identify knowledge gaps. METHODS: We conducted a systematic review of published manuscripts evaluating the therapeutic efficacy in mIBD. We quantified and compared the global therapeutic response score across treatments and conditions. In a subset of conditions, biomarkers of longitudinal therapeutic response were evaluated in comparison to non-monogenic pediatric IBD cohorts. RESULTS: Responses to 35 therapeutics across the 102 known genetic causes of mIBD were evaluated in 241 articles and 669 patients, summarizing 302 gene-drug responses. The efficacy of at least one pharmacological intervention was identified in 61% (n&#x2009;=&#x2009;62/102) of the mIBD conditions, highlighting a major unmet need for effective medications in many others. Gene- and pathway-specific responses were demonstrated for several therapies, including allogeneic hematopoietic stem cell transplantation, gene therapy, and advanced therapies such as anti-TNF agents, IL-1 inhibitors, mTOR inhibitors, as well as eculizumab in CD55 deficiency, abatacept in CTLA4 deficiency, and the immunometabolic agent empagliflozin in glycogen storage disease type 1b. CONCLUSIONS: This study highlights the potential of precision medicine approaches tailored to genetic and pathway-specific mechanisms, while underscoring the urgent need for effective therapies in many monogenic conditions that remain without established treatment options.

Humans↗
PubMed2026

The Long Road to Long-Acting: What Oral PrEP and CAB-LA Teach Us About Scaling Lenacapavir.

Despite significant biomedical advances, human immunodeficiency virus (HIV) remains a persistent global health crisis, with over 40 million people affected as of 2023, two-thirds of whom live in the World Health Organization (WHO) African Region. However, from an HIV prevention perspective, the more urgent concern is the continued occurrence of approximately 1.3 million new infections annually, particularly in sub-Saharan Africa and in settings where incidence is stable or increasing. This commentary explores the evolving landscape of HIV prevention, focusing on the trajectory of oral pre-exposure prophylaxis (PrEP), long-acting injectable cabotegravir (CAB-LA), and the newly emerging lenacapavir. While oral PrEP opened new possibilities, adherence challenges have limited its impact. CAB-LA demonstrated superior efficacy but encountered access, cost, and delivery barriers that restricted uptake. Lenacapavir, offering 6-monthly subcutaneous dosing with &#x2265;&#xa0;99.9% efficacy in trials, holds the potential to overcome these hurdles. As of May 2026, lenacapavir had received regulatory approval in 17 countries, including several African nations, while regulatory reviews remained ongoing in multiple additional countries, reflecting the rapid global expansion of access to this long-acting HIV prevention option. However, its success depends on clinical promise, timely licensing, affordability, and integration into health systems. Drawing from real-world lessons of oral PrEP and CAB-LA, this paper argues that a proactive, coordinated rollout of lenacapavir could dramatically expand prevention reach. With global stakeholders aiming for 3 million users by 2028 and strategic licensing in 120 countries, the groundwork is in place. The recent release of WHO guidance recommending lenacapavir as an additional PrEP option further strengthens this momentum. Yet, equitable delivery, user-centred models, and strong policy backing will be critical. Ultimately, long-acting PrEP is not just a clinical breakthrough; it is a test of health systems' ability to deliver innovation at scale.

Humans↗
PubMed2026

The future of TCR-Treg therapies is renewables.

Cell therapy has longstanding roots in haematopoietic stem cell transplantation and early immune cell transfers in infectious disease and transplantation, where patient- or donor-derived cells have achieved therapeutic benefit in selected contexts. The modern era has been driven largely by oncology, with engineered modalities such as tumour-infiltrating lymphocytes, CAR-T cells and TCR-engineered T cells delivering transformative responses but requiring complex, costly manufacturing. These platforms are now being adapted for autoimmune diseases to induce durable, antigen-specific immune tolerance, yet broad application is limited by safety concerns, process complexity and access. Non-engineered cell therapies for autoimmunity, including mesenchymal stem cells, polyclonal regulatory T cells and tolerogenic dendritic cells, have shown acceptable safety and proof-of-principle for immune re-education, but clinical responses have been modest and inconsistent, with limited scalability. Engineered approaches such as CAR-T cells can induce reversible B cell depletion in B cell-mediated rheumatic diseases but only addresses antibody-driven pathology and not T cell-mediated autoimmunity. TCR-engineered Tregs have emerged as a promising antigen-specific strategy, offering localized, antigen-linked suppression with bystander tolerance. Preclinical and early clinical data suggest superior potency, stability and disease control compared with polyclonal Tregs at similar or lower doses, but translation is constrained by the rarity and fragility of Tregs and by labour-intensive, CAR-T-like manufacturing. This review highlights emerging solutions for closed, automated and decentralised production, and discusses allogeneic approaches using gene-edited or banked Tregs with HLA engineering or matching. Together, these advances support the development of scalable, "off-the-shelf" TCR-Treg products with potential to provide safe, affordable tolerance-restoring therapies for autoimmune disease.

Humans↗
PubMed2026

Introgression shapes the genomic conflict landscape of Malus, providing evidence for a reticulate backbone in a woody crop lineage.

Phylogenomic discordance is widespread across plants, but its evolutionary significance is often obscured when conflict is treated primarily as analytical noise rather than as evidence of underlying processes. In woody lineages in particular, incomplete lineage sorting, introgression, and genome duplication can interact over long timescales to produce complex genomic histories that are not adequately summarized by a strictly bifurcating tree. Here, we use Malus as a model woody genus to investigate how these processes structure conflict across a genus-scale, accession-based phylogenomic framework. Using broad taxon sampling, hundreds of nuclear loci, plastid genomes, and genome-wide SNP summaries, we reconstruct a robust nuclear backbone for sampled Malus lineages and evaluate where discordance is concentrated and which processes best explain it. Nuclear analyses resolve eight major clades, whereas conflict is non-random and localized to recurrent hotspots rather than evenly distributed across the tree. Cytonuclear discordance is similarly concentrated, especially around Clade H, represented by sampled accessions of M. tschonoskii, where localized plastid-nuclear disagreement is consistent with candidate plastid capture or organellar introgression. Multiple complementary analyses further indicate that the strongest conflict is not explained by ILS alone, but instead reflects lineage-structured introgression, while polyploid complexes represent additional localized sources of evolutionary complexity. Together, these results provide evidence for a reticulate genomic backbone in Malus and show how integrating nuclear, plastid, and genome-wide conflict analyses can help distinguish background discordance from process-specific signals in woody plant radiations. Several lineage-level reticulation hypotheses identified here should now be tested with broader population-level sampling and curated reference accessions.

Malus↗
PubMed2026

Meniscal preservation in the age of biologics: toward a quantitative decision algorithm for personalized repair.

BACKGROUND: Despite advances in arthroscopic repair and biologic augmentation, surgical indication for meniscal tears remains heterogeneous. No standardized framework currently integrates biomechanical, clinical, and biological determinants to guide repair versus resection. PURPOSE: To develop a quantitative decision model-the Meniscal Preservation Score (MPS)-that unifies biomechanical and biological evidence to stratify reparability potential and standardize treatment selection in meniscal surgery. METHODS: A systematic evidence synthesis conducted in accordance with PRISMA 2020 reporting standards of studies published from 2000 to 2025 in PubMed, Embase, and Scopus identified key determinants of meniscal healing. Five consistent predictors-patient age, vascularity, tear morphology, associated pathology, and activity profile-were weighted through a two-round modified Delphi consensus among ten experienced knee surgeons. The resulting 0-9-point MPS was incorporated into a stepwise decision tree linking lesion morphology, biological context, and surgical strategy. Conceptual validation used 50 simulated cases and a retrospective cohort of 45 patients to test agreement between algorithm recommendations and expert surgical decisions. RESULTS: The MPS achieved 86% concordance with expert judgment in simulation and 84% agreement in clinical validation. In this retrospective exploratory cohort, cases in which surgical management was concordant with MPS recommendations demonstrated higher mean IKDC scores at 24&#xa0;months and lower observed reoperation rates. These findings should be interpreted as associative rather than causal, as treatment allocation was not controlled and discordant cases may have represented inherently more complex pathology. CONCLUSION: The MPS represents an evidence-informed decision-support framework designed to systematize reparability assessment. While exploratory analyses suggest structural coherence with expert reasoning, prospective implementation and external validation are required before clinical adoption as a predictive tool. LEVEL OF EVIDENCE: conceptual model with exploratory validation.

Humans↗