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PubMed2026

CAR-T Cell Therapy: Manufacturing Platforms and Clinical Consequences.

Chimeric antigen receptor (CAR) T-cell therapy has transformed hematological cancer care, yet variability in efficacy, durability, and safety cannot be explained solely by antigen selection or patient factors. We propose that manufacturing platforms are active biological determinants of outcome. Viral vectors, used in all licensed products, provide stable genomic integration and durable expression but are limited by cost, cargo capacity, and centralized production. Nonviral strategies, including transposons, CRISPR knock-ins, and messenger RNA delivery, enable faster, less-expensive manufacturing with larger payloads, while introducing distinct safety and persistence profiles. This review presents a three-layer mechanistic framework that reframes manufacturing as biology: integration biology determines genomic risk and transgene stability; clonal fitness shapes persistence, dominance, and exhaustion; and epigenomic imprinting, influenced by gene transfer method, cytokines, and culture stress, preconfigures functional trajectories. Clinical observations link platform choice to immune recovery, where prolonged B-cell aplasia and delayed T-cell reconstitution contribute to infection-related nonrelapse mortality, and hematopoietic reserve at apheresis emerges as a practical predictor. Finally, manufacturing is positioned as the key to democratizing cell therapy. Decentralized, nonviral production aligned with regulatory standards may enable equitable access and transition CAR-T therapy from innovation to sustainable global care.

Humans↗
PubMed2026

In vivo genome-wide CRISPR screens identify FOXR1 as a suppressor of CD8+ T cell antitumor immunity.

T cell dysfunction critically limits the efficacy of T cell-based immunotherapies in solid tumors, yet the intrinsic regulators of T cell dysfunction remain incompletely understood. Through an in vivo genome-wide CRISPR screen in tumor-infiltrating CD8+ T cells, we identified Forkhead Box R1 (FOXR1) as a potent transcriptional suppressor of CD8+ T cell effector functions. Genetic ablation of FOXR1 significantly enhanced cytokine production and cytotoxic capacity in both murine and human CD8+ T cells, whereas its overexpression impaired T cell activation and effector molecule expression. Mechanistically, multiomics integration of RNA-seq, CUT&Tag-seq, and ATAC-seq revealed that FOXR1 binds directly to promoter regions of key effector genes, including IL2, GZMB, and PRF1, and represses their expression. Importantly, FOXR1 deletion in human anti-CD19 CAR T cells improved their efficacy against solid tumors, demonstrating that FOXR1 is a checkpoint of T cell effector function and targeting FOXR1 is a promising strategy to enhance CAR T cell efficacy against solid tumors.

Animals↗
PubMed2026

Recovery of polysaccharides from marc and pomace through sequential extractions assisted by ultrasound, enzymes and acid maceration.

This study evaluated the pilot-scale recovery of polysaccharides from Vitis vinifera pomace/marc using sequential extraction strategies combining high-power ultrasound (UAE), enzymes (EAE), and acid maceration (AAE). Laboratory-scale trials identified optimal conditions for enzyme dosage and liquid/solid ratio (L/S). Pilot-scale trials demonstrated that the extraction sequence and the processing byproducts influenced extraction efficiency, total soluble polysaccharide in the extract (TSP), and polysaccharide composition. Post-maceration at pH 3.2, with/without the maximum enzyme dose after UAE in a L/S of 1.3/1, improved structural polysaccharide extraction from Viura pomace, while Tempranillo marc showed better recovery of pectic families and TSP with UAE + EAE. Separating grape pomace extract (UAE) from the post-maceration stage at pH 3.2 produced two extracts: E1, with higher yield (19.9%), enriched in structural polysaccharides and oligosaccharides, and E2, enriched in high and medium molecular weight pectic polysaccharides (58.03%), a low degree of esterification (17.1%) and more complex rhamnogalacturan structures.

Polysaccharides↗
PubMed2026

Deciphering CD8+ T cell exhaustion in human cancers through single-cell and spatial transcriptomics.

Exhausted CD8+ T cells (Tex) within the tumor microenvironment (TME) represents a critical barrier limiting anti-tumor immune responses. Tex cells are characterized by upregulated inhibitory immune checkpoint receptors, reduced cytotoxicity, and functional heterogeneity. Their genomic features and regulatory networks remain poorly defined, and only a minority of patients respond to immune checkpoint blockade (ICB) therapy. Single-cell RNA sequencing (scRNA-seq), through high-resolution transcriptomic profiling, has revealed diverse Tex subpopulations, identified subpopulation-specific marker genes and regulatory pathways. Spatial transcriptomics has further mapped the spatial distribution of Tex and their interaction networks with immune cells, tumor cells, and stromal cells, elucidating the impact of spatial heterogeneity on Tex functionality. Current studies indicate that the exhausted state of Tex is dynamic and modifiable, with functional differences among subpopulations closely associated with tumor progression and therapeutic response. However, the genomic characteristics, epigenetic regulation, and spatial interaction mechanisms of Tex require further exploration. This review summarizes recent advances in high-resolution omics technologies for precisely dissecting Tex heterogeneity, functional features, and interactions with other cells. It emphasizes the central value of optimizing Tex-targeted tumor immunotherapy strategies, providing theoretical foundations and directional guidance for developing more effective anti-tumor immunotherapies.

Humans↗
PubMed2026

Nephropathies Associated with Sickle Cell Trait and How to Study Them.

Sickle cell trait (SCT), which carries a single point mutation in the hemoglobin-β (HBB) gene, has long been considered a benign condition. However, epidemiological evidence challenges this assumption, revealing that individuals with SCT face an elevated risk of renal dysfunction. However, this field of study remains ill-defined as it has focused on sickle cell disease (SCD), where renal complications are severe. As SCT is more prevalent than SCD, consequences of nephropathies in this group translate into a substantial and largely unaddressed public health burden. Clinical data, primarily observational, implicate age and sex in the development of SCT-associated nephropathies. These manifestations span glomerular hyperfiltration, tubular damage, hematuria, renal papillary necrosis, renal medullary carcinoma, and progression to chronic kidney disease, all complications that cluster disproportionately in older male individuals. Despite this, the mechanistic basis of SCT nephropathy, the thresholds at which renal injury becomes clinically significant, and the optimal strategies for early identification and prevention remain inadequately defined. In vitro studies have primarily focused on SCD blood cell biology, with SCT receiving comparatively little attention. Humanized murine models (i.e., Berkeley and Townes) have recapitulated some SCT-associated renal phenotypes but need to be more fully characterized. This review aims to provide an overview of the biology of sickle cell trait nephropathies, the gaps in our knowledge, and the model systems we can use to fill those gaps.

Journal Article↗
PubMed2026

Exploring Primary Care Clinicians' Sexual and Reproductive Health Care Delivery to Male Adolescents and Young Adults.

INTRODUCTION: Despite existing guidance for adolescent sexual and reproductive health (SRH) care, male adolescent SRH care receipt is inadequate. Limited research has explored factors affecting clinicians' provision of SRH care to male adolescents, specifically. METHODS: This mixed-method study with 12 primary care clinicians included a brief survey assessing care delivery practices and confidence, followed by an in-depth interview to explore factors affecting SRH care delivery. RESULTS: Clinicians reported high confidence delivering male adolescent SRH care (mean ± SD: 8.31 ± 1.71 out of 10), but delivered only about half the recommended services (20 items out of 38). Factors influencing care delivery included gaps in education/training, assumptions about male SRH care, and behavioral constraints at various levels. DISCUSSION: Findings underscore the need to strengthen male adolescent SRH care by enhancing provider training, increasing clinic-level supports, and addressing structural barriers. CONCLUSIONS: Findings can inform strategies to improve the quality and comprehensiveness of SRH services for male adolescents in primary care settings.

Humans↗
PubMed2026

Morphology-Encoded Colorimetric Hydrogen Sensing Using Embedded Reactive Pd Absorbers in Fabry-Perot Cavities.

Chemical reactions offer a powerful strategy for generating visible optical responses through localized changes in absorption, dielectric environment, and interfacial wetting. A palladium (Pd)-embedded Fabry-Perot cavity is introduced as a reaction-active optical platform in which structural color is governed by intracavity absorption coupled with reaction-induced dielectric perturbation. Positioning Pd within the dielectric spacer creates a spatially controllable reactive absorber whose vertical location relative to the standing-wave field dictates wavelength-selective absorption within the cavity. The morphology of the embedded Pd layer provides an additional design parameter by modulating both optical loss and interfacial wetting. Under hydrogen exposure in the presence of oxygen, catalytic water formation at the Pd/polymer interface generates localized dielectric heterogeneity and interfacial water droplets, thereby perturbing the optical path length and amplifying the visible response. As a result, the cavity exhibits pronounced, morphology-dependent color transitions that are inaccessible through dielectric-layer engineering or Pd/PdH refractive-index changes alone, enabling direct visual hydrogen sensing under ambient light, as well as flexible optical devices capable of large-area patterning. These findings establish a design framework for reaction-active optical cavities that translate localized chemistry into a colorimetric hydrogen sensing mechanism.

Fabry–Perot resonator↗
PubMed2026

To longevity and beyond: A systems view of aging and stress resilience.

Aging is a dynamic and time-dependent process characterized by progressive functional decline across biological systems. Key hallmarks, including genomic instability, telomere attrition, loss of proteostasis, mitochondrial dysfunction, and immunosenescence, have been widely described, each reflecting distinct yet interconnected mechanistic frameworks. Rather than acting in isolation, these processes arise from complex interactions among cellular stressors, impaired repair mechanisms, and the cumulative burden of maladaptive responses. This system-level perspective explains the inter-individual variability in aging trajectories. Centenarians represent an extreme and informative model of successful aging, in which the balance between damage accumulation and repair is shifted toward the maintenance of physiological function. Their exceptional longevity is supported by coordinated genetic, epigenetic, metabolic, and immunological adaptations that enhance resilience to age-related stressors. Here, we summarize the biological drivers and theoretical frameworks of aging within an integrative context, focusing on mechanisms associated with extended healthspan in centenarians. We also examine the contribution of major animal models, highlighting their complementary roles in elucidating conserved and species-specific aging pathways. Overall, aging outcomes reflect a dynamic equilibrium between damage and repair processes. Understanding how this balance is modulated in long-lived individuals may inform strategies to promote healthy aging and delay the onset of age-related diseases.

Humans↗
PubMed2026

Proteomics in environmental pollution research: Advances, challenges, and future directions.

Environmental proteomics has emerged as a powerful approach for elucidating the molecular mechanisms underlying pollutant-induced biological effects. Although this field has developed rapidly, the systematic review of recent proteomics applications in environmental pollution research remains limited. This review explored the emerging roles of toxicoproteomics in biomarker discovery and mechanistic elucidation, as well as ecotoxicoproteomics in ecological risk assessment and bioremediation strategies. Here, we review the field, highlighting recent trends such as the integration of proteomics with genomics, transcriptomics, and metabolomics to provide a comprehensive view of biological responses to environmental stressors. We further discuss the growing application of artificial intelligence in improving proteomics data interpretation and accelerating biomarker discovery. In addition, recent technological advances in environmental proteomics are highlighted, including next-generation tissue microarray proteomics, nanoscale proteomics, single-cell proteomics, and spatial proteomics. Despite its potential, proteomics faces challenges, such as high operational costs, computational complexity in analysis, and technical limitations in low-abundance protein detection. We propose that the convergence of proteomics with artificial intelligence and multi-omics approaches offers promising solutions to these challenges, enhancing the practical application of proteomics in environmental monitoring and risk assessment.

Proteomics↗
PubMed2026

Integrated Telehealth Rehabilitation and Quality of Life in Mechanically Ventilated Adults: A Randomized Clinical Trial.

IMPORTANCE: Whether integrated rehabilitation strategies spanning intensive care unit (ICU), hospital, and postdischarge phases improve quality of life after acute respiratory failure is uncertain. OBJECTIVE: To evaluate the effect of an integrated multicomponent telehealth-based rehabilitation intervention on health-related quality of life at 90 days after hospital discharge among adults with acute hypoxemic respiratory failure requiring invasive mechanical ventilation. DESIGN, SETTING, AND PARTICIPANTS: This stepped-wedge cluster randomized clinical trial in ICUs of 20 public hospitals in Brazil enrolled adults with acute hypoxemic respiratory failure requiring invasive mechanical ventilation between June 2024 and May 2025, with follow-up through September 2025. INTERVENTIONS: A multicomponent telehealth-based rehabilitation program integrating an ICU telehealth-based rehabilitation intervention focused on ventilator liberation; a ward telehealth-based rehabilitation intervention targeting risk stratification and initiation of individualized rehabilitation plans; and a postdischarge telehealth-based rehabilitation intervention consisting of a 2-month personalized centralized telerehabilitation program. MAIN OUTCOMES AND MEASURES: Health-related quality of life at 90 days after hospital discharge, measured using the EuroQol 5-Dimension 3-Level (EQ-5D-3L) utility score (range, -0.17 [worse than death] to 1 [best health state], with 0 representing death). RESULTS: Among 1916 enrolled patients (mean [SD] age, 60.6 [17.3] years; 43.6% female), 1063 were assigned to the intervention and 853 to usual care per local protocols. At 90 days after hospital discharge, mean (SD) EQ-5D-3L utility scores were higher in the intervention group than in the usual care group (0.16 [0.31] vs 0.12 [0.28]; adjusted difference, 0.049; 95% CI, 0.0002 to 0.098; P&#x2009;=&#x2009;.04) but did not differ among survivors (0.60 [0.32] vs 0.59 [0.32]; adjusted difference, -0.045; 95% CI, -0.138 to 0.045; P&#x2009;=&#x2009;.34). Compared with usual care, the intervention resulted in lower 90-day all-cause mortality (71.8% [676 of 941] vs 78.3% [584 of 746]; adjusted difference, -7.6%; 95% CI, -14.7% to -0.6%; P&#x2009;=&#x2009;.03) and shorter mean (SD) mechanical ventilation duration (9.9 [10.3] vs 15.5 [15.9] days; adjusted difference, -6.2 days; 95% CI, -8.5 to -3.9; P&#x2009;<&#x2009;.001). CONCLUSIONS AND RELEVANCE: In this study, an integrated telehealth-based rehabilitation strategy delivered across ICU, hospital, and postdischarge phases improved 90-day health-related quality of life, potentially influenced by reduced mortality. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06343545.

Humans↗
PubMed2026

Emphysematous pyelonephritis in children: Lessons from a case report and systematic review.

BACKGROUND: Emphysematous pyelonephritis (EPN) is a rare, life-threatening gas-producing renal infection. Literature on pediatric EPN remains scarce. OBJECTIVE: To describe a case of pediatric EPN and systematically review the data on clinical presentations, diagnostic modalities, management strategies, and prognosis in pediatric emphysematous pyelonephritis. METHODS: A comprehensive search in PubMed, Embase and Web of Science using defined search terms was done, along with the Joanna Briggs Institute (JBI) critical appraisal checklist for quality assessment. RESULTS: Of 100 records, 20 studies (n = 21) were included in the review. The median (IQR) age of presentation was 48 (8-138) months. The major risk factor was reflux/obstructive nephropathy (52.3 %), and E. coli was the common organism. Management included antibiotics (47.6 %), minimally invasive procedures (33.3 %), or nephrectomy (19 %). We additionally report an adolescent girl with Type 1 diabetes mellitus and class 3A right-sided EPN. She improved with antibiotics and percutaneous nephrostomy (PCN) insertion. CONCLUSION: Obstructive or reflux nephropathy is a major risk factor for pediatric EPN. Antibiotics are the mainstay for treatment with supportive management. Refractory cases may require percutaneous drainage or partial/total nephrectomy.

Humans↗
PubMed2026

School-based sexual violence prevention: A systematic review.

PURPOSE: Sexual violence profoundly affects the health and development of children, adolescents, and young adults, representing a persistent challenge to public policy. This systematic review examined the effectiveness of school-based interventions aimed at prevention. METHODS: Eighteen randomized controlled trials published between 2012 and 2024 were retrieved from four major databases. The programs were implemented in primary, secondary, and higher education settings and targeted children, adolescents, and young adults. RESULTS: The results revealed improvements in knowledge and attitude, particularly regarding consent and awareness, whereas evidence supporting behavioral changes was less frequent and often limited. Methodological limitations, such as short follow-up periods and participant attrition, restricted the assessment of long-term outcomes. CONCLUSIONS: This review highlights the importance of multicomponent, participatory, and culturally sensitive approaches, along with the integration of digital tools and continuous evaluation systems, to strengthen the role of schools as safe and transformative spaces in the prevention of sexual violence. IMPLICATIONS AND CONTRIBUTIONS: This systematic review suggests that school-based interventions hold significant potential for the prevention of sexual violence. It identifies promising strategies and reinforces the importance of culturally sensitive, sustained, evidence-based approaches to ensure learning environments that are safe, protective, and promotive of gender equity.

Humans↗
PubMed2026

Nursing students' perspective of dignity: A systematic review.

AIM: This review synthesizes research on nursing students' perceptions of dignity shaped by education and clinical experiences. BACKGROUND: Respect for human dignity is central to nursing ethics. While dignity is well studied in patient care, less focus has been given to how nursing students perceive and experience dignity during their education. DESIGN: A systematic review of quantitative, qualitative, and mixed-methods studies. METHODS: A comprehensive search was conducted across the Medline, PubMed, ScienceDirect, Scopus, and Web of Science databases for English-language studies published from 2000 to 2025. Quality was assessed using the Joanna Briggs Institute Critical Appraisal Checklist and the Mixed Methods Appraisal. Tool. Data were synthesized thematically. Reporting followed PRISMA guidelines. RESULTS: A total of 24 articles were included. Students viewed patient dignity as linked to respect, privacy, and autonomy. Although students had solid theoretical knowledge, they encountered institutional and professional barriers in delivering dignified care. Supportive environments and participation in decision-making enhanced their sense of dignity. Finally, educational strategies such as role-playing, simulations, and empathy exercises enhanced emotional and psychosocial awareness. CONCLUSIONS: These findings indicate that dignity is crucial in shaping nursing students' professional identity and ethical awareness throughout their education. Reinforcing ethical values and dignity in nursing education is essential for high-quality care.

Humans↗
PubMed2026

Recent advances in electrode materials for electrochemical detection of zearalenone.

Zearalenone (ZEN) is an estrogenic mycotoxin commonly found in cereals, animal feed, and processed foods, making it an important concern for food safety and public health. Conventional chromatographic and immunological methods can detect ZEN; however, they often require expensive instruments, lengthy sample preparation, and skilled personnel, which restrict their use for rapid and on-site testing. Electrochemical sensors have attracted enormous interest of the scientific community because of their high sensitivity, rapid response, low cost, miniaturization potential, and compatibility with portable systems. The analytical performance of the electrochemical sensors is strongly influenced by electrode materials, morphology, conductivity, porosity, surface functionality, and the efficiency of bioreceptor immobilization. Despite several reviews on mycotoxin detection, a systematic assessment connecting electrode-material design, modification strategies, sensing mechanisms, and electroanalytical performance specifically for ZEN sensing remain limited. This review critically evaluates recent advances in metal oxides, carbon-based materials, metal-organic- and covalent organic frameworks, MXenes, polymers, and hybrid composites for electrochemical ZEN detection. Particular attention has been given to their roles in electron transfer, analyte enrichment, selectivity, and real-sample analysis. The review also compares the major limitations of current sensing systems, including complex fabrication, matrix interference, insufficient long-term stability, poor inter-electrode reproducibility, and limited scalability. Finally, future directions for developing robust, cost-effective, portable, and commercially viable ZEN sensors are discussed.

Journal Article↗
PubMed2026

Watershed-scale risk assessment of cadmium contamination in Chinese cropland soils: Dual pathways of irrigation input and flood-driven transport.

Irrigation and flood events serve as critical pathways for the transport of cadmium (Cd) from industrial sources into cropland soils at the watershed scale, constituting a major driver of widespread Cd contamination in China's cropland soil. This study evaluated the risk of Cd contamination in cropland soils across China's nine major river basins at the watershed scale, focusing on the contributions of irrigation and flood events, and conducted a sensitivity analysis of key risk factors. The assessment was conducted within a framework that considered factors including hazard, exposure, and vulnerability. The results revealed that numerous watersheds in southeastern China are exposed to dual pressures of Cd contamination risks in cropland soils, driven by both irrigation practices and flood events. Watersheds categorized as High-High, High-Moderate, or Moderate-High risk, reflecting combined Cd contamination risks from irrigation and flood, are vital to China's grain production, contributing 67.1 % of the national cropland area and 66.4 % of the grain yield. The study suggests localized strategies for managing cropland soils Cd contamination risks from irrigation and flood at the watershed scale in China, alongside strengthened cross-regional collaboration in southeastern China.

Cadmium↗
PubMed2026

Beyond Photometric Consistency: Addressing Loss Insensitivity to Depth Noise in Endoscopic Estimation via Error Calibration.

Self-supervised monocular depth estimation in endoscopy is fundamentally constrained by the ill-posed nature of photometric supervision. In this work, we identify a critical yet overlooked cause of this ambiguity: the inherent insensitivity of photometric loss to depth noise. To overcome this intrinsic limitation, we propose Depth Error Calibration Learning (DECL), a two-stage framework that suppresses prediction variance and mitigates residual errors in self-supervised depth estimation. In Stage I (Variance Reduction), a cyclic depth generation strategy produces multiple depth hypotheses for the input image. The per-pixel empirical variance is quantified and integrated into a dedicated variance loss term, which penalizes inconsistent predictions and encourages the network to generate more stable and reliable depth estimates. In Stage II (Bias Calibration), an image-conditioned diffusion model refines the Stage-I depth prior and mitigates structured residuals through iterative denoising, thereby improving geometric accuracy and global consistency. Extensive experiments on three public endoscopic datasets demonstrate that DECL achieves consistent improvements over representative self-supervised monocular depth estimation methods under the evaluated protocols. Moreover, ablation studies on two representative backbones indicate that DECL is not restricted to a single network implementation, while broader validation on additional backbone families remains necessary. The source code is publicly available at https://github.com/DavidLuBit/EndoDenoising.

Journal Article↗
PubMed2026

Assessing AI literacy and attitudes among medical students: implications for integration into&#xa0;healthcare practice.

PURPOSE: This study aims to assess AI literacy and attitudes among medical students and explore their implications for integrating AI into healthcare practice. DESIGN/METHODOLOGY/APPROACH: A quantitative research design was employed to comprehensively evaluate AI literacy and attitudes among 374 Lusaka Apex Medical University medical students. Data were collected from April 3, 2024, to April 30, 2024, using a closed-ended questionnaire. The questionnaire covered various aspects of AI literacy, perceived benefits of AI in healthcare, strategies for staying informed about AI, relevant AI applications for future practice, concerns related to AI algorithm training and AI-based chatbots in healthcare. FINDINGS: The study revealed varying levels of AI literacy among medical students with a basic understanding of AI principles. Perceptions regarding AI's role in healthcare varied, with recognition of key benefits such as improved diagnosis accuracy and enhanced treatment planning. Students relied predominantly on online resources to stay informed about AI. Concerns included bias reinforcement, data privacy and over-reliance on technology. ORIGINALITY/VALUE: This study contributes original insights into medical students' AI literacy and attitudes, highlighting the need for targeted educational interventions and ethical considerations in AI integration within medical education and practice.

Students, Medical↗
PubMed2026

Embedding cardiovascular risk assessment into routine BTK inhibitor management in chronic lymphocytic leukemia.

INTRODUCTION: Cardiovascular (CV) toxicities remain a major challenge during Bruton tyrosine kinase inhibitor (BTKi) therapy for chronic lymphocytic leukemia (CLL). Selecting the optimal BTKi based solely on a history of overt CV disease may underestimate underlying cardiovascular vulnerability. AREAS COVERED: We performed a targeted, non-systematic review of PubMed and MEDLINE to examine the association between baseline CV comorbidities and BTKi-related CV toxicities in CLL. Current evidence indicates that preferential use of BTKis with more favorable CV safety profiles, coupled with appropriate cardio-oncology surveillance, reduces the risk of CV adverse events in patients with pre-existing CV disease. In patients without established CV disease, the Systematic Coronary Risk Evaluation 2 (SCORE2) and SCORE2-Older Persons (SCORE2-OP) may help identify clinically meaningful latent CV risk, enabling early optimization of modifiable risk factors in line with the proactive cardiovascular management strategy endorsed by the 2026 European Hematology Association (EHA) CLL guidelines. EXPERT OPINION: A structured, risk-adapted approach integrating standardized CV risk assessment, early management of modifiable risk factors, individualized BTKi selection, and multidisciplinary cardio-oncology collaboration may improve the safety and tolerability of BTKi therapy in CLL. Pending prospective validation, SCORE2 and SCORE2-OP should complement, rather than replace, dedicated cardio-oncology evaluation.

Humans↗