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CD163 is a transmembrane scavenger receptor predominantly expressed by activated M2-like macrophages and is involved in inflammatory processes. Oxysterols, which accumulate in atherosclerotic lesions, are known to induce oxidative stress and apoptosis in macrophages. However, the relationship between CD163 expression and apoptosis induced by oxysterols remains poorly understood. Our brief report presents an examination of the effects of an atheroma-relevant mixture of 7β-hydroxycholesterol and 7-ketocholesterol (2mix) on cell surface CD163. THP-1 monocytes/macrophages were exposed to 2mix, and the surface expressions of CD163, apoptosis, and reactive oxygen species (ROS) production were assessed using flow cytometry and fluorescence microscopy. Exposure to 7-oxysterols induced a dose-dependent reduction in cell surface CD163 expression, with significant decreases observed in R1 and R2 cell populations but not in R3. This decrease was accompanied by a significant increase in apoptosis and ROS production. Notably, CD163 expression was inversely correlated with both apoptotic cell death and oxidative stress levels. Our findings suggest that macrophage surface CD163 may exert a protective role against 7-oxysterol-induced apoptosis and oxidative stress. This indicates a potential function of CD163 in macrophage survival and highlights its possible importance for plaque stability in atherosclerotic lesions. Full article

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11 pages, 534 KB

Open AccessReview

Perioperative Systemic Therapies in Resectable Non-Small Cell Lung Cancer: Opportunities and Challenges

by Natalia Kwiatkowska, Alain Gelibter, Piotr Gabryel and Cezary Piwkowski

J. Clin. Med. 2026, 15(13), 5009; https://doi.org/10.3390/jcm15135009 (registering DOI) - 27 Jun 2026

Abstract

Background/Objectives: Recent advancements in immunotherapy have significantly reduced recurrence rates and improved distant outcomes of patients with non-small cell lung cancer. This review synthesizes literature from 2020 to 2025, concentrating on preoperative immunotherapy outcomes. Methods: We analyzed treatment regimens, focusing on primary endpoints, the percentage of patients who underwent initial surgery, type of surgery, R0 rate, immune-related adverse events and chemotherapy-related toxicities as well as the rate of surgery delays and cancelations. Results: Our findings emphasize the importance of optimizing patient selection, effectively managing adverse events, and implementing strategies to minimize surgical delays and cancelations. Conclusions: We defined areas for improvement, such as increasing the implementation of minimally invasive surgeries and avoiding pneumonectomies. These priorities are essential for increasing the efficacy of immunotherapy in surgical settings for NSCLC, and improving patient outcomes. Full article

(This article belongs to the Special Issue Surgical Treatment for Lung Cancer—2nd Edition)

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29 pages, 4739 KB

Open AccessReview

Research Progress on Intelligent Prediction, Debittering Technologies, and Multi-Dimensional Evaluation for Bitter Peptides

by Jun-Tong Wang, Cheng Luo, Cai-Xia Jiang and Xi-Qun Zheng

Foods 2026, 15(13), 2301; https://doi.org/10.3390/foods15132301 (registering DOI) - 27 Jun 2026

Abstract

Bioactive peptides have health benefits, but the intense bitterness associated with their hydrolysis severely restricts their industrial applications. This paper systematically constructs a collaborative theoretical framework that integrates intelligent prediction, targeted debittering, and multi-dimensional evaluation. Firstly, it reviews the core applications of deep learning (such as quantitative structure–activity relationship (QSAR) and graph convolutional network (GCN)) combined with molecular docking technology in the high-throughput identification of bitter peptides and the analysis of target receptor interaction mechanisms. Secondly, it discusses how artificial intelligence and computational simulation can improve the efficiency of traditional debittering processes, emphasizing the advantages of multifunctional composite wall materials in the targeted encapsulation and delivery of bitter peptides, as well as the metabolic regulatory mechanisms behind controlling microbial fermentation for the debittering of specific peptide substrates. Finally, to provide a high-fidelity data closed loop for artificial intelligence (AI) models, a three-dimensional cross-validation system integrating standardized quantitative sensory evaluation and biomimetic electronic tongues was established. Future research should focus on developing large models for flavor generation to drive the green and targeted creation of low-bitterness and highly active peptides. Full article

(This article belongs to the Special Issue Artificial Intelligence-Driven Research into Functional Proteins and Peptides)

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18 pages, 318 KB

Open AccessArticle

A Quantitative Hardy Scale for Mixed Local–Fractional Energies and Applications to Singular Schrödinger Forms

by Ghaliah Alhamzi, Riyaz Ahmad Padder, Zahoor Ahmad Rather, Veena Beleyur, Prakash Jadhav, Aadil Hussain Dar and Mdi Begum Jeelani

Axioms 2026, 15(7), 482; https://doi.org/10.3390/axioms15070482 (registering DOI) - 26 Jun 2026

Abstract

We develop a quantitative Hardy scale for mixed quadratic energies combining the classical Dirichlet form and a fractional Dirichlet form, [...] Read more.

We develop a quantitative Hardy scale for mixed quadratic energies combining the classical Dirichlet form and a fractional Dirichlet form,

E_{λ, s} (u) = \int_{R^{n}} {| \nabla u (x) |}^{2} d x + λ \int_{R^{n}} {| {(- Δ)}^{s / 2} u (x) |}^{2} d x, 0 < s < 1, λ > 0 .

Here, the word scale denotes a parameterized family with a fixed interpolation variable, explicit constants, and the scaling exponent forced by the coexistence of the orders 2 and

2 s

. For

n \geq 3

, we prove weighted

L^{2}

inequalities indexed by

γ \in [s, 1]

, which control

{| x |}^{- 2 γ}

E_{λ, s}

with the factor

λ^{- θ}

, where

θ = (1 - γ) / (1 - s)

. In dimension

n = 2

, the local endpoint is replaced by the logarithmic Hardy weight and gives a mixed log–power family governed by the same parameter. The novelty lies in organizing the endpoint Hardy estimates into a

λ

-adapted form suitable for mixed-order operators, with explicit constants, scaling-level optimality of the

λ

exponent, a planar endpoint formulation, and directly usable singular-potential thresholds. The operator consequences are stated at the level of form boundedness, coercivity, spectral lower bounds on bounded domains, semigroup generation, and variational well-posedness; they are presented as consequences of the Hardy scale rather than as a separate spectral theory. Full article

(This article belongs to the Section Mathematical Analysis)

28 pages, 3348 KB

Open AccessArticle

Coconut Water Microfiltration Optimization Using Response Surface Modeling, Neural Networks, and Genetic Algorithms: Performance and Nutritional Retention

by José Diogo da Rocha Viana, Arthur Claudio Rodrigues de Souza, Paulo Riceli Vasconcelos Ribeiro, Lorena Mara Alexandre Silva, Kirley Marques Canuto, Katia Rezzadori, Giordana Demaman Arend, Ana Paula Dionísio and José Carlos Cunha Petrus

Membranes 2026, 16(7), 221; https://doi.org/10.3390/membranes16070221 (registering DOI) - 26 Jun 2026

Abstract

Although coconut water is recognized for its desirable sensory appeal and nutritional composition, its broader industrial use is constrained by the rapid deterioration that occurs after extraction. In this study, crossflow microfiltration of coconut water with a silicon carbide membrane was optimized by investigating pressure and temperature through a face-centered design (FCD) and artificial neural network modeling coupled with a genetic algorithm (ANN–GA). Permeate flux and fouling index were used as process responses, and the optimized condition was further examined in terms of hydraulic resistance, fouling behavior, and retention of minerals and primary metabolites. Pressure and temperature affected the process differently: permeate flux showed marked nonlinear behavior, whereas fouling index was governed mainly by pressure. At the sample level, ANN described permeate flux more accurately than FCD (R² = 0.99 vs. 0.96), whereas FCD showed better grouped cross-validated predictivity across unseen pressure–temperature conditions (Q² = 0.85 vs. 0.57). For the fouling index, FCD outperformed ANN in both sample-level fit and grouped validation (R² = 0.95 vs. 0.60; Q² = 0.70 vs. 0.61). Both approaches converged on the same favorable operating window, and experimental validation at 60 kPa and 35 °C yielded 1085.23 ± 23.12 L h⁻¹ m⁻² and 83.56 ± 1.56%. During concentration mode, flux decline was severe but predominantly reversible, with high clean-water permeance recovery after chemical cleaning. Resistance partition and fouling modeling indicated that the main hydraulic limitation was associated with concentration polarization and external cake-layer buildup rather than irreversible membrane damage. The clarified fraction also preserved high transmission of major minerals and relevant primary metabolites, indicating that the selected condition combined high productivity, manageable fouling, and satisfactory nutritional retention. Full article

(This article belongs to the Special Issue Application of Membrane Technologies in Food Processing)

19 pages, 745 KB

Open AccessArticle

Connectivity of Networks Modeled by Weighted Graphs

by Pedro García-Vázquez

Axioms 2026, 15(7), 481; https://doi.org/10.3390/axioms15070481 (registering DOI) - 26 Jun 2026

Abstract

A graph

G = (V, E)

together with two positive real-valued weight-functions

w_{V} : V \to R_{> 0}

and

w_{E} : E \to R_{> 0}

is called a weighted graph and is denoted by [...] Read more.

A graph

G = (V, E)

together with two positive real-valued weight-functions

w_{V} : V \to R_{> 0}

and

w_{E} : E \to R_{> 0}

is called a weighted graph and is denoted by

(G; w_{V}; w_{E})

. In this paper, we introduce the concepts of connectivity, edge-connectivity, and restricted edge-connectivity for a weighted graph

(G; w_{V}; w_{E})

, and we prove general bounds analogous to those in the unweighted case. Furthermore, we study the connectivity and edge-connectivity of the line graph and the

P_{2}

-path graph of a weighted graph, establishing upper and lower bounds for each of these parameters. Full article

(This article belongs to the Special Issue Graph Invariants and Their Applications)

28 pages, 464 KB

Open AccessArticle

A Noble Gas-Centered Coordinate for Within-Period Atomic Property Trends

by Jonathan Washburn, Megan Simons and Elshad Allahyarov

Symmetry 2026, 18(7), 1087; https://doi.org/10.3390/sym18071087 (registering DOI) - 26 Jun 2026

Abstract

We introduce a single dimensionless landscape function

J_{chem} (ρ) = cosh (ρ ln φ) - 1

, with

φ = (1 + \sqrt{5}) / 2

, defined on the noble gas-centred coordinate [...] Read more.

We introduce a single dimensionless landscape function

J_{chem} (ρ) = cosh (ρ ln φ) - 1

, with

φ = (1 + \sqrt{5}) / 2

, defined on the noble gas-centred coordinate

ρ = d / L_{p} \in [0, 1)

, and show that it organizes four central within-period atomic observables, first ionization energy

{IE}_{1}

, electron affinity

EA

, Mulliken electronegativity

χ_{M}

, and Pearson chemical hardness

η

, on a single periodic-table axis. The outward step

Δ J_{chem}^{+}

delivers

{IE}_{1}

, the inward gap

Δ J_{chem}^{-} = J_{chem} (1) - J_{chem} (ρ)

delivers

EA

and

η

, and

χ_{M}

follows from Mulliken’s identity. Benchmarked against NIST and Pearson tabulated atomic data, the framework reproduces the within-period

{IE}_{1}

envelope across periods 2–6 and localizes every upward deviation on the textbook anomaly sites

{p^{3}, d^{5}, f^{7}, s^{2}, d^{10}}

; it yields two parameter-free golden ratio ionization-energy identities (

φ^{1 / 4}

on heavy noble gas pairs and

φ^{2}

on halogen/alkali pairs, agreeing with data to MAD

\approx 1 %

and

\approx 5 %

); and it provides single-parameter analytical fits for

EA

(MAE

0.3

–

0.4

eV), Pearson hardness

η

, and Mulliken

χ_{M}

(

R^{2} = 0.73

on a 15-atom 4-class benchmark). By assembling four periodic-table observables under one golden ratio cosh coordinate, the construction provides a compact analytical reference against which relativistic and shell-anomaly corrections can be quantified. Full article

(This article belongs to the Topic Advanced Electromagnetic Modeling and Simulation for Multidisciplinary Engineering Systems)

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14 pages, 295 KB

Open AccessFeature PaperArticle

A Formula Similar to a Consequence of the Join Theorem

by Yasuhiko Kamiyama

Axioms 2026, 15(7), 480; https://doi.org/10.3390/axioms15070480 (registering DOI) - 26 Jun 2026

Abstract

Let

u : (C^{m}, 0) \to (C, 0)

and

v : (C^{n}, 0) \to (C, 0)

be holomorphic function germs that have isolated critical points at the origin. It [...] Read more.

Let

u : (C^{m}, 0) \to (C, 0)

and

v : (C^{n}, 0) \to (C, 0)

be holomorphic function germs that have isolated critical points at the origin. It is known that

μ (u + v) = μ (u) \cdot μ (v)

holds, where

μ

denotes the Milnor number. In this paper, we consider a formula similar to the above one. More precisely, for Morse functions

f : M \to R

and

g : N \to R

, let

C (f + g)

denote the fiber product of two copies of

f + g

. Two of the main results are as follows: Firstly, under a generic condition on the critical values of f and g, the equation

χ (C (f + g)) = χ (C (f)) \cdot χ (C (g))

holds. Here

χ

denotes the Euler characteristic. Secondly, under a certain condition, the converse of the first result is also true. Full article

(This article belongs to the Section Geometry and Topology)

20 pages, 3476 KB

Open AccessArticle

Coupled Hydro-Mechanical Investigation of Fracture Propagation and Seismicity of Hydrofracturing in Naturally Fractured Rock

by Yanxin Lv, Xiaoyu Fang, Jiang Lu, Pu Yang, Haibo Li, Guifeng Wang, Yi Xin and Weiji Liu

Processes 2026, 14(13), 2091; https://doi.org/10.3390/pr14132091 (registering DOI) - 26 Jun 2026

Abstract

Hydraulic fracturing in naturally fractured rock is governed by complex interactions between fluid flow, rock deformation, fracture propagation, and induced seismicity. In this study, a fully coupled hydro-mechanical framework based on the FDEM is developed to investigate fracture evolution and seismic responses during fluid injection in fractured rock masses. Three representative horizontal stress ratios (R = 1.0, 1.5, and 2.0) were considered to investigate the influence of stress anisotropy on fracture propagation and induced seismicity. The results demonstrate that stress anisotropy exerts a dominant control on fracture propagation patterns, fluid pressure diffusion, and induced seismicity. Under low stress ratios, fracture propagation is diffuse and strongly influenced by pre-existing fractures, whereas higher stress ratios promote localized, directional fracture growth controlled primarily by the stress field. Fluid pressure becomes increasingly concentrated with increasing stress ratio, leading to higher injection pressures and more pronounced pressure fluctuations. The spatial and temporal evolution of mean stress and volumetric strain closely follows that of fluid pressure, indicating that fluid pressurization directly controls effective stress reduction and associated deformation. Seismic analysis reveals a systematic decrease in the Gutenberg–Richter b-value with increasing stress ratio, indicating a transition from distributed micro-fracturing to more coherent fracture reactivation and larger seismic events. Under quasi-steady injection pressure conditions, fracture propagation is found to be episodic and unstable, as evidenced by pronounced positive and negative spikes in the fracture volume change rate and associated pressure fluctuations; these are accompanied by intermittent fracture opening and closure, stress redistribution, and temporary reductions in cumulative seismic moment. These findings provide new insights into the coupled mechanisms governing hydrofracturing-induced seismicity and have important implications for the assessment and mitigation of seismic risks in subsurface engineering applications. Full article

(This article belongs to the Section Process Control, Modeling and Optimization)

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13 pages, 464 KB

Open AccessArticle

Psychological Factors Associated with Learning in Bioscience Courses Among Undergraduate Nursing Students

by Kyriakos Kiourtidis, Andrea Paola Rojas Gil, Athina Patelarou, Sotirios G. Zarogiannis and Erasmia Rouka

Nurs. Rep. 2026, 16(7), 221; https://doi.org/10.3390/nursrep16070221 (registering DOI) - 26 Jun 2026

Abstract

Background/Objectives: Undergraduate nursing students consider bioscience courses essential to their education and clinical practice, yet they often find them challenging. This study explored the associations among achievement goal orientations, perceived stress, and self-esteem to examine factors associated with bioscience learning in nursing education. Methods: A quantitative cross-sectional study was conducted with undergraduate nursing students enrolled in the first-year courses “Biology–Clinical Biochemistry” and “Genetics”. Data were gathered using the Perceived Stress Scale-14 (PSS14); the Achievement Goal Questionnaire-Revised (AGQ-R), divided into four subscales, each representing a goal type (mastery-approach or AGQ MA, mastery-avoidance or AGQ MAV, performance-approach or AGQ PA, performance-avoidance or AGQ PAV); and the Rosenberg Self-Esteem Scale (RSES). Univariate and multiple regression analyses were conducted using SPSS v26.0, with significance set at p < 0.05. Results: Perceived stress was negatively associated with self-esteem in both Biology–Clinical Biochemistry and Genetics (p < 0.001). The assessment of potential links between quantitative variables and the study topic using univariate analysis showed an association of course category with the PSS14 score (p= 0.008). This finding remained significant in the regression analysis (p = 0.004), which also identified an effect of gender on the same scale (p = 0.029). Multiple regression further revealed associations between AGQ MA and the subject of study (p = 0.047), AGQ MAV and gender (p = 0.001), AGQ PAV and gender (p = 0.016), and RSES Total and type of secondary education (p = 0.007). Conclusions: Psychological factors interact dynamically with the demands of bioscience education within tertiary nursing curricula, varying according to demographic and academic traits. Full article

(This article belongs to the Section Nursing Education and Leadership)

20 pages, 339 KB

Open AccessArticle

The Existence of Mild Solutions for Hilfer Fractional Differential Equations with Infinite Delay in Orlicz Space

by Renqing Suonan, Yuhang Jin, Yanan Wang, Jia Mu and Ling Guo

Fractal Fract. 2026, 10(7), 438; https://doi.org/10.3390/fractalfract10070438 (registering DOI) - 26 Jun 2026

Abstract

The Hilfer fractional derivative effectively captures non-locality, historical dependence, and memory effects, making it valuable for modeling real-world systems, and exponential growth can describe explosive growth phenomena in real-world problems. This paper focuses on the existence of mild solutions for infinite-delay differential equations [...] Read more.

{(- Δ)}^{δ}

, and exponentially growing functions in Orlicz spaces. First, by utilizing standard

L^{p}

L^{q}

estimates for strongly continuous semigroups generated by fractional Laplacian operator, the existence of global solutions in the Orlicz space

exp L^{p} (R^{d})

and the time-weighted

L^{z} (R^{d})

space is established. Then, by leveraging Hölder’s interpolation inequality, the existence of local solutions in

L^{1} (R^{d}) \cap L^{\infty} (R^{d})

is established. Full article

(This article belongs to the Section General Mathematics, Analysis)

13 pages, 2189 KB

Open AccessArticle

First Record of Hepatospora eriocheir Infection in the Chinese Mitten Crab Eriocheir sinensis in the Baltic Sea

by Magdalena Stachnik, Monika Normant-Saremba and Anna Kycko

Pathogens 2026, 15(7), 681; https://doi.org/10.3390/pathogens15070681 (registering DOI) - 26 Jun 2026

Abstract

Hepatospora eriocheir is a microsporidian parasite of the Chinese mitten crab Eriocheir sinensis, an invasive decapod now widely distributed in European inland and coastal waters. Although the host is common across much of Europe, confirmed European records of H. eriocheir have remained scarce and, until now, have not included the Baltic Sea region. In this study, 15 adult E. sinensis collected from the Vistula Lagoon, southern Baltic Sea, were examined using gross pathological assessment, wet-mount microscopy, histopathology, PCR amplification, Sanger sequencing, and phylogenetic analyses of parasite SSU rRNA and host COI sequences. Hepatopancreatic alterations were observed in several individuals, ranging from pale discolouration and friability to loss of normal tissue organisation. Spores were detected in fresh squash preparations from affected tissue, and histology revealed epithelial disruption, intratubular spore accumulation, and necrotic changes consistent with progressive microsporidian infection. Molecular screening confirmed H. eriocheir in 60.0% of crabs, with positive cases occurring in both females and males. The parasite sequences formed a single, well-supported clade and were highly similar to previously reported H. eriocheir sequences from the United Kingdom and China. Host COI sequences represented three mitochondrial haplotypes, indicating that the infection occurred across more than one host mitochondrial haplotype background. These findings constitute the first record of H. eriocheir in E. sinensis from the Baltic Sea and support the hypothesis that infected crabs reaching the Vistula Lagoon are connected with the wider North Sea invasion system rather than an isolated Baltic lineage. Full article

(This article belongs to the Special Issue Pathogens of Fish and Shellfish)

31 pages, 7092 KB

Open AccessArticle

Biocontrol Microbial Inoculants Suppress Fusarium oxysporum-Associated Disease Symptoms in Rice and Reshape Multicompartment Microbiomes

by Assemgul K. Sadvakasova, Dilnaz E. Zaletova, Meruyert O. Bauenova, Bekzhan D. Kossalbayev, Tao Xu, Dariga K. Kirbayeva, Lazzat Asylbekkyzy, Huma Balouch, Dauren Botbayev and Altynbek A. Abseyt

Plants 2026, 15(13), 1986; https://doi.org/10.3390/plants15131986 (registering DOI) - 26 Jun 2026

Abstract

Fusarium oxysporum-associated disease symptoms in rice (Oryza sativa L.) seedlings represent an experimentally tractable model for evaluating microbiome-mediated disease suppression under controlled conditions. Biological control of Fusarium-associated disease development in rice provides a promising ecological alternative to chemical fungicides. However, the mechanisms underlying the spatial reconfiguration of the host plant multicompartment microbiome in response to complex inoculants remain insufficiently understood. In this study, we investigated the ability of the monoculture Bacillus amyloliquefaciens Bn1 (B. amyloliquefaciens Bn) and phototrophic–heterotrophic consortia composed of Nostoc sp. J-1 and B. amyloliquefaciens Bn1 to suppress Fusarium oxysporum infection, with parallel profiling of bacterial and fungal communities in rhizosphere soil, the root endosphere, and the phyllosphere using 16S rRNA and ITS amplicon sequencing. Phenotypic screening showed that microbial inoculant application significantly reduced the disease index by up to 55% while maintaining plant dry weight. The protective phenotype was not primarily associated with shifts in alpha diversity, but rather with compartment-specific reorganization of microbial communities. These findings suggest that biological control efficacy was associated less with the overall taxonomic scale of microbiome disturbance than with the formation of a functionally balanced, compartment-specific holobiont architecture but by the formation of a functionally balanced, compartment-specific holobiont architecture, providing a conceptual basis for the targeted design of next-generation phototrophic–heterotrophic biopreparations. Full article

(This article belongs to the Special Issue New Advancements in Plant–Microbes Interactions)

18 pages, 358 KB

Open AccessArticle

Medication Adherence and Its Discordance with Glycemic Control in Type 2 Diabetes: A Real-World Study in Primary Health Care in the Brazilian Amazon

by Laila de Castro Araújo, Valéria dos Santos Lourenço, Valéria de Castro Fagundes, Alana Ferreira de Oliveira, Ana Cristina Lo Prete, Carolina Heitmann Mares Azevedo Ribeiro, Érica dos Santos Sarges, Luana Pereira Margalho, Phelipe Augusto Rabelo Paixão, Stefani Gisele Bastos Dornas, Wherveson de Araújo Ramos, Bianca de Jesus Quintino, Paula Gabrielle Gomes Candido, Victor Mesquita Eguchi, Isaac Antonio Duarte da Silva, William Rodrigues de Lima, Victor de Castro Araújo, Thaty Hanny Feuerstein do Nascimento, Maria Pantoja Moreira de Sena and Luann Wendel Pereira de Sena

Pharmacoepidemiology 2026, 5(3), 20; https://doi.org/10.3390/pharma5030020 (registering DOI) - 26 Jun 2026

Abstract

Background/Objectives: Medication adherence is a critical determinant of therapeutic outcomes in type 2 diabetes mellitus (T2DM); however, its relationship with glycemic control remains inconsistent, particularly in real-world and socially vulnerable settings. This study aimed to evaluate medication adherence using multiple validated instruments, assess disease-related knowledge, and examine their relationship with glycemic control, with a focus on potential discordance between self-reported adherence and objective metabolic outcomes. Methods: A cross-sectional analytical study was conducted with 237 adults with T2DM receiving care in a primary health care (PHC) unit in the Brazilian Amazon. Medication adherence was assessed using the Almeida Adherence Scale, ARMS-12, and the Haynes–Sackett test, while disease-related knowledge was evaluated using the Batalla–Martínez questionnaire. Glycemic control was determined based on glycated hemoglobin (HbA1c) values obtained from clinical records within the previous three months. Descriptive and comparative analyses were performed. Results: The study population was predominantly female (64.1%) and aged 40–59 years (55.7%), with a high prevalence of socioeconomic vulnerability. Non-adherence was identified in 55.7% of participants using the Almeida Adherence Scale, whereas higher adherence rates were observed with ARMS-12 (91.1%) and the Haynes–Sackett test (72.2%). Inadequate disease-related knowledge was found in 77.2% of participants. Among individuals with available HbA1c data (n = 116), the mean HbA1c was 8.63% (SD = 1.65), and 81.9% presented inadequate glycemic control (HbA1c ≥ 7%). Notably, among participants classified as adherent by the ARMS-12 scale (91.1%), inadequate glycemic control was nonetheless present in 81.9% of those with available HbA1c data, illustrating the magnitude of the observed discordance between self-reported adherence and objective metabolic outcomes. Cross-tabulation of each adherence instrument against glycemic control showed no statistically significant associations (chi-square with Yates correction; ARMS-12: p = 0.631, φ = 0.045; Almeida Adherence Scale: p = 0.301, φ = 0.096; Haynes–Sackett: p = 0.800, φ = 0.024). Multivariable logistic regression (Nagelkerke R² = 0.321; AUC = 0.834) identified older age (aOR = 0.92; 95% CI: 0.87–0.96; p < 0.001) and higher income (aOR = 9.96; 95% CI: 2.05–48.32; p = 0.004) as independent predictors of glycemic outcome, while no adherence measure was independently associated with HbA1c ≥ 7%. A sensitivity analysis using HbA1c ≥ 8.0% revealed poor control in 59.5% of participants (n = 69/116). Conclusions: Despite varying levels of self-reported medication adherence, inadequate glycemic control was highly prevalent. The absence of statistically significant associations between self-reported adherence and HbA1c, combined with the high prevalence of poor glycemic control regardless of adherence status, is consistent with the hypothesis that adherence alone does not fully explain metabolic outcomes in T2DM. Given the cross-sectional design, no causal inferences can be drawn. These findings highlight the need for integrated care strategies in primary health care, including improved health literacy, structured pharmacotherapeutic follow-up, and the use of multiple adherence assessment tools to better inform clinical decision-making. Full article

20 pages, 6633 KB

Open AccessSystematic Review

Efficacy and Safety of IL-4Rα and IL-5/IL-5R Targeted Biologic Therapies in Type 2 Inflammatory Airway Diseases: A Systematic Review and Meta-Analysis

by Zhuojun Li, Maoyu Jiang, Maiqi Chen and Yehai Liu

J. Clin. Med. 2026, 15(13), 5004; https://doi.org/10.3390/jcm15135004 (registering DOI) - 26 Jun 2026

Abstract

Background/Objectives: Severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) frequently coexist and are associated with type 2 inflammation, leading to poor symptom control and high healthcare burden. Biologic therapies targeting IL-4Rα and IL-5/IL-5R have shown efficacy in type 2 inflammatory asthma and CRSwNP, but comprehensive evidence on their efficacy, safety, and research trends is limited. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating dupilumab, mepolizumab, benralizumab, or reslizumab in patients with type 2 inflammatory asthma and/or CRSwNP. Primary outcomes included lung function (FEV1), symptom control (ACQ, SNOT-22, nasal polyp score), and serious adverse events (SAEs). Risk of bias was assessed using the Cochrane RoB 2.0 tool. Publication bias was evaluated with funnel plots and Trim-and-Fill analysis. Bibliometric analysis was performed to identify publication trends and emerging research directions. Results: A total of 23 RCTs involving 8758 participants were included. Biologic therapy was not associated with a significant increase in serious adverse events (RR = 1.15, 95% CI: 0.89–1.50). Compared with control treatment, biologics significantly improved FEV1 (MD = 100.67 mL, 95% CI: 65.94–135.40) and ACQ scores (MD = −0.40, 95% CI: −0.54 to −0.25). In patients with CRSwNP and comorbid asthma, biologics also improved SNOT-22 scores (MD = −13.16, 95% CI: −24.85 to −1.47) and nasal polyp scores (MD = −1.31, 95% CI: −1.95 to −0.68). Dupilumab trials showed larger reductions in nasal polyp score than IL-5/IL-5R-targeted trials, although this indirect comparison should be interpreted cautiously. Bibliometric analysis indicated increasing research attention to upstream epithelial targets such as TSLP. Conclusions: Both IL-4Rα and IL-5/IL-5R-targeted biologics are effective and well-tolerated in type 2 inflammatory airway diseases. IL-4Rα inhibition shows favorable upper-airway outcomes in CRSwNP with asthma, but head-to-head trials are needed to clarify its comparative efficacy relative to IL-5/IL-5R-targeted therapies. Emerging research directions are shifting toward upstream epithelial alarmin antibodies. Full article

(This article belongs to the Section Immunology & Rheumatology)

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