To examine how organizations assess their innovation readiness (IR) maturity using the Maastricht Innovation Readiness Approach (MIRA) Questionnaire. Cross-sectional study in 21 Dutch long-term care organizations. Health care professionals with insight into their organization's IR completed the questionnaire, including those in care, management, human resource management, communication, and client representation. Data were collected using the MIRA Questionnaire, based on the IR framework, containing 4 domains: strategic direction, organization of innovation, leadership for innovation, and learning climate. The response options include 5 IR positions: "not," "informal," "occasionally," "consistently," and "optimally," reflecting a progression in IR maturity and a "no insight" position. The MIRA Questionnaire was completed by 409 participants in 21 long-term care organizations. Across nearly all (n = 20) organizations, "consistently" was most frequently selected (mean [after which is M] = #21, 38%), particularly within the "strategic direction" domain (M = #21, 43%). In the "learning environment" domain, however, the "not" and "informal" positions were most frequently chosen (M = #21, 34%), suggesting that these factors were either not implemented or put in practice or only implemented without formalization. Questions about the active involvement of managers and intended end users (clients and family members) received more frequent responses in the "not and informal" positions (M = #21, 47%, 21%) and fewer responses in the "occasionally, consistently, and optimally" positions (M = #21, 25%, 59%). The main findings indicate that most health care organizations' attention goes to strategy and organizing for innovation but less to leadership and the learning climate. This might indicate a temporal order in organizing the IR factors. Improving IR requires balanced attention to all factors of the IR framework. MIRA can support organizations by identifying specific steps to improve IR. Additional research is necessary to longitudinally track whether and how organizations translate MIRA use into actions that improve their IR. Policymakers can utilize these findings to develop sector-wide programs that promote learning for sustainable IR.
In this study, a novel nucleic acid detection method based on multienzyme isothermal rapid amplification (MIRA) combined with the Pyrococcus furiosus Argonaute (PfAgo) cleavage system (MIRA-PfAgo) was developed for the detection of Tembusu virus (TMUV), an important pathogen threatening the waterfowl industry. The method targets the highly conserved NS5 gene of TMUV. Target nucleic acids are rapidly enriched by MIRA under isothermal conditions at 39 °C, followed by PfAgo-mediated cleavage guided by sequence-specific guide DNA (gDNA), enabling visual detection through fluorescence signal output. Systematic optimization identified 0.5 μM gDNA, 1 μM PfAgo, and 5 mM Mn²⁺ as the optimal reaction conditions. The assay exhibited excellent specificity for TMUV, with no cross-reactivity observed with common waterfowl pathogens, including H9 subtype avian influenza virus (AIV-H9), duck enteritis virus (DEV), goose parvovirus (GPV), Muscovy duck reovirus (MDRV), Newcastle disease virus (NDV), and duck circovirus (DuCV). The sensitivity reached as low as 10⁰ copies/μL. In the analysis of 21 clinical samples, the results of the MIRA-PfAgo assay were fully consistent with those obtained by RT-PCR. This method does not require complex thermal cycling equipment and combines high sensitivity, strong specificity, and operational simplicity, providing a reliable and practical technical tool for rapid on-site monitoring of TMUV.
Novel goose astrovirus (NGAstV) and goose circovirus (GoCV) are two major pathogens responsible for disease outbreaks in goslings, causing substantial economic losses to the goose farming industry. In this study, two duplex multienzyme isothermal rapid amplification (MIRA) assays were developed for the simultaneous detection of NGAstV and GoCV, and the specificity and sensitivity of these detection methods were evaluated. Both MIRA assays demonstrated high specificity for NGAstV and GoCV, with no cross-reactivity observed with six waterfowl pathogens, including duck enteritis virus, goose parvovirus, fowl adenovirus serotype 4, H9 subtype avian influenza virus, Muscovy duck reovirus and duck Tembusu virus. The basic duplex MIRA assay completed amplification within 25 min under a constant temperature of 25 °C, with minimum detection limits of 1 × 102 copies/µL for NGAstV and 1 × 103 copies/µL for GoCV. In contrast, the duplex MIRA-qPCR assay reduced the reaction time to 20 min at 39 °C, and increased the sensitivity to 1 × 101 copies/µL for NGAstV and 1 × 10² copies/µL for GoCV. Fluorescence imaging technology enables differentiation of infection types based on color variations: mixed infections appear yellow, single NGAstV infections show green fluorescence, and single GoCV infections exhibit red fluorescence. In the clinical sample testing, the detection rates of the two pathogens were relatively high, with a mixed infection rate of up to 18%. This method significantly improves pathogen detection efficiency and serves as an effective tool for the rapid identification of NGAstV and GoCV.
Global warming has resulted in frequent droughts worldwide, significantly affecting plant normal growth and development. Polyphenol oxidase (PPO), a copper-containing redox enzyme in plants, serves multiple functions. However, limited research has investigated the role of PPO in regulating plant drought adaptation. In this study, PmPPO was isolated from Prunus mira Koehne, the wild ancestor of cultivated peaches, which is a rare tree species known for its high stress tolerance under extreme conditions. Our results indicated that PmPPO was preferentially expressed in young roots, with its expression significantly induced by drought and abscisic acid (ABA). Overexpression of PmPPO in plants demonstrated enhanced tolerance to drought stress. Under drought stress, transgenic plants exhibited increased antioxidant enzyme activity, improved reactive oxygen species (ROS) scavenging capacity, and reduced cellular damage compared to wild-type (WT). Moreover, PmPPO overexpression facilitated anthocyanin accumulation by regulating the expression of genes involved in anthocyanin biosynthesis following drought treatment. Additionally, yeast two-hybrid (Y2H) and Luciferase complementation imaging (LCI) assays confirmed interactions between PmPPO and both PmRad23d and PmRGLG2. These findings introduce new molecular targets for genetic manipulation in peach germplasm improvement and present potential candidate genes for screening stress tolerance through molecular breeding.
Given the continuous threat posed by emerging and re-emerging infectious diseases worldwide, a rapid, sensitive, and practical molecular detection technology is urgently required for timely point-of-care (POC) diagnosis. Although the quantitative real-time PCR (qPCR) based technologies exhibit high sensitivity and specificity compared with traditional pathogen detection methods, they are not applicable for POC detection scenarios. Based on the photocontrolled principle, this study established a universal photoactivation strategy for LbCas12a by modifying four sites in the repeat region of LbCas12a crRNA with the photocleavable protecting group 6-nitropiperonyloxymethyl (NPOM). This strategy was integrated with multienzyme isothermal rapid amplification (MIRA) to develop a photocontrolled one-pot rapid detection method for monkeypox virus (MPXV), termed the temporally controlled MIRA-CRISPR/Cas12a (TC-MIRA-CRISPR/Cas12a) assay. The TC-MIRA-CRISPR/Cas12a assay exhibited a 100-fold improvement in detection sensitivity over the conventional one-step assay, achieving a limit of detection (LOD) of 3.9 copies per reaction, which was comparable to stepwise detection assay. The entire assay can be completed within 40 min, faster than the widely used qPCR. In clinical sample detection, this method showed good consistency with qPCR, with a Kappa coefficient of 0.980 (P < 0.001), a sensitivity of 98.4%, and a specificity of 100%. This method effectively avoids amplicon contamination while maintaining high sensitivity, and exhibits excellent universality and expandability. It enables detection of other pathogens simply by modifying the spacer sequence of crRNA, providing a novel technical approach and research perspective for POC detection of MPXV and other pathogens.
The aim of this study was to evaluate the effect of two plaque disclosing agents on the color stability of four different restorative materials. Twenty disc-shaped specimens (8 mm diameter, 2 mm thickness) were prepared for each material: Z250 (3M ESPE), Charisma Diamond (Heraeus Kulzer), Estelite Universal Flow Medium (Tokuyama Dental Corporation Inc.), and Beautifil II (Shofu Inc.). Baseline color measurements were conducted using the VITA Easyshade Compact after numbering the specimens and immersing them in distilled water at 37°C for 24 hours. Two plaque disclosing agents were applied to the specimens: Mira-2-Ton (Hager & Werken) to 10 specimens and ProPind plaque indicator gel (Promida Co.), containing erythrosin dye, to the remaining 10 specimens. Ten seconds after the application, each specimen was rinsed under running water for 30 seconds and air-dried. Color changes in the specimens were calculated using the CIEDE2000 formula. Statistical analysis was performed using One-way ANOVA, Kruskal-Wallis, and Mann-Whitney U tests (p<0.05). The color changes were perceptible (ΔE00 > 0.8) in all experimental groups. Clinically unacceptable color changes (ΔE00 >1.8) were observed in all groups following Mira-2-Ton application, with Charisma Diamond exhibiting the highest color change (7.18 ± 2.65) and Z250 the lowest (2.98 ± 1.13). In contrast, all groups stained with ProPind gel showed clinically acceptable color changes (ΔE00 <1.8), with no statistically significant differences among materials (p>0.05). Plaque disclosing agents can significantly impact the color stability of restorative materials. Understanding the chemical composition of plaque disclosing agents is essential for clinicians to ensure the long term aesthetic stability of restorative materials. Further in vitro and in vivo studies are needed to assess the underlying mechanisms of discoloration caused by disclosing agents.
Large language models (LLMs) show great potential for clinical decision-making, yet most applications remain narrow, task-specific chat tools rather than systems integrated into clinical workflows1,2. However, building physician copilots will require models that operate within the electronic health record (EHR), with governed access to patient data and the ability to initiate permitted EHR actions within defined safety constraints. Yet it remains unproven whether such a system can manage patient cases with physician-level performance. Here we show that MIRA (Medical Intelligence for Reasoning and Action), an autonomous artificial intelligence agent operating in a sandboxed EHR environment, can navigate a large clinical action space to obtain patient histories; order and interpret laboratory, imaging and microbiology tests; generate differential diagnoses; and formulate treatment plans such as prescribing medications, scheduling surgical procedures and planning admissions. In simulations on real patient cases spanning multiple diagnoses, MIRA outperformed physicians in diagnostic accuracy and made guideline-concordant, medication-safe and appropriate admission decisions. Compared with previous LLM applications that addressed isolated subtasks or provided free-text advice, these results suggest that an EHR-integrated artificial intelligence agent can turn clinical intent into structured, actionable EHR operations, possibly making it a more effective decision-support partner for physicians. Further work is needed to establish generalization, safety and governance through prospective, real-world studies.
Firefighters are routinely exposed to combustion-derived toxicants. This exploratory study examined associations between occupational exposure, DNA methylation, and reproductive hormones. Genome-wide methylome profiling using MIRA-seq was performed on pooled blood samples from six male firefighters and four matched controls. Candidate genes were validated by bisulfite sequencing. Jurkat and U937 cells were exposed to benzo[a]pyrene and a phthalate mixture to assess methylation and gene expression. Plasma reproductive hormones were measured in 17 firefighters and 17 matched controls. Firefighters showed 960 differentially methylated genes enriched in reproductive pathways. KLHL17 promoter hypomethylation and increased expression were reproduced in vitro. Hormone analyses demonstrated elevated anti-Müllerian hormone, service year-dependent increases in follicle-stimulating hormone, and reduced testosterone and estradiol. Occupational exposure in firefighters is associated with epigenetic and endocrine alterations potentially affecting reproductive health in firefighters.
Previous efforts to link Palaeolithic cultural records to specific populations through DNA analysis have focused on materials from archaeological floor deposits such as bones, sediments, and artefacts. In this study, we explore whether rock art, a spatially distinct expression of human activity, can also preserve DNA traces from its creators. We analyse DNA preservation in pigment samples collected in and around 24 rock art panels from 11 caves across Spain and Portugal, including simple marks (from nine sites), hand stencils (Maltravieso Cave, Extremadura, Spain), and figurative paintings (Cave of Altamira, Cantabria, Spain). We recover traces of ancient human mitochondrial and nuclear DNA, unaccompanied by faunal DNA, from a pigmented calcite crust at Escoural Cave (Portugal), as well as from an unpigmented cave wall sample from the same site. The absence of faunal DNA in both samples suggests direct DNA deposition through human contact. In contrast, three additional unpigmented samples, from Escoural and Covarón Cave (Asturias, Spain), yielded mixtures of human and faunal DNA, suggesting indirect deposition. Although our results do not conclusively link ancient human DNA preservation to the generation of cave art, we show that traces of human DNA can persist on cave walls for thousands of years.
In recent years, the detection rates of bovine astrovirus (BoAstV) and bovine norovirus (BNoV) in Chinese farms have continued to rise, resulting in significant economic losses to the livestock industry. To meet the need for rapid on-site screening, this study established a dual nucleic acid detection system capable of simultaneously detecting BoAstV and BNoV using the multi-enzyme isothermal rapid amplification technology. Its specificity, sensitivity, and repeatability were further validated using clinical samples. The experimental results showed that the established MIRA method specifically amplified the target nucleic acids of BoAstV and BNoV, while exhibiting no cross-reaction with other common diarrhea-associated pathogens, such as bovine rotavirus (BRV), bovine viral diarrhea virus, and bovine coronavirus, indicating good specificity. The method demonstrated high sensitivity, with detection limits of 920 copies/μL for BoAstV and 6,100 copies/μL for BNoV. In the repeatability tests, all the coefficients of variation were below 10%, confirming the high stability of the method. In clinical sample testing, the method showed strong agreement with conventional dye-based quantitative PCR results (Kappa value = 0.887), while offering shorter detection time and higher detection rates. In summary, the detection method established in this study demonstrated high sensitivity, strong specificity, and a short turnaround time, making it suitable for the rapid detection of bovine astrovirus and bovine norovirus in clinical samples of cattle.
Age-related hearing loss arises from multiple cochlear pathologies. However, linking audiometric thresholds to their underlying cellular mechanisms remains a challenge. We present a biophysically grounded framework linking audiograms to the survival of inner and outer hair cells (IHCs and OHCs) along the cochlear partition. This approach uses a nonlinear, time-domain model of the peripheral auditory system, integrating cochlear mechanics, hair-cell transduction, and auditory-nerve responses. Using postmortem human data combining audiograms and histological hair-cell counts (Wu et al., 2020), we show that audiograms can be predicted from the spatial distribution of surviving hair cells. Prediction is most accurate at low frequencies and becomes less accurate toward the high frequencies. We further examine how well audiograms can reveal the underlying pattern of hair-cell loss. A key finding is that OHC dysfunction primarily affects high-frequency thresholds. Reduced OHC function alters cochlear mechanics, including cochlear amplification, the location of maximal basilar membrane response, and cochlear tuning. These effects are most pronounced in the basal cochlear region, making the audiogram primarily sensitive to the overall level of OHC dysfunction rather than to the detailed spatial distribution of OHC survival. These findings indicate that audiograms provide partial information about cochlear pathology. They are more sensitive to IHC dysfunction and to OHC-related changes in the high-frequency region. The proposed framework establishes a quantitative link between audiometric measures and underlying cellular damage. It also highlights the limitations of inferring detailed cochlear pathology solely from threshold data.
Beyond inherited genes and environmentally induced changes in gene expression, phenotypes can also be shaped by parental effects-an effect from a parental phenotype that causes modifications in offspring traits, which cannot be solely explained by the parental or offspring genomes. Such effects may prepare offspring for future environmental conditions and contribute to phenotypic plasticity, including responses to temperature. While temperature-induced plasticity has been extensively studied, the relative contributions of parental versus direct environmental cues remain poorly understood. The fruit fly Drosophila melanogaster is a powerful model for studying physiological and behavioral adaptation to temperature. Flies inhabit environments spanning broad thermal ranges and show evidence of parental effects, such as increased heat tolerance in offspring from warm-reared parents. Here, we exposed mothers to two experimental temperatures and split their broods between the same two temperatures to estimate the relative importance of maternal and developmental effects on adult physiological and developmental responses to temperature. We find that the reaction norms of locomotor activity under gradually increasing temperatures, responses to heat-shock and cold-shock, and fecundity are mostly governed by direct plastic responses to developmental environment. We detected comparatively weak maternal effects in the response to heat-shock, fecundity, and grand-offspring survival where matched environments counteracted the effects of direct offspring experience. We conclude that thermal experience during development is the primary determinant of phenotypic plasticity in D. melanogaster, while maternal experience contributes a small but non-negligible component.
To assess the use of dental services among depressed individuals and whether the association is independent from the need for dental care. Data were from the National Health and Nutrition Examination Survey (NHANES) (2017-2020), a cross-sectional survey of U.S. adults. Depression status was assessed using the Patient Health Questionnaire-9 (PHQ-9), dental visits and routine dental visits were assessed through self-reported questionnaires in NHANES. Licensed dentists assessed participants' need for immediate dental care. Caries was also assessed using WHO (2013) criteria. Two weighted regression models were used to evaluate the association between the depression and use of dental services. A total of 6565 participants aged 20 years and older were included. Participants with depression had lower odds for visiting the dentist in the previous year, Odds Ratio (OR) 0.72, 95% Confidence Interval (CI): 0.57, 0.91, p < 0.01 and lower odds for routine dental visits (OR 0.66, 95% CI: 0.50, 0.86, p < 0.01) than those without depression in models adjusting for gender, age, race/ethnicity, number of decayed teeth and dental care recommendation. After additionally adjusting for smoking, education and income, the relationships lost significance in both models. Higher socioeconomic conditions were significantly associated with routine dental visits. Even though they needed dental care, people with depression were less likely to see a dentist; however, this association disappeared when socioeconomic factors were taken into consideration. For people with depression, adverse socioeconomic status was an additional barrier to dental visits.
COVID-19 pandemic has significantly impacted global health, particularly evident in the detection of lung lesions via chest computed tomography scans. This study investigates the role of biomarkers in lung injury among COVID-19 patients and patients with idiopathic pulmonary fibrosis (IPF). This single-center prospective study included 154 hospitalized and 10 outpatient COVID-19 patients, 62 IPF patients, and 40 healthy volunteers, and evaluated biomarkers of alveolar epithelial cell dysfunction, extracellular matrix (ECM) and fibroblast dysfunction, and macrophage/monocyte activation (Galectin-3, CXCL13). Findings were further validated in an independant confirmation cohort (DisCoVeRy trial). COVID-19 patients had higher levels of biomarkers compared to healthy controls, except for SP-D. Compared to IPF patients, COVID-19 patients had significantly higher plasma levels of OPN, Galectin-3 and CXCL13 at admission. Elevated CXCL13 and Galectin-3 levels in COVID-19 were associated with greater lung injury. Multivariate logistic regression and Kaplan Meier analysis confirmed the role of CXCL13 in predicting severe lung injury (odd ratio 3.17, 95% CI 1.03-9.76) and in-hospital mortality (p = 0.04), with consistent results observed in the confirmation cohort. COVID-19 is characterized by increased ECM and macrophage activation biomarkers compared with IPF. CXCL13 may serve as a relevant biomarker for assessing lung injury and improving risk stratification at hospital admission.
The scheduled update of the S2k guideline "Diagnosis and treatment of endometriosis", published by the Association of the Scientific Medical Societies in Germany (AWMF; registry number 015/045), was released on April 1, 2025. The guideline was developed under the coordination of the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (ÖGGG), and the Swiss Society for Gynecology and Obstetrics (SGGG), together with 34 scientific societies (including the German Pain Society), professional organizations and associations, and three patient self-help groups. The systematic literature search followed a predefined algorithm and covered the period from 2019 to 2023. In a structured consensus process, 73 recommendations and 25 statements were formulated in accordance with AWMF regulations. Compared to the 2020 guideline, the following changes were made regarding pain management: core therapeutic principles were expanded to include chapters on pharmacological symptomatic pain treatment, psychosomatic therapy, complementary therapy, and additional as well as multimodal treatment approaches. A tiered, multimodal treatment strategy for chronic endometriosis-related pain was recommended. The updated S2k guideline incorporates key concepts of pain medicine, including pain mechanisms (nociceptive, neuropathic, and nociplastic), risk factors for chronification, and biopsychosocial models. Recommendations for pharmacological and non-pharmacological interventions, including tiered multimodal treatment approaches, were developed and agreed upon in an interdisciplinary process based on current evidence and feasibility. HINTERGRUND: Die planmäßige Aktualisierung der S2k-Leitlinie „Diagnostik und Therapie der Endometriose“ der Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF), Registernummer 015/045, wurde am 01.04.2025 veröffentlicht. Die Leitlinie wurde unter Koordination der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe (DGGG), der Österreichischen Gesellschaft für Gynäkologie und Geburtshilfe (ÖGGG) und der Schweizerischen Gesellschaft für Gynäkologie und Geburtshilfe (SGGG) von 34 wissenschaftlichen Fachgesellschaften (inklusive der Deutschen Schmerzgesellschaft), Organisationen und Berufsverbänden und drei Selbsthilfeorganisationen entwickelt. Die systematische Literaturrecherche erfolgte nach definiertem Algorithmus für den Zeitraum 2019–2023. In einem strukturierten Konsensusprozess wurden 73 Empfehlungen und 25 Statements gemäß AWMF-Regelwerk erstellt. Gegenüber der Leitlinie von 2020 ergaben sich bezüglich der Schmerzmedizin folgende Änderungen: Ergänzungen der therapeutischen Grundprinzipien um Kapitel zur medikamentösen symptomatischen Schmerztherapie, psychosomatischen Therapie, komplementären Therapie sowie zu weiteren Behandlungsmöglichkeiten und multimodalen Therapieansätzen. Eine abgestufte, multimodale Therapie bei chronischen Endometrioseschmerzen wurde empfohlen. Die aktualisierte S2k-Leitlinie berücksichtigt zentrale Konzepte der Schmerzmedizin wie Schmerzmechanismen (nozizeptiv, neuropathisch, noziplastisch), Risikofaktoren für Chronifizierung und biopsychosoziale Modelle. Empfehlungen zu medikamentösen und nichtmedikamentösen Verfahren bis hin zu einer abgestuften, multimodalen Therapie wurden interdisziplinär anhand aktueller Evidenz und Umsetzbarkeit entwickelt und konsentiert.
One of the most common chronic disorders in children is type 1 diabetes (T1D). It requires regular evaluation, stringent glycemic control, and comprehensive education on disease management. The aim of this work is to evaluate the effectiveness of Audio-visual technology as a tool for self-management education in pediatric patients with T1D attending diabetes outpatient clinics in Health Insurance Hospitals. his interventional pre-post study was conducted on 100 patients with T1D at the Diabetes Endocrine Metabolic Pediatric Unit (DEMPU) of Cairo University Children's Hospital and the Diabetes Outpatient Clinic of 6th October Hospital for Health Insurance, Egypt, between May 2016 and February 2017. Participants were consecutively recruited from eligible patients attending routine outpatient clinic visits during the study period. A structured questionnaire assessing diabetes self-management knowledge was administered at baseline, immediately post-intervention, and at 2- and 4-month follow-up after a video-based educational program. Diabetes-related knowledge scores significantly improved from 36.36 ± 7.94 at baseline to 42.07 ± 7.82 post-intervention, with sustained retention at 4 months (42.61 ± 8.47, p< 0.001). HbA1c levels significantly decreased at 4 months (mean change -0.81 ± 1.18%), with 78% of participants showing improvement (p< 0.001). The proportion achieving target glycemic control increased from 19% to 29%, while poor control decreased from 41% to 30%. Knowledge gain was independently associated with HbA1c reduction. A structured diabetes self-management education program using high-definition video technology was associated with significant improvements in diabetes knowledge and glycemic control. These findings support the role of structured educational interventions as an effective and scalable strategy for improving clinical outcomes in patients with type 1 diabetes. This study highlights the utility of high-definition video technology as an effective educational tool to improve diabetes knowledge and self-management in pediatric patients with T1D, offering a scalable solution for diabetes education programs.
From preclinical promise to clinical translation in intervertebral disc degeneration (IDD). Robust preclinical evidence supports a range of biologic therapies, with consistent improvements in imaging, extracellular matrix composition, inflammation, and behavior. However, a substantial translational gap persists, driven by key challenges including the discordance between IDD and pain, patient heterogeneity, inadequate phenotyping, placebo effects, limitations of preclinical models, hostile disc microenvironment, and practical/clinical trial barriers. A precision medicine framework is crucial to overcome these limitations, based on improved patient stratification, definition of molecular and clinical endotypes linked to targeted therapies, integration of advanced biomarkers, development of more sensitive outcome measures, and optimization of clinical trial design, ultimately aiming to enable successful clinical translation. Biologic therapies for intervertebral disc degeneration (IDD) have shown strong preclinical promise, yet clinical translation for discogenic low back pain (LBP) remains limited. This gap reflects the inconsistent relationship between degeneration and pain, compounded by heterogeneous patient populations, insufficient phenotyping, and inadequate selection of truly discogenic LBP patients in current trials. Emerging evidence indicates that IDD and LBP comprise distinct biological endotypes, requiring matched therapeutic strategies, or “theratypes”, rather than uniform approaches. In this narrative review, we critically examined the current evidence on biologic therapies for IDD, focusing on the translational gap between preclinical success and clinical outcomes. We analyzed key methodological and biological limitations, including patient heterogeneity, pain misclassification, inadequate phenotyping, and suboptimal trial design. Additionally, we reviewed emerging concepts such as disease phenotyping, mechanism‐based patient selection, and stage‐adapted therapeutic approaches. Multiple barriers hinder clinical translation of biologic therapies for IDD, including incomplete understanding of disc biology, limited intrinsic regenerative capacity, and a hostile tissue microenvironment. Preclinical models frequently fail to replicate the complexity of human pathology and pain, while clinical trials rely heavily on subjective outcomes and are often confounded by strong placebo effects. Furthermore, regulatory, logistical, and economic challenges limit widespread clinical adoption. Progress in the field will require a shift toward precision medicine approaches to align therapies with specific endotypes, pain phenotypes, and stages of IDD. Greater standardization, transparency, and community‐wide reporting practices are also essential to improve reproducibility. Advancing biologic therapies for IDD will depend on the development of more precise and biologically informed clinical strategies. Improved patient stratification, better alignment between therapeutic mechanisms and disease biology, and the adoption of standardized and clinically meaningful outcome measures are critical. Despite recent progress, key pathophysiological mechanisms remain poorly understood, underscoring the need for rigorous and multidisciplinary research efforts.
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Recent regulatory and pharmacopeial guidance highlights attention to host cell protein (HCP) impurities in biologics. Advances in liquid chromatography-mass spectrometry (LC-MS) enable molecular-level characterization of HCPs beyond immunoassay measurements. This article examines how LC-MS-based HCP profiling strengthens impurity risk assessment, improves process understanding, and supports analytical strategies for biologics quality and safety.