Analytical chemistry plays a central role in research and innovation, yet its environmental impacts remain insufficiently represented in sustainability assessments. Current score-based "greenness" indicators-defined as the compliance to the 12 green analytical chemistry principles-often overlook upstream and downstream processes, such as instrument manufacturing and data management. This study applies life cycle assessment (LCA) to characterize the environmental performance of four representative workflows in a cosmetic industry R&I setting: an untargeted UPLC-PDA/HRMS analysis of natural extracts and three phenoxyethanol quantification methods (GC-MS, HPLC-UV, UPLC-UV). Inventories were structured to distinguish sample preparation, instrumental analysis, and data processing from supporting flows like consumables and energy. The results reveal distinct environmental hotspots for each protocol. The UPLC-PDA/HRMS workflow exhibited a climate change impact of 4.30 kg CO₂eq, driven by the amortization of the devices and the sample transport. In contrast, the GC-MS workflow (3.82 kg CO₂eq) was heavily influenced by dichloromethane production, while the HPLC-UV protocol reached 6.84 kg CO₂eq due to consumable-related flows and longer run times. These findings demonstrate that environmental burdens are highly workflow-specific and that commonly cited factors, such as solvent use, are not always the primary drivers. The study concludes that the normalization factors from the product environmental footprint (PEF) method are inadequate for analytical laboratory contexts and suggests that quantitative LCA provides a necessary complement to score-based metrics like the analytical greenness metric (AGREE) for supporting robust eco-design and corporate sustainability initiatives.
Germany faces a severe nursing shortage, increasingly addressed by international recruitment. This shift results in growing socio-cultural and educational diversity within nursing teams. While the experiences of migrant nurses are well-documented, how receiving teams manage this diversity in daily practice remains under-researched. This study investigates team-level patterns of navigating diversity and identifies factors influencing successful integration. A qualitative, comparative case study design was employed across six nursing teams (four hospitals, two nursing homes) in Germany. Teams were selected through purposive sampling based on high levels of socio-cultural and educational diversity. Data collection (March 2022-August 2023) included 203 h of participant observation, 25 semi-structured interviews, and 8 focus groups with both nursing management and non-managerial nursing staff focusing on daily cooperation, professional and socio-cultural differences, and team integration processes. Inductive analysis followed the documentary method to reconstruct implicit orientation patterns. Social Identity Theory (SIT) served as the theoretical framework for describing the different team dynamics. Three distinct team-level approaches to diversity were identified: (1) Routine-based Teams normalise diversity within a stable framework, valuing individual competencies as a natural asset and seamlessly integrating differences into everyday practices. (2) Transition-based Teams actively engage with shifting team configurations through supportive structures but experience operational ambivalence as newly developing learning processes occasionally collide with ingrained routines. (3) Friction-based Teams exhibit a defensive, problem-oriented stance toward diversity, characterised by rigid boundary maintenance, perceived competence conflicts, and a tendency toward social fragmentation under structural strain. Key influencing factors include the facility's location and patienthood and the role of nursing management. Successful team collaboration depends on fostering a shared professional framework that recognises and utilises diverse individual competencies. Nursing management must provide stable resources for reciprocal knowledge transfer and actively address structural barriers regarding the valuation of international qualifications. To ensure high-quality care and sustainable staff retention, managerial interventions should implement targeted support measures tailored to the specific dynamics of a team type. Not applicable.
Active post-marketing surveillance of prescribing behavior of high-risk drugs may provide early warning of unforeseen issues in a population, yet analysis approaches for surveillance using real-world data are underdeveloped. This paper evaluates a modified statistical process control (SPC) method for surveillance of risk minimization measures derived from administrative claims data. The approach detects changes in population-level prescribing behaviors and informs investigators of the timing and nature of any detected changes. We investigated prescription drug claims for tapentadol extended release (ER) from the Colorado All-Payers Claims Database (2012-2019). The cohort was 2702 unique patients receiving their first prescriptions of tapentadol ER (an opiate with an FDA Risk Evaluation and Mitigation Strategy). The risk minimization measures were the prescribing rate and the proportion of prescriptions with appropriate dosing. A statistical model was fitted to data from January-December 2012 to establish a stable baseline and then updated biweekly through June 2019. We conducted surveillance with our modified SPC method and a classical SPC method, controlling the false alarm rate to 0.005 for each, and compared how detections aligned with external policy actions. Our method detected two periods of unusual prescribing behavior beginning in March 2015 (p < 0.005) and April 2016 (p < 0.005). The classical method detected a single period in October 2016 (p < 0.005). Our detections aligned with risk minimization activities in Colorado; the classical method aligned with only the second activity, 6 months later. Our modified SPC method, which monitors model misspecification rather than raw prescribing data, detects more periods of changing behavior that better temporally align with risk minimization actions. This tool may be useful for regulatory agencies to independently monitor for emerging risks and prescribing trends to complement REMS assessments.
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Skin tape stripping is a minimally invasive, skin-specific method for biomarker collection that has gained increasing interest in dermatologic research. However, the lack of standardized protocols for protein and nucleic acid extraction from tape strips has limited its broader application. This study aimed to establish robust and broadly compatible protocols for biomarker extraction from tape strip samples to enable reliable downstream proteomic and transcriptomic analyses. We systematically evaluated key technical parameters influencing biomarker recovery, including collection and storage conditions, buffer composition, and lysis strategies. Protein and nucleic acid extraction protocols were optimized for maximum yield and quality across a range of downstream applications, including immunoassays and transcriptomic profiling. The optimized protein extraction protocol demonstrated improved total yield and compatibility with multiple assay platforms. A parallel nucleic acid extraction method yielded high-quality RNA suitable for gene expression analyses. Notably, we found that disease-relevant biomarkers were detectable in the most superficial tape strips, indicating that fewer total strips may be sufficient for effective analysis. We present practical and standardized methods for protein and nucleic acid extraction from skin tape strip samples. These protocols address current technical barriers and support broader implementation of tape stripping as a biomarker collection strategy in clinical dermatology and related fields.
Whether the manufacturing protocol (build orientation and sintering schedule) of additively manufactured (AM) zirconia impacts the bond strength compared with subtractively manufactured (SM) zirconia remains unclear. The purpose of this in vitro study was to evaluate the effect of build orientation (45 degrees and vertical), sintering schedule (1-step and 2-step), and resin cement on the shear bond strength (SBS) and failure mode of AM zirconia bonded to dentin compared with that of SM zirconia. One hundred fifty 3Y-TZP zirconia cylinders (Ø2×4 mm) were produced by AM (INNI Cera BCM-W1000) or SM (IPS e.max ZirCAD MT). AM specimens were printed vertically at 90 degrees or at 45 degrees and subjected to 1-step or 2-step sintering; SM specimens were milled and sintered. The specimens were divided into 3 subgroups to be luted to human dentin (n=10) with 3 dual-polymerizing resin cements (SpeedCEM Plus; Ivoclar AG, RelyX Ultimate; 3M Dental, Panavia V5; Kuraray Noritake Dental). Dentin and zirconia surfaces were pretreated per cement and manufacturer protocols. After 24 hours, SBS was measured, and failure modes evaluated. The data were analyzed using 2-way ANOVA to assess the effects of manufacturing technique (AM or SM) and resin cement and using 3-way ANOVA exclusively within the AM group to evaluate the effects of build orientation, sintering schedule, and resin cement, followed by Tukey post hoc tests (α=.05). According to the 2-way ANOVA, zirconia manufacturing technique (AM or SM) did not significantly influence SBS, whereas resin cement had a significant effect (P<.001). Within the AM groups, the 3-way ANOVA revealed that resin cement was also the only factor significantly affecting SBS (P<.001), with no significant effects of build orientation or sintering schedule (P>.05). SpeedCEM Plus (8.9 ±3.7 MPa) showed the significantly lowest SBS and RelyX Ultimate (15.1 ±5.3 MPa), and Panavia V5 (15.7 ±4.9 MPa) yielded similar SBS. No significant difference was found in failure mode between AM and SM zirconia (P=.647), but differences existed between cements (P<.001). Almost all failures (98%) in SpeedCEM Plus groups were adhesive at the dentin-cement interface. The RelyX Ultimate and Panavia V5 groups had approximately 20% adhesive and approximately 50% cohesive failures within dentin. No significant differences in SBS or failure mode were found between AM and SM zirconia. Build orientation and sintering schedule of AM zirconia had no influence on the bond strength of zirconia to dentin, whereas resin cement had a significant effect. In general, SpeedCEM Plus resulted in the significantly lower bond strength of AM and SM zirconia to dentin than did RelyX Ultimate or Panavia V5.
While atherothrombosis accounts for the majority of acute coronary syndrome (ACS) cases, non-atherosclerotic mechanisms like coronary embolism are important considerations in end-stage renal disease (ESRD). A 52-year-old woman with ESRD and tertiary hyperparathyroidism presented with myocardial infarction. Echocardiography identified mobile mitral valve masses. Angiography showed a left anterior descending artery occlusion, but intravascular ultrasound revealed minimal plaque burden. Histopathological analysis of aspirated material confirmed calcified necrotic debris rather than thrombus. Despite concurrent COVID-19 infection, the rigid mechanical behavior of the masses during attempted percutaneous aspiration distinguished the pathology from infective endocarditis. This case highlights calcific coronary embolism as a rare ACS cause in ESRD patients. Multimodal imaging and histopathology are crucial for accurate diagnosis.
In seasonally humid Amazonia, rainfed plant establishment can be co-limited by high irradiance and seasonal water deficits. We tested whether temporary shade reduces leaf evaporative demand without reducing photosynthetic carbon assimilation during early field establishment of the Amazon palm Euterpe precatoria Mart. Seedlings were planted in Rio Branco, Acre, Brazil, and grown under five shade levels: 0, 18, 35, 50, and 65%. From 2 to 12 months after planting (MAP), we measured plant height, stem diameter, canopy diameter, and leaf number. At 6 MAP, we measured leaf gas exchange, chlorophyll index, and leaf microclimate. Antecedent climate was represented by 60-day mean air temperature and cumulative rainfall before each survey. Intermediate shade, especially near 50%, maximized net photosynthetic rate, chlorophyll index, and water-use efficiency, while reducing transpiration and leaf vapor pressure deficit. Growth increments were consistently associated with wetter 60-day windows, whereas temperature effects were not consistent after accounting for developmental stage and previous plant size. ANCOVA indicated that shade-related increases in photosynthesis were not fully explained by stomatal conductance alone, although this inference remains indirect because mesophyll conductance and A-Ci or A-PPFD curves were not measured. Integrated field indicators identified a Pareto-efficient shade window near 45-55%, combining rapid canopy development with lower thermal and evaporative risk. Moderate shade therefore provides a practical management window to improve rainfed plant establishment of E. precatoria in cultivation, agroforestry, and restoration systems.
More effective therapies are required for advanced breast cancer. We report results from 58 women with locally advanced unresectable or metastatic hormone-receptor (HR)-negative, human epidermal growth factor receptor 2 (HER2)-low breast cancer enrolled in arm 6 of the multicenter, open-label phase 1b/2 BEGONIA platform trial, who received durvalumab (1,120 mg) plus trastuzumab deruxtecan (T-DXd; 5.4 mg kg-1) intravenously every 3 weeks as first-line treatment. Objective response rate (ORR) and safety were primary endpoints; duration of response (DoR), progression-free survival (PFS) and overall survival (OS) were secondary endpoints. Median follow-up was 20.6 months (range: 1-37). ORR was 62.1% (95% confidence interval (CI): 48.4-74.5), which did not meet the protocol-specified objective of 38/57 (66.6%) responses. Median DoR was 15.2 months (95% CI: 8.44-not calculable), PFS was 12.6 months (95% CI: 8.4-16.3) and OS was 30.3 months (95% CI: 18.8-not calculable). The safety profile of the combination treatment was consistent with those of the individual therapies. Adjudicated, drug-related interstitial lung disease or pneumonitis occurred in 20.7% of participants (grades 1 and 2, 19.0%; grade 5, 1.7%). Durvalumab plus T-DXd demonstrated clinically relevant efficacy for first-line treatment of metastatic HR-negative, HER2-low breast cancer, with no unexpected toxicities observed. ClinicalTrials.gov identifier: NCT03742102 .
In a globally ageing population, epilepsy in older adults has gained increased clinical relevance. This includes both individuals who have grown old with epilepsy and those who develop epilepsy later in life. Whether seizure outcomes and treatment patterns differ between these groups remains insufficiently characterised. In this retrospective study, we included patients aged ≥ 65 years treated at three outpatient epilepsy clinics in Berlin between 2010 and 2025. Patients were categorised according to age at epilepsy onset. Early-onset persistent epilepsy (EOPE) was defined as onset < 40 years, and late-onset epilepsy (LOE) as onset ≥ 65 years. The primary endpoint was seizure freedom during the last 12 months. Secondary endpoints included markers of antiseizure medication burden, adverse effects and quality of life. A total of 243 patients were included (114 EOPE, 129 LOE). Seizure freedom was less frequent in EOPE compared to LOE (50.0% vs. 69.0%, p = 0.003). Patients with EOPE had a significantly higher drug load (median defined daily dose 1.00 vs. 0.67; p < 0.001). EOPE was independently associated with, among other variables, lower odds of seizure freedom (adjusted odds ratio (adjOR) 0.34, 95%CI 0.16-0.71) and more frequent use of first- or second-generation ASM (adjOR 5.99, 95%CI 2.47-14.54). The latter finding remained robust in a sensitivity analysis restricted to seizure-free patients. In older adults, EOPE and LOE are associated with differing clinical characteristics. Patients with EOPE show lower seizure freedom and higher treatment burden as compared to LOE. In seizure-free patients with long-standing epilepsy, ASM simplification may be considered.
The in vitro micronucleus (IVMN) assay is a genetic toxicity assay routinely conducted in early drug development to evaluate clastogenicity and aneugenicity. At this discovery stage, synthetic routes for potential active pharmaceutical ingredients (API) are not optimized, which can lead to incomplete purification or solvation. API in genetic toxicity screens often contain residual solvent(s) in higher quantities than will be present in the GMP material. Understanding when solvents used either in API synthesis or as a vehicle may interfere with genetic toxicity screening results of APIs is important. In this work, twenty solvents commonly used in API synthesis were analyzed in the IVMN assay. These twenty solvents include acetonitrile, formic acid, anisole, dichloromethane, heptane, isopropyl amine, dimethyl sulfoxide, sodium hexafluorophosphate, N,N-Dimethylethylamine, N,N-Dimethylformamide, cyclopentyl methyl ether, 2-propanol, 1-butanol, 1-Methyl-2-pyrrolidinone, methanol, tetrahydrofuran, 2-Methyltetrahydrofuran, ethyl acetate, trifluoroacetic acid, and 2,6-Di-tert-butyl-4-methylphenol. When the in vitro data was correlated to available in vivo genotoxicity data published in the literature, only 5 of the 14 positively correlated. However, when a 10 mM limit of exposure was applied to the solvents, 13 of the 14 correlated to the in vivo literature results. While the results do not consider vehicle interaction within the assay, the data demonstrates that residual solvent carryover from API or other sources is generally not of concern. The 10 mM limit also reduces the false-positive risk of this assay. Baseline cytotoxicity and micronucleus formation from the solvents in this system provide a ranking on which solvents may produce confounding results in the assay.
Characterization of total particle emissions from an Airbus A350-900 during the ECLIF3 campaign is presented. Ground measurements ∼24.5 m behind the engine were conducted on three fuels: Jet A-1, HEFA-SPK, and a HEFA Jet A-1 mix. Data include number-mobility size distributions of total and nonvolatile PM (tPM and nvPM), nvPM mass, and size-resolved volatile PM (vPM) mass. LII analysis estimated primary particle size (dp) and specific surface area (SSA). At small sizes and low power, vPM number contributed up to 50% of tPM, with high-sulfur fuels producing the largest number of vPM and tPM. Fuels with higher hydrogen and lower aromatic content had smaller nvPM aggregate sizes (Dp) and lower mass, but larger dp, indicating more compact particles. SSA ranged from 160-200 m2/g, varied nonlinearly with thrust, and was lower for high-hydrogen fuels, potentially affecting toxicity. Combined data from this study and others revealed a strong inverse correlation between dp/Dp ratio vs Dp, relevant for ice nuclei (IN) modeling and climate impacts. vPM mass was dominated by lubrication oil, highly variable at low thrust, and wind-direction dependent; thus, even with Net Zero fuels (no sulfur, high hydrogen, no aromatics), engines may still emit IN via lubrication oil.
Shiva family toxins are naturally occurring insecticidal peptides that target insect nicotinic acetylcholine receptors (nAChRs) and show strong utility as bioinsecticides. However, the molecular basis of their interaction with insect nAChRs remains poorly understood. In this study, we demonstrate that Shiva toxins exhibit no cross-resistance with spinosad, indicating that they do not interact with the Drosophila nAChR α6 subunit. Using CRISPR-generated Drosophila melanogaster lines carrying homozygous knockout alleles of individual nAChR subunit, insect bioassays revealed that the nAChR β1 subunit is critical for Shiva toxin activity. To further define the interaction site, Drosophila nAChR α4 and β1 subunits (Dmα4-β1) were heterologously co-expressed in Xenopus oocytes and examined by two-electrode voltage clamp (TEVC). Shiva toxins directly activated Dmα4-β1 receptors and also acted as positive allosteric modulators (PAM), enhancing acetylcholine-evoked currents with EC₅₀ values in the nanomolar range. Consistent with the bioassay results, electrophysiological analysis confirmed the essential role of the β1 subunit in Shiva toxin interaction. Site-directed mutagenesis identified two residues, E206 and I231, within the Drosophila nAChR β1 subunit that are required for Shiva toxin activity. Together, these results further clarify the molecular mechanism underlying Shiva toxin interaction with insect nAChRs and provide insights into their mode of action as bioinsecticides.
Recent regulatory and voluntary initiatives to estimate supply chain greenhouse gas (GHG) emission intensity of liquefied natural gas (LNG) have emphasized the use of direct measurements as activity-based national inventories tend to systematically underestimate GHG emission intensities. In this work, we demonstrate how measurement data can be integrated into a life cycle assessment (LCA) framework for assessing the GHG emissions of LNG supply chains by synthesizing results from a three year measurement campaign over 54 sites across production, midstream, and liquefaction stages. Measurement-informed GHG emission intensity ranges from 13.8 to 17.2 g of CO2 equiv/MJ of LNG produced, about 19-39% higher than those derived from an activity-based inventory assessment. We also observe large variation in the contribution of each stage to the total supply chain emission intensity. Critically, we find that stages downstream of gas production account for up to 73% of the production to liquefaction GHG emission intensity of LNG. Thus, relying on aggregate production-only emission intensities as the basis to assess the emission impact of the LNG is likely to underestimate emissions, leading to potentially ineffective public or corporate policies. Finally, we find that supply-chain-specific GHG intensities can significantly differ from basin-level, representative GHG intensities; thus, assessments of the GHG intensity of LNG can benefit from being tied to individual transactions and specific gas pathways where data allow.
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Family caregivers provide essential support to older adults, but their extended caregiving networks can be strained during crises. This study examines which characteristics of caregivers' personal networks were associated with discontinued support during the early stage of the COVID-19 pandemic, a period of widespread social disruption. We analyzed data from the Care Network Connections over Time (CNCT) study, a longitudinal, nationally representative study of U.S. caregivers. Respondents (N = 2,116) reported on support before and during COVID-19. Multilevel logistic regression models assessed associations between discontinued support and network/caregiver characteristics while controlling for clustering within networks. Support loss occurred among 5.84% of previously supportive network members. Discontinued support was significantly more likely when alters were Hispanic or of "other/multiple" race/ethnicity, aged <18 or > 64, or were distant relatives or nonrelatives. Highly connected alters and those providing support to care recipients were less likely to have withdrawn support. At the network level, caregivers with low density, more diverse, or low care-recipient-supporting networks were more vulnerable to support discontinuation. Results demonstrate how caregiver network composition and connectivity shape social resilience under stress. Caregiving networks that have higher "bonding" social capital-densely interconnected and including close relatives and others who provide support to both caregivers and care recipients-may be more resilient due to strong support coordination and communication. Study insights can inform the development of support intervention strategies for caregivers. Findings suggest that promoting bonding capital in caregiver networks may help protect against the loss of critical support during crises.
Transparent conductive materials still face significant challenges in simultaneously achieving high optical transmittance, broadband electromagnetic interference (EMI) shielding, and excellent environmental stability. In this work, a hexagonal-Voronoi composite metal mesh (HV-CMM) is proposed by integrating a periodic hexagonal framework with stochastic Voronoi substructures, which effectively suppresses optical diffraction while maintaining structural stability. By tuning the characteristic size of the Voronoi features, a synergistic optimization of optical and electromagnetic performance is achieved. The fabricated HV-CMM exhibits high optical transmittance of 78-83% and low haze of 4.5-4.8% in the visible range. Owing to the disruption of long-range periodicity, coherent diffraction is effectively suppressed, leading to improved visual uniformity. In the 1-18 GHz frequency range, the samples demonstrate stable EMI shielding performance, with an average shielding effectiveness of 38.5 dB and a maximum value of 47.8 dB at 12 GHz. In addition, the HV-CMM shows rapid and uniform electrothermal response, reaching a temperature of 143 °C within 150 s under an applied voltage of 1 V. The introduction of a Ni passivation layer significantly enhances environmental stability, reducing the variation in sheet resistance from 152.9% for pure Cu to 42.4% after 240 h under 85 °C/85% RH conditions. This work presents a structure-material co-design strategy, providing a new pathway for multifunctional transparent conductive meshes in applications such as optical windows, defogging/deicing systems, and electromagnetic protection.
Teratoma in the head and neck region is an extremely rare germ cell neoplasm composed of tissues from the three germ cell layers (endoderm, mesoderm, and ectoderm). We present a report of a cystic neck teratoma in a 36-year-old man. The mass was excised following comprehensive diagnostic evaluation and surgical intervention. Histological examination revealed squamous epithelium, sebaceous glands, hair material, and disorganized smooth muscle bundles, while fluorescence in situ hybridization (FISH) demonstrated a gain of chromosome 12p in 24% of nuclei. These findings confirmed the diagnosis of primary cervical teratoma, and subsequent testicular ultrasound excluded a gonadal primary. This report highlights the importance of integrating morphology and molecular testing within a multidisciplinary approach to adult neck masses. The rarity of this entity and the detection of a chromosome 12p alteration provide new insights into the molecular characteristics of adult neck teratomas and their potential biological behavior.
Implementing multi-area disability prevention activities is an effective and efficient strategy for preventing the transition to frailty and the need for long-term care among older adults. In this study, we aimed to investigate the actual conditions and factors associated with implementing these prevention activities in daily function, nutritional status, and oral function. In this cross-sectional study, a mailed questionnaire was sent to 1,800 randomly selected older adults. Ten locations were selected to minimize bias in population characteristics, including urban, rural, and mountainous areas. The questionnaire included items on the actual conditions of disability prevention activities concerning daily function, nutritional status, and oral function; their content and frequency of implementation; and variables considered to be associated with the total number of activities. Respondents who did not engage in any disability prevention activities or who had incomplete data were excluded from the analysis. Participants were classified into two groups: those who implemented disability prevention activities in all three areas and those who implemented at least one but not all three. Overall, 364 older adults were included in the analysis, of whom 178 (48.9%) implemented disability prevention activities in all three areas. This kind of implementation was significantly associated with the following factors: aged 75-79 years (adjusted odds ratio [aOR] = 2.31), female sex (aOR = 2.13), hypertension (aOR = 0.61), cognitive impairment (aOR = 0.56), and use of mobile applications for disability prevention (aOR = 6.56) (p < 0.05). These findings identify factors associated with the implementation of multi-area disability prevention activities and underscore the need to reconsider current support strategies.
This study investigated the feasibility of evaluating crystal polymorphs of active pharmaceutical ingredients (APIs) using 1H NMR relaxation measurements with time-domain NMR (TD-NMR). Desloratadine, linagliptin, and carbamazepine, each exhibiting multiple polymorphic forms, were selected as model APIs. T1 relaxation times were measured, and the results showed that T1 relaxation behavior differed for each crystal form of the APIs. For desloratadine, an amorphous sample was also prepared and evaluated. It was demonstrated that the T1 relaxation time of the amorphous form was shorter than those of the crystal polymorphs, indicating higher molecular mobility. T1 relaxation curves were further analyzed using multivariate statistical process control (MSPC) based on principal component analysis, and Hotelling's T² and Q statistics successfully distinguished different crystalline forms. In the latter part of this study, physical mixtures of crystal polymorphs were tested to evaluate the detection sensitivity of the MSPC approach. The results demonstrated that this method could identify polymorphic admixtures with a detection limit of approximately 5-10%, depending on the API. TD-NMR offers practical advantages, including rapid measurement, minimal sample preparation, and non-destructive analysis using low-field benchtop instruments. These results indicate that TD-NMR combined with MSPC provides a practical at-line method for monitoring crystal polymorphism and detecting polymorphic contamination during pharmaceutical manufacturing.