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Assessment of symptom severity and functional status in patients with carpal tunnel syndrome: reliability and functionality of the Turkish version of the Boston Questionnaire.

OBJECTIVES: The aim of this study was to develop a Turkish version of the Boston Questionnaire and assess its reliability and validity. METHODS: Sixty-seven patients with idiopathic carpal tunnel syndrome were included in the study. The Turkish version of Boston Questionnaire was obtained after translation process, and was then administered to subjects twice within seven days. Reliability was assessed by internal consistency (Cronbach's alpha and item-total correlation), and reproducibility. Validity was examined by correlating the Boston Questionnaire scores to general health status (Short Form-36), pain severity (Visual Analogue Scale) and pinch and grip strength measures. RESULTS: Reliability of the Turkish version was very good, with high internal consistency (Cronbach's alpha 0.82 for symptom severity scale, and 0.88 for functional status scale), and reproducibility (Pearson correlation coefficient 0.60 for symptom severity scale, and 0.77 for functional status scale). The Boston Questionnaire scores were correlated with Visual Analogue Scale, physical functioning, physical role, bodily pain and emotional role subscales of Short Form-36, pinch and grip strength scores to obtain coefficients for external construct validity. CONCLUSION: Adaptation of the Boston Questionnaire for use in Turkey was successful. Our results seem to support previous finding of the English version, indicating that it is valid and reliable.

Adult↗

The German cervical cancer screening model: development and validation of a decision-analytic model for cervical cancer screening in Germany.

BACKGROUND: We sought to develop and validate a decision-analytic model for the natural history of cervical cancer for the German health care context and to apply it to cervical cancer screening. METHODS: We developed a Markov model for the natural history of cervical cancer and cervical cancer screening in the German health care context. The model reflects current German practice standards for screening, diagnostic follow-up and treatment regarding cervical cancer and its precursors. Data for disease progression and cervical cancer survival were obtained from the literature and German cancer registries. Accuracy of Papanicolaou (Pap) testing was based on meta-analyses. We performed internal and external model validation using observed epidemiological data for unscreened women from different German cancer registries. The model predicts life expectancy, incidence of detected cervical cancer cases, lifetime cervical cancer risks and mortality. RESULTS: The model predicted a lifetime cervical cancer risk of 3.0% and a lifetime cervical cancer mortality of 1.0%, with a peak cancer incidence of 84/100,000 at age 51 years. These results were similar to observed data from German cancer registries, German literature data and results from other international models. Based on our model, annual Pap screening could prevent 98.7% of diagnosed cancer cases and 99.6% of deaths due to cervical cancer in women completely adherent to screening and compliant to treatment. Extending the screening interval from 1 year to 2, 3 or 5 years resulted in reduced screening effectiveness. CONCLUSIONS: This model provides a tool for evaluating the long-term effectiveness of different cervical cancer screening tests and strategies.

Adolescent↗

PGR expression as a pharmacogenomic companion biomarker to GENE70-derived genomic risk in ER-positive/HER2-negative breast cancer.

BACKGROUND: The biology of the estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancers is heterogeneous even when they are categorized by their risk via genomics. Transcriptomic PGR expression reflects endocrine pathway activity and may provide complementary biological information within established GENE70-derived genomic-risk categories. Whether this molecular marker improves the biological interpretation of genomic-risk stratification beyond conventional clinicopathological assessment remains uncertain. OBJECTIVES: The aim of this study was to determine whether transcriptomic PGR expression provides complementary biological and prognostic information within reconstructed GENE70-derived genomic-risk categories and refines the characterization of endocrine-related tumour biology in ER-positive/HER2-negative breast cancer. METHODS: This study analysed publicly available transcriptomic and clinical data from three cohorts: METABRIC (discovery cohort), GSE96058/SCAN-B cohort (validation cohort) and TCGA-BRCA cohort (molecular validation cohort). The GENE70-derived genomic-risk score was reconstructed for each cohort using matched genes. Cox regression, Kaplan-Meier analysis and subgroup comparisons were used to assess relationships between PGR expression, clinicopathologic variables, molecular features and survival outcomes. RESULTS: Across the three independent cohorts, low transcriptomic PGR expression was consistently associated with higher GENE70-derived genomic risk, increased MKI67 expression, reduced ESR1 expression and enrichment of the Luminal B subtype. Survival findings differed between cohorts. In the discovery METABRIC cohort, transcriptomic PGR expression showed heterogeneous associations with survival, particularly within GENE70-derived high-risk subgroups, whereas the external GSE96058/SCAN-B validation cohort demonstrated consistent associations between low PGR expression and poorer overall survival in both the overall ER-positive/HER2-negative population and GENE70-derived high-risk subgroups. CONCLUSION: These findings suggest that transcriptomic PGR provides complementary biological and prognostic information within GENE70-derived genomic-risk categories. However, because treatment response was not evaluated in the present study, the findings should not be interpreted as evidence of predictive or pharmacogenomic utility and prospective studies incorporating treatment-response analyses are required before such applications can be established.

Humans↗

Report from the techa river dosimetry review workshop held on 8-10 December 2003 at The State Research Centre Institute of Biophysics, Moscow, Russia.

Large releases of fission products into the Techa River, in the Southern Urals, occurred in 1950 and 1951, during the early years of operation of the Mayak Production Association (Mayak PA), which produced plutonium for nuclear weapons. Increases of leukemia and of solid cancers with radiation dose have been noted in the population of about 30,000 people who lived in the settlements downstream of the site of the radioactive releases; that population has been studied for several decades by Russian scientists, notably in the framework of cooperation with American and European scientists. The radiation doses are currently estimated by means of the Techa River Dosimetry System-2000 (TRDS-2000). Recently, a scientist from Mayak PA has suggested in several publications that the doses calculated using TRDS-2000 might be underestimated substantially. A special international Workshop, held in Moscow on 8-10 December 2003, aimed to resolve some of the pressing issues related to the determination of the external and internal doses received by the Techa River population and to give recommendations on the further development of methodologies used for dose reconstruction. The authors of this article were selected by the organizers of the Workshop to draw the conclusions of the meeting. They express the view that, while the dose reconstruction system TRDS-2000 is basically sound, additional work is needed and the results of any epidemiological studies making use of TRDS-2000 should be qualified as preliminary, pending resolution of several issues. The most important of these issues is the re-evaluation of the activities released, using additional information that could be obtained with the help of Mayak experts. Other specific suggestions aiming to improve the dose reconstruction methodology for the Techa River cohort, i.e., continued measurements of accumulated dose in environmental samples and human tissues, validation of external dose estimates with thermoluminescence measurements of bricks and with electron paramagnetic resonance measurements of teeth, estimation of individual doses instead of group doses, detailed account of the contributions to dose of medical examinations and of other releases from the Mayak complex, and careful assessment of the uncertainties, were made by the meeting participants.

Dose-Response Relationship, Radiation↗

Validity of selected physical activity questions in white Seventh-day Adventists and non-Adventists.

The validity and reliability of selected physical activity questions were assessed in both Seventh-day Adventist (N = 131) and non-Adventist (N = 101) study groups. Vigorous activity questions similar to those used by others and new questions that measured moderate and light activities were included. Validation was external, comparing questionnaire data with treadmill exercise time, resting heart rate, and body mass index (kg.m-2), and internal, comparing data with other similar questions. Both Adventist and non-Adventist males showed significant age-adjusted correlations between treadmill time and a "Run-Walk-Jog Index" (R = 0.28, R = 0.48, respectively). These correlations increased substantially when restricting analysis to exercise speeds exceeding 3 mph (R = 0.39, R = 0.71, respectively). Frequency of sweating and a vigorous physical activity index also correlated significantly with treadmill time in males. Correlations were generally weaker in females. Moderate- and light-intensity questions were not correlated with physical fitness. Internal correlations R = 0.50-0.78) between the above three vigorous activity questions were significant in all groups, and correlations (R = 0.14-0.60) for light and moderate activity questions were also documented. Test-retest reliability coefficients were high for vigorous activity questions (R = 0.48-0.85) and for one set of moderate activity questions (R = 0.43-0.75). No important differences in validity and reliability were found between Adventist and non-Adventists, but the validity of vigorous activity measures was generally weaker in females.

Adult↗

Coping subtypes for men with coronary heart disease: relationship to well-being, stress and Type-A behaviour.

We used cluster analysis to delineate coping subtypes in a sample of 166 men with coronary heart disease who completed the Antwerp out-patient rehabilitation programme. These subtypes were identified on the basis of three well-defined superordinate traits that were selected from a comprehensive taxonomy: negative affectivity, social inhibition, and self-deception. Using Ward's minimum variance method and the cubic clustering criterion, we identified four coping subtypes; low-negative affectivity (N = 48), high-negative affectivity (N = 30), inhibited (N = 62), and repressive (N = 26) individuals. The accuracy of the resulting classification was demonstrated across parallel data sets and was further validated against external, health-related correlates that were not included in the clustering. The identified coping subtypes were significantly related to self-reports of subjective distress/perceived stress, ratings of Type A behaviour and anger-in, return to work, prevalence of chest-pain complaints, and use of minor tranquillizers and sleeping pills. The major findings of this study suggest that (a) male coronary patients represent a heterogeneous population with distinctly different coping subtypes, and that (b) a relatively small number of homogeneous subtypes can account for a substantial amount of variance in subjective well-being, coronary-prone behaviour, and return to work. These findings indicate that psychosomatic research should focus on how superordinate traits interact within individuals and corroborate the appropriateness of a class model to describe coping styles of male coronary patients. It is argued that discrepant findings across studies of Type-A behaviour and hostility may be related to the coping subtypes of the subject sample. Further attempts to cross-validate this classification scheme and to examine its health-related correlates are needed.

Adaptation, Psychological↗

[A validation of the applicability of the Severity of Dependence Scale (SDS) in a nationwide mental hospital survey on substance-related psychiatric disorders].

We studied the applicability of the Severity of Dependence Scale (SDS) in a nationwide mental hospital survey on substance-related psychiatric disorders in 2002. The SDS is an easily administered five-item scale used to assess psychological dependence, especially the compulsive use of a wide range of substances. The SDS was translated into Japanese (SDS-J) and administered as a part of a questionnaire to 114 patients with substance-dependence syndrome in the survey. The SDS-J had a good internal consistency as demonstrated by the high Cronbach's alpha (0.76). Principal component analyses (PCA) with varimax rotation on the five items revealed a single-factor solution that accounted for 50.8% of the variance. Pearson's correlation coefficient between each item and total score ranged from 0.68 to 0.76, all of which were significant (p<.01). The total score of the SDS-J and the total number of items and psychological dependence-related items in the diagnostic guideline of dependence syndrome of the ICD-10 had rather low Pearson's correlation coefficients (0.17 and 0.23), but those correlations were significant (p < .05 and p < .01). The PCA for the patients with methamphetamine dependence also revealed a single-factor solution that accounted for 55.0% of the total variance. The results indicate that the SDS-J has satisfactory internal and structural reliability and external criteria validity. It also suggests that the SDS-J might be useful for assessing dependence syndrome in clinical settings in Japan, where those substances having properties of causing particularly severe psychological dependence, such as methamphetamine and solvents, are the most common substances of abuse.

Adult↗

Rapid and sensitive method for the determination of sertraline in human plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

A method for the determination of sertraline, a new antidepressant drug and a selective serotonin reuptake inhibitor (SSRI), in human plasma is described. Therapeutic drug monitoring (TDM) necessitates efficient, fast and reliable analytical methods validated by external quality control. We therefore devised a simple, rapid and sensitive isocratic reversed-phase liquid chromatographic-tandem mass spectrometric method equipped with Turbo Ion spray (TIS) source, operating in the positive ion and selective reaction monitoring (SRM) acquisition mode to quantify sertraline in human plasma. A new and superior procedure of solid-phase extraction (SPE) (compared to liquid-liquid extraction) was followed to extract sertraline and imipramine as internal standard (IS) from the human plasma. Sample preparation was performed using waters hydrophilic-lipophilic balance (HLB) cartridge and this method yielded extremely clean extracts with very good recovery, 81.47 and 85.79% for sertraline and IS, respectively. Both were analyzed by combined reverse phase liquid chromatography and tandem mass spectrometry (LC-MS/MS) with positive ion TIS ionization using SRM acquisition mode. The response of the LC-MS/MS method for sertraline was linear over the dynamic range of 0.5-60.0 ng/ml with correlation coefficient r>or=0.9996. The coefficient of variance (%CV) was 8.53% at 0.5 ng/ml and the accuracy was well within the accepted limit of +/-20% at lower limit of quantification (LLOQ) and +/-15% at all the other concentrations in the linear range. This method was fully validated for the accuracy, precision and stability studies. The above findings indicate that the method is very much accurate and precise and can be successfully applied for bioequivalence studies in human subjects.

Chromatography, Liquid↗

Sex difference in the validity of vertebral deformities as an index of prevalent vertebral osteoporotic fractures: a population survey of older men and women.

Morphometric methods have been developed for standardized assessment of vertebral deformities in clinical and epidemiologic studies of spinal osteoporosis. However, vertebral deformity may be caused by a variety of other conditions. To examine the validity of morphometrically assessed vertebral deformities as an index of osteoporotic vertebral fractures, we developed an algorithm for radiological differential classification (RDC) based on a combination of quantitative and qualitative assessment of lateral spinal radiographs. Radiographs were obtained in a population of 50- to 80-year-old German women (n = 283) and men (n = 297) surveyed in the context of the European Vertebral Osteoporosis Study (EVOS). Morphometric methods (Eastell 3 SD and 4 SD criteria, McCloskey) were validated against RDC and against bone mineral density (BMD) at the femur and the lumbar spine. According to RDC 36 persons (6.2%) had at least one osteoporotic vertebral fracture; among 516 (88.9%) nonosteoporotics 154 had severe spondylosis, 132 had other spinal disease and 219 had normal findings; 14 persons (2.4%) could not be unequivocally classified. The prevalence of morphometrically assessed vertebral deformities ranged from 7.3% to 19.2% in women and from 3.5% to 16.6% in men, depending on the stringency of the morphometric criteria. The agreement between RDC and morphometric methods was poor. In men, 62-86% of cases with vertebral deformities were classified as nonosteoporotic (severe spondylosis or other spinal disease) by RDC, compared with 31-68% in women. Among these, most had wedge deformities of the thoracic spine. On the other hand, up to 80% of osteoporotic vertebral fractures in men and up to 48% in women were missed by morphometry, in particular endplate fractures at the lumbar spine. In the group with osteoporotic vertebral fractures by RDC the proportion of persons with osteoporosis according to the WHO criteria (T-score < -2.5 SD) was 90.0% in women and 86.6% in men, compared with 67.9-85.0% in women and 20.8-50.0% in men with vertebral deformities by various methods. Although vertebral deformities by most definitions were significantly and inversely related to BMD as a continuous variable in both sexes [OR; 95% CI ranged between (1.70; 1.07-2.70) and (3.69; 1.33-10.25)], a much stronger association existed between BMD and osteoporotic fractures defined by RDC [OR; 95% CI between (4.85; 2.30-10.24) and (15.40; 4.65-51.02)]. In the nonosteoporotic group individuals with severe spondylosis had significantly higher BMD values at the femoral neck (p < 0.01) and lumbar spine (p < 0.0004) compared with the normal group. On the basis of internal (RDC) and external (BMD) validation, we conclude that assessment of vertebral osteoporotic fracture by quantitative methods alone will result in considerable misclassification, especially in men. Criteria for differential diagnosis as used within RDC can be helpful for a standardized subclassification of vertebral deformities in studies of spinal osteoporosis.

Aged↗

Quality over quantity: biopsy-anchored CT radiogenomics models outperform all-lesion training in a multi-tumour cohort despite a smaller sample size.

OBJECTIVE: Radiogenomics aims to non-invasively predict tumour genotypes from imaging, but most studies assume molecular homogeneity by assigning a single biopsy-derived label to all lesions within a patient. This approach risks substantial label noise given well-documented interlesional heterogeneity. We investigated whether anchoring training to biopsy-confirmed lesions improves radiogenomic model performance and generalisability. MATERIALS AND METHODS: We retrospectively analysed 1646 patients (11473 segmented lesions) with contrast-enhanced CT and EGFR mutation status from next-generation sequencing at the Netherlands Cancer Institute, alongside an external NSCLC radiogenomics cohort (n&#x2009;=&#x2009;158). All visible lesions were segmented, and the exact biopsy site was matched to its segmentation. Radiomic features were extracted, and machine learning models were trained with three lesion selection strategies: all lesions, non-biopsied lesions only, and biopsy-confirmed lesions only. To disentangle label quality from sample size, we created size-matched variants (one lesion per patient) for all-lesion and non-biopsied strategies. RESULTS: All models achieved significant discrimination of EGFR status on internal validation (AUC&#x2009;=&#x2009;0.62-0.68). However, performance of the all-lesion and non-biopsied models declined on external validation (AUC&#x2009;=&#x2009;0.55-0.63), while the biopsy-anchored model maintained stable performance (AUC&#x2009;=&#x2009;0.62), despite having only 1/10th of the training sample size. When training sets were size-matched, the biopsy-anchored approach significantly outperformed a model trained on all available lesions on external validation (p&#x2009;=&#x2009;0.037). CONCLUSIONS: Radiogenomic models trained on biopsy-confirmed lesions outperform conventional all-lesion strategies in external validation, despite using an order of magnitude fewer samples. Prioritising lesion-level label fidelity can mitigate heterogeneity-driven noise, enhancing robustness and clinical translation of imaging-based genomic prediction. KEY POINTS: Question Does assigning biopsy-derived molecular labels to all lesions introduce heterogeneity-driven label noise that reduces the generalisability of radiogenomic models? Findings Models trained exclusively on biopsy-confirmed lesions demonstrated superior external generalisability compared with all-lesion approaches, despite being trained on substantially fewer samples. Clinical relevance Biopsy-anchored radiogenomics improves the reliability of non-invasive mutation prediction by accounting for tumour heterogeneity, potentially supporting clinical decision-making when tissue sampling is limited or molecular results are discordant across lesions.

Humans↗

Effect of Tertiary Lymphoid Structures on Immune Cell Infiltration in the Tumor Microenvironment and Prognosis in Lung Adenocarcinoma.

Tertiary lymphoid structures (TLSs) modulate immune responses in various solid tumors, but their comprehensive role in lung adenocarcinoma (LUAD) remains unclear. In this study, we analyzed RNA-seq data from 539 LUAD patients in The Cancer Genome Atlas (TCGA) and microarray data from 223 samples from the Gene Expression Omnibus (GEO, GSE13213, and GSE37745). TLS signatures were evaluated via unsupervised consensus clustering based on 12 chemokine transcriptome signatures. The relationships between TLS and clinical characteristics, tumor microenvironment (TME) cell infiltration, and prognosis were assessed using ESTIMATE and CIBERSORT. A prognostic model was established using LASSO regression and validated with external datasets. Additionally, H&E and IHC analyses were performed to explore associations between intratumoral TLS density, immune-related molecular expression, and patient prognosis in LUAD. Consensus clustering of the TCGA cohort revealed two distinct LUAD patient clusters according to TLS abundance. Cluster 1 exhibited greater immune cell infiltration, more favorable prognosis, and increased expression of immune checkpoint molecules. We developed a prognostic model comprising eight survival-associated genes that act as independent prognostic factors for patient survival. H&E/IHC analyses revealed that TLS density-regardless of pathological stage-was associated with better prognosis; higher intratumoral TLS density/proportion was also related to more favorable outcomes. IHC confirmed that survival-associated genes (CD5, HLA-DMB, and P2RY13) are independent prognostic indicators in LUAD. Our study demonstrated the close relationship between TLS signatures and an active immune microenvironment, highlighting their potential as independent prognostic indicators in LUAD.

Humans↗

Clinical evaluation of His-bundle electrogram recorded from the body surface.

A noninvasive method of recording His-bundle activity was developed in our laboratory. This technique is based on the principle of high-gain amplification of the external signals, use of appropriate filters to eliminate random noise, and averaging of the amplified signals over 200-500 cardiac cycles to improve the signal-to-noise ratio. Using this technique we were able to demonstrate external His-bundle activity and to measure the extent His-bundle-ventricular (H-V) interval in 29 of 51 (60%) patients referred to our unit for evaluation of conduction abnormalities or history of collapse. The external technique was validated by the intracardiac electrode method. External H-V interval was reproducible when tested i eight normal subjects and four patients of variation was 4.5% for external H-V interval of 30-90 ms duration). Failure to obtain distinct external His-bundle deflection was largely due to contamination with atrial or ventricular noise. Analysis of all the records showed that the demonstration of external His-bundle activity was directly proportional to the length of the PR segment. The external H-V interval could be measured in all patients with PR segments longer than 100 ms but in less than half in whom the PR segment was shorter than 55 ms. We conclude that the noninvasive technique of recording His-bundle activity is simple and reproducible and can be used at the bedside. It possesses a distinct advantage over the intracardiac technique in that it can be employed in sequential studies. However, in its present state of development, its use is mainly confined to the analysis of conduction disturbances.

Adolescent↗

The measurement of culture shock.

This paper describes the development and evaluation of a new questionnaire to measure culture shock. The population was young British volunteers working in a variety of cultural settings overseas (N = 380). Core culture shock items were derived from a consensus statement from the literature on culture shock. Additional items were obtained from an analysis of reports by previous volunteers. Internal consistency of items, as determined by correlation coefficients and factor analysis, was satisfactory; this also lends some empirical support to the concept of culture shock. External criterion validity was established by reference to the country of destination and correlation with a measure of cultural distance. A 12-item questionnaire to measure culture shock is offered for further use and evaluation.

Adult↗

Evaluating diagnostic criteria: a latent class paradigm.

A latent class analysis paradigm for evaluating and developing diagnostic criteria was presented. How latent class analysis statistically models the conceptual structure of diagnostic systems was demonstrated. These models were then used to study the Taylor and Abrams diagnostic criteria for schizophrenia. The findings of this analysis were used in reanalyzing a previous study, yielding improved results. Finally, the nature of internal and external construct validity, and the particular appropriateness for diagnostic research of models with discrete variables was discussed.

Diagnosis, Differential↗

Measurement of particle clearance from the alveolar region of the rabbit respiratory tract.

This paper describes a method for the measurement of the clearance of inert, insoluble radioactively tagged tracer particles from the alveolar region of the rabbit respiratory tract. The technique uses a fixed detector for noninvasive, external monitoring. Validation of the method is presented, as is the clearance pattern of 3.5-micron latex particles as measured for 56 days postexposure. The clearance of latex deposited within the alveolar region can be described by two phases within this time frame, having half-times of 4.9 and 30.1 days, respectively. Clearance of latex initially deposited on the tracheobronchial tree was essentially complete by 2 days after exposure.

Animals↗

QSPR-based prediction of gas/particle partitioning of polychlorinated biphenyls in the atmosphere.

By reviewing the existing models for describing gas/particle partitioning of semi-volatile organic compounds in the atmosphere, it was assumed that gas/particle partition coefficient, expressed as Kp, may be predicted using molecular descriptors. Overall 14 molecular descriptors of each compound calculated using semi-empirical method parametric model 3 (PM3) were tested against logKp of selected PCBs to determine the best ones governing partitioning. Eight descriptors molecular weight (Mw), molecular volume (Mv), total energy (TE), electronic energy (EE), squared atom electron densities on carbon, hydrogen and chlorine atoms in a given molecule (Summation qC2, Summation qCl2, Summation qH2) and average molecular polarizability (alpha m) were found to be highly correlated with logKp compared to other molecular descriptors. Using Partial Least-Squares Regression method (PLS), two-, three- and four-descriptor QSPR models with high fitting characters were successfully developed and their robustness and predictive power were further validated by internal cross-validation and external test. Finally, the gas/particle partition coefficients of all 209 PCBs were predicted for the first time.

Air Pollutants↗

Multivariate optimization of the factors influencing the solid-phase microextraction of pyrethroid pesticides in water.

A method based on solid-phase microextraction (SPME) and gas chromatography with micro-electron capture detection (GC-microECD) has been optimized for the analysis of pyrethroids in water samples. The influence of parameters such as temperature, fibre coating, salting-out effect and sampling mode on the extraction efficiency has been studied by means of a mix-level factorial design, which allowed the study of main effects as well as two factor interactions. Finally, a method based on direct SPME at 50 degrees C, using polydimethylsiloxane fibre is proposed. The method showed good linearity (R2>0.995) and repeatability (RSD<or=16%) for all compounds, with detection limits ranging from 0.05 pg/mL for transfluthrin to 2.18 pg/mL for permethrin, and in general <or=1 pg/mL for most pyrethroids. Reliability was demonstrated through the evaluation of the recoveries in different water samples, such as tap water, groundwater, river water, runoff water, and wastewater. These studies demonstrated the validity of external standard calibration to quantify the target compounds in real samples, including a simple dilution step for the most complex matrices, which notoriously simplifies quantification by SPME.

Chromatography, Gas↗

Colorectal Liver Metastasis Pathomics Model: Integrating Single-Cell and Spatial Transcriptome Analysis With Pathomics for Predicting Liver Metastasis in Colorectal Cancer.

The liver is the primary target organ for hematologic metastasis of colorectal cancer (CRC), and CRC liver metastasis (CRLM) often precludes radical resection, making it the leading cause of death in patients with CRC. To improve the identification and prediction of liver metastasis risk, we identified a cell type of liver metastasis--triggering malignant cells (LMTMCs) through integrating single-cell RNA sequencing and spatial transcriptome analysis. Multiomics cell communication analysis indicated that the interaction between fibroblasts and LMTMCs through the COL1A1-CD44/SDC4 and LAMA4-CD44 signaling axes could promote CRLM. By applying the one-class logistic regression algorithm, we developed a CRLM scoring system in the bulk RNA-sequencing data according to the abundance of LMTMCs in each individual. Using the grouping labels derived from the CRLM scoring system in the bulk data and the corresponding whole-slide images without any manual annotations at the region or pixel level, processed via slide-level weakly supervised learning, a deep-learning model based on the ResNet18 architecture, called Colorectal Liver Metastasis Pathomics Model, was developed to predict the risk of liver metastasis in patients with CRC. The Colorectal Liver Metastasis Pathomics Model achieved an area under the curve of 0.84 at the internal test set of The Cancer Genome Atlas-CRC histology images. In the external independent validation sets, namely the Affiliated Hospital of Southwest Medical University and the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University cohorts, the areas under the curve were 0.89 and 0.72, respectively, indicating effective classification performances. This study provided new insights and tools for the early identification of CRLM and demonstrated the potential of combining multiomics with deep learning-based pathomics in cancer research.

Humans↗