CCL4 as a potential serum factor in differential diagnosis of central nervous system inflammatory diseases and gliomas.

Computed tomography (CT) scans and magnetic resonance imaging (MRI) are commonly utilized to detect brain gliomas and central nervous system inflammation diseases. However, there are instances where depending solely on medical imaging for a precise diagnosis may result in unsuitable medications or treatments. Pathological analysis is regarded as the definitive method for diagnosing brain gliomas or central nervous system inflammation diseases. To achieve this, a craniotomy or stereotaxic biopsy is necessary to collect brain tissue, which can lead to complications such as cerebral hemorrhage, neurological deficits, cerebrospinal fluid leaks, and cerebral edema. Consequently, the advancement of non-invasive or minimally invasive diagnostic techniques is currently a high priority. This study included samples from four glioma patients and five patients with central nervous system inflammatory diseases, comprising both serum and paired cerebrospinal fluid (CSF). A total of 40 human cytokines were identified in these samples. We utilized a receiver operating characteristic (ROC) analysis to assess the sensitivity and specificity for distinguishing central nervous system inflammation diseases and gliomas. Additionally, we examined the correlation of these factors between serum and CSF in the patients. Ultimately, the identified factors were validated using serum from patients with clinically confirmed gliomas and central nervous system inflammation diseases followed by detection and statistical analysis through ELISA. The levels of serum factors IL-4, IFN-α, IFN-γ, IL-6, TNF-α, CCL4, CCL11, and VEGF were found to be significantly higher in gliomas compared with inflammatory diseases of the central nervous system (p < 0.05). Furthermore, a strong correlation was observed between the levels of CCL4 in serum and CSF, with a correlation coefficient of r = 0.92 (95% CI = 0.20-0.99, p = 0.027). We gathered more clinical samples to provide further validation of the abundance of CCL4 expression. A clinical study analyzing serum samples from 19 glioma patients and 22 patients with central nervous system inflammation diseases revealed that CCL4 levels were notably elevated in the inflammatory group compared with the glioma group (p < 0.001). These results suggest that assessing serum CCL4 levels may be useful in distinguishing those patients for clinical diagnostic purposes.

Mapping the evolution of 3D printing in cardio-thoracic diseases: a global bibliometric analysis.

BACKGROUND: Despite the growing research on 3D printing (3DP) in cardio-thoracic diseases, comprehensive bibliometric analyses remain scarce. This study aims to bridge this gap by identifying key research trends and hotspots within the field. METHODS: A bibliometric analysis was conducted on publications from 1991 to 2024 using data from the Web of Science Core Collection, with analysis performed using VOSviewer, CiteSpace, and the R package 'bibliometrix'. RESULTS: The analysis included 2,836 documents authored by 14,206 researchers across 85 countries. A significant rise in annual publications was observed, with the United States, China, and the United Kingdom leading in contributions. Prominent institutions, including Stanford University, were highlighted, while Scientific Reports and Biomaterials were identified as influential journals. Key research areas encompass cardiovascular, lung, and breast diseases, along with chest wall reconstructions, with emerging trends focusing on advanced materials for drug delivery and tissue engineering. CONCLUSION: This comprehensive bibliometric analysis of 3DP in cardio-thoracic diseases reveals global research trends, emerging themes, and the crucial role of 3DP in advancing medical education and personalized treatment, highlighting areas for future research and development.

The chromodomain protein CDYL confers forebrain identity to human cortical organoids by inhibiting neuronatin.

Fate determination of neural stem cells (NSCs) is crucial for cortex development and is closely linked to neurodevelopmental disorders when gene expression networks are disrupted. The transcriptional corepressor chromodomain Y-like (CDYL) is widely expressed across diverse cell populations within the human embryonic cortex. However, its precise role in cortical development remains unclear. Here, we show that CDYL is critical for human cortical neurogenesis and that its deficiency leads to a substantial increase in gamma-aminobutyric acid (GABA)-ergic neurons in cortical organoids. Subsequently, neuronatin (NNAT) is identified as a significant target of CDYL, and its abnormal expression obviously influences the fate commitment of cortical NSCs. Cross-species comparisons of CDYL targets unravel a distinct developmental trajectory between human cortical organoids and the mouse cortex at an analogous stage. Collectively, our data provide insight into the evolutionary roles of CDYL in human cortex development, emphasizing its critical function in maintaining the fate of human cortical NSCs.

O-GlcNAcylation of ribosome-associated proteins is concomitant with translational reprogramming during proteotoxic stress.

Protein O-GlcNAc modification, similar to phosphorylation, supports cell survival by regulating key processes like transcription, cell division, trafficking, signaling, and stress tolerance. However, its role in protein homeostasis, particularly in protein synthesis, folding, and degradation remains poorly understood. Our previous research shows that O-GlcNAc cycling enzymes associate with the translation machinery during protein synthesis and modify ribosomal proteins. Protein translation is closely linked to 26S proteasome activity, which recycles amino acids and clears misfolded proteins during stress, preventing aggregation and cell death. In this study, we demonstrate that pharmacological perturbation of the proteasome-like that used in cancer treatment- leads to the increased abundance of OGT and OGA in a ribosome-rich fraction, concurrent with O-GlcNAc modification of core translational and ribosome-associated proteins. This interaction is synchronous with eIF2α-dependent translational reprogramming. We also found that protein ubiquitination depends partly on O-GlcNAc metabolism in MEFs, as OGT-depleted cells show decreased ubiquitination under stress. Using an O-GlcNAc-peptide enrichment strategy followed by LC-MS/MS, we identified 84 unique O-GlcNAc sites across 55 proteins, including ribosomal proteins, nucleolar factors, and the 70-kDa heat shock protein family. Hsp70 and OGT colocalize with the translational machinery in an RNA-independent manner, aiding in partial protein translation recovery during sustained stress. O-GlcNAc cycling on ribosome-associated proteins collaborates with Hsp70 to restore protein synthesis during proteotoxicity, suggesting a role in tumor resistance to proteasome inhibitors.

Unraveling how hydrogen-bonding networks affect the capture of amphetamine-type stimulants by polymerized deep eutectic solvent modified magnetic biochar: Coupling quantum chemical calculations with experiment.

The abuse of amphetamine-type stimulants (ATSs) has caused irreversible harm to public safety and ecosystems. A novel polymerized deep eutectic solvent modified magnetic pomelo peel biochar (PMBC) was prepared, and the differences in adsorption of four abused amphetamine-type stimulants (ATSs: AMP, MAMP, MDA and MDMA) were due to varying hydrogen bonds quantities and strengths. PMBC showed excellent chemical reactivity to MDMA, with a maximum adsorption capacity of 926.13 µg g-1, which was 3.25, 2.52 and 1.15 times higher than that of AMP, MAMP and MDA, respectively. Modern spectral analysis showed that there were a series of active centers (-COOH, -NH2 and -OH) on the PMBC, which could form hydrogen bond networks with the nitrogen and oxygen functional groups of ATSs. In various chemical environments: pH level (4-11), inorganic ion and organic matter (humic acid), PMBC maintained high activity towards four ATSs. Additionally, the quantum chemical calculations revealed that the methylenedioxy bridge of ATSs can increase the active sites, and the -NH- and -NH2 groups had different hydrogen bond formation capabilities, which together resulted in the adsorption order of PMBC on the four ATSs: MDMA > MDA > MAMP > AMP. Moreover, the hydrogen-bonding binding energies of several common hydrogen-bonding types were compared, including O-H····O, N-H····O/O-H····N and N-H···N. This study laid an empirical and theoretical foundation for the efficient capture of ATSs in water and contributed to the innovative design of materials.

Microvascular and cellular dysfunctions in Alzheimer's disease: an integrative analysis perspective.

Alzheimer's disease (AD) is the most common cause of dementia, characterized by memory loss, cognitive decline, personality changes, and various neurological symptoms. The role of blood-brain barrier (BBB) injury, extracellular matrix (ECM) abnormalities, and oligodendrocytes (ODCs) dysfunction in AD has gained increasing attention, yet the detailed pathogenesis remains elusive. This study integrates single-cell sequencing of AD patients' cerebrovascular system with a genome-wide association analysis. It aims to elucidate the associations and potential mechanisms behind pericytes injury, ECM disorder, and ODCs dysfunction in AD pathogenesis. Finally, we identified that abnormalities in the pericyte PI3K-AKT-FOXO signaling pathway may be involved in the pathogenic process of AD. This comprehensive approach sheds new light on the complex etiology of AD and opens avenues for advanced research into its pathogenesis and therapeutic strategies.

Global research trends on the associations between the microbiota and lung cancer: a visualization bibliometric analysis (2008-2023).

Numerous papers have been published on the microbiota in lung cancer in recent years. However, there is still a lack of bibliometric analysis of the microbiota in lung cancer in this field. Our paper did bibliometric analyses and elucidated the knowledge structure and study hotspots related to the microbiota in lung cancer patients. We screened publications reporting on the microbiota in lung cancer from 2008 to 2023 from the Web of Science Core Collection (WoSCC) database, and carried out bibliometric analyses by the application of the VOSviewers, CiteSpace and R package "bibliometrix." The 684 documents enrolled in the analysis were obtained from 331 institutions in 67 regions by 4,661 authors and were recorded in 340 journals. Annual papers are growing rapidly, and the countries of China, the United States and Italy are contributing the most to this area of research. Zhejiang University is the main research organization. Science and Cancer had significant impacts on this area. Zhang Yan had the most articles, and the Bertrand Routy had the most co-cited times. Exploring the mechanism of action of the lung and/or gut microbiota in lung cancer and therapeutic strategies involving immune checkpoint inhibitors in lung cancer are the main topics. Moreover, "gut microbiota," "immunotherapy," and "short-chain fatty acids" are important keywords for upcoming study hotspots. In conclusion, microbiota research offers promising opportunities in lung cancer, with pivotal studies exploring the mechanisms that link lung and gut microbiota to therapeutic strategies, particularly through immune checkpoint inhibitors. Moreover, the gut-lung axis emerges as a novel target for innovative treatments. Further research is essential to unravel the detailed mechanisms of this connection.

The impact mechanism and empirical analysis of financial efficiency of science and technology empowering regional real economy growth.

With the aim of exploring the impact mechanism of scientific and technological financial efficiency on regional real economy growth in the context of ecological civilization construction, this study introduces environmental regulation as a mediating factor. By analyzing changes in science and financial efficiency of science and technology, we provide an effective basis for regional real economy development. To achieve this goal, we define concepts such as science and financial efficiency of science and technology and regional real economy, measure data from 2012 to 2021, analyze the impact of science and financial efficiency of science and technology on economic growth using intermediary models, test mediation effects with bootstrap methods, and identify significant differences between regions. It indicates that enhancing science and financial efficiency of sci-tech benefits China's regional real economy growth, but there's unbalanced development across regions. Additionally, environmental regulation serves as a crucial intermediary in the relationship between sci-tech finance and economic growth. There exist regional disparities in the mediation effects of environmental regulation, with eastern regions demonstrating stronger effects compared to central and western regions.

Dermal fibroblasts retain site-specific transcriptomic identity in keloids.

BACKGROUND: Human skin displays extensive spatial heterogeneity and maintains distinct positional identity. However, the impact of disease processes on these site-specific differences remains poorly understood, especially in keloid, a skin disorder characterized by pronounced spatial heterogeneity. OBJECTIVE: This study aimed to assess whether the spatial heterogeneity and positional identity observed in different anatomic sites persist in keloids. METHODS: Transcriptome sequencing was conducted on 139 keloid dermal tissues and 19 keloid fibroblast samples spanning seven distinct anatomic sites to identify the spatial transcriptomic heterogeneity. In addition, single-cell RNA sequencing data were utilized to elucidate the contributions of various cell types to the maintenance of positional identity. RESULTS: Keloid dermal tissues from diverse sites were categorized into three anatomic groupings: trunk and extremity, ear, and mandible regions. Enrichment analysis of differentially expressed genes unveiled that keloids across distinct regions retained unique anatomically-related gene expression profiles, reminiscent of those observed in normal skin. Notably, regional disparities consistently prevailed and surpassed inter-donor variations. Single-cell RNA sequencing further revealed that mesenchymal cells, particularly fibroblasts, made major contributions to positional identity in keloids. Moreover, gene expression profiles in primary keloid fibroblasts demonstrated a remarkable persistence of positional identity, enduring even after prolonged in vitro propagation. CONCLUSION: Taken together, these findings imply that keloids remain positional identity and developmental imprinting characteristic of normal skin. Fibroblasts predominantly contribute to the spatial heterogeneity observed in keloids.

Clinical Implications of Left Ventricular Apex Mechanics in Patients With Apical Hypertrophic Cardiomyopathy.

BACKGROUND: Apical hypertrophic cardiomyopathy (ApHCM) is a unique disease with pathologic hypertrophy mainly at the left ventricular (LV) apex. Although previous studies have indicated apical dysfunction in ApHCM, how apical mechanics change during disease progression has not been thoroughly examined. The aims of this study were to characterize the mechanics of the LV apex in patients with ApHCM at different disease stages and to explore the clinical significance of these alterations. METHODS: One hundred four patients with ApHCM were divided into three subtypes on the basis of LV apical maximum wall thickness (AMWT) and extent of hypertrophy: relative type (isolated apical hypertrophy with AMWT < 15 mm), pure type (isolated apical hypertrophy with AMWT ≥ 15 mm), and mixed type (both apical and midventricular hypertrophy with AMWT ≥ 15 mm). Two-dimensional speckle-tracking echocardiography was used to analyze LV segmental strain, global strain, and twist. Comparisons of these parameters were performed among ApHCM subtypes and 30 healthy control subjects. Logistic regression and Cox proportional-hazards regression analyses were used to explore associations between myocardial mechanics and clinical indicators. A composite outcome of new-onset atrial fibrillation, heart failure hospitalization, myectomy, and all-cause mortality was assessed. RESULTS: Even in relative ApHCM patients, apical longitudinal strain (LS), circumferential strain, and radial strain (RS) were significantly impaired compared with control subjects (LS: -14.6 ± 4.1% vs -20.0 ± 1.7% [P = .001]; circumferential strain: -19.6 ± 2.5% vs -25.6 ± 3.7% [P = .002]; RS: 26.6 ±7.4% vs 35.6 ± 11.1% [P = .026]), while apical rotation and LV twist remained unchanged. In patients with greater apical hypertrophy (mixed and pure patients), apical LS and RS were more abnormal. Moreover, apical rotation showed significant reductions compared with relative-type patients. After adjusting for clinical and myocardial mechanical parameters, apical rotation was independently associated with New York Heart Association functional class ≥ II (odds ratio, 0.81; 95% CI, 0.66-0.99; P = .036) and the composite outcome (hazard ratio, 0.82; 95% CI, 0.73-0.91; P = .001). CONCLUSIONS: Relative ApHCM demonstrates apical dysfunction but sparing of apical rotation, which was abnormal in more extensive phenotypes. LV apex mechanics were closely related to clinical patterns, with apical rotation correlated with both New York Heart Association functional class ≥ II and clinical events.

Long-term outcomes of anterior cervical dynamic implants: motion-sparing or a delayed fusion?

BACKGROUND CONTEXT: Use of an anterior cervical dynamic implant (ACDI) is generally considered a non-fusion technique for treating cervical degenerative disorders. However, there is limited research focused on evaluating the long-term clinical and radiographic outcomes of ACDI. PURPOSE: To analyze the long-term clinical and radiographic outcomes of ACDI in the treatment of degenerative cervical disorders. STUDY DESIGN: A retrospective cohort study PATIENTS SAMPLE: Patients with degenerative cervical disorders who underwent anterior cervical discectomy and dynamic cervical implant (DCI) implantation between May 2012 and August 202 at our institution were included in this study. OUTCOME MEASURES: Clinical outcomes were assessed using the modified Japanese Orthopedic Association (mJOA), visual analog scale (VAS) scores and patient reported satisfaction rate. Imaging assessment parameters included intervertebral height (IH), intervertebral disc height (IDH), C2-7 range of motion (ROM), segmental ROM, the degree of DCI subsidence and anterior migration, heterotopic ossification (HO) as well as adjacent segment degeneration (ASD). METHODS: JOA and VAS scores were obtained through questionnaire. The patient reported satisfaction was rated as very satisfied, satisfied, less satisfied and dissatisfied at the final follow-up. The position of the implants, IDH and IH were evaluated on lateral radiographs. ROM at C2-7, ROM at operated level were measured on dynamic radiographs. Cervical three -dimensional computer tomography (CT) and magnetic resonance image (MRI) images were used to assess the presence of HO and ASD. The clinical and radiologic variables between the preoperative period and different follow-up time point were statistically analyzed by unpaired t-tests or chi-square tests. Statistical significance was defined as p<0.05. RESULTS: A total of 92 patients (51 males and 41 females) were included in this study. Among them, there were 36 cases of cervical spondylotic myelopathy, 26 cases of cervical radiculopathy, and 30 cases of myeloradiculopathy. The mean age was 55.1±12.6 years. The number of operated levels was single level in 57 patients, two levels in 31 patients, and three levels in 4 patients. The average follow-up period was 81.3 months (range: 35-135 months). The mean JOA scores showed a gradual increase at one month, one year, and the final follow-up (12.0±0.7,13.5±0.8, and14.4±1.1 respectively) compared to the preoperative score (9.1±0.9, p<0.01). VAS scores significantly decreased at one month, one year, and the final follow-up (4.1±0.7,2.3±0.9, and 2.0±0.8 respectively) compared to the preoperative score (7.2±l .2, p<0 .01). At the final follow-up, the patient reported satisfaction was rated as very satisfied, satisfied, less satisfied and dissatisfied (79%, 10%, 10%, 1% respectively). Revision surgery was not required for any of the patients during the follow-up period, either due to instrumentation failure or adjacent segmental diseases. In the radiographic assessment, there was a notable increase in IH and IDH after surgery compared to preoperative values (33.0±4.0mm vs 30.7±3.0mm, p<0.01 and 6.7±2.4mm vs 4.6±0.9mm, p<0.01 respectively), which gradually decreased at 1 year and the final follow-up (IH: 32.1±2.5 vs 30.9±3.5 p=0.024; IDH: 5.3±1.5 mm vs 4.3±0.6 mm, p=0.043 respectively). At the one-month postoperative follow-up, the segmental ROM exhibited a decrease compared with preoperative values (6.2±1.8° vs 7.5±2.0° p=0.044), followed by an increase at the one-year follow-up (6.2±1.8° vs 6.4±1.5° p=0 .078), but ultimately decreased at the final follow-up (6.4±1.5° vs 2.9±0.6°, p<0.01). HO was observed in approximately 81.5% of cases (75/92), while a great proportion (41.3%) of patients experienced varying degrees of prosthesis subsidence and anterior migration during the follow-up. CONCLUSION: At the long-term follow-up, a high incidence of HO, along with varying degrees of subsidence and migration of the prosthesis, were observed in most patients. As the motion preservation capability of the ACDI gradually diminishes, delayed intervertebral autofusion becomes a more likely outcome compared to motion sparing.

p21 Regulates Wnt-Notch balance via DREAM/MMB/Rb-E2F1 and maintains intestinal stem cell homeostasis.

The crosstalk and balance regulation of Wnt-Notch have been known to be essential for cell fate decision and tissue regeneration, however, how this balance is maintained and how the Wnt-Notch pathways are connected with cell cycle regulation is still not clear. By analyzing the molecular alterations in mouse model with accelerated aging phenotypes due to loss of p21 function in a Werner syndrome background, we observed that Wnt3 and ß-Catenin were down-regulated, while Notch1 and Hes1 were up-regulated. This disruption in Wnt-Notch signaling was accompanied by the loss of intestinal stem cell compartment, increase in Bmi1 positive cells, loss of Olfm4/Lgr5 positive cells, and reduced secretory Paneth cells and goblet cells in the intestinal crypts of p21TKO mice. BrdU incorporation, cleaved caspase 3, and Tunel assay results revealed the fast turnover of intestinal epithelia, which may result in abnormal stem cell mobilization and exhaustion of the stem cell reservoir in the intestinal crypts. We further identified shift of DREAM complex towards MMB complex due to the loss of p21 as the cause for faster turnover of intestinal epithelia. Importantly, we identified the E2F1 as the transcriptional regulator for Notch1, which linked the p21-DREAM/MMB/Rb-E2F1 pathway with Wnt-Notch pathway. The overexpression of p21 rescued the DREAM pathway, as well as the imbalance of Wnt-Notch pathway. In summary, our data identify p21 as an important factor in maintaining sequential mobilization, proliferation, and homeostasis of intestinal stem cells.

Development and validation of a prognostic nomogram for esophageal cancer patients based on SEER Asian population.

This study aims to develop and validate a nomogram for predicting overall survival (OS) in Asian patients with Esophageal Cancer (EC). Data from Asian EC patients were collected from the Surveillance, Epidemiology, and End Results (SEER) database. The patients were randomly divided into training and validation cohorts in a 7:3 ratio. The Least Absolute Shrinkage and Selection Operator (LASSO) regression was used for initial variable selection, followed by multivariate Cox regression analysis to identify independent prognostic factors. A nomogram was subsequently constructed based on these factors. The predictive performance of the nomogram was evaluated using receiver operating characteristic (ROC) curves and calibration curves, while the clinical utility of the nomogram was assessed through decision curve analysis (DCA). The LASSO regression and multivariate Cox regression analysis identified age, sex, marital status, tumor size, M stage, surgery, and chemotherapy as independent prognostic factors. The ROC curve results demonstrated that the area under the curve (AUC) values for predicting 1-year, 3-year, and 5-year OS in the training cohort were 0.770, 0.756, and 0.783, respectively. In the validation cohort, the AUC values were 0.814, 0.763, and 0.771, respectively. Calibration curves indicated a high concordance between predicted and actual OS. The DCA demonstrated that the nomogram has significant clinical applicability. This nomogram provides reliable predictions and valuable guidance for personalized survival estimates and high-risk patient identification.

The kynurenine pathway regulated by intestinal innate lymphoid cells mediates postoperative cognitive dysfunction.

Postoperative cognitive dysfunction (POCD) is a prevalent neurological complication that can impair learning and memory for days, months, or even years after anesthesia/surgery. POCD is strongly associated with an altered composition of the gut microbiota (dysbiosis), but the accompanying metabolic changes and their role in gut-brain communication and POCD pathogenesis remain unclear. Here, the present study reports that anesthesia/surgery in aged mice induces elevated intestinal indoleamine 2,3-dioxygenase (IDO) expression and activity, which shifts intestinal tryptophan (TRP) metabolism toward more IDO-catalyzed kynurenine (KYN) and less gut bacteria-catabolized indoleacetic acid (IAA). Both anesthesia/surgery and intraperitoneal KYN administration induce increased KYN levels that correlate with impaired spatial learning and memory, whereas dietary IAA supplementation attenuates the anesthesia/surgery-induced cognitive impairment. Mechanistically, anesthesia/surgery increases interferon-γ (IFN-γ)-producing group 1 innate lymphoid cells (ILC1) in the small intestine lamina propria and elevates intestinal IDO expression and activity, as indicated by the higher ratio of KYN to TRP. The IDO inhibitor 1-MT and antibodies targeting IFN-γ or ILCs mitigate anesthesia/surgery-induced cognitive dysfunction, suggesting that intestinal ILC1 expansion and the ensuing IFN-γ-induced IDO upregulation may be the primary pathway mediating the shift to the KYN pathway in POCD. The ILC1-KYN pathway in the intestine could be a promising therapeutic target for POCD.

CD24-Targeted NIR-II Fluorescence Imaging Enables Early Detection of Colorectal Neoplasia.

Colorectal cancer (CRC) continues to be a major health issue even though screening methods have facilitated early detection. Despite the high sensitivity of white-light colonoscopy, it frequently overlooks invasive flat or depressed lesions, which can lead to the development of larger, advanced tumors. Fluorescence molecular imaging (FMI) offers a promising approach for early tumor detection by targeting specific molecular characteristics of lesions. CD24 is upregulated during the adenoma-to-CRC transition, providing a potential target for FMI. Here, we developed a second near-infrared window (NIR-II) fluorescent probe with a high affinity for CD24 and evaluated its efficacy and targeting ability in cellular models, murine models, and clinical samples of CRC. CD24 expression was elevated in 76% of adenomas and 80% of CRCs. In a colitis-associated cancer mouse model, NIR-II imaging with the CD24-targeted probe achieved a significantly higher tumor-to-background ratio compared to conventional NIR-I imaging. The probe demonstrated exceptional sensitivity (92%) and specificity (92%) for detecting CRC, including small lesions less than 1 mm in size. This led to the identification of precancerous lesions missed by white-light detection and lesions missed by NIR-I imaging. Moreover, ex vivo human tissue incubation with the probe supported the potential for intraprocedural lesion identification via topical probe application during colonoscopy. In conclusion, this study successfully demonstrates the potential of CD24-targeted NIR-II imaging for identifying colorectal neoplasia, highlighting its significance for early CRC detection in the gastrointestinal tract.

Deep learning model based on primary tumor to predict lymph node status in clinical stage IA lung adenocarcinoma: a multicenter study.

Objective: To develop a deep learning model to predict lymph node (LN) status in clinical stage IA lung adenocarcinoma patients. Methods: This diagnostic study included 1,009 patients with pathologically confirmed clinical stage T1N0M0 lung adenocarcinoma from two independent datasets (699 from Cancer Hospital of Chinese Academy of Medical Sciences and 310 from PLA General Hospital) between January 2005 and December 2019. The Cancer Hospital dataset was randomly split into a training cohort (559 patients) and a validation cohort (140 patients) to train and tune a deep learning model based on a deep residual network (ResNet). The PLA Hospital dataset was used as a testing cohort to evaluate the generalization ability of the model. Thoracic radiologists manually segmented tumors and interpreted high-resolution computed tomography (HRCT) features for the model. The predictive performance was assessed by area under the curves (AUCs), accuracy, precision, recall, and F1 score. Subgroup analysis was performed to evaluate the potential bias of the study population. Results: A total of 1,009 patients were included in this study; 409 (40.5%) were male and 600 (59.5%) were female. The median age was 57.0 years (inter-quartile range, IQR: 50.0-64.0). The deep learning model achieved AUCs of 0.906 (95% CI: 0.873-0.938) and 0.893 (95% CI: 0.857-0.930) for predicting pN0 disease in the testing cohort and a non-pure ground glass nodule (non-pGGN) testing cohort, respectively. No significant difference was detected between the testing cohort and the non-pGGN testing cohort (P = 0.622). The precisions of this model for predicting pN0 disease were 0.979 (95% CI: 0.963-0.995) and 0.983 (95% CI: 0.967-0.998) in the testing cohort and the non-pGGN testing cohort, respectively. The deep learning model achieved AUCs of 0.848 (95% CI: 0.798-0.898) and 0.831 (95% CI: 0.776-0.887) for predicting pN2 disease in the testing cohort and the non-pGGN testing cohort, respectively. No significant difference was detected between the testing cohort and the non-pGGN testing cohort (P = 0.657). The recalls of this model for predicting pN2 disease were 0.903 (95% CI: 0.870-0.936) and 0.931 (95% CI: 0.901-0.961) in the testing cohort and the non-pGGN testing cohort, respectively. Conclusions: The superior performance of the deep learning model will help to target the extension of lymph node dissection and reduce the ineffective lymph node dissection in early-stage lung adenocarcinoma patients.

A patient with positive anti-IFN-γ autoantibody and monoclonal gammaglobulinemia masquerading as multiple myeloma: Case report and literature review.

Key Clinical Message: Adult-onset immunodeficiency (AOID) is an emerging acquired immunodeficiency, characterized by multiple opportunistic infections including non-tuberculous mycobacterium (NTM) due to the presence of anti-IFN-γ autoantibody (AIGA). This case highlights the challenges of accurate diagnosis of monoclonal gammaglobulinemia with NTM infection and favorable outcomes of anti-plasma cell therapy in AOID. Abstract: Adult-onset immunodeficiency (AOID) is an emerging acquired immunodeficiency due to anti-IFN-γ autoantibody (AIGA) with low morbidity, frequent disseminated infections, a prolonged course, difficult diagnosis and treatment, and a poor prognosis. Here, we report a patient with positive AIGA and monoclonal gammaglobulinemia who was mimicking symptomatic multiple myeloma and resulting in a non-tuberculous mycobacterial (NTM) infection. While he achieved an excellent therapeutic effect with anti-plasma cell therapy, it also serves as a warning that monoclonal gammaglobulinemia with NTM infection is easily misdiagnosed as symptomatic multiple myeloma, and the screening for AIGA should not be ignored in patients with NTM infection.