A taxonomy for advancing systematic error analysis in multi-site electronic health record-based clinical concept extraction.

BACKGROUND: Error analysis plays a crucial role in clinical concept extraction, a fundamental subtask within clinical natural language processing (NLP). The process typically involves a manual review of error types, such as contextual and linguistic factors contributing to their occurrence, and the identification of underlying causes to refine the NLP model and improve its performance. Conducting error analysis can be complex, requiring a combination of NLP expertise and domain-specific knowledge. Due to the high heterogeneity of electronic health record (EHR) settings across different institutions, challenges may arise when attempting to standardize and reproduce the error analysis process. OBJECTIVES: This study aims to facilitate a collaborative effort to establish common definitions and taxonomies for capturing diverse error types, fostering community consensus on error analysis for clinical concept extraction tasks. MATERIALS AND METHODS: We iteratively developed and evaluated an error taxonomy based on existing literature, standards, real-world data, multisite case evaluations, and community feedback. The finalized taxonomy was released in both .dtd and .owl formats at the Open Health Natural Language Processing Consortium. The taxonomy is compatible with several different open-source annotation tools, including MAE, Brat, and MedTator. RESULTS: The resulting error taxonomy comprises 43 distinct error classes, organized into 6 error dimensions and 4 properties, including model type (symbolic and statistical machine learning), evaluation subject (model and human), evaluation level (patient, document, sentence, and concept), and annotation examples. Internal and external evaluations revealed strong variations in error types across methodological approaches, tasks, and EHR settings. Key points emerged from community feedback, including the need to enhancing clarity, generalizability, and usability of the taxonomy, along with dissemination strategies. CONCLUSION: The proposed taxonomy can facilitate the acceleration and standardization of the error analysis process in multi-site settings, thus improving the provenance, interpretability, and portability of NLP models. Future researchers could explore the potential direction of developing automated or semi-automated methods to assist in the classification and standardization of error analysis.

Assessing Severity of Low Anterior Resection Syndrome After Intersphincteric Resection for Ultralow Rectal Cancer: A Pilot Study Using an Exploratory Instrument.

BACKGROUND: The Delphi consensus identified 8 symptoms and 8 consequences as the highest priorities for defining low anterior resection syndrome. OBJECTIVE: To describe an exploratory scoring instrument correlating the Delphi consensus on low anterior resection syndrome with functional and quality-of-life scores following intersphincteric resection for ultralow rectal cancer. DESIGN: This was a prospective pilot study. In accordance with the Wexner incontinence score, 5 frequency responses ranging from never (score 0) to always (score 4) were used to measure the severity of symptom- and consequence-specific variables. SETTINGS: Colorectal surgery referral center. PATIENTS: Among 161 eligible patients, 137 participants (85%) completed an electronic self-assessment survey regarding function and quality of life at scheduled follow-up, including 3 to 6, 12, and ≥24 months after ileostomy reversal. MAIN OUTCOME MEASURES: Outcome measures included patient-reported severity of the identified priorities, and their correlation with condition-specific quality of life. RESULTS: The most frequent symptom and consequence were "emptying difficulties" and "dissatisfaction with the bowels," respectively. Aside from "emptying difficulties," the proportions of negative symptom domains increased after reversal. In particular, neither the frequency responses nor the severity scores of "emptying difficulties" differed between groups. The percentages of "always" selection for consequence domains improved at 12-month follow-up, whereas a higher rate was observed at 24 months, except for "toilet dependence" and "dissatisfaction with the bowels." We found significant improvements in the summary score of the Fecal Incontinence Quality-of-Life Scale ( p = 0.04) and our exploratory instrument ( p = 0.009) but not in functional scores measured by traditional questionnaires. Furthermore, the condition-specific quality of life strongly correlated with the Delphi consensus severity score ( rs = -0.73). LIMITATIONS: Single-institution data and limited sample size. CONCLUSIONS: The important priorities identified by the Delphi consensus might enable a comprehensive overview and a better assessment of low anterior resection syndrome after intersphincteric resection. See Video Abstract . EVALE LA GRAVEDAD DEL SNDROME DE RESECCIN ANTERIOR BAJA DESPUS DE LA RESECCIN INTERESFINTRICA PARA EL CNCER DE RECTO ULTRABAJO UN ESTUDIO PILOTO QUE UTILIZA UN INSTRUMENTO EXPLORATORIO: ANTECEDENTES:El consenso Delphi identificó ocho síntomas y ocho consecuencias como las máximas prioridades para definir el síndrome de resección anterior baja.OBJETIVO:Describir un instrumento de puntuación exploratorio que correlaciona el consenso Delphi sobre el síndrome de resección anterior baja con puntuaciones funcionales y de calidad de vida después de la resección interesfinteriana para el cáncer de recto ultrabajo.DISEÑO:Este fue un estudio piloto prospectivo. De acuerdo con la puntuación de incontinencia de Wexner, se utilizaron cinco respuestas de frecuencia que van desde nunca (puntuación 0) hasta siempre (puntuación 4) para medir la gravedad de las variables específicas de los síntomas y las consecuencias.AJUSTES:Centro de referencia de cirugía colorrectal.PACIENTES:Entre 161 pacientes elegibles, 137 (85%) participantes completaron una encuesta electrónica de autoevaluación sobre la función y la calidad de vida en el seguimiento programado, incluidos 3 a 6, 12 y ≥ 24 meses después de la reversión de la ileostomía.MEDIDAS PRINCIPALES DE RESULTADO:Las medidas de resultado incluyeron la gravedad de estas prioridades informada por los pacientes, así como su correlación con la calidad de vida específica de la afección.RESULTADOS:El síntoma y la consecuencia más frecuentes fueron "dificultades para vaciar" e "insatisfacción con las deposiciones", respectivamente. Aparte de las "dificultades de vaciado", las proporciones de dominios de síntomas negativos aumentaron después de la reversión. En particular, tanto las respuestas de frecuencia como las puntuaciones de gravedad de las "dificultades para vaciar" no difirieron entre los grupos. Los porcentajes de "opción siempre" para los dominios de consecuencias mejoraron a los 12 meses de seguimiento, mientras que se observó una tasa más alta a los 24 meses después, excepto para "dependencia del baño" e "insatisfacción con los intestinos". Encontramos mejoras significativas en la puntuación resumida de la Escala de calidad de vida de incontinencia fecal ( p = 0,04) y nuestro instrumento exploratorio ( p = 0,009), pero no en las puntuaciones funcionales medidas con los cuestionarios tradicionales. Además, la calidad de vida específica de la condición se correlacionó fuertemente con la puntuación de gravedad del consenso Delphi (rs = -0,73).LIMITACIONES:Datos de una sola institución y tamaño de muestra limitado.CONCLUSIONES:Las importantes prioridades identificadas por el consenso Delphi podrían permitir una visión global y una mejor evaluación del síndrome de resección anterior baja después de la resección interesfintérica. (Traducción-Dr. Yesenia Rojas-Khalil ).

Global scientific trends in healthy aging in the early 21st century: A data-driven scientometric and visualized analysis.

Background: According to the World Health Organization (WHO), healthy aging is the process of developing and maintaining the functional capacity for health in old age. A rapidly growing number of research studies on healthy aging have been conducted worldwide. The purpose of this research work is to explore global scientific landscape of healthy aging research over the last 22 years. Methods: Scientific publications on healthy aging from January 1, 2000 to October 11, 2022 were retrieved from the Web of Science Core Collection (WoSCC) on October 11, 2022. A total of 6420 publications were included in the scientometric analysis. VOSviewer (1.6.18) was used to conduct scientometric and visualized analysis. Results: The publication growth rate was 35.68 from 2000 to 2021. The United States of America (USA) led in both productivity and citations. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA was prominent in terms of both the highest citation count and the highest average citation count. The National Institute on Aging (NIA) and Evans, Michele K. were the most influential organization and author, respectively. Research hotspots in healthy aging were identified based on the co-occurrence analysis of keywords: (1) physical activity and mental health of older adults; (2) diseases impacting the health and lifespan of older adults; and (3) neuroscience. Our analysis indicates that gut microbiota, loneliness, frailty, mitochondria and resilience were the emerging themes in healthy aging research. Conclusions: The quantity of annual publications on healthy aging has rapidly increased over the past 22 years, especially during 2018-2021. This analysis identified the status, trends, hot topics, and frontiers of healthy aging research. These findings will help researchers quickly understand the global representation of healthy aging research, influence resource dissemination, promote international collaborations, guide policy formulation, and improve health services for older adults.

Mechanism of DaiTongXiao in the treatment of gouty arthritis through the NLRP3 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: DaiTongXiao (DTX) is a traditional Chinese Dai folk formulation utilized for gouty arthritis treatment, with substantial evidence supporting its anti-inflammatory properties. The NLRP3 inflammasome disorder is tightly linked to the development of many inflammatory diseases. AIM OF THE STUDY: To elucidate the therapeutic efficacy of DTX in gouty arthritis and reveal its potential underlying mechanism. MATERIALS AND METHODS: The primary active constituents in DTX were determined through ultraviolet spectrophotometry and gas chromatography. Rats underwent induction with monosodium urate (MSU), followed by treatment of J774A.1 cells with adenosine triphosphate (ATP) activation and lipopolysaccharide (LPS) induction and the subsequent culture in Dulbecco's modified Eagle's medium. The degree of foot joint swelling in rats was assessed, and ankle joints were evaluated through H&E staining. Enzyme-linked immunosorbent assay was performed to measure the levels of interleukin (IL)-1ß, IL-6, IL-8, and tumor necrosis factor (TNF)-α in both serum and cells. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to determine the relative mRNA expression levels of NLRP3, ASC, Caspase-1, and NF-κB in J774A.1 macrophages. The expression of NLRP3, ASC, Caspase-1, and NF-κB was examined by western blotting. RESULTS: DTX could alleviate MSU-induced joint swelling in rats, as evidenced by a reduction in joint inflammation. Moreover, DTX effectively enhanced the survival rate of J774A.1 cells following LPS induction and ATP activation. Furthermore, DTX significantly reduced IL-1ß, IL-6, IL-8, and TNF-α levels in both cell culture medium and rat serum. RT-PCR results revealed that DTX notably downregulated the mRNA expression levels of NLRP3, ASC, Caspase-1, and NF-κB in J774A.1 cells. Additionally, DTX downregulated NLRP3, ASC, NF-κB, and Caspase-1 expression in the joint tissue. CONCLUSIONS: DTX exerts a significant anti-gouty arthritis effect, with its mechanism being tightly linked to the NLRP3 inflammatory signaling pathway. This pathway may be modulated by inhibiting IL-1ß differentiation and maturation by downregulating NLRP3, ASC, Caspase-1, and NF-κB protein expression. This, in turn, leads to a reduction in the release of IL-6, IL-8, and TNF-α, ultimately impeding gouty arthritis progression.

Sample average treatment effect on the treated (SATT) analysis using counterfactual explanation identifies BMT and SARS-CoV-2 vaccination as protective risk factors associated with COVID-19 severity and survival in patients with multiple myeloma.

Patients with multiple myeloma (MM), an age-dependent neoplasm of antibody-producing plasma cells, have compromised immune systems and might be at increased risk for severe COVID-19 outcomes. This study characterizes risk factors associated with clinical indicators of COVID-19 severity and all-cause mortality in myeloma patients utilizing NCATS' National COVID Cohort Collaborative (N3C) database. The N3C consortium is a large, centralized data resource representing the largest multi-center cohort of COVID-19 cases and controls nationwide (>16 million total patients, and >6 million confirmed COVID-19+ cases to date). Our cohort included myeloma patients (both inpatients and outpatients) within the N3C consortium who have been diagnosed with COVID-19 based on positive PCR or antigen tests or ICD-10-CM diagnosis code. The outcomes of interest include all-cause mortality (including discharge to hospice) during the index encounter and clinical indicators of severity (i.e., hospitalization/emergency department/ED visit, use of mechanical ventilation, or extracorporeal membrane oxygenation (ECMO)). Finally, causal inference analysis was performed using the Coarsened Exact Matching (CEM) and Propensity Score Matching (PSM) methods. As of 05/16/2022, the N3C consortium included 1,061,748 cancer patients, out of which 26,064 were MM patients (8,588 were COVID-19 positive). The mean age at COVID-19 diagnosis was 65.89 years, 46.8% were females, and 20.2% were of black race. 4.47% of patients died within 30 days of COVID-19 hospitalization. Overall, the survival probability was 90.7% across the course of the study. Multivariate logistic regression analysis showed histories of pulmonary and renal disease, dexamethasone, proteasome inhibitor/PI, immunomodulatory/IMiD therapies, and severe Charlson Comorbidity Index/CCI were significantly associated with higher risks of severe COVID-19 outcomes. Protective associations were observed with blood-or-marrow transplant/BMT and COVID-19 vaccination. Further, multivariate Cox proportional hazard analysis showed that high and moderate CCI levels, International Staging System (ISS) moderate or severe stage, and PI therapy were associated with worse survival, while BMT and COVID-19 vaccination were associated with lower risk of death. Finally, matched sample average treatment effect on the treated (SATT) confirmed the causal effect of BMT and vaccination status as top protective factors associated with COVID-19 risk among US patients suffering from multiple myeloma. To the best of our knowledge, this is the largest nationwide study on myeloma patients with COVID-19.

Investigation of drag reduction by slurry-like drag-reducing agent in microtube flow using response surface methodology (RSM).

In this study, we investigated the drag reduction property of a premixed slurry drag reducer in a millimeter-scale pipe. The aim of this study is to establish the correlation between Darcy friction factor and drag reducer concentration (C) and volume flow (Q). First, the experimental plan was designed by using the response surface method (RSM), and then the experimental data were processed to establish the quadratic correlation between the response variable and the description variable. After that, ANOVA analysis of variance was used to verify the accuracy of the experimental data and the correlation. Finally, the prediction model is extended to a larger concentration and volume flow range, and it is found that the accuracy between the predicted value of friction coefficient and the experimental value is ± 30%, thus verifying that the correlation is suitable for the small-scale fully turbulent region. Compared with traditional experimental design and correlation methods, the implementation of Response Surface Methodology (RSM) in this study not only reduces the experimental time but also yields a more robust correlation for predicting the friction coefficient.

Construction and evaluation of a novel prognostic risk model of aging-related genes in bladder cancer.

Background: Bladder cancer (BLCA) is the most common malignancy of the urinary system. Muscle-invasive bladder cancer (MIBC), which constitutes approximately 25% of all BLCA cases, is characterized by frequent recurrence and early onset of metastasis. Bladder cancer most commonly occurs in elderly patients and is significantly associated with aging. However, the prognostic value of age-related genes in BLCA, especially in MIBC, remains unclear. Materials and methods: Training and testing sets were obtained from The Cancer Genome Atlas BLCA project. Differentially expressed genes between BLCA and normal samples intersected with human aging-related genes. Univariate Cox regression and least absolute shrinkage and selection operator regression analyses were used to identify prognostic aging-related signatures, followed by the construction of a risk score model and nomogram. Kaplan-Meier and receiver operating characteristic analyses were conducted to assess the predictive power. An independent BLCA cohort of 165 samples was included for external validation. The CIBERSORT algorithm was used to explore the characteristics of the immune microenvironment. Results: Seven genes (IGF1, NGF, GCLM, PYCR1, EFEMP1, APOC3, and IFNB1) were identified by Cox and least absolute shrinkage and selection operator analyses. After combining the gene signature with the clinical parameters of patients with BLCA, a risk-prognosis model and nomogram were constructed and validated with the testing set. Bladder cancer cases with high 7-gene signature scores (high-risk group) and low scores (low-risk group) showed distinct prognoses. Furthermore, 7 types of immune cells were significantly altered between the low- and high-risk groups. Conclusions: Collectively, our data provide a 7-gene signature that serves as a potential biomarker for BLCA, especially MIBC. Moreover, this 7-gene signature highlights the role of the tumor immune microenvironment in prognosis and thus might be related to the response to anti-programmed cell death protein 1-based immunotherapy.

Type 2 Biomarkers for the Indication and Response to Biologics in CRSwNP.

PURPOSE OF REVIEW: Three biologics targeting type 2 inflammation have been approved for the treatment of severe and uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP). Nevertheless, around 40-60% of patients do not respond well to these biological treatments. Selecting appropriate patients is crucial to improve treatment outcome of biologics. This review summarizes the literature data on type 2 biomarkers, with a specific focus on the indication to biologics for severe CRSwNP. RECENT FINDINGS: No consensus has been reached on how to define mucosal type 2 inflammation in CRSwNP. Clinical markers (e.g., 22-item Sino-nasal Outcome Test (SNOT-22) score, Lund-Mackay CT score (LMS), ethmoid/maxillary sinus CT score, and CT-radiomics), nasal secretion biomarkers (e.g., eosinophil cationic protein and interleukin-5), blood and nasal cytology eosinophil counts, and nasal swab eosinophil peroxidase activity have been reported to be associated with type 2 inflammation in CRSwNP. The time duration since the last surgery, SNOT-22 score at 1 week of treatment, and baseline serum osteoprotegerin levels might indicate the response to dupilumab. LMS and asthma control test scores were found to have moderate predictive value for acceptable improvement after 24-week treatment of omalizumab. High blood eosinophil levels at baseline were associated with treatment response to mepolizumab and benralizumab. Although several clinical and biological markers might be associated with type 2 inflammation and response to biologics in patients with CRSwNP, their validity requires further investigation. Identifying clinically applicable biomarkers for biologic treatment holds significant promise for advancing personalized approaches to biologics and optimizing treatment outcomes for patients with CRSwNP.

Does anastomotic leakage after intersphincteric resection for ultralow rectal cancer influence long-term outcomes? A retrospective observational study.

PURPOSE: To determine whether anastomotic leakage (AL) following intersphincteric resection (ISR) for ultralow rectal cancer (uLRC) is associated with long-term negative outcomes. METHODS: Between June 2011 and January 2022, 236 consecutive patients who underwent ISR with diverting ileostomy for uLRC were included. The primary outcome was long-term clinical consequences of AL, including chronic stricture, stoma reversal, and oncological and functional results. RESULTS: Forty-one (17.4%) patients developed symptomatic AL, whereas only two (0.8%) required re-laparotomy due to severe leakage. Patients with leaks had a significantly increased incidence of chronic stricture (29.3% vs. 8.7%, P = 0.001) and stoma non-reversal (34.1% vs. 4.6%, P < 0.0001) than controls. The severe consequences were particularly common in patients with anastomotic separation, resulting in 60% of those presenting with chronic stricture and 50% ending up with stoma non-reversal. After a median follow-up of 59 (range, 7-139) months, AL did not compromise long-term oncological outcomes, including tumor recurrence (9.8% vs. 5.6%, P = 0.3), 5-year disease-free, and overall survival (73.4% vs. 74.8% and 85.1% vs. 85.4%, P = 0.56 and P = 0.55). A total of 149 patients with bowel continuity who completed self-assessment questionnaires were enrolled for functional evaluation. The median follow-up was 24 (range, 12-94) months after ileostomy reversal, and functional results were comparable between patients with and without leaks. CONCLUSION: AL is an unfortunate reality for patients who underwent ISR for uLRC, but the rate of severe leakage is limited. Leaks contribute to possible adverse impacts on chronic stricture and stoma non-reversal, especially for patients with anastomotic separation. However, long-term oncological and functional results may not be compromised. TRIAL REGISTRATION: Chictr.org.cn identifier: ChiCTR-ONC-15007506 and ChiCTR2100051614.

High-power green-light laser endoscopic submucosal dissection for non-muscle-invasive bladder cancer: A technical improvement and its initial application.

Background: The technique of laser en bloc resection of bladder tumor (ERBT) has been a valuable alternative technique to transurethral resection of bladder tumor (TURBT). However, the combination of laser ERBT and endoscopic submucosal dissection (ESD) technique has not been well studied. Here, a novel technique integrating a high-power green-light laser with ESD was presented. This study aimed to evaluate the safety and efficacy of high-power green-light laser endoscopic submucosal dissection (HPL-ESD) for the treatment of primary non-muscle-invasive bladder cancer (NMIBC). Materials and Methods: From January 2015 to December 2018, a total of 56 patients with NMIBC underwent HPL-ESD. All tumors were transurethral en bloc resected in the ESD technique. Perioperative clinical data were retrospectively collected and analyzed. Results: All operations were safely performed by the technique of HPL-ESD without blood transfusion. The mean tumor diameter was 2.04 ± 0.65 cm, ranging from 0.5 to 3.5 cm. The mean operative time was 28.39 ± 16.04 min. The average serum hemoglobin decrease was 0.88 ± 0.54 g/dL. The mean postoperative catheterization time was 2.88 ± 0.94 days. The pathologic stages included pTa (32 cases), and pT1 (24 cases). Double-J stent indwelling was not performed for four patients whose tumors were adjacent to the ureteral orifice and no postoperative hydronephrosis was observed. Only one case of ectopic bladder tumor recurred due to irregular bladder irrigation during the 36-month follow-up. Conclusion: HPL-ESD is a safe and effective alternative for the treatment of primary NMIBCs, especially for tumors adjacent to the ureteral orifice.

Human Bone Marrow Mesenchymal Stem Cells-Derived Exosomal miRNA-21-5p Inhibits Lidocaine-Induced Apoptosis in SH-SY5Y Neuroblastoma Cells.

Background: Local anesthetic lidocaine is one of the most common pain therapies, but high concentration of lidocaine induced neurotoxicity and its mechanism is unclear. Exosomal microRNAs (miRNAs) is implicated in neuronal diseases, but its role in lidocaine induced neurotoxicity remains to be elucidated. Methods: All the experiments were performed at Huzhou Key Laboratory of Molecular Medicine, Huzhou City, Jiangsu Province, China in 2022. Lidocaine was used to induce apoptosis of SH-SY5Y cells. Exosomes isolated from bone marrow mesenchymal stem cells (BMSC-exos) were used to co-treat SH-SY5Y cells with lidocaine. Cell apoptosis was measured using a flow cytometer. PKH-67 Dye was used for exosome uptake assay. miR-21-5p mimics/inhibitors, or negative controls were transfected with Lipo2000 to study its effect on lid-induced injury. Interactions between miR-21-5p and PDCD4 was analyzed by luciferase reporter assay. Results: Administration of BMSC-exo protected SH-SY5Y cells against lidocaine induced apoptosis. Suppressing miR-21-5p dramatically enhanced PDCD4, but miR-21-5p overexpression sharply down-regulated PDCD4. Mechanism study showed that miR-21-5p bound to 3'-UTR of PDCD4 to inhibit it. Suppressing miR-21-5p reversed the effect of BMSC-exo on Lid-induced injury. Results also indicate that miR-21-5p regulated lidocaine-induced injury through targeting PDCD4. Conclusion: BMSC-exos protected SH-SY5Y cells against lidocaine induced apoptosis through miR-21-5p by targeting PDCD4, which may develop new strategy in the management of lidocaine-induced neurotoxicity.

Transportation of whey protein-derived peptides using Caco-2 cell model and identification of novel cholesterol-lowering peptides.

Background: The increasing morbidity and mortality of cardiovascular disease have become a major factor in human death. Serum cholesterol is considered to be an important risk factor for inducing coronary heart disease, atherosclerosis and other cardiovascular diseases. To screen intestinal absorbable functional small peptides with cholesterol-lowering activity by enzymatic hydrolysis of whey protein and develop cholesterol-based functional food that may become a substitute for chemically synthesized drugs, providing new ideas for diseases caused by high cholesterol. Objective: This study aimed to evaluate the cholesterol-lowering activity of intestinal absorbable whey protein-derived peptides hydrolyzed by alkaline protease, trypsin and chymotrypsin, respectively. Method: The whey protein hydrolysates acquired by enzymatic hydrolysis under optimal conditions were purified by a hollow fiber ultrafiltration membrane with a molecular weight cutoff of 10 kDa. The fractions obtained by Sephadex G-10 gel filtration chromatography were transported through a Caco-2 cell monolayer. The transported peptides were detected in the basolateral aspect of Caco-2 cell monolayers using ultra- performance liquid chromatography-tandem mass spectrometry (UPLC-MS). Results: His-Thr-Ser-Gly-Tyr (HTSGY), Ala-Val-Phe-Lys (AVFK) and Ala-Leu-Pro-Met (ALPM) were unreported peptides with cholesterol-lowering activity. The cholesterol-lowering activities of the three peptides did not change significantly during simulated gastrointestinal digestion. Conclusion: This study not only provides theoretical support for the development of bioactive peptides that can be directly absorbed by the human body, but also provides new treatment ideas for hypercholesterolemia.

Silencing information regulator 1 ameliorates lipopolysaccharide-induced acute lung injury in rats via the upregulation of caveolin-1.

BACKGROUND: Acute lung injury (ALI) is an intractable medical problem linked with to high morbidity and mortality all over the worldglobally. The prognosis of advanced acute lung injury remains persistently poor due to its underlying mechanisms remain unclear.Despite advancements in medical research, the its prognosis of advanced ALI remains persistently poor due to unclear underlying mechanisms. We aimed to investigate the protective effects of silencing information regulator 1 (SIRT1) on lipopolysaccharide (LPS)-induced acute lung injuryALI and to reveal its underlying molecular mechanism. METHODS: Male Sprague--Dawley rats were divided grouped into 4 groupsfour: normal saline group (group NS), lipopolysaccharide group (group L), SIRT1 activator SRT1720-pretreated group (group S), and SIRT1 inhibitor EX527- pretreated group (group E). Rats They were intranasally dripped with LPS to establish the model of ALI modelsacute lung injury respectively. We investigated the effect of SIRT1 on acute lung injury by analysing We analyzed the CT images of the rat lungs and used, HE staining, lung wet-to-dry ratio, inflammatory factor expression, lung injury marker expression, immunohistochemistry, and related mRNA expression to determine the effect of SIRT1 on ALI. RESULTS: Our results show that LPS induction produced resulted in acute lung injury, ALI and disrupting disrupted normal SIRT1 expression, which led to the overexpression of STAT3, TLR4, TNF-ɑ, and IL-6 and suppression of Cav-1 expression. Upregulation The upregulation of Cav-1 protein and mRNA following the administration of an SIRT1 agonist resulted in reduced lung injury. SRT1720 pretreatment was closely associated with reduced expressions of STAT3,TLR4, TNF-ɑ, and IL-6. ALI lung injury was more severeworsened after administration of SIRT1 inhibitors, and the changes in the above indicators were reversed. CONCLUSIONS: These results suggest that SIRT1 may protect against LPS-induced acute lung injuryALI via by counteracting inflammatory remissionion, and this protective effect might may be mediated by suppressing STAT3 to activate the expression ofinduce Cav-1 expression.

Mechanisms of Yajieshaba in the treatment of liver fibrosis through the Keap1-Nrf2 signaling pathway.

Yajieshaba (YJSB), a traditional Dai medicine formula containing botanical drugs, is commonly employed in Yunnan due to its significant therapeutic effects on liver protection. Consequently, to determine the efficacy of YJSB and the mechanism of action of Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) pathway against liver fibrosis. We wanted to see if YJSB could treat CCl4-induced liver fibrosis by regulating the Keap1-Nrf2 signaling pathway. YJSB significantly improved liver function biochemical indices, liver fibrosis quadruple, hydroxyproline (Hyp), and transforming growth factor-ß1 (TGF-ß1) levels. The staining results demonstrated that the degree of liver fibrosis was significantly reduced. YJSB reduced the content of malondialdehyde (MDA) and elevated the content of superoxide dismutase (SOD) in the liver, exhibiting antioxidant effects; meanwhile, it regulated the expression of Keap1-Nrf2 pathway protein, increased the expression of NAD(P)H: Quinone oxidoreductase (NQO1), Heme Oxygenase 1 (HO-1), Glutamate cysteine ligase modifier subunit (GCLM), and Glutamate cysteine ligase catalytic subunit (GCLC) expression in the liver decreased while Nrf2 expression increased. Fluorescence immunoassay studies demonstrated that YJSB promoted the trans-nuclearization of Nrf2. YJSB possesses anti-liver fibrosis pharmacological effects that improve liver function and effectively counteract CCl4-induced liver fibrosis damage. The mechanism of action might be related to the regulation of protein expression of the Keap1-Nrf2 pathway, increasing the ability of the body to resist oxidative stress and reduce oxidative stress injury.

Geographic and Temporal Trends in COVID-Associated Acute Kidney Injury in the National COVID Cohort Collaborative.

BACKGROUND: AKI is associated with mortality in patients hospitalized with coronavirus disease 2019 (COVID-19); however, its incidence, geographic distribution, and temporal trends since the start of the pandemic are understudied. METHODS: Electronic health record data were obtained from 53 health systems in the United States in the National COVID Cohort Collaborative. We selected hospitalized adults diagnosed with COVID-19 between March 6, 2020, and January 6, 2022. AKI was determined with serum creatinine and diagnosis codes. Time was divided into 16-week periods (P1-6) and geographical regions into Northeast, Midwest, South, and West. Multivariable models were used to analyze the risk factors for AKI or mortality. RESULTS: Of a total cohort of 336,473, 129,176 (38%) patients had AKI. Fifty-six thousand three hundred and twenty-two (17%) lacked a diagnosis code but had AKI based on the change in serum creatinine. Similar to patients coded for AKI, these patients had higher mortality compared with those without AKI. The incidence of AKI was highest in P1 (47%; 23,097/48,947), lower in P2 (37%; 12,102/32,513), and relatively stable thereafter. Compared with the Midwest, the Northeast, South, and West had higher adjusted odds of AKI in P1. Subsequently, the South and West regions continued to have the highest relative AKI odds. In multivariable models, AKI defined by either serum creatinine or diagnostic code and the severity of AKI was associated with mortality. CONCLUSIONS: The incidence and distribution of COVID-19-associated AKI changed since the first wave of the pandemic in the United States. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_08_08_CJN0000000000000192.mp3.

Representing and utilizing clinical textual data for real world studies: An OHDSI approach.

Clinical documentation in electronic health records contains crucial narratives and details about patients and their care. Natural language processing (NLP) can unlock the information conveyed in clinical notes and reports, and thus plays a critical role in real-world studies. The NLP Working Group at the Observational Health Data Sciences and Informatics (OHDSI) consortium was established to develop methods and tools to promote the use of textual data and NLP in real-world observational studies. In this paper, we describe a framework for representing and utilizing textual data in real-world evidence generation, including representations of information from clinical text in the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM), the workflow and tools that were developed to extract, transform and load (ETL) data from clinical notes into tables in OMOP CDM, as well as current applications and specific use cases of the proposed OHDSI NLP solution at large consortia and individual institutions with English textual data. Challenges faced and lessons learned during the process are also discussed to provide valuable insights for researchers who are planning to implement NLP solutions in real-world studies.

Case report: Sarcomatoid urothelial carcinoma of the renal pelvis masquerading as a renal abscess.

Sarcomatoid urothelial carcinoma (SUC), a rare tumor of the urinary tract epithelium, exhibits a high degree of malignancy and therefore a poor prognosis. Due to the absence of specific clinical presentations and imaging findings, SUC of the renal pelvis masquerades as a renal abscess is frequently under-recognized or misdiagnosed as benign inflammatory disease, resulting in delayed or erroneous treatment. Here, we report a patient with SUC of the renal pelvis who presented with a renal abscess. Repeated anti-inflammatory treatment was ineffective. Unexpectedly, cancerous cells were detected in subsequent exfoliative cytology of nephrostomy drainage fluid. In accordance with this, radical surgery and postoperative chemotherapy were conducted. Fortunately, neither recurrence nor metastasis occurred during a one-year follow-up.

Reproducible variability: assessing investigator discordance across 9 research teams attempting to reproduce the same observational study.

OBJECTIVE: Observational studies can impact patient care but must be robust and reproducible. Nonreproducibility is primarily caused by unclear reporting of design choices and analytic procedures. This study aimed to: (1) assess how the study logic described in an observational study could be interpreted by independent researchers and (2) quantify the impact of interpretations' variability on patient characteristics. MATERIALS AND METHODS: Nine teams of highly qualified researchers reproduced a cohort from a study by Albogami et al. The teams were provided the clinical codes and access to the tools to create cohort definitions such that the only variable part was their logic choices. We executed teams' cohort definitions against the database and compared the number of subjects, patient overlap, and patient characteristics. RESULTS: On average, the teams' interpretations fully aligned with the master implementation in 4 out of 10 inclusion criteria with at least 4 deviations per team. Cohorts' size varied from one-third of the master cohort size to 10 times the cohort size (2159-63 619 subjects compared to 6196 subjects). Median agreement was 9.4% (interquartile range 15.3-16.2%). The teams' cohorts significantly differed from the master implementation by at least 2 baseline characteristics, and most of the teams differed by at least 5. CONCLUSIONS: Independent research teams attempting to reproduce the study based on its free-text description alone produce different implementations that vary in the population size and composition. Sharing analytical code supported by a common data model and open-source tools allows reproducing a study unambiguously thereby preserving initial design choices.

High strength chitin/chitosan-based aerogel with 3D hierarchically macro-meso-microporous structure for high-efficiency adsorption of Cu(II) ions and Congo red.

A high-strength aerogel with a 3D hierarchically macro-meso-microporous structure (HPS-aerogel) was designed based on biological macromolecules of chitin and chitosan. The macropores can be created within HPS-aerogel after CaCO3 removal, and meso-micropores resulting from water sublimation during freeze-drying. The macro-meso-microporous structure endowed HPS-aerogel with high porosity, good mechanical properties, and excellent compression strength (1472 kPa at strain of 80 %). The HPS-aerogel exposed many adsorption sites and was used as an adsorbent to simultaneously remove Cu(II) and Congo red (CR) from water for the first time. The adsorption capability for Cu(II) and CR was 59.21 mg/g and 2074 mg/g at 303 K, respectively, and the adsorption processes matched Pseudo-second-order and Langmuir models with spontaneous and endothermic nature. Additionally, HPS-aerogel showed good anti-interference ability for coexisting pollutant. Importantly, HPS-aerogel exhibited an effective fixed-bed column adsorption performance for dynamic Cu(II) and CR with superior reusability and stability. Furthermore, HPS-aerogel showed outstanding adsorption efficiencies for Cu(II) and CR in real samples. The main adsorption mechanism for Cu(II) was attributed to the electrostatic attraction and chelation, and which was electrostatic attraction, Schiff base, and hydrogen bonding for CR. Therefore, HPS-aerogel should to be a promising adsorbent for removing both heavy-metal ions and dyes from wastewater.

Quality of Life and Functional Outcomes After Intersphincteric Resection for Ultralow Rectal Cancer: A Prospective Observational Study.

BACKGROUND: Intersphincteric resection is the ultimate sphincter-preserving surgical technique for ultralow rectal cancer, but quality-of-life changes after surgery remain unclear. It is also unknown which questionnaire has better associations with functional results for capturing clinical variation in quality of life. OBJECTIVE: This study aimed to assess change in the quality of life and its correlation with functional outcomes among patients undergoing intersphincteric resection for ultralow rectal cancer. DESIGN: This was a prospective, observational, single-center study. SETTINGS: Colorectal surgery referral center. PATIENTS: Patients with ultralow rectal cancer who underwent intersphincteric resection were included. MAIN OUTCOME MEASURES: The primary outcomes were quality-of-life and functional results at 3 to 6, 12, and 24 months after ileostomy closure using validated questionnaires. The secondary outcome was the relationship between quality of life and neorectal function. RESULTS: A total of 102 patients (62.7% men) completed follow-up surveys. Wexner incontinence score and Kirwan's incontinence score significantly improved at 12 months after ileostomy reversal, but such improvement in low anterior resection syndrome score was proved until 24 months later ( p = 0.01). Condition-specific quality-of-life domains improved over time, with significant changes in lifestyle ( p = 0.02) and coping/behavior ( p = 0.01), as well as the summary score of Fecal Incontinence Quality of Life ( p = 0.02) and visual analog scale score ( p < 0.001). Among health-related quality-of-life domains, the subscale scores did not differ significantly. The functional systems scores were significantly correlated with all the domains of condition-specific quality-of-life but only a few health-related quality-of-life domains. Only weak to moderate associations with the functional outcomes were observed for both quality-of-life questionnaires. LIMITATIONS: Single-center data and limited sample size. CONCLUSIONS: Although low anterior resection syndrome persists for years after intersphincteric resection, condition-specific quality of life and functional outcomes improve over time. Compared to health-related quality-of-life questionnaires, condition-specific quality-of-life instruments might be preferable to evaluate changes in quality-of-life after surgery. See Video Abstract at http://links.lww.com/DCR/C130 . CALIDAD DE VIDA Y RESULTADOS FUNCIONALES DESPUS DE UNA RESECCIN INTERESFINTRICA EN CASO DE CNCER RECTAL ULTRABAJO ESTUDIO PROSPECTIVO OBSERVACIONAL: ANTECEDENTES:La resección inter-esfintérica es la última técnica quirúrgica conservadora de esfínteres en casos de cáncer rectal ultrabajo, pero los cambios en la calidad de vida después de la cirugía siguen sin estar claros. Se desconoce también, qué tipo de cuestionario tiene mejor asociación con los resultados funcionales para así captar las variaciones clínicas en la calidad de vida.OBJETIVO:Evaluar el cambio en la calidad de vida y su correlación con los resultados funcionales durante el período postoperatorio en pacientes sometidos a resección interesfintérica por cáncer de recto ultrabajo.DISEÑO:Estudio prospectivo, observacional y de un solo centro.AJUSTES:Centro de referencia de cirugía colorrectal.PACIENTES:Se incluyeron pacientes con cáncer de recto ultra bajo que se sometieron a resección interesfintérica con el cierre de la ileostomía.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue la calidad de vida y los resultados funcionales a los 3-6, 12 y 24 meses después del cierre de la ileostomía utilizando cuestionarios validados. El resultado secundario fue la relación entre la calidad de vida y la función del néorecto.RESULTADOS:Un total de 102 pacientes (62,7% hombres) completaron las encuestas de seguimiento. La puntuación de incontinencia de Wexner y la puntuación de incontinencia de Kirwan mejoraron significativamente a los 12 meses después del cierre de la ileostomía, pero dicha mejoría en la puntuación del síndrome de resección anterior baja se demostró solo hasta 24 meses después ( p = 0,01). Las condiciones en el dominio de la calidad de vida específicos mejoraron con el tiempo, con cambios significativos en el estilo de vida ( p = 0,02) y el afrontamiento/comportamiento ( p = 0,01), así como la puntuación general de la calidad de vida y de la incontinencia fecal ( p = 0,02), puntuación de la escala analógica visual ( p < 0,001). Entre los dominios de la calidad de vida relacionada con la salud, las puntuaciones de las sub-escalas no difirieron significativamente. Las puntuaciones de los sistemas funcionales se correlacionaron significativamente con todos los dominios de la calidad de vida específica de la nueva condición, pero solo con pocos dominios de calidad de vida relacionados con la salud. Solo se observaron asociaciones débiles a moderadas con los resultados funcionales para ambos cuestionarios de calidad de vida.LIMITACIONES:Datos de un solo centro y tamaño de muestra limitado.CONCLUSIONES:Aunque el síndrome de resección anterior baja persiste durante años después de la resección interesfintérica, la calidad de vida específica de la nueva condición y los resultados funcionales mejoran con el tiempo. En comparación con los cuestionarios de calidad de vida relacionados con la salud, los instrumentos de calidad de vida específicos de la nueva condición pueden ser preferibles para evaluar los cambios en la calidad de vida después de la cirugía. Consulte Video Resumen en http://links.lww.com/DCR/C130 . (Traducción-Dr. Xavier Delgadillo ).