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.

An in-depth evaluation of federated learning on biomedical natural language processing for information extraction.

Language models (LMs) such as BERT and GPT have revolutionized natural language processing (NLP). However, the medical field faces challenges in training LMs due to limited data access and privacy constraints imposed by regulations like the Health Insurance Portability and Accountability Act (HIPPA) and the General Data Protection Regulation (GDPR). Federated learning (FL) offers a decentralized solution that enables collaborative learning while ensuring data privacy. In this study, we evaluated FL on 2 biomedical NLP tasks encompassing 8 corpora using 6 LMs. Our results show that: (1) FL models consistently outperformed models trained on individual clients' data and sometimes performed comparably with models trained with polled data; (2) with the fixed number of total data, FL models training with more clients produced inferior performance but pre-trained transformer-based models exhibited great resilience. (3) FL models significantly outperformed pre-trained LLMs with few-shot prompting.

Feasibility, Indications, and Prognostic Significance of Selective Lateral Pelvic Lymph Node Dissection After Preoperative Chemoradiotherapy in Middle/Low Rectal Cancer: Results of a Multicenter Lateral Node Study in China.

BACKGROUND: Lateral pelvic lymph node dissection after preoperative chemoradiotherapy can decrease local recurrence to lateral compartments, thereby providing survival benefits. OBJECTIVE: The safety of lateral pelvic lymph node dissection after preoperative chemoradiotherapy was investigated, and the surgical indications and survival benefits of lateral pelvic lymph node dissection were established on the basis of preoperative characteristics. DESIGN: A multicenter retrospective study. SETTINGS: Three hospitals in China. PATIENTS: Four hundred nine patients with clinical evidence of lateral pelvic lymph node metastasis. INTERVENTIONS: Patients who received lateral pelvic lymph node dissection were divided into 2 groups depending on whether they received chemoradiotherapy (n = 139) or not (n = 270). MAIN OUTCOME MEASURES: The safety, indications, and survival benefits of lateral pelvic lymph node dissection after preoperative chemoradiotherapy were investigated. RESULTS: The surgery times were significantly prolonged by preoperative chemoradiotherapy (291.3 vs 265.5 min; p = 0.021). Multivariate analysis demonstrated that poor/mucinous/signet-ring adenocarcinoma (OR = 4.42, 95% CI, 2.24-11.27; p = 0.031) and postchemoradiotherapy lateral pelvic lymph node short-axis diameter ≥7 mm (OR = 15.2, 95% CI, 5.89-53.01; p < 0.001) were independent predictive factors for lateral pelvic lymph node metastasis. Multivariate prognostic analysis showed that swollen lateral pelvic lymph nodes beyond the obturator or internal iliac as well as the involvement of 3 or more lateral pelvic lymph nodes were independent adverse prognostic factors. LIMITATIONS: The retrospective nature of the study and the small sample size were the limitations of this study. CONCLUSIONS: Preoperative chemoradiotherapy combined with lateral pelvic lymph node dissection is a practicable procedure with acceptable morbidity. Postchemoradiotherapy lateral pelvic lymph node short-axis diameter ≥7 mm and poor/signet/mucinous adenocarcinoma could be used for predicting lateral pelvic lymph node metastasis after chemoradiotherapy. However, lateral pelvic lymph node dissection should be carefully considered in patients with swollen lateral pelvic lymph nodes beyond the obturator or internal iliac region or involvement of multiple lateral pelvic lymph nodes. See Video Abstract at http://links.lww.com/DCR/C133 . VIABILIDAD, INDICACIONES E IMPORTANCIA PRONSTICA DE LA DISECCIN SELECTIVA DE GANGLIOS LINFTICOS PLVICOS LATERALES DESPUS DE QUIMIORRADIOTERAPIA PREOPERATORIA EN CNCER DE RECTO MEDIO/INFERIOR RESULTADOS DE UN ESTUDIO MULTICNTRICO DE GANGLIOS LATERALES EN CHINA: ANTECEDENTES:La disección de los ganglios linfáticos pélvicos laterales después de la quimiorradioterapia preoperatoria puede disminuir la recurrencia local en los compartimentos laterales, lo que brinda beneficios de supervivencia.OBJETIVO:Se investigó la seguridad de la disección de los ganglios linfáticos pélvicos laterales después de la quimiorradioterapia preoperatoria, y se establecieron las indicaciones quirúrgicas y los beneficios de supervivencia de la disección de los ganglios linfáticos pélvicos laterales en función de las características preoperatorias.DISEÑO:Estudio retrospectivo multicéntrico.ESCENARIO:Tres hospitales en China.PACIENTES:Cuatrocientos nueve pacientes con evidencia clínica de metástasis en los ganglios linfáticos pélvicos laterales.INTERVENCIONES:Los pacientes que recibieron disección de ganglios linfáticos pélvicos laterales se dividieron en dos grupos dependiendo de si recibieron quimiorradioterapia (n = 139) o no (n = 270).PRINCIPALES MEDIDAS DE RESULTADO:Se investigaron la seguridad, las indicaciones y los beneficios de supervivencia de la disección de los ganglios linfáticos pélvicos laterales después de la quimiorradioterapia preoperatoria.RESULTADOS:Los tiempos de cirugía se prolongaron significativamente con la quimiorradioterapia preoperatoria (291,3 vs 265,5 min, p = 0,021). El análisis multivariable demostró que el adenocarcinoma mal diferenciado/mucinoso/en anillo de sello (odds ratio = 4,42, intervalo de confianza del 95%, 2,24-11,27; p = 0,031) y el diámetro del eje corto de los ganglios linfáticos pélvicos laterales después de la quimiorradioterapia ≥7 mm (odds ratio = 15,2, intervalo de confianza del 95%, 5,89-53,01; p < 0,001) fueron factores predictivos independientes de metástasis en los ganglios linfáticos pélvicos laterales. El análisis pronóstico multivariable mostró que la inflamación de los ganglios linfáticos pélvicos laterales más allá del obturador o la ilíaca interna, así como la afectación de tres o más ganglios linfáticos pélvicos laterales, eran factores pronósticos adversos independientes.LIMITACIONES:La naturaleza retrospectiva del estudio y el pequeño tamaño de la muestra.CONCLUSIONES:La quimiorradioterapia preoperatoria combinada con la disección de los ganglios linfáticos pélvicos laterales es un procedimiento practicable con una morbilidad aceptable. Posterior a la quimiorradioterapia, el diámetro del eje corto de los ganglios linfáticos pélvicos laterales ≥7 mm y el adenocarcinoma pobre/en sello/mucinoso podrían usarse para predecir la metástasis en los ganglios linfáticos pélvicos laterales después de la quimiorradioterapia. Sin embargo, la disección de los ganglios linfáticos pélvicos laterales debe considerarse cuidadosamente en pacientes con ganglios linfáticos pélvicos laterales inflamados más allá del obturador o de la región ilíaca interna o compromiso de múltiples ganglios linfáticos pélvicos laterales. Consulte Video Resumen en http://links.lww.com/DCR/C133 . (Traducción-Dr. Felipe Bellolio ).

ERK1/2-dependent activity of SOX9 is required for sublytic C5b-9-induced expression of FGF1, PDGFα, and TGF-ß1 in rat Thy-1 nephritis.

Mesangial proliferative glomerulonephritis (MsPGN) and its related rat model Thy-1 nephritis (Thy-1N) are associated with C5b-9 deposition and are characterized by proliferation of glomerular mesangial cell (GMC) and expansion of extracellular matrix (ECM) expansion, alongside overexpression of multiple growth factors. Although fibroblast growth factor 1 (FGF1), platelet-derived growth factor alpha (PDGFα), and transforming growth factor beta 1 (TGF-ß1) are well known for their proproliferative and profibrotic roles, the molecular mechanisms responsible for regulating the expression of these growth factors have not been thoroughly elucidated. In this study, we found that sublytic C5b-9 induction of sex-determining region Y-box 9 (SOX9) transactivated FGF1, PDGFα, and TGF-ß1 genes in GMCs, resulting in a significant increase in their mRNA and protein levels. Besides, sublytic C5b-9 induction of activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) phosphorylated SOX9 at serine 181 and serine 64, which enhanced SOX9's ability to transactivate FGF1, PDGFα, and TGF-ß1 genes in GMCs. Furthermore, we demonstrated that inhibiting ERK1/2 activation or silencing either ERK1/2 or SOX9 gene led to reduced SOX9 phosphorylation, decreased generation of FGF1, PDGFα, and TGF-ß1, and ameliorated glomerular injury in rat Thy-1N. Overall, these findings suggest that expression of FGF1, PDGFα, and TGF-ß1 is promoted by ERK1/2-mediated phosphorylation of SOX9, which may provide a valuable insight into the pathogenesis of MsPGN and offer a potential target for the development of novel treatment strategies for MsPGN.

Applications of Near-Infrared Fluorescence Imaging and Angiography of Inferior Vesical Artery in Laparoscopic Lateral Lymph Node Dissection: A Prospective Nonrandomized Controlled Study.

BACKGROUND: Near-infrared imaging with indocyanine green has been used to guide lateral lymph node dissection, yet its efficacy and benefits need further investigation. OBJECTIVE: To investigate the efficacy and feasibility of near-infrared fluorescence imaging and angiography of the inferior vesical artery in laparoscopic lateral lymph node dissection. DESIGN: A prospective nonrandomized controlled study. SETTINGS: Single-center study. PATIENTS: Patients with lower rectal cancer who underwent total mesorectal excision plus lateral lymph node dissection. MAIN OUTCOME MEASURES: A cohort of 108 patients was enrolled. After propensity score matching, 29 patients in the near-infrared group and 50 patients in the non-near-infrared group were matched. The total number of harvested lateral lymph nodes, positive lateral lymph nodes, inferior vesical artery preservation, and postoperative urinary function were compared. RESULTS: After propensity score matching, both groups had similar baseline characteristics. The total number of harvested lateral lymph nodes in the near-infrared group was significantly higher (12 vs 9, p = 0.013), but positive lateral lymph nodes were similar between the 2 groups (1 vs 1, p = 0.439). The inferior vesical artery preservation ratio was significantly increased with the aid of indocyanine green angiography (93.1% vs 56.0%, p < 0.001). The non-near-infrared group required more days for urinary catheter removal than the near-infrared group (5 vs 4, p = 0.046). Urinary recatheterization tended to occur more frequently in the non-near-infrared group, with a marginally significant trend (16% vs 0%, p = 0.059). The non-near-infrared group tended to have more cases with residual urine volume ≥50 mL than the near-infrared group (20.0% vs 3.4%, p = 0.087), especially in the bilateral dissection subgroup (41.2% vs 0%, p = 0.041). LIMITATIONS: Small sample size. CONCLUSIONS: Near-infrared imaging increased the number of harvested lateral lymph nodes, whereas real-time indocyanine green fluorescence angiography ensured the preservation of the inferior vesical artery and tended to improve postoperative urinary function.

Survival nomograms for simultaneous resection of primary and hepatic lesions without neoadjuvant chemotherapy in patients with resectable colorectal liver metastasis.

Background: No well-performing nomogram has been developed specifically to predict individual-patient cancer-specific survival (CSS) and overall survival (OS) among patients with resectable colorectal liver metastasis (CRLM) who undergo simultaneous resection of primary and hepatic lesions without neoadjuvant chemotherapy (NAC). We aim to investigate the prognosis of patients with resectable CRLM undergoing simultaneous resection of primary and hepatic lesions without NAC. Methods: Data of patients with CRLM in the Surveillance, Epidemiology and End Results Program (cohort, n = 225) were collected as the training set, and data of patients with CRLM treated at the National Cancer Center (cohort, n = 180) were collected as the validation set. The prognostic value of the clinicopathological parameters in the training cohort was assessed using Kaplan‒Meier curves and univariate and multivariate Cox proportional hazards models, and OS and CSS nomograms integrated with the prognostic variables were constructed. Calibration analyses, receiver operating characteristic (ROC) curves, and decision curve analyses (DCAs) were then performed to evaluate the performance of the nomograms. Results: There was no collinearity among the collected variables. Three factors were associated with OS and CSS: the pretreatment carcinoembryonic antigen (CEA) concentration, pathologic N (pN) stage, and adjuvant chemotherapy (each p < 0.05). OS and CSS nomograms were constructed using these three parameters. The calibration plots revealed favorable agreement between the predicted and observed outcomes. The areas under the ROC curves were approximately 0.7. The DCA plots revealed that both nomograms had satisfactory clinical benefits. The ROC curves and DCAs also confirmed that the nomogram surpassed the tumor, node, and metastasis staging system. Conclusion: The herein-described nomograms containing the pretreatment CEA concentration, pN stage, and adjuvant chemotherapy may be effective models for predicting postoperative survival in patients with CRLM.

A cross-institutional evaluation on breast cancer phenotyping NLP algorithms on electronic health records.

Objective: Transformer-based language models are prevailing in the clinical domain due to their excellent performance on clinical NLP tasks. The generalizability of those models is usually ignored during the model development process. This study evaluated the generalizability of CancerBERT, a Transformer-based clinical NLP model, along with classic machine learning models, i.e., conditional random field (CRF), bi-directional long short-term memory CRF (BiLSTM-CRF), across different clinical institutes through a breast cancer phenotype extraction task. Materials and methods: Two clinical corpora of breast cancer patients were collected from the electronic health records from the University of Minnesota (UMN) and Mayo Clinic (MC), and annotated following the same guideline. We developed three types of NLP models (i.e., CRF, BiLSTM-CRF and CancerBERT) to extract cancer phenotypes from clinical texts. We evaluated the generalizability of models on different test sets with different learning strategies (model transfer vs locally trained). The entity coverage score was assessed with their association with the model performances. Results: We manually annotated 200 and 161 clinical documents at UMN and MC. The corpora of the two institutes were found to have higher similarity between the target entities than the overall corpora. The CancerBERT models obtained the best performances among the independent test sets from two clinical institutes and the permutation test set. The CancerBERT model developed in one institute and further fine-tuned in another institute achieved reasonable performance compared to the model developed on local data (micro-F1: 0.925 vs 0.932). Conclusions: The results indicate the CancerBERT model has superior learning ability and generalizability among the three types of clinical NLP models for our named entity recognition task. It has the advantage to recognize complex entities, e.g., entities with different labels.

Approach to Access Benzo[j]phenanthridinones from 1,7-Enynes and Aryldiazonium Salts via a Domino Radical Relay Process Enabled by a P/N-Heteroleptic Cu(I)-Photosensitizer.

A mild approach for the synthesis of benzo[j]phenanthridin-6(5H)-one derivatives from 1,7-enynes and aryldiazonium salts has been successfully developed involving a domino radical relay process enabled by a heteroleptic Cu(I)-photosensitizer under visible-light-driven photocatalytic conditions. Mechanistic studies disclosed that the oxidative quenching of the excited state of PS 4 with aryldiazonium salts via an SET process generated aryl radicals, which could play a radical initiator-terminator dual role within the whole radical relay process, namely, at the initial step acting as a radical donor to trigger the radical addition to the olefin moieties of 1,7-enynes while at the final stage serving as a radical acceptor to complete the cyclization.

Matrix stiffness-mediated tenogenesis of tendon stem/progenitor cells via integrin-αm for tendon regeneration.

Tendon injuries, commonly associated with sports activities, pose significant challenges in terms of treatment and recovery due to limited tendon regeneration and the formation of proliferative scars. Stem cell-based therapy has shown promising application, but there are still challenges. Physical and biological cues are instrumental in guiding stem cell differentiation and maturation. This study focuses on exploring the effects of matrix biomechanics on tendon stem/progenitor cells (TSPCs) differentiation. We fabricated polydimethylsiloxane (PDMS) substrates with different elastic modulus to mimic the mechanical characteristics of healthy tendons. A tissue-engineered culture system was developed for tenogenesis, and pre-differentiated tissue-engineered tendons were transplanted in vivo to assess their efficacy in regenerating patella tendon injuries. Furthermore, we demonstrated that the biomechanical stimuli activated the integrin-αm to enhance the tenogenesis capacity of TSPCs. Our findings highlight the importance of biomechanics in tendon tissue engineering and provide a novel perspective for enhancing tendon regeneration.

MRI-based Radiomics Model for Preoperative Prediction of Lateral Pelvic Lymph Node Metastasis in Locally Advanced Rectal Cancer.

RATIONALE AND OBJECTIVES: To develop a magnetic resonance imaging (MRI)-based radiomics model for preoperative prediction of lateral pelvic lymph node (LPLN) metastasis (LPLNM) in patients with locally advanced rectal cancer MATERIALS AND METHODS: We retrospectively enrolled 263 patients with rectal cancer who underwent total mesorectal excision and LPLN dissection. Radiomics features from the primary lesion and LPLNs on baseline MRI images were utilized to construct a radiomics model, and their radiomics scores were combined to develop a radiomics scoring system. A clinical prediction model was developed using logistic regression. A hybrid predicting model was created through multivariable logistic regression analysis, integrating the radiomics score with significant clinical risk factors (baseline Carcinoembryonic Antigen (CEA), clinical circumferential resection margin status, and the short axis diameter of LPLN). This hybrid model was presented with a hybrid clinical-radiomics nomogram, and its calibration, discrimination, and clinical usefulness were assessed. RESULTS: A total of 148 patients were included in the analysis and randomly divided into a training cohort (n = 104) and an independent internal testing cohort (n = 44). The hybrid clinical-radiomics model exhibited the highest discrimination, with an area under the receiver operating characteristic (AUC) of 0.843 [95% confidence interval (CI), 0.706-0.968] in the testing cohort compared to the clinical model [AUC (95% CI) = 0.772 (0.589-0.856)] and radiomics model [AUC (95% CI) = 0.731 (0.613-0.849)]. The hybrid prediction model also demonstrated good calibration, and decision curve analysis confirmed its clinical usefulness. CONCLUSION: This study developed a hybrid MRI-based radiomics model that incorporates a combination of radiomics score and significant clinical risk factors. The proposed model holds promise for individualized preoperative prediction of LPLNM in patients with locally advanced rectal cancer. DATA AVAILABILITY STATEMENT: The data presented in this study are available on request from the corresponding author.

Fascia- vs vessel-oriented lateral lymph node dissection for rectal cancer: Short-term outcomes and prognosis in a single-center experience.

BACKGROUND: For the management of lateral lymph node (LLN) metastasis in patients with rectal cancer, selective LLN dissection (LLND) is gradually being accepted by Chinese scholars. Theoretically, fascia-oriented LLND allows radical tumor resection and protects of organ function. However, there is a lack of studies comparing the efficacy of fascia-oriented and traditional vessel-oriented LLND. Through a preliminary study with a small sample size, we found that fascia-oriented LLND was associated with a lower incidence of postoperative urinary and male sexual dysfunction and a higher number of examined LLNs. In this study, we increased the sample size and refined the postoperative functional outcomes. AIM: To compare the effects of fascia- and vessel-oriented LLND regarding short-term outcomes and prognosis. METHODS: We conducted a retrospective cohort study on data from 196 patients with rectal cancer who underwent total mesorectal excision and LLND from July 2014 to August 2021. The short-term outcomes included perioperative outcomes and postoperative functional outcomes. The prognosis was measured based on overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 105 patients were included in the final analysis and were divided into fascia- and vessel-oriented groups that included 41 and 64 patients, respectively. Regarding the short-term outcomes, the median number of examined LLNs was significantly higher in the fascia-oriented group than in the vessel-oriented group. There were no significant differences in the other short-term outcomes. The incidence of postoperative urinary and male sexual dysfunction was significantly lower in the fascia-oriented group than in the vessel-oriented group. In addition, there was no significant difference in the incidence of postoperative lower limb dysfunction between the two groups. In terms of prognosis, there was no significant difference in PFS or OS between the two groups. CONCLUSION: It is safe and feasible to perform fascia-oriented LLND. Compared with vessel-oriented LLND, fascia-oriented LLND allows the examination of more LLNs and may better protect postoperative urinary function and male sexual function.

Prognostic value of consolidation-to-tumor ratio on computed tomography in NSCLC: a meta-analysis.

BACKGROUND: Although several studies have confirmed the prognostic value of the consolidation to tumor ratio (CTR) in non-small cell lung cancer (NSCLC), there still remains controversial about it. METHODS: We systematically searched the PubMed, Embase, and Web of Science databases from inception to April, 2022 for eligible studies that reported the correlation between CTR and prognosis in NSCLC. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were extracted and pooled to assess the overall effects. Heterogeneity was estimated by I2 statistics. Subgroup analysis based on the cut-off value of CTR, country, source of HR and histology type was conducted to detect the sources of heterogeneity. Statistical analyses were performed using STATA version 12.0. RESULTS: A total of 29 studies published between 2001 and 2022 with 10,347 patients were enrolled. The pooled results demonstrated that elevated CTR was associated with poorer overall survival (HR = 1.88, 95% CI 1.42-2.50, P < 0.01) and disease-free survival (DFS)/recurrence-free survival (RFS)/progression-free survival (PFS) (HR = 1.42, 95% CI 1.27-1.59, P < 0.01) in NSCLC. According to subgroup analysis by the cut-off value of CTR and histology type, both lung adenocarcinoma and NSCLC patients who had a higher CTR showed worse survival. Subgroup analysis stratified by country revealed that CTR was a prognostic factor for OS and DFS/RFS/PFS in Chinese, Japanese, and Turkish patients. CONCLUSIONS: In NSCLC patients with high CTR, the prognosis was worse than that with low CTR, indicating that CTR may be a prognostic factor.

Prognostic role of pretreatment skeletal muscle index in gastric cancer patients: A meta-analysis.

Background: The association between pretreatment skeletal muscle index (SMI) and long-term survival of gastric cancer patients remains unclear up to now. The aim of this meta-analysis was to identify the prognostic value of pretreatment SMI in gastric cancer. Methods: The PubMed, EMBASE and Web of Science electronic databases were searched up to 5 June 2022 for relevant studies. The primary outcome was overall survival (OS) and the second outcomes were disease-free survival (DFS) and cancer-specific survival (CSS). The hazard ratios (HRs) and 95% confidence intervals (CIs) were combined to assess the relationship between pretreatment SMI and survival of gastric cancer patients. All statistical analyses were conducted by STATA 15.0 software. Results: A total of 31 retrospective studies involving 12,434 patients were enrolled in this meta-analysis. The pooled results demonstrated that lower pretreatment was significantly associated with poorer OS (HR = 1.53, p < 0.001). Besides, lower pretreatment SMI was also related with worse DFS (HR = 1.39, p < 0.001) and CSS (HR = 1.96, p < 0.001). Conclusion: Pretreatment SMI was significantly associated with prognosis of gastric cancer patients and lower SMI predicted worse survival. However, more prospective high-quality studies are still needed to verify our findings.

Advanced silk materials for musculoskeletal tissue regeneration.

Musculoskeletal diseases are the leading causes of chronic pain and physical disability, affecting millions of individuals worldwide. Over the past two decades, significant progress has been made in the field of bone and cartilage tissue engineering to combat the limitations of conventional treatments. Among various materials used in musculoskeletal tissue regeneration, silk biomaterials exhibit unique mechanical robustness, versatility, favorable biocompatibility, and tunable biodegradation rate. As silk is an easy-to-process biopolymer, silks have been reformed into various materials formats using advanced bio-fabrication technology for the design of cell niches. Silk proteins also offer active sites for chemical modifications to facilitate musculoskeletal system regeneration. With the emergence of genetic engineering techniques, silk proteins have been further optimized from the molecular level with other functional motifs to introduce new advantageous biological properties. In this review, we highlight the frontiers in engineering natural and recombinant silk biomaterials, as well as recent progress in the applications of these new silks in the field of bone and cartilage regeneration. The future potentials and challenges of silk biomaterials in musculoskeletal tissue engineering are also discussed. This review brings together perspectives from different fields and provides insight into improved musculoskeletal engineering.

Surgical outcomes of left hemicolon sparing resection versus extensive resection in treating synchronous colorectal cancer involving the right-sided colon and sigmoid colon or rectum.

BACKGROUND: There are different surgical strategies that can treat synchronous colorectal cancer (SCRC) involving separate segments, namely extensive resection (EXT) and left hemicolon-sparing resection (LHS). We aim to comparatively analyze short-term surgical results, bowel function, and long-term oncological outcomes between SCRC patients treated with the two different surgical strategies. METHODS: One hundred thirty-eight patients with SCRC lesions located in the right hemicolon and rectum or sigmoid colon were collected at the Cancer Hospital, Chinese Academy of Medical Sciences, and the Peking University First Hospital from January 2010 to August 2021 and divided into EXT group (n = 35) and LHS group (n = 103), depending on their surgical strategies. These two groups of patients were compared for postoperative complications, bowel function, the incidence of metachronous cancers, and prognosis. RESULTS: The operative time for the LHS group was markedly shorter compared with the EXT group (268.6 vs. 316.9 min, P = 0.015). The post-surgery incidences of total Clavien-Dindo grade ≥ II complications and anastomotic leakage (AL) were 8.7 vs. 11.4% (P = 0.892) and 4.9 vs. 5.7% (P = 1.000) for the LHS and EXT groups, respectively. The mean number of daily bowel movements was significantly lower for the LHS group than for the EXT group (1.3 vs. 3.8, P < 0.001). The proportions of no low anterior resection syndrome (LARS), minor LARS, and major LARS for the LHS and EXT groups were 86.5 vs. 80.0%, 9.6 vs. 0%, and 3.8 vs. 20.0%, respectively (P = 0.037). No metachronous cancer was found in the residual left colon during the 51-month (median duration) follow-up period. The overall and disease-free survival rates at 5 years were 78.8% and 77.5% for the LHS group and 81.7% and 78.6% for the EXT group (P = 0.565, P = 0.712), respectively. Multivariate analysis further confirmed N stage, but not surgical strategy, as the risk factor that independently affected the patients' survival. CONCLUSIONS: LHS appears to be a more appropriate surgical strategy for SCRC involving separate segments because it exhibited shorter operative time, no increase in the risk of AL and metachronous cancer, and no adverse long-term survival outcomes. More importantly, it could better retain bowel function and tended to reduce the severity of LARS and therefore improve the post-surgery life quality of SCRC patients.

Establishing and validating predictive nomograms for lateral pelvic lymph node metastasis in patients with rectal cancer based on radiologic factors and clinicopathologic characteristics.

INTRODUCTION: It is critical to accurately predict the occurrence of lateral pelvic lymph node (LPN) metastasis. Currently, verified predictive tools are unavailable. This study aims to establish nomograms for predicting LPN metastasis in patients with rectal cancer who received or did not receive neoadjuvant chemoradiotherapy (nCRT). MATERIALS AND METHODS: We carried out a retrospective study of patients with rectal cancer and clinical LPN metastasis who underwent total mesorectal excision (TME) and LPN dissection (LPND) from January 2012 to December 2019 at 3 institutions. We collected and evaluated their clinicopathologic and radiologic features, and constructed nomograms based on the multivariable logistic regression models. RESULTS: A total of 472 eligible patients were enrolled into the non-nCRT cohort (n = 312) and the nCRT cohort (n = 160). We established nomograms using variables from the multivariable logistic regression models in both cohorts. In the non-nCRT cohort, the variables included LPN short diameter, cT stage, cN stage, histologic grade, and malignant features, and the C-index was 0.930 in the training cohort and 0.913 in the validation cohort. In the nCRT cohort, the variables included post-nCRT LPN short diameter, ycT stage, ycN stage, histologic grade, and post-nCRT malignant features, and the C-index was 0.836 in the training dataset and 0.827 in the validation dataset. The nomograms in both cohorts were moderately calibrated and well-validated. CONCLUSIONS: We established nomograms for patients with rectal cancer that accurately predict LPN metastasis. The performance of the nomograms in both cohorts was high and well-validated.

Safety Flight Control Design of a Quadrotor UAV With Capability Analysis.

This article considers the safety control problem of a quadrotor unmanned aerial vehicle (UAV) subject to actuator faults and external disturbances, based on the quantization of system capability and safety margin. First, a trajectory function is constructed online with backpropagation of system dynamics. Therefore, a degraded trajectory is gracefully regenerated, via the tradeoff between the remaining system capability and the expected derivatives (velocity, jerk, and snap) of the trajectory. Second, a control-oriented model is established into a form of strict feedback, integrating actuator malfunctions and disturbances. Therefore, a retrofit dynamic surface control (DSC) scheme based on the control-oriented model is developed to improve the tracking performance. When comparing to the existing control methods, the compensation ability is analyzed to determine whether the faults and disturbances can be handled or not. Finally, simulation and experimental studies are conducted to highlight the efficiency of the proposed safety control scheme.

Feasibility and safety of lateral pelvic lymph node dissection for elderly patients with middle-low rectal cancer: results of a large multicenter lateral node collaborative group study in China.

BACKGROUND: Lateral pelvic lymph node (LPN) dissection can improve local control in certain rectal cancer patients with LPN metastasis. However, the effects of this technically complex procedure on perioperative safety and long-term survival of elderly patients (≥ 70 years) remain unclear. METHODS: Locally advanced middle-low rectal cancer patients diagnosed with LPN metastasis who underwent total mesorectal excision (TME) with LPN dissection at three institutions from January 2012 to December 2019 were included in this study. Additionally patients who had neoadjuvant chemoradiotherapy (nCRT) and those who did not were compared. RESULTS: In total there were 407 patients, including 49 elderly and 358 non-elderly patients, of which 249 were male, with a median age of 58 years (range:18-85 years). In the whole cohort, operation time (280.7 vs. 292.0 min, p = 0.498) and estimated blood loss (100 vs. 100 ml, p = 0.384) were comparable in the elderly and non-elderly groups. There was no significant difference in the incidences of overall complications (24.5% vs. 19.8%, p = 0.448) and severe (Clavien-Dindo grade 3-5) surgical complications (8.2% vs. 7.5%, p = 0.778) between the two groups. However, the incidence of urinary retention (14.3% vs. 5.6%, p = 0.032) and intensive care unit admission (16.3% vs. 6.1%, p = 0.018) was significantly higher in the elderly group compared with those in the non-elderly group. The 3-year overall survival (88.7% vs. 82.1%, p = 0.516) and disease-free survival (81.2% vs. 70.7%, p = 0.352) were comparable between the two groups. Moreover, results in the nCRT cohort were comparable to those in the overall cohort. CONCLUSIONS: Even with nCRT, TME combined with LPN dissection is safe and feasible for elderly patients, demonstrating low mortality and acceptable morbidity. Elderly and non-elderly patients with LPN metastasis who undergo LPN dissection can achieve comparable 3-year survival outcomes. TRAIL REGISTRATION: ClinicalTrials.gov Identifier: NCT04850027.

Mesorectal excision with or without lateral lymph node dissection for elderly patients with mid-low rectal cancer: safety and feasibility analysis.

OBJECTIVE: The perioperative safety and survival benefits of lateral lymph node dissection in elderly patients have been less reported. This study aimed to compare short-term and survival outcomes of total mesorectal excision and total mesorectal excision + lateral lymph node dissection in elderly patients. METHODS: A total of 444 elderly patients (≥65 years) with middle-low rectal cancer were enrolled in three institutions and divided into the total mesorectal excision + lateral lymph node dissection group (n = 110) and the total mesorectal excision group (n = 334). Eighty-three matched pairs were selected for evaluation after propensity matching. Data of 297 patients (age <65 years) with middle-low rectal cancer who underwent total mesorectal excision + lateral lymph node dissection were also collected and reviewed. Clinical and pathological features, postoperative outcomes and survival data were collected and analyzed. RESULTS: Compared with the total mesorectal excision group, the operation time of patients in the total mesorectal excision + lateral lymph node dissection group was significantly longer (277.6 vs. 171.4 min, P < 0.001), and the estimated blood loss was significantly more (119.6 vs. 57.5 ml, P = 0.014). Although there was no significant difference in overall complications (24.1% vs. 14.4%, P = 0.115) and grade 3-5 complications (9.6% vs. 7.2%, P = 0.576) between the two groups, the incidence of urinary retention (10.8% vs. 2.4%, P = 0.029) was higher in the total mesorectal excision + lateral lymph node dissection group. Two groups of patients achieve a similar 3-year overall survival (92.8% vs. 85.4%, P = 0.195) and 3-year disease-free survival (81.5% vs. 73.0%, P = 0.625). In addition, we compared long-term outcomes in 110 elderly patients with total mesorectal excision + lateral lymph node dissection and 297 non-elderly patients with total mesorectal excision + lateral lymph node dissection, and the results showed that 3-year (89.2% vs. 80.9%, P = 0.546) and disease-free survival (76.4% vs. 70.4%, P = 0.346) were similar between elderly and non-elderly patients. CONCLUSIONS: Although urinary retention is closely related to the implementation of lateral lymph node dissection in elderly patients, total mesorectal excision with lateral lymph node dissection could be performed safely with accepted overall and grade 3-5 postoperative complications in elderly patients with rectal cancer. Moreover, elderly patients with clinical lateral lymph node metastasis can also benefit from lateral lymph node dissection as well as younger patients. Prospective studies with large sample sizes are needed to verify our results further.