Arthroscopic Capsular Release Versus Manipulation under Anesthesia for Refractory Frozen Shoulder: A Systematic Review with Meta-Analysis.

OBJECTIVE: Frozen shoulder (FS) is a painful and debilitating condition affecting the shoulder joint. When patients fail to improve after conservative treatments, operative treatments including arthroscopic capsular release (ACR) and manipulation under anesthesia (MUA) are recommended. However, the comparison between these two interventions remains controversial. This study aimed to compare the efficacy and safety of ACR and MUA for refractory FS. METHODS: A systematic review and meta-analysis was conducted following the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) guidelines. PubMed, EMBASE, Cochrane Library, and Web of Science were searched for eligible studies until December 10, 2023. Meta-analyses were conducted using Manager V.5.3.3. Pooled effect sizes were expressed as the weighted mean difference (WMD) or odds ratio (OR) with 95% confidence intervals (CIs). RESULTS: A total of eight comparative studies with 768 patients were included. Compared with MUA, ACR had statistically better Δ VAS (WMD, -0.44; 95% CI, -0.71 to -0.18; I2 = 6%; p = 0.001) at over 12-month follow-up, which did not reach the minimal clinically important difference (MCID). Other outcomes regarding pain relief, function, and range of motion (ROM) improvements were not statistically different between the two groups at different follow-up timepoints. Compared with the MUA group, the ACR group had a significantly higher rate of severe complications (OR, 4.14; 95% CI, 1.01 to 16.94; I2 = 0%; p = 0.05), but comparable rates of mild complications and additional intervention. CONCLUSIONS: In treating refractory FS, ACR demonstrated comparable pain relief, functional and ROM improvements, rates of mild complications and additional intervention but a higher risk of severe complications to MUA during short-term follow-up periods. Notably, ACR exhibited statistically superior improvement in the long-term pain relief compared to the MUA group, although it did not reach the MCID.

PMFFNet: A hybrid network based on feature pyramid for ovarian tumor segmentation.

Ovarian cancer is a highly lethal malignancy in the field of oncology. Generally speaking, the segmentation of ovarian medical images is a necessary prerequisite for the diagnosis and treatment planning. Therefore, accurately segmenting ovarian tumors is of utmost importance. In this work, we propose a hybrid network called PMFFNet to improve the segmentation accuracy of ovarian tumors. The PMFFNet utilizes an encoder-decoder architecture. Specifically, the encoder incorporates the ViTAEv2 model to extract inter-layer multi-scale features from the feature pyramid. To address the limitation of fixed window size that hinders sufficient interaction of information, we introduce Varied-Size Window Attention (VSA) to the ViTAEv2 model to capture rich contextual information. Additionally, recognizing the significance of multi-scale features, we introduce the Multi-scale Feature Fusion Block (MFB) module. The MFB module enhances the network's capacity to learn intricate features by capturing both local and multi-scale information, thereby enabling more precise segmentation of ovarian tumors. Finally, in conjunction with our designed decoder, our model achieves outstanding performance on the MMOTU dataset. The results are highly promising, with the model achieving scores of 97.24%, 91.15%, and 87.25% in mACC, mIoU, and mDice metrics, respectively. When compared to several Unet-based and advanced models, our approach demonstrates the best segmentation performance.

The Gradient Effect on Cyclic Behavior of 316L Stainless Steel in the Ultrasonic Bending Test.

Nanoindentation measurements were conducted to investigate the high-cycle response of 316L stainless steel in bending fatigue. Hardness variation owing to the gradient flexure stress amplitude for different curvatures was plotted along with the thickness and length, respectively. Scanning electron microscopy (SEM) was subsequently conducted to explore the deformation characteristics in multiple layers, which had cyclic gradient stress, on the cross-section of specimens. The nanoindentation results indicated that the cyclic hardening response of 316L stainless steel is correlated with the level of stress amplitude in the high-cycle fatigue (HCF) regime. Furthermore, an analytical model was proposed to clarify the relationship between nanohardness and stress amplitude. Finally, the evolution of damage accumulation due to irreversible plastic deformation is continuous during stress reduction up to the neighboring zone at the neutral surface of the flexure beam in some individual grains.

Colchicine ameliorates myocardial injury induced by coronary microembolization through suppressing pyroptosis via the AMPK/SIRT1/NLRP3 signaling pathway.

BACKGROUND: Coronary microembolization(CME)is a common complication in acute coronary syndrome and percutaneous coronary intervention, which is closely related to poor prognosis. Pyroptosis, as an inflammatory programmed cell death, has been found to be associated with CME-induced myocardial injury. Colchicine (COL) has potential benefits in coronary artery disease due to its anti-inflammatory effect. However, the role of colchicine in pyroptosis-related CME-induced cardiomyocyte injury is unclear. This study was carried out to explore the effects and mechanisms of colchicine on myocardial pyroptosis induced by CME. METHODS: The CME animal model was constructed by injecting microspheres into the left ventricle with Sprague-Dawley rats, and colchicine (0.3 mg/kg) pretreatment seven days before and on the day of modeling or compound C(CC)co-treatment was given half an hour before modeling. The study was divided into 4 groups: Sham group, CME group, CME + COL group, and CME + COL + CC group (10 rats for each group). Cardiac function, serum myocardial injury markers, myocardial histopathology, and pyroptosis-related indicators were used to evaluate the effects of colchicine. RESULTS: Colchicine pretreatment improved cardiac dysfunction and reduced myocardial injury induced by CME. The main manifestations were the improvement of left ventricular systolic function, the decrease of microinfarction area, and the decrease of mRNA and protein indexes related to pyroptosis. Mechanistically, colchicine increased the phosphorylation level of adenosine monophosphate-activated protein kinase (AMPK), promoted the expression of silent information regulation T1 (SIRT1), and inhibited the expression of NOD-like receptor pyrin containing 3 (NLRP3) to reduce myocardial pyroptosis. However, after CC co-treatment with COL, the effect of colchicine was partially reversed. CONCLUSION: Colchicine improves CME-induced cardiac dysfunction and myocardial injury by inhibiting cardiomyocyte pyroptosis through the AMPK/SIRT1/NLRP3 signaling pathway.

Application of an Innovative Data Mining Approach Towards Safe Polypharmacy Practice in Older Adults.

INTRODUCTION: Polypharmacy is common and is associated with higher risk of adverse drug event (ADE) among older adults. Knowledge on the ADE risk level of exposure to different drug combinations is critical for safe polypharmacy practice, while approaches for this type of knowledge discovery are limited. The objective of this study was to apply an innovative data mining approach to discover high-risk and alternative low-risk high-order drug combinations (e.g., three- and four-drug combinations). METHODS: A cohort of older adults (≥ 65 years) who visited an emergency department (ED) were identified from Medicare fee-for-service and MarketScan Medicare supplemental data. We used International Classification of Diseases (ICD) codes to identify ADE cases potentially induced by anticoagulants, antidiabetic drugs, and opioids from ED visit records. We assessed drug exposure data during a 30-day window prior to the ED visit dates. We investigated relationships between exposure of drug combinations and ADEs under the case-control setting. We applied the mixture drug-count response model to identify high-order drug combinations associated with an increased risk of ADE. We conducted therapeutic class-based mining to reveal low-risk alternative drug combinations for high-order drug combinations associated with an increased risk of ADE. RESULTS: We investigated frequent high-order drug combinations from 8.4 million ED visit records (5.1 million from Medicare data and 3.3 million from MarketScan data). We identified 5213 high-order drug combinations associated with an increased risk of ADE by controlling the false discovery rate at 0.01. We identified 1904 high-order, high-risk drug combinations had potential low-risk alternative drug combinations, where each high-order, high-risk drug combination and its corresponding low-risk alternative drug combination(s) have similar therapeutic classes. CONCLUSIONS: We demonstrated the application of a data mining technique to discover high-order drug combinations associated with an increased risk of ADE. We identified high-risk, high-order drug combinations often have low-risk alternative drug combinations in similar therapeutic classes.

Exploring the Incorporation of a Novel Cardiotoxicity Mobile Health App Into Care of Patients With Cancer: Qualitative Study of Patient and Provider Perspectives.

BACKGROUND: Cardiotoxicity is a limitation of several cancer therapies and early recognition improves outcomes. Symptom-tracking mobile health (mHealth) apps are feasible and beneficial, but key elements for mHealth symptom-tracking to indicate early signs of cardiotoxicity are unknown. OBJECTIVE: We explored considerations for the design of, and implementation into a large academic medical center, an mHealth symptom-tracking tool for early recognition of cardiotoxicity in patients with cancer after cancer therapy initiation. METHODS: We conducted semistructured interviews of >50% of the providers (oncologists, cardio-oncologists, and radiation oncologists) who manage cancer treatment-related cardiotoxicity in the participating institution (n=11), and either interviews or co-design or both with 6 patients. Data were coded and analyzed using thematic analysis. RESULTS: Providers indicated that there was no existing process to enable early recognition of cardiotoxicity and felt the app could reduce delays in diagnosis and lead to better patient outcomes. Signs and symptoms providers recommended for tracking included chest pain or tightness, shortness of breath, heart racing or palpitations, syncope, lightheadedness, edema, and excessive fatigue. Implementation barriers included determining who would receive symptom reports, ensuring all members of the patient's care team (eg, oncologist, cardiologist, and primary care) were informed of the symptom reports and could collaborate on care plans, and how to best integrate the app data into the electronic health record. Patients (n=6, 100%) agreed that the app would be useful for enhanced symptom capture and education and indicated willingness to use it. CONCLUSIONS: Providers and patients agree that a patient-facing, cancer treatment-related cardiotoxicity symptom-tracking mHealth app would be beneficial. Additional studies evaluating the role of mHealth as a potential strategy for targeted early cardioprotective therapy initiation are needed.

Situs Ambiguus Is Associated With Adverse Clinical Outcomes in Children With Primary Ciliary Dyskinesia.

BACKGROUND: Primary ciliary dyskinesia (PCD) is a rare disorder of motile cilia associated with situs abnormalities. At least 12% of patients with PCD have situs ambiguus (SA), including organ laterality defects falling outside normal arrangement (situs solitus [SS]) or mirror image inversion (situs inversus totalis [SIT]). RESEARCH QUESTION: Do patients with PCD and SA achieve worse clinical outcomes compared with those with SS or SIT? STUDY DESIGN AND METHODS: This cross-sectional, multicenter study evaluated participants aged 21 years or younger with PCD. Participants were classified as having SA, including heterotaxy, or not having SA (SS or SIT). Markers of disease severity were compared between situs groups, adjusting for age at enrollment and severe CCDC39 or CCDC40 genotype, using generalized linear models and logistic and Poisson regression. RESULTS: In 397 participants with PCD (mean age, 8.4 years; range, 0.1-21), 42 patients were classified as having SA, including 16 patients (38%) with complex cardiovascular malformations or atrial isomerism, 13 patients (31%) with simple CVM, and 13 patients (31%) without cardiovascular malformations. Of these, 15 patients (36%) underwent cardiac surgery, 24 patients (57%) showed an anatomic spleen abnormality, and seven patients (17%) showed both. The remaining 355 participants did not have SA, including 152 with SIT and 203 with SS. Overall, 70 participants (17%) harbored the severe CCDC39 or CCDC40 genotype. Compared with participants without SA, those with SA showed lower median BMI z scores (P = .03), lower FVC z scores (P = .01), and more hospitalizations and IV antibiotic courses for acute respiratory infections during the 5 years before enrollment (P < .01). Participants with cardiovascular malformations requiring surgery or with anatomic spleen abnormalities showed lower median BMI z scores and more hospitalizations and IV therapies for respiratory illnesses compared with participants without SA. INTERPRETATION: Children with PCD and SA achieve worse nutritional and pulmonary outcomes with more hospitalizations for acute respiratory illnesses than those with SS or SIT combined. Poor nutrition and increased hospitalizations for respiratory infections in participants with SA and PCD are associated with cardiovascular malformations requiring cardiac surgery, splenic anomalies, or both. TRIAL REGISTRY: ClinicalTrials.gov; Nos.: NCT02389049 and NCT00323167; URL: www. CLINICALTRIALS: gov.

A new arthroscopic repair technique for triangular fibrocartilage complex using an intracapsular suture: an outside-in transfer all-inside repair.

BACKGROUND: Arthroscopic repair is a promising, minimally invasive surgical technique for patients with Palmer type 1B peripheral triangular fibrocartilage complex (TFCC) tears. Although several arthroscopic techniques are effective for repairing Palmer type 1B TFCC tears, some shortcomings remain. So, we report an arthroscopic repair technique for the treatment of Palmer type 1B Atzei class 1 TFCC tears using an intracapsular suture: an outside-in transfer all-inside repair. METHODS: A retrospective analysis of 38 Palmer type 1B TFCC injury patients admitted to our hospital were randomly divided into 2 groups. The group A was sutured from the outside to the inside, with a total of 21 cases; the group B was sutured with the new arthroscopic repair technique, with a total of 17 cases. Observe and compare the VAS scores and modified Mayo wrist function scores of all patients before 3, and 6 months after the operation and evaluate the incidence of thread knots in patients with different treatment methods. The methodology was performed an arthroscopic intracapsular suture using an outside-in transfer, all-inside repair technique, which is a modified method of the outside-in and all-inside technique using the needle of a 10-mL sterile syringe, for Palmer type 1B TFCC tears. A No. 2 polydioxanone suture was threaded through the needle and entered the wrist joint. Next, the needle was withdrawn carefully along the suture to the proximal tear ulnar surface of the TFCC and penetrated the TFCC, exiting the articular cavity surface of the ulnar side of the torn TFCC. Finally, arthroscopic knotting was performed. RESULTS: This new treatment was as effective as the previously arthroscopic techniques and had the advantages of no additional incision and decreased risk of operation-related complications. The incidence of thread knots in the group A (28.57%) was significantly higher than that in the group B (0%), and the difference was statistically significant (P = 0.024). There was no significant difference in VAS score and modified Mayo wrist function scores between the two groups (P > 0.05). CONCLUSIONS: The outside-in transfer, the all-inside repair technique is suitable for Palmer type 1B Atzei class 1 TFCC tears. We recommend this technique as a useful alternative to the conventional methods of repairing Palmer type 1B TFCC tears.

Histologic characterization of primary ciliary dyskinesia chronic rhinosinusitis.

KEY POINTS: We present the largest cohort of structured histopathology reports on primary ciliary dyskinesia-related chronic rhinosinusitis (PCD-CRS). Despite endoscopic differences, PCD-CRS and cystic fibrosis-related chronic rhinosinusitis (CF-CRS) had similar structured histopathology reports. Compared to healthy patients and those with idiopathic chronic rhinosinusitis without nasal polyps, patients with PCD-CRS had an increased neutrophil count.

Osteosarcoma Multi-Omics Landscape and Subtypes.

Osteosarcoma (OS) is the most common primary bone malignancy that exhibits remarkable histologic diversity and genetic heterogeneity. The complex nature of osteosarcoma has confounded precise molecular categorization, prognosis, and prediction for this disease. In this study, we performed a comprehensive multiplatform analysis on 86 osteosarcoma tumors, including somatic copy-number alteration, gene expression and methylation, and identified three molecularly distinct and clinically relevant subtypes of osteosarcoma. The subgrouping criteria was validated on another cohort of osteosarcoma tumors. Previously unappreciated osteosarcoma-type-specific changes in specific genes' copy number, expression and methylation were revealed based on the subgrouping. The subgrouping and novel gene signatures provide insights into refining osteosarcoma therapy and relationships to other types of cancer.

Generalizability of machine learning methods in detecting adverse drug events from clinical narratives in electronic medical records.

We assessed the generalizability of machine learning methods using natural language processing (NLP) techniques to detect adverse drug events (ADEs) from clinical narratives in electronic medical records (EMRs). We constructed a new corpus correlating drugs with adverse drug events using 1,394 clinical notes of 47 randomly selected patients who received immune checkpoint inhibitors (ICIs) from 2011 to 2018 at The Ohio State University James Cancer Hospital, annotating 189 drug-ADE relations in single sentences within the medical records. We also used data from Harvard's publicly available 2018 National Clinical Challenge (n2c2), which includes 505 discharge summaries with annotations of 1,355 single-sentence drug-ADE relations. We applied classical machine learning (support vector machine (SVM)), deep learning (convolutional neural network (CNN) and bidirectional long short-term memory (BiLSTM)), and state-of-the-art transformer-based (bidirectional encoder representations from transformers (BERT) and ClinicalBERT) methods trained and tested in the two different corpora and compared performance among them to detect drug-ADE relationships. ClinicalBERT detected drug-ADE relationships better than the other methods when trained using our dataset and tested in n2c2 (ClinicalBERT F-score, 0.78; other methods, F-scores, 0.61-0.73) and when trained using the n2c2 dataset and tested in ours (ClinicalBERT F-score, 0.74; other methods, F-scores, 0.55-0.72). Comparison among several machine learning methods demonstrated the superior performance and, therefore, the greatest generalizability of findings of ClinicalBERT for the detection of drug-ADE relations from clinical narratives in electronic medical records.

Engineered exosomes reprogram Gli1+ cells in vivo to prevent calcification of vascular grafts and autologous pathological vessels.

Calcification of autologous pathological vessels and tissue engineering blood vessels (TEBVs) is a thorny problem in clinic. However, there is no effective and noninvasive treatment that is available against the calcification of TEBVs and autologous pathological vessels. Gli1+ cells are progenitors of smooth muscle cells (SMCs) and can differentiate into osteoblast-like cells, leading to vascular calcification. Our results showed that the spatiotemporal distribution of Gli1+ cells in TEBVs was positively correlated with the degree of TEBV calcification. An anticalcification approach was designed consisting of exosomes derived from mesenchymal stem cells delivering lncRNA-ANCR to construct the engineered exosome-Ancr/E7-EXO. The results showed that Ancr/E7-EXO effectively targeted Gli1+ cells, promoting rapid SMC reconstruction and markedly inhibiting Gli1+ cell differentiation into osteoblast-like cells. Moreover, Ancr/E7-EXO significantly inhibited vascular calcification caused by chronic kidney disease. Therefore, Ancr/E7-EXO reprogrammed Gli1+ cells to prevent calcification of vascular graft and autologous pathological vessel, providing unique insights for an effective anticalcification.

Simplified Rapid Hydration Prevents Contrast-Associated Acute Kidney Injury Among CKD Patients Undergoing Coronary Angiography.

BACKGROUND: Patients with chronic kidney disease (CKD) undergoing coronary angiography (CAG) are at high risk of contrast-associated acute kidney injury (CA-AKI) and mortality. Therefore, there is a clinical need to explore safe, convenient, and effective strategies for preventing CA-AKI. OBJECTIVES: This study sought to assess whether simplified rapid hydration is noninferior to standard hydration for CA-AKI prevention in patients with CKD. METHODS: This multicenter, open-label, randomized controlled study was conducted across 21 teaching hospitals and included 1,002 patients with CKD. Patients were randomized to either simplified hydration (SH) (SH group, with normal saline from 1 hour before to 4 hours after CAG at a rate of 3 mL/kg/h) or standard hydration (control group, with normal saline 12 hours before and 12 hours after CAG at a rate of 1 mL/kg/h). The primary endpoint of CA-AKI was a ≥25% or 0.5-mg/dL rise in serum creatinine from baseline within 48 to 72 hours. RESULTS: CA-AKI occurred in 29 of 466 (6.2%) patients in the SH group and in 38 of 455 (8.4%) patients in the control group (relative risk: 0.8; 95% CI: 0.5-1.2; P = 0.216). In addition, the risk of acute heart failure and 1-year major adverse cardiovascular events did not differ significantly between the groups. However, the median hydration duration was significantly shorter in the SH group than in the control group (6 vs 25 hours; P < 0.001). CONCLUSIONS: In CKD patients undergoing CAG, SH is noninferior to standard hydration in preventing CA-AKI with a shorter hydration duration.

A kinome-wide CRISPR screen identifies CK1α as a target to overcome enzalutamide resistance of prostate cancer.

Enzalutamide (ENZA), a second-generation androgen receptor antagonist, has significantly increased progression-free and overall survival of patients with metastatic prostate cancer (PCa). However, resistance remains a prominent obstacle in treatment. Utilizing a kinome-wide CRISPR-Cas9 knockout screen, we identified casein kinase 1α (CK1α) as a therapeutic target to overcome ENZA resistance. Depletion or pharmacologic inhibition of CK1α enhanced ENZA efficacy in ENZA-resistant cells and patient-derived xenografts. Mechanistically, CK1α phosphorylates the serine residue S1270 and modulates the protein abundance of ataxia telangiectasia mutated (ATM), a primary initiator of DNA double-strand break (DSB)-response signaling, which is compromised in ENZA-resistant cells and patients. Inhibition of CK1α stabilizes ATM, resulting in the restoration of DSB signaling, and thus increases ENZA-induced cell death and growth arrest. Our study details a therapeutic approach for ENZA-resistant PCa and characterizes a particular perspective for the function of CK1α in the regulation of DNA-damage response.

Identification and verification of the temozolomide resistance feature gene DACH1 in gliomas.

Introduction: The most important chemotherapy treatment for glioma patients is temozolomide. However, the development of drug resistance severely restricts the use of temozolomide. Therefore, elucidating the mechanism of temozolomide resistance, enhancing temozolomide sensitivity, and extending patient survival are urgent tasks for researchers. Methods: Temozolomide resistance hub differential genes were identified using differential analysis and protein interaction analysis from the GEO datasets (GSE100736 and GSE113510). These genes were further studied in glioma patients treated with temozolomide in the TCGA and CGGA databases. Patients from the mRNAseq_325 dataset (CGGA) were considered as the training set to construct a risk model for predicting glioma sensitivity to temozolomide, while patients from the mRNAseq_693 dataset (CGGA) and TCGA-GBM dataset were considered as the validation set to evaluate the performance of models. PCR and western blot were performed to determine the difference in expression of the feature gene DACH1 between glioma cells and temozolomide-resistant glioma cells. The alterations in the sensitivity of tumor cells to temozolomide were also observed after DACH1 was silenced. The patients were then divided into two groups based on the expression of DACH1, and the differences in patient survival rates, molecular pathway activation, and level of immune infiltration were compared. Results: Based on four signature genes (AHR, DACH1, MGMT, and YAP1), a risk model for predicting glioma sensitivity to temozolomide was constructed, and the results of timeROC in both the training and validation sets showed that the model had good predictive performance. The expression of the signature gene DACH1 was significantly downregulated in temozolomide-resistant cells, according to the results of the PCR and western blot experiments. The sensitivity of tumor cells to temozolomide was significantly reduced after DACH1 was silenced. DACH1 probably regulates temozolomide resistance in glioblastoma through the transcriptional dysregulation in cancer and ECM. Discussion: This study constructs a risk model that can predict glioma susceptibility to temozolomide and validates the function of the feature gene DACH1, which provides a promising target for the research of temozolomide resistance.

Laterality Defects in Primary Ciliary Dyskinesia: Relationship to Ultrastructural Defect or Genotype.

Rationale: The association between organ laterality abnormalities and ciliary ultrastructural defect or genotype in primary ciliary dyskinesia is poorly understood. Objectives: To determine if there is an association between presence and/or type of laterality abnormality and ciliary ultrastructural defect or genotype. Methods: Participants with primary ciliary dyskinesia in a multicenter, prospective study were grouped based on ciliary ultrastructural defect or genotype. In a retrospective analysis of these data, the association of ciliary ultrastructural defect or genotype and likelihood of a laterality abnormality was evaluated by logistic regression adjusted for presence of two loss-of-function versus one or more not-loss-of-function variants. Results: Of 559 participants, 286 (51.2%), 215 (38.5%), and 58 (10.4%) were identified as having situs solitus, situs inversustotalis, and situs ambiguus, respectively; heterotaxy, defined as situs ambiguus with complex cardiovascular defects, was present in 14 (2.5%). Compared with the group with inner dynein arm defects with microtubular disorganization, laterality defects were more likely in the outer dynein arm defects group (odds ratio [OR], 2.07; 95% confidence interval [CI], 1.21-3.54; P < 0.01) and less likely in the normal/near normal ultrastructure group (OR, 0.04; 95% CI, 0.013-0.151; P < 0.01). Heterotaxy was present in 11 of 242 (4.5%) in the outer dynein arm defects group but 0 of 96 in the inner dynein arm defects with microtubular disorganization group (P = 0.038). Conclusion: In primary ciliary dyskinesia, risk of a laterality abnormality differs by ciliary ultrastructural defect. Pathophysiologic mechanisms underlying these differences require further exploration.

Potential antiplatelet aggregation metabolites from the discarded sorghum (Sorghum bicolor L.) root.

Sorghum (Sorghum bicolor L.) is the fifth largest crop in the world and has potential health benefits, but vast quantities of sorghum roots are discarded after harvest. Based on the previous antiplatelet aggregation for this species, two new multi-substituted 3H-indole alkaloids sorghumine A (1) and sorghumine B (2), together with 14 known compounds (3-16), were found from the water extract of sorghum roots. Compounds 1-2 were identified by analyzing their spectroscopic data and physic and chemical properties, and the absolute configuration was further determined by electronic circular dichroism (ECD) analysis and calculations. 1-2, 4, 6-8 and 13-15 showed significant inhibition of platelet aggregation induced by adenosine diphosphate. 2-4, 6-9 and 11 showed significant inhibition of platelet aggregation induced by collagen. 4-6, 8, 10-11 and 16 showed significant inhibition on platelet aggregation induced by thrombin. Furthermore, molecular docking showed that active compounds can bind to P2Y12 and COX-1 receptors in platelet.

Radiomic-Based MRI for Classification of Solitary Brain Metastases Subtypes From Primary Lymphoma of the Central Nervous System.

BACKGROUND: Differential diagnosis of brain metastases subtype and primary central nervous system lymphoma (PCNSL) is necessary for treatment decisions. The application of machine learning facilitates the classification of brain tumors, but prior investigations into primary lymphoma and brain metastases subtype classification have been limited. PURPOSE: To develop a machine-learning model to classify PCNSL, brain metastases with primary lung and non-lung origin. STUDY TYPE: Retrospective. POPULATION: A total of 211 subjects with pathologically confirmed PCNSL or brain metastases (training cohort 168 and testing cohort 43). FIELD STRENGTH/SEQUENCE: A 3.0 T axial contrast-enhanced T1-weighted spin-echo inversion recovery sequence (T1WI-CE), axial T2-weighted fluid-attenuation inversion recovery sequence (T2FLAIR) ASSESSMENT: Several machine-learning models (support vector machine, random forest, and K-nearest neighbors) were built with least absolute shrinkage and selection operator (LASSO) using features from T1WI-CE, T2FLAIR, and clinical. The model with the highest performance in the training cohort was selected to differentiate lesions in the testing cohort. Then, three radiologists conducted a two-round classification (with and without model reference) using images and clinical information from testing cohorts. STATISTICAL TESTS: Five-fold cross-validation was used for model evaluation and calibration. Model performance was assessed based on sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUC). RESULTS: Twenty-five image features were selected by LASSO analysis. Random forest classifier was selected for its highest performance on the training set with an AUC of 0.73. After calibration, this model achieved an accuracy of 0.70 on the testing set. Accuracies of all three radiologists improved under model reference (0.49 vs. 0.70, 0.60 vs. 0.77, 0.58 vs. 0.72, respectively). DATA CONCLUSION: The random forest model based on conventional MRI and clinical data can diagnose PCNSL and brain metastases subtypes (lung and non-lung origin). Model classification can help foster the diagnostic accuracy of specialists and streamline prognostication workflow. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Gastric Bypass Versus Sleeve Gastrectomy: Comparison of Patient Outcomes, Satisfaction, and Quality of Life in a Single-Center Experience.

Background: Laparoscopic sleeve gastrectomy (LSG) is the most common primary bariatric operation performed in the United States. Its relative technical ease, combined with a decreased risk for anatomic and malabsorptive complications make LSG an attractive option compared to laparoscopic gastric bypass (LGB) for many patients and surgeons. However, emerging evidence for progressive gastroesophageal reflux disease (GERD) after LSG, and the inferior weight loss in many studies, suggests that the enthusiasm for LSG requires reassessment. We hypothesized that patient satisfaction and quality of life (QoL) may be lower after LSG compared to LGB because of these differences. Methods: We distributed a survey querying weight-loss outcomes, complications, foregut symptoms, QoL, and overall satisfaction to patients who underwent bariatric operations at our institution between 2000 and 2020 and who had electronic mail contact information available. Mean follow-up was 2.75 ± 2.41 years for LGB patients and 3.37 ± 2.18 (P = .021) years for LSG patients. We compared these groups for weight-loss outcomes, changes in foregut symptoms, gastrointestinal QoL, postbariatric QoL, and overall satisfaction using appropriate statistical tests. Results: Among 323 respondents, 126 underwent LGB and 197 underwent LSG. LGB patients had larger body mass index (BMI) reduction than LSG patients (-17.16 ± 9.07 kg/m2 versus -14.87 ± 7.4 kg/m2, P = .023). LGB patients reported less reflux (P = .003), with decreased heartburn (P < .0001) and regurgitation (P = .0027). However, a greater proportion of LGB patients reported at least one complication (P = .025). Despite this, more LGB patients reported satisfaction (92.86%) than LSG patients (73.6%). Conclusion: LGB patients are significantly more likely to be satisfied than LSG patients. Factors contributing to the higher level of satisfaction include less GERD and better BMI decrease.

Atorvastatin attenuates ferroptosis-dependent myocardial injury and inflammation following coronary microembolization via the Hif1a/Ptgs2 pathway.

Objectives: Coronary microembolization (CME) represents a serious periprocedural complication after percutaneous coronary intervention. Ferroptosis has been identified in multiple cardiovascular diseases. In this study, we aimed to investigate the effects of atorvastatin (ATV) on ferroptosis and inflammation following CME and elucidate the underlying mechanism. Methods: We established a rat model of CME by injecting microspheres into the left ventricle. Deferoxamine (DFO), a selective ferroptosis inhibitor, or ATV was pretreated before modeling. Cardiac function and cardiac troponin T (cTnT) levels were detected. Levels of ferroptosis-associated genes, malondialdehyde (MDA), glutathione (GSH), and ferrous iron (Fe2+) were measured to validate ferroptosis. Levels of tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1ß) were assayed to determine the inflammation. Chromatin immunoprecipitation was performed to determine the binding of hypoxia-inducible factor 1 subunit alpha (Hif1a) to the promoter of prostaglandin-endoperoxide synthase-2 (Ptgs2). Results: Ferroptosis and inflammation were induced following CME with increased levels of MDA (∼2.5 fold, p < 0.01), Fe2+ (∼1.5 fold, p < 0.01), TNF-α, and IL-1ß and decreased GSH levels (∼42%, p < 0.01). Meanwhile, the level of Ptgs2 was significantly increased, while those of glutathione peroxidase 4 (Gpx4) and solute carrier family 7 member 11 (Slc7a11) were decreased. The level of cTnT was increased by 7-fold (p < 0.01). Left ventricular ejection fraction (LVEF) was significantly reduced (∼85% in the sham group versus ∼45% in the CME group, p < 0.01). DFO or Ptgs2 silencing inhibited the increase of MDA, Ptgs2, TNF-α, and IL-1ß, and induced the levels of GSH and Gpx4, followed by reduction in cTnT levels by approximately 50% (p < 0.01). LVEF was improved by approximately 2 fold (p < 0.01). Mechanistically, the transcription factor Hif1a bound to the promoter of Ptgs2 and upregulated its expression. In addition, ATV inhibited the activation of the Hif1a/Ptgs2 axis and attenuated cardiac ferroptosis and inflammation, thus ameliorating CME-induced myocardial injury (LVEF, ∼34% elevation; cTnT, ∼1.8 fold decrease, p < 0.01). Conclusion: Atorvastatin ameliorates ferroptosis-mediated myocardial injury and inflammation following CME via the Hif1a/Ptgs2 pathway.