Indirubin induces tolerogenic dendritic cells via aryl hydrocarbon receptor activation and ameliorates allergic asthma in a murine model by expanding Foxp3-expressing regulatory T cells.

BACKGROUND: Allergic asthma is a chronic bronchial inflammatory disease closely associated with abnormal immune responses of dendritic cells (DCs) and allergen-specific type 2 T helper (Th2) cells. Indirubin (IR), a natural aryl hydrocarbon receptor (AhR) ligand, exerts anti-inflammatory and immunomodulatory properties. PURPOSE: In this study, we aimed to clarify whether IR exhibits immunomodulatory action on DCs via AhR activation and investigated the antiallergic effects of IR in a mouse model of allergic asthma. METHODS: Lipopolysaccharide (LPS)-activated bone marrow-derived DCs were treated with IR. Their mRNA expressions, cytokine production, and phenotype patterns were determined by a quantitative real-time PCR, ELISA, flow cytometry, and RNA sequencing. The mixed lymphocyte reaction was utilized to evaluate the regulatory function of IR-treated DCs on T-cell differentiation. Moreover, mice with ovalbumin (OVA)-induced allergic asthma were treated with IR. Thereafter, the airway hyperresponsiveness (AHR), allergen-specific IgE production, cytokine levels, airway inflammation, and T-cell responses were evaluated. RESULTS: Treatment of LPS-stimulated DCs with 20 µM IR significantly reduced IL-12 and TNF-α production while increasing IL-10 secretion. Meanwhile, these DCs expressed decreased levels of CD80 but increased levels of Jagged 1 surface molecules. However, the effects of IR on DCs were reversed by pretreatment with the AhR antagonist, CH223191. Additionally, the coculture of these tolerogenic-like DCs with allogeneic CD4+T cells promoted the generation of Foxp3+ regulatory T (Treg) cells. A transcriptomic analysis identified several downregulated genes that are involved in regulating cell migration, cytokine secretion, and inflammatory responses in DCs after IR treatment. In an asthmatic murine model, oral administration of 25 mg kg-1 body weight of IR efficiently alleviated the development of AHR, OVA-specific IgE production, and levels of Th2-type cytokines (IL-4, IL-5, and IL-13) and the CCL11 chemokine. IR treatment also attenuated inflammatory cell recruitment and mucus production in the lungs. Notably, an enhanced frequency of Foxp3+ Treg cells and reduced effector T-cell proliferation associated with increased levels of IL-10 and TGF-ß were observed in IR-treated mice. CONCLUSION: IR can induce tolerogenic-like BMDCs which promote the differentiation of Treg cells. Importantly, the expansion of Foxp3+ Treg cells contributed to the therapeutic efficacy of IR against allergic asthma.

A simple model to predict early recurrence of hepatocellular carcinoma after liver resection.

PURPOSE: Multiple studies have reported models for predicting early recurrence of hepatocellular carcinoma (HCC) after liver resection (LR). However, these models are too complex to use in daily practice. We aimed to develop a simple model. METHOD: We enrolled 1133 patients with newly diagnosed HCC undergoing LR. The Kaplan - Meier method and log-rank test were used for survival analysis and Cox proportional hazards analysis to identify prognostic factors associated with early recurrence (i.e., recurrence within two years after LR). RESULTS: Early recurrence was identified in 403 (35.1%) patients. In multivariate analysis, alpha-fetoprotein (AFP) 20-399 vs. < 20 ng/ml (HR = 1.282 [95% confidence interval = 1.002-1.639]; p = 0.048); AFP ≥ 400 vs. < 20 ng/ml (HR = 1.755 [1.382-2.229]; p < 0.001); 7th edition American Joint Committee on Cancer (AJCC) stage 2 vs. 1 (HR = 1.958 [1.505-2.547]; p < 0.001); AJCC stage 3 vs. 1 (HR = 4.099 [3.043-5.520]; p < 0.001); and pathology-defined cirrhosis (HR = 1.46 [1.200-1.775]; p < 0.001) were associated with early recurrence. We constructed a predictive model with these variables, which provided three risk strata for recurrence-free survival (RFS): low risk, intermediate risk, and high risk, with two-year RFS of 79%, 57%, and 35%, respectively (p < 0.001). CONCLUSION: We developed a simple model to predict early recurrence risk for patients undergoing LR for HCC.

Evaluation of Tibial Slope on Radiographs in Pediatric Patients With Tibial Spine Fractures: An Age- and Sex-Matched Study.

Background: A recent study has reported that the radiographic measurement of posterior tibial slope (PTS) is larger in male pediatric patients with tibial spine fractures (TSF) than in controls. However, they found no difference in PTS between female patients and controls. Purpose: (1) To identify whether PTS is larger in female pediatric patients with TSF than in female controls and (2) to validate the relationship between PTS and pediatric TSF in male patients. Study Design: Cross-sectional study; Level of evidence, 3. Methods: After an a priori power analysis, 84 pediatric patients with TSF (50 female patients and 34 male patients) and 84 age- and sex-matched controls were enrolled in this study. Demographic information, including sex, age, and race, was recorded. Skeletal maturity was determined based on the stage of epiphyseal union on knee radiographs. PTS was defined as the angle between a line perpendicular to the longitudinal axis of the tibia and the posterior inclination of the medial tibial plateau on standard knee lateral radiographs. Results: The mean age when the TSF occurred was 11.2 ± 2.7 years for female patients and 12.9 ± 2.5 years for male patients. There was no significant difference in skeletal maturity between female patients and female controls or between male patients and male controls. The mean PTS was not significantly different between female patients (8.8°± 2.8°) and female controls (8.3°± 3.1°) (P = .366) or between male patients (9.0°± 2.8°) and male controls (9.3°± 2.6°) (P = .675). Those with a PTS >1 SD (2.9°) above the mean (8.8°) had no greater odds (1.0 [95% CI, 0.4-2.5]; P≥ .999) of having a TSF than others. Conclusion: PTS was not found to be a risk factor for pediatric TSF in female or male patients in this study.

Perioperative alpha blockers in voiding dysfunction secondary to prostate biopsy: A meta-analysis.

Introduction and Objectives: Voiding dysfunction remains a common side effect postprostate biopsy leading to significant morbidity. Alpha blockers have emerged as a potential therapeutic option to mitigate this risk, with various centres already incorporating its use in practice. Despite this, the literature regarding its efficacy remains inconclusive. Hence, a systematic review was performed to quantify the effect of perioperative alpha blockers on prostate biopsy-related voiding function. Methods: A systematic search in MEDLINE, Embase and PubMed between January 1989 and July 2023 was performed to identify relevant articles. Two independent reviewers independently screened abstracts, full texts and performed data extraction. Data including International Prostate Symptom Scores (IPSS), voiding flow rates (Qmax), postvoid residuals (PVR), rates of acute urinary retention (AUR) and quality of life (QoL) scores were extracted. Results were combined in an inverse variance random effects meta-analysis. Results: A total 808 patients from six randomised controlled trials (RCTs) comparing alpha blockers to controls were included. All articles excluded patients with pre-existing voiding dysfunction. Pooled outcomes demonstrated statistically significant differences favouring alpha blocker usage in all objective and subjective measures including IPSS (mean difference 4.21, 95% confidence interval [CI] 2.58-5.84, p < 0.00001), PVR (mean difference 20.41 mL, 95% CI 3.44-37.39, p = 0.02), Qmax (mean difference 3.07 mL/s, 95% CI 2.55-3.59, p < 0.00001), QoL (weighted-mean difference 0.82, CI 0.17-1.48, p = 0.01) as well as overall risk of AUR (odds ratio 0.22, CI 0.09-0.55, p = 0.001). There was variable heterogeneity (I 2 = 0-86%) between outcomes. Conclusions: This review highlights the potential role of alpha blockers in improving urinary function and reducing adverse voiding outcomes postprostate biopsy. The standard practice of incorporating the usage of perioperative alpha blockers may be considered to reduce the morbidity of voiding complications secondary to prostate biopsy.

A Recess Is Observed Between the Posterior Knee Capsule and the Meniscotibial Ligament Complex in Pediatric Specimens.

Purpose: To define the surgical anatomy of the meniscotibial ligament complex of the pediatric medial and lateral menisci and their relation to the proximal tibial physis and posterior joint capsule. Methods: Fourteen pediatric cadaveric knee specimens (aged 3 months to 11 years) were dissected to clarify the relation of the posterior knee capsule, the meniscus, and the meniscotibial ligament complex. Metallic markers were placed marking the meniscotibial ligament capsular attachment on the proximal tibia. Specimens underwent computed tomography scanning to evaluate pin placement and relation to the physis. A digital measurement tool was used to measure the distances between the proximal tibial physis and the pins (placed at 5 points on both the lateral and medial menisci). Results: In each specimen, clear separation was noted between the posterior joint capsule from the meniscus and meniscotibial ligament complex in the medial and lateral compartments. There was an increase in the distance between the proximal tibial physis and the insertion points of the meniscotibial ligament complex with increasing specimen age. For both the medical and lateral menisci in group 1, the median meniscotibial ligament insertion points were often less than 7 mm (interquartile range, 0.00-7.8 mm) away from the physis. The median meniscotibial ligament insertion points in group 2 tended to be farther from the physis but always less than 20 mm (interquartile range, 2.5-17.5 mm)-and as close as less than 5 mm (lateral posterior root). Conclusions: In this anatomic study of pediatric knees, we observed a distinct recess/cul-de-sac space between the posterior knee capsule and meniscal attachments in all specimens. This defines a distinct plane between the posterior knee capsule and the meniscotibial ligament complex, with a distance between the physis and meniscotibial ligament capsular attachments that increases with age. Clinical Relevance: The anatomic parameters evaluated in our study should be considered as future meniscal repair and transplantation techniques aim to restore the meniscal anatomy, stability, and mobility provided by the meniscotibial ligament complex and capsule structures.

Effect of Age and Sex on Anterior Cruciate Ligament Functional Tests Approximately 6 Months After Anterior Cruciate Ligament Reconstruction.

Purpose: To examine age- and sex-related differences in postoperative functional outcomes at approximately 6 months after anterior cruciate ligament reconstruction (ACLR). Methods: In this study, patients who underwent primary ACLR performed a series of return-to-sport functional tests at 5 to 8 months after surgery. Functional tests included strength tests (knee extensors, knee flexors, hip abductors, and hip extensors), a balance test (Y-balance composite score), and hop tests (single, triple, crossover, and 6-m timed hop tests). Limb symmetry was calculated to compare the reconstructed limb with the uninvolved limb. A 2-way multivariate analysis of covariance was used, and effect size was calculated for data analysis. Results: A total of 176 subjects were included in this study. There were no significant interaction between age and sex on return-to-sport functional tests after ACLR. Also, no main effects of age and sex on return-to-sport functional tests were found in our data. Conclusions: Age and sex do not significantly affect functional test performance after ACLR 6 months postoperatively. Level of Evidence: Level III, retrospective review of prospective cohort study.

Advancements in electrochemical biosensing of cardiovascular disease biomarkers.

Cardiovascular diseases (CVDs) stand as a predominant global health concern, introducing vast socioeconomic challenges. In addressing this pressing dilemma, enhanced diagnostic modalities have become paramount, positioning electrochemical biosensing as an instrumental innovation. This comprehensive review navigates the multifaceted terrain of CVDs, elucidating their defining characteristics, clinical manifestations, therapeutic avenues, and intrinsic risk factors. Notable emphasis is placed on pivotal diagnostic tools, spotlighting cardiac biomarkers distinguished by their unmatched clinical precision in terms of relevance, sensitivity, and specificity. Highlighting the broader repercussions of CVDs, there emerges an accentuated need for refined diagnostic strategies. Such an exploration segues into a profound analysis of electrochemical biosensing, encapsulating its foundational principles, diverse classifications, and integral components, notably recognition molecules and transducers. Contemporary advancements in biosensing technologies are brought to the fore, emphasizing pioneering electrode architectures, cutting-edge signal amplification processes, and the synergistic integration of biosensors with microfluidic platforms. At the core of this discourse is the demonstrated proficiency of biosensors in detecting cardiovascular anomalies, underpinned by empirical case studies, systematic evaluations, and clinical insights. As the narrative unfolds, it addresses an array of inherent challenges, spanning intricate technicalities, real-world applicability constraints, and regulatory considerations, finally, by casting an anticipatory gaze upon the future of electrochemical biosensing, heralding a new era of diagnostic tools primed to revolutionize cardiovascular healthcare.

Deciphering the Transcription Factor Landscape in Neuroendocrine Prostate Cancer Progression: A Novel Approach to Understand NE Transdifferentiation.

Background and Objective: Prostate cancer (PCa) is a leading cause of cancer mortality in men, with neuroendocrine prostate cancer (NEPC) representing a particularly resistant subtype. The role of transcription factors (TFs) in the progression from prostatic adenocarcinoma (PRAD) to NEPC is poorly understood. This study aims to identify and analyze lineage-specific TF profiles in PRAD and NEPC and illustrate their dynamic shifts during NE transdifferentiation. Methods: A novel algorithmic approach was developed to evaluate the weighted expression of TFs within patient samples, enabling a nuanced understanding of TF landscapes in PCa progression and TF dynamic shifts during NE transdifferentiation. Results: unveiled TF profiles for PRAD and NEPC, identifying 126 shared TFs, 46 adenocarcinoma-TFs, and 56 NEPC-TFs. Enrichment analysis across multiple clinical cohorts confirmed the lineage specificity and clinical relevance of these lineage-TFs signatures. Functional analysis revealed that lineage-TFs are implicated in pathways critical to cell development, differentiation, and lineage determination. Novel lineage-TF candidates were identified, offering potential targets for therapeutic intervention. Furthermore, our longitudinal study on NE transdifferentiation highlighted dynamic TF expression shifts and delineated a three-phase hypothesis for the process comprised of de-differentiation, dormancy, and re-differentiation. and proposing novel insights into the mechanisms of PCa progression. Conclusion: The lineage-specific TF profiles in PRAD and NEPC reveal a dynamic shift in the TF landscape during PCa progression, highlighting three distinct phases of NE transdifferentiation.

A preoperative model to predict overall survival in patients with hepatoma undergoing resection.

BACKGROUND: We aimed to develop a preoperative model to predict overall survival (OS) in patients with hepatoma undergoing liver resection (LR). METHODS: Patients who underwent LR for Barcelona Clinic Liver Cancer (BCLC) stage 0, A, or B hepatoma were enrolled. Tumor burden score (TBS) scores were determined using the following equation: TBS (Pinna et al., 2018) 2 = (largest tumor size [in cm])(Pinna et al., 2018) 2 â€‹+ â€‹(tumor number) (Pinna et al., 2018) 22. The cutoff values for radiographic TBS were based on our recently published paper: low, <2.6; medium, 2.6-7.9; high, >7.9. RESULTS: Multivariate analysis showed that radiographic TBS (low: referent; medium: HR â€‹= â€‹2.89; 95 â€‹% CI: 1.60-5.21; p â€‹< â€‹0.001; high, HR â€‹= â€‹7.60; 95 â€‹% CI: 3.80-15.2; p â€‹< â€‹0.001), AFP (<400 â€‹ng/mL: referent; ≧400 â€‹ng/mL: HR â€‹= â€‹1.67, 95 â€‹% CI: 1.11-2.52, p â€‹= â€‹0.014), and cirrhosis (absence: referent; presence: HR â€‹= â€‹1.88, 95 â€‹% CI: 1.30-2.72, p â€‹< â€‹0.001) were associated with OS. A simplified risk score was superior to BCLC system in concordance index (0.688 vs. 0.623). CONCLUSIONS: We have developed a preoperative model that performs better in predicting OS than the BCLC system.

Vocal convergence and social proximity shape the calls of the most basal Passeriformes, New Zealand Wrens.

Despite extensive research on avian vocal learning, we still lack a general understanding of how and when this ability evolved in birds. As the closest living relatives of the earliest Passeriformes, the New Zealand wrens (Acanthisitti) hold a key phylogenetic position for furthering our understanding of the evolution of vocal learning because they share a common ancestor with two vocal learners: oscines and parrots. However, the vocal learning abilities of New Zealand wrens remain unexplored. Here, we test for the presence of prerequisite behaviors for vocal learning in one of the two extant species of New Zealand wrens, the rifleman (Acanthisitta chloris). We detect the presence of unique individual vocal signatures and show how these signatures are shaped by social proximity, as demonstrated by group vocal signatures and strong acoustic similarities among distantly related individuals in close social proximity. Further, we reveal that rifleman calls share similar phenotypic variance ratios to those previously reported in the learned vocalizations of the zebra finch, Taeniopygia guttata. Together these findings provide strong evidence that riflemen vocally converge, and though the mechanism still remains to be determined, they may also suggest that this vocal convergence is the result of rudimentary vocal learning abilities.

CD47-mediated immune evasion in early-stage lung cancer progression.

Alveolar and interstitial macrophages play crucial roles in eradicating pathogens and transformed cells in the lungs. The immune checkpoint CD47, found on normal and malignant cells, interacts with the SIRPα ligand on macrophages, inhibiting phagocytosis, antigen presentation, and promoting immune evasion. In this study, we demonstrated that CD47 is not only a transmembrane protein, but that it is also highly concentrated in extracellular vesicles from lung cancer cell lines and patient plasma. Abundant CD47 was observed in the cytoplasm of lung cancer cells, aligning with our finding that it was packed into extracellular vesicles for physiological and pathological functions. In our clinical cohort, extracellular vesicle CD47 was significantly higher in the patients with early-stage lung cancer, emphasizing innate immunity inactivation in early tumor progression. To validate our hypothesis, we established an orthotopic xenograft model mimicking lung cancer development, which showed increased serum soluble CD47 and elevated IL-10/TNF-α ratio, indicating an immune-suppressive tumor microenvironment. CD47 expression led to reduced tumor-infiltrating macrophages during progression, while there was a post-xenograft increase in tumor-associated macrophages. In conclusion, CD47 is pivotal in early lung cancer progression, with soluble CD47 emerging as a key pathological effector.

Osseous and Cartilaginous Trochlear Development in the Pediatric Knee: A Cadaveric Computed Tomography Study.

Background: The anatomy of the trochlea plays a significant role in patellar stability. The developmental anatomy of the trochlea and its relationship to patellar stability remains poorly understood. Purpose: To describe the developmental changes of the osseous and cartilaginous trochlear morphology in skeletally immature specimens. Study Design: Descriptive laboratory study. Methods: A total of 65 skeletally immature cadaveric knees between the ages of 2 months and 11 years were evaluated using computed tomography scans. The measurements in the axial plane of both cartilage and bone include medial, central, and lateral trochlear height; sulcus height; medial and later trochlear facet length; trochlear sulcus angle; patellar sulcus angle; condylar height asymmetry; and trochlear facet asymmetry. Additional measurements included trochlear depth and lateral trochlear inclination angle. In the sagittal plane, measurements included curvilinear trochlear length, direct trochlear length, condylar height, and patellar sulcus angle. Results: Analysis of trochlear morphology using condylar height, condylar height asymmetry, and trochlear depth all increased with increasing age. The osseous and cartilaginous sulcus angles became deeper with age until age 8 and then plateaued. This corresponded with an increase in trochlear depth that also plateaued around age 8. Osseous condylar asymmetry increased with age but flipped from a larger medial condyle to a larger lateral condyle around age 8. The continued growth of the trochlea with age was further demonstrated in all measures in the sagittal view. Conclusion: This cadaveric analysis demonstrated that there is an increase in condylar height as age increased by all measurements analyzed. These changes in condylar height continued to be seen through age 11, suggesting a still-developing trochlea past this age. By age 8, a plateau in sulcus angle, and sulcus depth suggests more proportionate growth after this point. Similar changes in trochlear and patellar shape with age suggests that the 2 structures may affect each other during development. Clinical Relevance: This information can help design, develop, and determine timing of procedures that may alter the anatomy and stabilize the trochlear and patellofemoral joint.

Patients undergoing liver resection for non-alcoholic fatty liver disease-related hepatocellular carcinoma and those for viral hepatitis-related hepatocellular carcinoma have similar survival outcomes.

Numerous studies have compared outcomes of liver resection (LR) of patients with non-alcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC) to those of patients with non-NAFLD-related HCC. However, results have been inconsistent. We aim to clarify this issue. We enrolled 801 patients with hepatitis B virus (HBV)-related HCC, 433 patients with hepatitis C virus (HCV)-related HCC, and 128 patients with NAFLD-related HCC undergoing LR. Overall survival (OS) and disease-free survival (DFS) of patients with different etiologies of chronic liver disease was compared using the Kaplan-Meier estimator and log-rank test after propensity score matching (PSM). After PSM, 83 patients remained in each group. The groups did not differ significantly in age, sex, the proportion of patients with pathological American Joint Committee on Cancer stage 1, tumor size > 50 mm, receipt of major resection, alpha-fetoprotein (AFP) ≥ 20 ng/ml, presence of cirrhosis, model for end-stage liver disease (MELD) score, and American Society of Anesthesiologists (ASA) classification. The five-year OS of patients with HBV-, HCV-, and NAFLD-related HCC was 78%, 75%, and 78%, respectively (p = 0.789). The five-year DFS of the HBV, HCV, and NAFLD groups was 60%, 45%, and 54%, respectively (p = 0.159). Perioperative morbidity was noted in 17 (20.5%) in the HBV group, 22 (26.5%) in the HCV group, and 15 (18.1%) in the NAFLD group (p = 0.398). The five-year OS, DFS, and perioperative morbidity of patients undergoing LR for NAFLD-related HCC and those for viral hepatitis-related HCC was similar.

Smoking as a Risk Factor for Very Late Recurrence in Surgically Resected Early-Stage Primary Hepatocellular Carcinoma.

Background: The risk of first recurrence of hepatocellular carcinoma (HCC) within years 5 to 10 after curative hepatectomy remains unknown. We aimed to assess the incidence and prognostic factors for very late recurrence among patients who achieved 5 years' recurrence-free survival (RFS) after primary resection. Methods: We retrospectively analyzed 337 patients with early-stage HCC underwent primary tumor resection and achieved more than 5 years' RFS. Results: A total of 77 patients (22.8%) developed very late recurrence. The cumulative very late recurrence rate increased from 6.9% and 11.7% to 16.6% at 6, 7, and 8 years, respectively. Patients stopped smoking had a higher rate of very late RFS. Conclusions: The high rates of very late recurrence in HCC indicate that patients warrant continued surveillance, even after 5 recurrence-free years. Moreover, smoking is a risk factor for very late HCC recurrence, and quitting smoking may reduce the risk of very late recurrence.

Prevalence and Predictors of Concomitant Meniscal Surgery During Pediatric and Adolescent ACL Reconstruction: Analysis of 4729 Patients Over 20 Years at a Tertiary-Care Regional Children's Hospital.

Background: The rate of concomitant meniscal procedures performed in conjunction with anterior cruciate ligament (ACL) reconstruction is increasing. Few studies have examined these procedures in high-risk pediatric cohorts. Hypotheses: That (1) the rates of meniscal repair compared with meniscectomy would increase throughout the study period and (2) patient-related factors would be able to predict the type of meniscal operation, which would differ according to age. Study Design: Cohort study (prevalence); Level of evidence, 2. Methods: Natural language processing was used to extract clinical variables from notes of patients who underwent ACL reconstruction between 2000 and 2020 at a single institution. Patients were stratified to pediatric (5-13 years) and adolescent (14-19 years) cohorts. Linear regression was used to evaluate changes in the prevalence of concomitant meniscal surgery during the study period. Logistic regression was used to determine predictors of the need for and type of meniscal procedure. Results: Of 4729 patients (mean age, 16 ± 2 years; 54.7% female) identified, 2458 patients (52%) underwent concomitant meniscal procedures (55% repair rate). The prevalence of lateral meniscal (LM) procedures increased in both pediatric and adolescent cohorts, whereas the prevalence of medial meniscal (MM) repair increased in the adolescent cohort (P = .02). In the adolescent cohort, older age was predictive of concomitant medial meniscectomy (P = .031). In the pediatric cohort, female sex was predictive of concomitant MM surgery and of undergoing lateral meniscectomy versus repair (P≤ .029). Female sex was associated with decreased odds of concomitant LM surgery in both cohorts (P≤ .018). Revision ACLR was predictive of concomitant MM surgery and of meniscectomy (medial and lateral) in the adolescent cohort (P < .001). Higher body mass index was associated with increased odds of undergoing medial meniscectomy versus repair in the pediatric cohort (P = .03). Conclusion: More than half of the young patients who underwent ACLR had meniscal pathology warranting surgical intervention. The prevalence of MM repair compared with meniscectomy in adolescents increased throughout the study period. Patients who underwent revision ACLR were more likely to undergo concomitant meniscal surgeries, which were more often meniscectomy. Female sex had mixed effects in both the pediatric and adolescent cohorts.

Knee Flexion Angle of Fixation During Anterolateral Ligament Reconstruction or Lateral Extra-articular Tenodesis: A Systematic Review and Meta-analysis of Lateral Extra-articular Reinforcement Techniques Performed in Conjunction With ACL Reconstruction.

Background: Anterolateral ligament reconstruction (ALLR) or lateral extra-articular tenodesis (LET) is being used more frequently in conjunction with anterior cruciate ligament reconstruction (ACLR). However, the knee flexion angle at which fixation of ALLR or LET is performed during the procedure is quite variable based on existing technique descriptions. Purpose/Hypothesis: The purpose of this study was to identify whether flexion angle at the time of ALLR/LET fixation affected postoperative outcomes in a clinical population. It was hypothesized that ALLR/LET fixation at low versus high flexion angles would lead to no statistically significant differences in patient-reported outcome measures and graft failure rates. Study Design: Systematic review; Level of evidence, 4. Methods: The PubMed, Embase, and Cochrane Library databases were searched according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to identify published clinical studies of ACLR with ALLR/LET in which the knee flexion angle at the time of ALLR/LET was reported. A priori, low flexion was defined as 0° to 30°, and high flexion was defined as 60° to 90°. Studies were excluded if the flexion angle was between 31° and 59° because these angles constituted neither low nor high flexion angles and including them in an analysis of high versus low flexion angle at fixation would have biased the study results toward the null. The overall risk of bias was assessed using the Newcastle-Ottawa Scale. The pooled results of the studies were analyzed using the International Knee Documentation Committee (IKDC), Lysholm, and Tegner scores, along with reported graft failure rates. Results: A total of 32 clinical studies (5230 patients) met inclusion criteria: 22 studies (1999 patients) in the low-flexion group and 10 studies (3231 patients) in the high-flexion group. The median Newcastle-Ottawa Scale score was 6. Comparisons of patients with a low flexion angle versus a high flexion angle demonstrated no differences in the IKDC (P = .84), Lysholm (P = .67), or Tegner (P = .44) scores or in graft failure (3.4% vs 4.1%, respectively; P = .69). Conclusion: The results of this review indicated that ACLR performed in conjunction with ALLR/LET provides good to excellent patient-reported outcomes and low graft failure rates when ALLR/LET fixation is performed in either low or high knee flexion.

Hepatitis B virus-related hepatocellular carcinoma has superior overall survival compared with other etiologies.

BACKGROUND: Whether the etiology of chronic liver disease (CLD) impacts the overall survival (OS) of patients with hepatocellular carcinoma (HCC) remains unclear. We aim to clarify this issue. MATERIALS AND METHODS: Between 2011 and 2020, 3941 patients who were newly diagnosed with HCC at our institution were enrolled in this study. In patients with multiple CLD etiologies, etiology was classified using the following hierarchy: hepatitis C virus (HCV) > hepatitis B virus (HBV) > alcohol-related > all negative. All negative was defined as negative for HCV, HBV, and alcohol use disorder. RESULTS: Among 3941 patients, 1407 patients were classified with HCV-related HCC, 1677 patients had HBV-related HCC, 145 patients had alcohol-related HCC, and 712 patients had all-negative HCC. Using the all-negative group as the reference group, multivariate analysis showed that HBV is an independent predictor of mortality (hazard ratio: 0.856; 95% confidence interval: 0.745-0.983; p = 0.027). Patients with HBV-related HCC had superior OS compared with patients with other CLD etiologies (p<0.001). Subgroup analyses were performed, for Barcelona Clinic Liver Cancer (BCLC) stages 0-A (p<0.001); serum alpha-fetoprotein (AFP) levels≧20 ng/ml (p<0.001); AFP levels < 20 ng/ml (p<0.001); age > 65 years (p<0.001); and the use of curative treatments (p = 0.002). No significant difference in OS between HBV and other etiologies was observed among patients aged ≤ 65 years (p = 0.304); with BCLC stages B-D (p = 0.973); or who underwent non-curative treatments (p = 0.1). CONCLUSION: Patients with HBV-related HCC had superior OS than patients with other HCC etiologies.

Giant X-Ray Circular Dichroism in a Time-Reversal Invariant Antiferromagnet.

X-ray circular dichroism, arising from the contrast in X-ray absorption between opposite photon helicities, serves as a spectroscopic tool to measure the magnetization of ferromagnetic materials and identify the handedness of chiral crystals. Antiferromagnets with crystallographic chirality typically lack X-ray magnetic circular dichroism because of time-reversal symmetry, yet exhibit weak X-ray natural circular dichroism. Here, the observation of giant natural circular dichroism in the Ni L3-edge X-ray absorption of Ni3TeO6 is reported, a polar and chiral antiferromagnet with effective time-reversal symmetry. To unravel this intriguing phenomenon, a phenomenological model is proposed that classifies the movement of photons in a chiral crystal within the same symmetry class as that of a magnetic field. The coupling of X-ray polarization with the induced magnetization yields giant X-ray natural circular dichroism, revealing typical ferromagnetic behaviors allowed by the symmetry in an antiferromagnet, i.e., the altermagnetism of Ni3TeO6. The findings provide evidence for the interplay between magnetism and crystal chirality in natural optical activity. Additionally, the first example of a new class of magnetic materials exhibiting circular dichroism is established with time-reversal symmetry.

Phenotype prediction from single-cell RNA-seq data using attention-based neural networks.

MOTIVATION: A patient's disease phenotype can be driven and determined by specific groups of cells whose marker genes are either unknown or can only be detected at late-stage using conventional bulk assays such as RNA-Seq technology. Recent advances in single-cell RNA sequencing (scRNA-seq) enable gene expression profiling in cell-level resolution, and therefore have the potential to identify those cells driving the disease phenotype even while the number of these cells is small. However, most existing methods rely heavily on accurate cell type detection, and the number of available annotated samples is usually too small for training deep learning predictive models. RESULTS: Here, we propose the method ScRAT for phenotype prediction using scRNA-seq data. To train ScRAT with a limited number of samples of different phenotypes, such as coronavirus disease (COVID) and non-COVID, ScRAT first applies a mixup module to increase the number of training samples. A multi-head attention mechanism is employed to learn the most informative cells for each phenotype without relying on a given cell type annotation. Using three public COVID datasets, we show that ScRAT outperforms other phenotype prediction methods. The performance edge of ScRAT over its competitors increases as the number of training samples decreases, indicating the efficacy of our sample mixup. Critical cell types detected based on high-attention cells also support novel findings in the original papers and the recent literature. This suggests that ScRAT overcomes the challenge of missing marker genes and limited sample number with great potential revealing novel molecular mechanisms and/or therapies. AVAILABILITY AND IMPLEMENTATION: The code of our proposed method ScRAT is published at https://github.com/yuzhenmao/ScRAT.

Therapeutic Decision Making in Prevascular Mediastinal Tumors Using CT Radiomics and Clinical Features: Upfront Surgery or Pretreatment Needle Biopsy?

The study aimed to develop machine learning (ML) classification models for differentiating patients who needed direct surgery from patients who needed core needle biopsy among patients with prevascular mediastinal tumor (PMT). Patients with PMT who received a contrast-enhanced computed tomography (CECT) scan and initial management for PMT between January 2010 and December 2020 were included in this retrospective study. Fourteen ML algorithms were used to construct candidate classification models via the voting ensemble approach, based on preoperative clinical data and radiomic features extracted from the CECT. The classification accuracy of clinical diagnosis was 86.1%. The first ensemble learning model was built by randomly choosing seven ML models from a set of fourteen ML models and had a classification accuracy of 88.0% (95% CI = 85.8 to 90.3%). The second ensemble learning model was the combination of five ML models, including NeuralNetFastAI, NeuralNetTorch, RandomForest with Entropy, RandomForest with Gini, and XGBoost, and had a classification accuracy of 90.4% (95% CI = 87.9 to 93.0%), which significantly outperformed clinical diagnosis (p < 0.05). Due to the superior performance, the voting ensemble learning clinical-radiomic classification model may be used as a clinical decision support system to facilitate the selection of the initial management of PMT.