Index Of Infiltration Research Articles

Pancancer analysis of the interactions between CTNNB1 and infiltrating immune cell populations.

Recently, evidence has indicated that CTNNB1 is important in a variety of malignancies. However, how CTNNB1 interacts with immune cell infiltration remains to be further investigated. In this study, we focused on the correlations between CTNNB1 and tumorigenesis, tumor progression, mutation, phosphorylation, and prognosis via gene expression profiling interaction analysis; TIMER 2.0, cBioPortal, GTEx, CPTAC, and GEPIA2 database analyses; and R software. CTNNB1 mutations are most found in uterine endometrioid carcinoma and hepatocellular carcinoma. However, no CTNNB1 mutations were found to be associated with a poor prognosis. In addition, CTNNB1 DNA methylation levels were higher in normal tissues than in tumor tissues in cancer except for breast invasive carcinoma, which had higher methylation levels in tumor tissues. The phosphorylation level of the S675 and S191 sites of CTNNB1 was greater in the primary tumor tissues in the clear cell renal cell carcinoma, liver hepatocellular carcinoma, lung adenocarcinoma, pancreatic adenocarcinoma, and breast cancer datasets but not in the glioblastoma multiform dataset. As for, with respect to immune infiltration, CD8 + T-cell infiltration was negatively correlated with the expression of CTNNB1 in thymoma and uterine corpus endometrial carcinoma. The CTNNB1 level was found to be positively associated with the infiltration index of the corresponding fibroblasts in the TCGA tumors of colon adenocarcinoma, human papillomavirus-negative head and neck squamous cell carcinoma, mesothelioma, testicular germ cell tumor, and thymoma. We also identified the top CTNNB1-correlated genes in the TCGA projects and analyzed the expression correlation between CTNNB1 and selected target genes, including PPP4R2, RHOA, and SPRED1. Additionally, pathway enrichment suggested that NUMB is involved in the Wnt pathway. This study highlights the predictive role of CTNNB1 across cancers, suggesting that CTNNB1 might serve as a potential biomarker for the diagnosis and prognosis evaluation of various malignant tumors.

Sex differences in mortality among patients with lupus nephritis

ObjectiveTo evaluate the prognostic importance of sex in lupus nephritis (LN).MethodsA retrospective cohort of 1048 biopsy-confirmed LN patients, diagnosed between January 1, 1996, and December 31, 2018, was analyzed. Demographics, clinical characteristics, laboratory findings, and renal pathology were assessed. The primary outcome was mortality, and the secondary outcomes included doubling of serum creatinine and end-stage renal disease (ESRD). Sex-associated risks were evaluated using Cox regression models.ResultsAmong the1048 patients, 178 (17%) were male and 870 (83%) were female. Male patients exhibited more aggressive features: higher blood pressure, earlier disease onset, and elevated levels of serum creatinine (Scr), uric acid, blood urea nitrogen. Intriguingly, male patients also displayed more severe histopathological alterations, such as more total crescents, cellular crescents formations, higher level of glomerular leukocyte infiltration and Activity Index (AI), even when overall renal pathology was comparable between sexes. During a median follow-up of 112 months, mortality was registered in 141 patients (15.3%). Mortality rates were conspicuously higher in males (24.2% males vs. 13.4% females, p = 0.0029). Secondary outcomes did not show significant sex differences. Cox regression analysis highlighted male, age of renal biopsy, eGFR, and Chronicity Index (CI) as independent risk factors for survival in LN patients. Notably, infections emerged as the leading cause of mortality among LN patients, with a significant higher rate in male patients.ConclusionIn our cohort with LN, there was a higher rate of all-cause mortality and proportion of infection-related death in male. Recognizing and further exploring these sex disparities is crucial for optimized LN patients care.Graphical

Predictive models for cholesterol crystals and plaque vulnerability in acute myocardial infarction: Insights from an optical coherence tomography study

BackgroundCholesterol crystals (CCs) are recognized as a risk factor for vulnerable atherosclerotic plaque rupture (PR) and major adverse cardiovascular events. However, their predictive factors and association with plaque vulnerability in patients with acute myocardial infarction (AMI) remain insufficiently explored. Therefore, This study aims to investigate the association between CCs and plaque vulnerability in culprit lesions of AMI patients, identify the factors influencing CCs formation, and develop a predictive model for CCs. MethodsA total of 431 culprit lesions from AMI patients who underwent pre-intervention optical coherence tomography (OCT) imaging were analyzed. Patients were divided into groups based on the presence or absence of CCs and PR. The relationship between CCs and plaque vulnerability was evaluated. A risk nomogram for predicting CCs was developed using the least absolute shrinkage and selection operator and logistic regression analysis. ResultsCCs were identified in 64.5 % of patients with AMI. The presence of CCs was associated with a higher prevalence of vulnerable plaque features, such as thin-cap fibroatheroma (TCFA), PR, macrophage infiltration, neovascularization, calcification, and thrombus, compared to patients without CCs. The CCs model demonstrated an area under the curve (AUC) of 0.676 for predicting PR. Incorporating CCs into the TCFA model (AUC = 0.656) significantly enhanced predictive accuracy, with a net reclassification improvement index of 0.462 (95 % confidence interval [CI]: 0.263–0.661, p < 0.001) and an integrated discrimination improvement index of 0.031 (95 % CI: 0.013–0.048, p = 0.001). Multivariate regression analysis identified the atherogenic index of plasma (odds ratio [OR] = 2.417), TCFA (OR = 1.759), macrophage infiltration (OR = 3.863), neovascularization (OR = 2.697), calcification (OR = 1.860), and thrombus (OR = 2.430) as independent risk factors for CCs formation. The comprehensive model incorporating these factors exhibited reasonable discriminatory ability, with an AUC of 0.766 (95 % CI: 0.717–0.815) in the training set and 0.753 (95 % CI: 0.704–0.802) in the internal validation set, reflecting good calibration. Decision curve analysis suggested that the model has potential clinical utility within a threshold probability range of approximately 18 % to 85 %. ConclusionsCCs were associated with plaque vulnerability in the culprit lesions of AMI patients. Additionally, this study identified key factors influencing CCs formation and developed a predictive model with potential clinical applicability.

Commentary: Immune cell infiltration and prognostic index in cervical cancer: insights from metabolism-related differential genes.

Commentary: Immune cell infiltration and prognostic index in cervical cancer: insights from metabolism-related differential genes.

Association between paravertebral muscle radiological parameter alterations and non-alcoholic fatty liver disease.

To assess changes in laboratory indices, paravertebral muscle (PVM) fat infiltration and multi b-value DWI parameters and their potential correlation with NAFLD. This retrospective analysis included 178 patients with histopathologically confirmed NAFLD, incluiding 76 with non-alcoholic steatohepatitis (NASH). Differences in PVM fat infiltration ratio (FIR), DWI parameters, and laboratory indices were compared between two groups. The correlation between FIR and NAFLD activity score (NAS) was also analysed. Binary logistic regression was used to identify the independent risk factors for NASH. The clinical utility of PVM fat infiltration, DWI parameters, and laboratory indices for diagnosing NASH in patients with NAFLD was evaluated using receiver operating characteristic (ROC) curves. The FIRs at the L2 and L3 levels were significantly higher in the with NASH group than those in the without NASH group. The heterogeneity index (α) and perfusion fraction (f) values at the L3 level of PVM were lower in the with NASH group. Moreover, the FIR at the L3 level was positively correlated with NAS. FIR at the L3 level was an independent risk factor for NASH along with alanine aminotransferase level. The area under the ROC curve (AUC) using L3 level PVM radiological parameters and laboratory indices for diagnosing NASH in patients with NAFLD was significantly higher than that using the degree of PVM fat infiltration, DWI parameters, or laboratory indices alone. Radiological parameters of the PVM were correlated with NAFLD. An integrated curve combining PVM radiological parameters may help distinguish NASH from NAFLD, thereby offering novel insights into the diagnosis of NASH.

Immune cell infiltration and prognostic index in cervical cancer: insights from metabolism-related differential genes.

Cervical cancer remains a significant gynecologic malignancy in both China and the United States, posing a substantial threat to women's lives and health due to its high morbidity and mortality rates. Altered energy metabolism and dysregulated mitochondrial function play crucial roles in the development, growth, metastasis, and recurrence of malignant tumors. In this study, we aimed to predict prognosis and assess efficacy of anti-tumor therapy in cervical cancer patients based on differential genes associated with mitochondrial metabolism. Transcriptomic data and clinical profiles of cervical cancer patients were retrieved from the TCGA and GEO databases. Differential gene-related cellular pathways were identified through GO, KEGG, and GSEA analyses. Prognostic indices were constructed using LASSO regression analysis. Immune cell infiltration was assessed using CIBERSORT and ssGSEA, and the correlation between immune checkpoint inhibitor genes and differential genes was examined. Tumor mutation load (TMB) and its association with prognostic indices were analyzed using nucleotide variant data from the TCGA database. Patient response to immunotherapy and sensitivity to antitumor drugs were determined using the TIDE algorithm and the oncoPredic algorithm, respectively. A prognostic index based on metabolism-related differential genes was developed to predict the clinical outcome of cervical cancer patients, enabling their classification into two distinct subtypes. The prognostic index emerged as an independent risk factor for unfavorable prognosis. The high-index group exhibited a significantly worse overall prognosis, along with elevated tumor mutation burden (TMB), increased immune cell infiltration, and lower TIDE scores, indicating a potential benefit from immunotherapy. Conversely, the low-index group demonstrated increased sensitivity to metabolism-related antitumor agents, specifically multikinase inhibitors. The aim of this study was to develop a prognostic index based on differential genes associated with mitochondrial metabolism, which could be used to predict cervical cancer patients' prognoses. When combined with TIDE and TMB analyses, this prognostic index offers insights into the immune cell infiltration landscape, as well as the potential efficacy of immunotherapy and targeted therapy. Our analysis suggests that the Iron-Sulfur Cluster Assembly Enzyme (ISCU) gene holds promise as a biomarker for cervical cancer immunotherapy.

Intramuscular fat infiltration influences mechanical properties during muscle contraction in older women.

Although evidence suggests that intramuscular fat infiltration may influence muscle strength, the precise mechanisms remain unclear. This study aimed to determine whether intramuscular fat infiltration affects muscle mechanical properties during contraction and whether these mechanical properties mediate the relationship between intramuscular fat infiltration and muscle strength. Seventy-nine healthy older women aged 75.1±6.8 years were included in this study. The echo intensity (EI) of the vastus lateralis (VL) was measured as an intramuscular fat infiltration index using B-mode ultrasonography. Maximum voluntary isometric contraction strength (MVIC) was assessed using a dynamometer. The VL shear elastic modulus (G), a mechanical property index, was measured using ultrasound shear wave elastography under various muscle contraction conditions, at rest and at 15%, 30%, and 45% MVIC (G0, G15, G30, and G45). To evaluate the degree of increase in the shear elastic modulus with increasing muscle contraction intensity, the slope of the regression line (Gslope) between muscle contraction and shear elastic modulus was calculated for each participant. The results showed that EI was significantly associated with G30 and G45 but not with G0 or G15. The EI can significantly explain the inter-individual differences in Gslope. Mediation analysis revealed that the effect of EI on MVIC through Gslope was significant (indirect effect = -0.31, 95% confidence interval (-0.57, -0.12)). These findings suggest that a greater EI is associated with a lower G during muscle contraction. Furthermore, our results show that the relationship between EI and MVIC is mediated by Gslope.

Comparison of lumbar muscle morphology in patients with chronic nonspecific low back pain with and without clinical lumbar segmental instability.

Evaluation of spinal muscle morphology may be critical because of its impact on segmental stability and control of the lumbar spine in the subset of patients with clinical lumbar segmental instability (LSI). The purpose of this study was to compare lumbar muscle morphology in CNLBP patients with clinical LSI, CNLBP patients without clinical LSI. This case-control study included 30 patients with CNLBP (15 with clinical LSI and 15 without clinical LSI) and 15 subjects without LBP. Axial magnetic resonance images from the L2 to S1 lumbar levels were used to evaluate the morphology of the lumbar muscles. A significant increase in the muscle-to-fat infiltration index and a significant decrease in the relative muscle cross-sectional area (rmCSA) of the multifidus muscle at the L3-L4 to L5-S1 levels were observed in both CNLBP groups compared to the control group (p<0.05). The mean erector spinae mean rmCSA was significantly greater in the clinical LSI group compared to the control group (SMD = 0.853, 95% CI = 0.105 to -1.6, P = 0.044) and also compared to the CNLBP without clinical LSI (SMD = 0.894, 95% CI = -1.645 to -0.144, P = 0.030) at the L4-L5 level. The atrophic changes of the multifidus muscle, in CNLBP patients with or without clinical LSI was observed. However, hypertrophic changes of the erector spinae muscle at the L4-L5 lumbar level were observed only in the clinical LSI group. Psaos major did not show significant atrophic or hypertrophic changes.

MiRNome targeting NF-κB signaling orchestrates macrophage-triggered cancer metastasis and recurrence

Whether and how tumor intrinsic signature determines macrophage-elicited metastasis remain elusive. Here, we show, in detailed studies of data regarding 7,477 patients of 20 types of human cancers, that only 13.8%± 2.6%/27.9%± 3.03% of patients with high macrophage infiltration index exhibit early recurrence/vascular invasion. In parallel, although macrophages enhance the motility of various hepatoma cells, their enhancement intensity is significantly heterogeneous. We identify that the expression of malignant Dicer, a ribonuclease that cleaves miRNA precursors into mature miRNAs, determines macrophage-elicited metastasis. Mechanistically, the downregulation of Dicer in cancer cells leads to defects in miRNome targeting NF-κB signaling, which in turn enhances the ability of cancer cells to respond to macrophage-related inflammatory signals and ultimately promotes metastasis. Importantly, transporting miR-26b-5p, the most potential miRNA targeting NF-κB signaling in hepatocellular carcinoma, can effectively reverse macrophage-elicited metastasis of hepatoma invivo. Our results provide insights into the crosstalk between Dicer-elicited miRNome and cancer immune microenvironments and suggest that strategies to remodel malignant cell miRNome may overcome pro-tumorigenic activities of inflammatory cells.

Evaluation of the beneficial effects of a GABA-based product containing Melissa officinalis on post-inflammatory irritable bowel syndrome: a preclinical study.

Visceral pain represents the most common digestive issue, frequently resulting from long-term inflammation, such as inflammatory bowel diseases. The lack of effective drugs prompted search of new therapeutic approaches. In this regard, gamma-aminobutyric acid (GABA) and Melissa officinalis (Mo) appear as excellent candidates as they were recognized to have several positive effects on the digestive system. The aim of this research was to evaluate the effects of a compound containing GABA and Mo (GABA-Mo 5:1) in inflammation-induced intestinal damage and visceral pain. Colitis was induced in rats by intrarectal 2,4-dinitrobenzenesulfonic acid (DNBS) administration. DNBS-treated animals received GABA-Mo (80mg/kg BID), starting 3days before DNBS administration, until 14days after colitis induction (preventive protocol), or starting 7days after DNBS until day 21 (curative protocol). Visceral pain was assessed by measuring the viscero-motor response (VMR) and the abdominal withdrawal reflex (AWR) to colorectal distension on day 7, 14 (both protocols) and 21 (curative protocol) after DNBS administration. In the preventive protocol, GABA-Mo reduced AWR at day 14 but had no effect on VMR. In the spinal cord, treatment with GABA-Mo significantly prevented microglia reactivity (Iba-1 positive cells). In the colon, the supplement significantly decreased malondialdehyde (MDA, index of oxidative stress) and IL-1β levels and counteracted the decreased expression of claudin-1. Moreover, GABA-Mo normalized the increased levels of plasma lipopolysaccharide binding protein (LBP, index of altered intestinal permeability). In the curative protocol, GABA-Mo significantly counteracted visceral hypersensitivity persistence in DNBS-treated animals (day 14 and 21). In the spinal cord, GABA-Mo significantly reduced GFAP positive cell density (astrocytes). Histological evaluations highlighted a mild but significant effect of GABA-Mo in promoting healing from DNBS-induced colon damage. Colonic MDA and myeloperoxidase (index of leukocyte infiltration) levels were reduced, while the decreased colonic claudin-1 expression was normalized. In addition, the increased levels of plasma LBP were normalized by GABA-Mo administration. In conclusion GABA-Mo, particularly in the curative protocol, was able to reduce visceral pain and intestinal inflammation, likely through a reinforcement of intestinal barrier integrity, thus representing a suitable approach for the management of abdominal pain, especially in the remission stages of colitis.

Abstract 13494: Histopathological Analysis Indicates a Significant Role of Myocardial Perfusion Disturbance in Tissue Lesion in Chronic Chagas’ Cardiomyopathy Experimental Model

Introduction: Coronary microvascular perfusion disturbance (MPD) is frequently found in Chronic Chagas' cardiomyopathy (CCC), but its role in tissue lesion and left ventricular dysfunction progression is still unclear. Hypothesis: As MPD is associated with more severe subendocardial myocardial injury, we tested the hypothesis that histopathological changes in subendocardial layer could be quantitatively correlated to MPD in experimental model of CCC in hamsters. Methods: Female Syrian hamsters (n=23) infected with 3.5x10 4 blood trypomastigote forms of T. cruzi ( Y strain ) and their respective controls (n=6) were studied. At 8 months after infection, the animals underwent in vivo high-resolution myocardial rest perfusion scintigraphy with 99m Tc-Sestamibi and transthoracic echocardiography. After euthanasia, the myocardial tissue was processed for quantitative histopathological analysis of mononuclear infiltrate index (MII) using hematoxylin-eosin staining and myocardial fibrosis using picrosirius staining in LV wall layers: subendocardium, mesocardium and subepicardium. Results: Fourteen animals (61%) presented rest MPD. The area of MPD was negatively correlated with LVEF (R=-0.5; p=0.02), and positively correlated with LV diastolic diameter (R=0.83; p&lt;0.01). Animals with MPD exhibited increased extent of myocardial fibrosis in the subendocardial layer (0.67 + 0.18%) as compared to control animals (0.47 + 0.15%), p=0.03. However, the extent of total transmural fibrosis or fibrosis in other myocardial layers were similar among groups. The group with MPD presented higher values of MII in every myocardial layer as compared to controls and animals without MPD. However, only the MII in the subendocardial layer presented positive correlation with the extent of rest MPD (R=0.55, p=0.001). Conclusions: Our results indicate that MPD is significantly correlated with histopathological changes located in the subendocardial layer of LV walls. These results suggest that MPD may act as an amplifying and localizing factor for inflammation and fibrosis, suggesting a relevant role for myocardial hypoperfusion in the mechanisms of myocardial injury in CCC.

Relating Threshold Changes in Soil Function to Structural Changes in Woody Vegetation Along Herbivore Utilization Gradients with Different Management Histories in an Arid Thicket Mosaic, South Africa

The hypothesis that transformation of rangelands by domestic herbivores follows state-and-transition models predicts that vegetation communities will cross ecological thresholds when shifting from one state to another. We test this hypothesis by identifying threshold responses of soil function in Gamka Thicket, a variation of Arid Thicket in South Africa. We relate indices of soil water infiltration, nutrient cycling, and soil retention (reflecting ecosystem function) to distance from artificial watering points in four piosphere treatments differing in rangeland management history. Furthermore, we compare the pattern, extent, and variation in transformation at the end regions of our piosphere treatments to each other and to a transformed and untransformed reference site. The changes to all the indices of ecosystem function support the hypothesis that functional thresholds have been crossed. We propose a conceptual model that suggests that Arid Thicket transformation due to herbivory transcends three vegetation states. We contend that during the process of transformation the crossing of structural thresholds lead to the crossing of functional thresholds that ultimately drive the formation of new vegetation states.

Identification of specific prognostic markers for lung squamous cell carcinoma based on tumor progression, immune infiltration, and stem index.

Lung squamous cell carcinoma (LUSC) is a unique subform of nonsmall cell lung cancer (NSCLC). The lack of specific driver genes as therapeutic targets leads to worse prognoses in patients with LUSC, even with chemotherapy, radiotherapy, or immune checkpoint inhibitors. Furthermore, research on the LUSC-specific prognosis genes is lacking. This study aimed to develop a comprehensive LUSC-specific differentially expressed genes (DEGs) signature for prognosis correlated with tumor progression, immune infiltration,and stem index. RNA sequencing data for LUSC and lung adenocarcinoma (LUAD) were extracted from The Cancer Genome Atlas (TCGA) data portal, and DEGs analyses were conducted in TCGA-LUSC and TCGA-LUAD cohorts to identify specific DEGs associated with LUSC. Functional analysis and protein-protein interaction network were performed to annotate the roles of LUSC-specific DEGs and select the top 100 LUSC-specific DEGs. Univariate Cox regression and least absolute shrinkage and selection operator regression analyses were performed to select prognosis-related DEGs. Overall, 1,604 LUSC-specific DEGs were obtained, and a validated seven-gene signature was constructed comprising FGG, C3, FGA, JUN, CST3, CPSF4, and HIST1H2BH. FGG, C3, FGA, JUN, and CST3 were correlated with poor LUSC prognosis, whereas CPSF4 and HIST1H2BH were potential positive prognosis markers in patients with LUSC. Receiver operating characteristic analysis further confirmed that the genetic profile could accurately estimate the overall survival of LUSC patients. Analysis of immune infiltration demonstrated that the high risk (HR) LUSC patients exhibited accelerated tumor infiltration, relative to low risk (LR) LUSC patients. Molecular expressions of immune checkpoint genes differed significantly between the HR and LR cohorts. A ceRNA network containing 19 lncRNAs, 50 miRNAs, and 7 prognostic DEGs was constructed to demonstrate the prognostic value of novel biomarkers of LUSC-specific DEGs based on tumor progression, stemindex, and immune infiltration. In vitro experimental models confirmed that LUSC-specific DEG FGG expression was significantly higher in tumor cells and correlated with immune tumor progression, immune infiltration, and stem index. In vitro experimental models confirmed that LUSC-specific DEG FGG expression was significantly higher in tumor cells and correlated with immune tumor progression, immune infiltration, and stem index. Our study demonstrated the potential clinical implication of the 7- DEGs signature for prognosis prediction of LUSC patients based on tumor progression, immune infiltration, and stem index. And the FGG could be an independent prognostic biomarker of LUSC promoting cell proliferation, migration, invasion, THP-1 cell infiltration, and stem cell maintenance.

Effect of Anterior Acromial Coverage on Functional and Radiological Outcomes After Arthroscopic Repair of Anteroposterior Massive Rotator Cuff Tears.

Rotator cuff tear size, fatty infiltration, and scapular morphology are correlated with tendon healing and functional outcomes after arthroscopic repair; however, the association between anteroposterior acromial coverage and the clinical outcomes of anteroposterior massive rotator cuff tears (AP-MRCTs; involving all 3 tendons) remains unclear. To identify the association between AP acromial coverage and functional and radiological outcomes after arthroscopic repair of AP-MRCTs. Cohort study; Level of evidence, 3. A total of 98 patients who underwent arthroscopic repair of AP-MRCTs between January 2015 and December 2020 were included in the study and classified according to whether anterior acromial coverage (AAC) was anterior (46 patients; positive AAC group) or posterior (52 patients; negative AAC group) to the scapular line on true lateral shoulder radiographs. Demographic characteristics, surgical details, and functional outcomes were prospectively collected. Acromial morphological features, global tear extension (GTE), the global fatty infiltration index (GFII), tendon integrity after repair, proximal humeral migration, and glenohumeral abduction were measured and calculated on radiographs or magnetic resonance imaging scans preoperatively and at 2 years postoperatively. Multivariate logistic regression was performed to identify the independent risk factors of a rotator cuff retear. The positive AAC group showed larger AAC, posterior acromial tilt, and anterior acromial slope as well as smaller posterior acromial coverage compared with the negative AAC group. Postoperatively, the American Shoulder and Elbow Surgeons score (82.5 ± 8.3 vs 77.2 ± 11.5, respectively; P = .013), active abduction (157.8°± 27.1° vs 142.7°± 39.6°, respectively; P = .048), and glenohumeral abduction (45.6°± 10.4° vs 39.7°± 14.9°, respectively; P = .041) in the positive AAC group were significantly higher than those in the negative AAC group, while the retear rate (23.9% vs 44.2%, respectively; P = .035) and proximal humeral migration (1.7 ± 1.0 vs 2.3 ± 1.2 mm, respectively; P = .006) were significantly lower in the positive AAC group than in the negative AAC group. Smaller AAC (odds ratio [OR], 0.93 [95% CI, 0.87-1.00]; P = .040), larger GTE (OR, 1.03 [95% CI, 1.01-1.06]; P = .017), and a higher GFII (OR, 3.49 [95% CI, 1.09-11.19]; P = .036) were associated with an increased risk of a rotator cuff retear. Increased AAC was associated with a lower retear rate and better functional outcomes after arthroscopic repair of AP-MRCTs. A preliminary risk evaluation integrating GTE, the GFII, and AAC is recommended to consider the necessity of additional procedures for patients in need of arthroscopic rotator cuff repair.

Treatment Response in First-Line Metastatic Pancreatic Ductal Adenocarcinoma Is Stratified By a Composite Index of Tumor Proliferation and CD8 T-Cell Infiltration.

Determinants of treatment outcomes to chemotherapy-based regimens in metastatic pancreatic ductal adenocarcinoma (PDA) remain ill-defined. Our aim was to examine tissue-based correlates of treatment response and resistance using matched baseline and on-treatment biopsies collected from patients with PDA treated in the first-line metastatic setting. Patients with treatment-naïve metastatic PDA were enrolled in a Phase II trial (NCT02077881) investigating gemcitabine plus nab-paclitaxel in combination with indoximod, an orally administered small-molecule inhibitor of the IDO pathway. Baseline and on-treatment biopsies (week 8) of metastatic lesions (88% liver) were collected from a cohort of responders (N = 8) and non-responders (N = 8) based on RECIST v1.1 and examined by multiplex IHC and mRNA sequencing. Treatment altered the transcriptional profile of metastatic lesions with a decrease in tumor cell proliferation independent of treatment response. The antiproliferative response was seen in both basal and classical PDA subtypes. PDA subtype was not associated with survival outcomes; instead, genes involved in immune activation distinguished responders from non-responders. Tumor response was associated with an increase in CD3+ and CD8+ T-cell infiltrates into metastatic lesions. A composite of decreased tumor proliferation in response to treatment and increased CD8 T-cell infiltration in metastatic lesions identified responders and associated with a favorable survival outcome. Our findings suggest that inhibiting cancer cell proliferation alone in PDA is insufficient to produce tumor responses and support a role for tumor-extrinsic mechanisms, such as CD8+ T cells, which combine with the cancer cell proliferation index to define treatment outcomes.

Revision rotator cuff repair: can a Sugaya III tendon considered to be healed or not

Sugaya etal described a classification system to assess postoperative rotator cuff tendon healing. Although Sugaya I and II tendons can be considered as healed and Sugaya type IV and V can be considered as retorn, the exact status of Sugaya III tendons remains unclear. The objective of this study was to evaluate the impact of Sugaya III tendons on postoperative functional scores in a population of patients undergoing revision rotator cuff repair. We retrospectively studied the records of all patients who underwent revision rotator cuff repair in one of 12 different institutions between July 2001 and December 2020. A total of 203 shoulders were included (59% males, mean age: 51±8 years old, mean follow-up 11.5 years [range: 2-28.8 yr]). Fifty-four patients (61% males, mean age 52±6 years old, mean follow-up 14.1 years [range: 10.4-28.8 yr]) had a follow-up≥10 years (mean 14.1 years [range: 10.4-28.8 yr]) and were included in a long-term follow-up subgroup analysis. Structural integrity of the repaired tendon was evaluated on magnetic resonance imaging at last follow-up. Functional scores, acromiohumeral index (AHI), and progression of fatty infiltration and of osteoarthritis were compared according to Sugaya type. Mean Constant score and mean strength were significantly higher in Sugaya I and II tendons than in Sugaya III (P=.021 and .003) and Sugaya IV and V tendons (P=.07 and .038), but did not differ between Sugaya III and Sugaya IV and V tendons. Mean Subjective Shoulder Value, pain, AHI were significantly higher and fatty infiltration and progression in the Hamada classification were significantly lower in Sugaya I and II tendons and in Sugaya III than in Sugaya IV and V tendons (P< .05), but did not differ between Sugaya I and II and Sugaya III tendons. Similar characteristics could also be observed in the long-term follow-up subgroup. Sugaya III tendons after revision rotator cuff repair do not allow restoration of strength thereby impacting the Constant score. However, there seems to be a protective effect of Sugaya III tendons with regard to pain, progression of proximal migration of the humeral head, osteoarthritis, and fatty infiltration, which seems to last at long-term follow-up.

Infiltration and shear strength characteristics of gully heads soil of typical vegetation on the gullied Loess Plateau, Northwest China.

Gully head is the main active part of gully erosion, which seriously affects the occurrence of gully headcut erosion. To investigate root distribution and soil physical and mechanical characteristics of typical vegetation gully head, we analyzed the infiltration, root distribution, physical and mechanical properties of soil-root complex of soil in different layers (0-1 m) in natural restoration gully head and artificial restoration gully head. The results showed that the variability of soil bulk and total porosity among different vegetation gully heads was low, with bulk density ranging from 1.10 to 1.37 g·cm-3 and total porosity ranging from 48.3% to 58.4%. Infiltration index of different vegetation gully heads generally decreased with increasing soil depth. The infiltration rate of different soil layers in natural restoration gully head tended to stabilize in 20-30 min, while that of artificial restoration gully head tended to stabilize in 40 min. The infiltration capacity and average infiltration rate of artificial restoration gully head were generally higher than those of natural restoration gully head in all soil layers. Root length density, root surface area density, and average diameter all tended to decrease with increasing soil depth. Except for the 20-40 cm soil layer, root length density, root surface area density and average diameter of natural restoration gully head were all lower than those of artificial restoration gully head. Root system of both vegetation gully heads mainly consisted of 0-0.5 mm roots, accounting for 84.2%-93.6% of the total root length. In the vertical depth, with the increases of water content, the cohesion force decreased linearly with the deepening of soil layer, ranging from 0.42 to 22.67 kPa. The average cohesion force of artificial restoration gully head was higher than natural restoration gully head at each level of water content. The study revealed the effects of vegetation on the gully head cut erosion, which could provide scientific basis for the effective prevention and control of soil erosion in the region.

Obesity management for the pre–liver transplant and post–liver transplant patient

Obesity management for the pre–liver transplant and post–liver transplant patient

Improved Yet Varied Clinical Outcomes Observed With Comparison of Arthroscopic Superior Capsular Reconstruction Versus Arthroscopy-Assisted Lower Trapezius Transfer for Patients With Irreparable Rotator Cuff Tears

To evaluate the outcomes of arthroscopic superior capsular reconstruction (SCR) and arthroscopy-assisted lower trapezius tendon transfer (LTT) for posterosuperior irreparable rotator cuff tears (IRCTs). Over an almost 6-year period (October 2015 to March 2021), all patients who underwent IRCT surgery with a minimum 12-month follow-up period were identified. For patients with a substantial active external rotation (ER) deficit or lag sign, LTT was preferentially selected. Patient-reported outcome scores included the visual analog scale (VAS) pain score, strength score, American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) score, Single Assessment Numeric Evaluation (SANE) score, and Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) score. We included 32 SCR patients and 72 LTT patients. Preoperatively, LTT patients had more advanced teres minor fatty infiltration (0.3 vs 1.1, P= .009), a higher global fatty infiltration index (1.5 vs 1.9, P= .035), and a higher presence of the ER lag sign (15.6% vs 48.6%, P < .001). At a mean follow-up of 2.9 ± 1.3 years (range, 1.0-6.3 years), no differences in patient-reported outcome scores were observed. Postoperatively, SCR patients had a lower VAS score (0.3 vs 1.1, P= .017), higher forward elevation (FE) (156° vs 143°, P= .004), and higher FE strength (4.8 vs 4.5, P= .005) and showed greater improvements in the VAS score (6.8 vs 5.1, P= .009), FE (56° vs 31°, P= .004), and FE strength (1.0 vs 0.4, P < .001). LTT patients showed greater improvement in ER (17° vs 29°, P= .026). There was no statistically significant between-cohort difference in complication rate (9.4% vs 12.5%, P= .645) or reoperation rate (3.1% vs 10%, P= .231). With adequate selection criteria, both SCR and LTT provided improved clinical outcomes for posterosuperior IRCTs. Additionally, SCR led to better pain relief and restoration of FE whereas LTT provided more reliable improvement in ER. Level III, treatment study with retrospective cohort comparison.

Pan-cancer analysis and experimental validation of DTL as a potential diagnosis, prognosis and immunotherapy biomarker

BackgroundDTL has been found to be related with multiple cancers. However, comprehensive analyses, which identify the prediction value of DTL in diagnosis, prognosis, immune infiltration and treatment, have rarely been reported so far.MethodsCombined with the data online databases, the gene expression, gene mutation, function enrichment and the correlations with the immunity status and clinical indexes of DTL were analyzed. Expression of DTL and the degree of immune cell infiltration were examined by immunofluorescence (IF) and immunohistochemistry (IHC) and analyzed by statistical analysis. Furthermore, the influences of DTL on the cell cycle, cell proliferation and apoptosis were detected by live cell imaging, IF and flow cytometric (FC) analysis. Genomic stability assays were conducted by chromosome slide preparation.ResultsDTL was widely expressed in various cells and tissues, while it was overexpressed in tumor tissues except acute myeloid leukemia (LAML). Pan-cancer bioinformatics analysis showed that the expression of DTL was correlated with the prognosis, immunotherapy, and clinical indexes in various cancers. In addition, gene set enrichment analysis (GSEA) uncovered that DTL was enriched in oocyte meiosis, pyrimidine metabolism, the cell cycle, the G2M checkpoint, mTORC1 signaling and E2F targets. Furthermore, the overexpression of DTL, and its association with immune cell infiltration and clinical indexes in liver hepatocellular carcinoma (LIHC), bladder urothelial carcinoma (BLCA) and stomach adenocarcinoma (STAD) were verified in our study. It was also verified that overexpression of DTL could regulate the cell cycle, promote cell proliferation and cause genomic instability in cultured cells, which may be the reason why DTL plays a role in the occurrence, progression and treatment of cancer.ConclusionsCollectively, this study suggested that DTL is of clinical value in the diagnosis, prognosis and treatment of various cancers, and may be a potential biomarker in certain cancers.