Morphological Classification System Research Articles

Spatial and Single-Cell Transcriptomics Unraveled Spatial Evolution of Papillary Thyroid Cancer.

Recurrence and metastasis are the major issues for papillary thyroid cancer (PTC). Current morphological and molecular classification systems are not satisfied for PTC diagnosis due to lacking variant-specific morphological criteria and high signal-to-noise in mutation-based diagnosis, respectively. Importantly, intratumor heterogeneity is largely lost in current molecular classification system, which can be resolved by single cell RNA sequencing (scRNA-seq). However, scRNA-seq loses spatial information and morphological features. Herein, scRNA-seq is integrated and spatially-resolved transcriptomics (SRT) to elaborate the mechanisms underlying the spatial heterogeneity, malignancy and metastasis of PTCs by associating transcriptome and local morphology. This results demonstrated that PTC cells evolved with multiple routes, driven by the enhanced aerobic metabolism and the suppressed mRNA translation and protein synthesis and the involvement of cell-cell interaction. Two curated malignant and metastatic footprints can discriminate PTC cells from normal thyrocytes. Ferroptosis resistance contributed to PTC evolution. This results will advance the knowledge of intratumor spatial heterogeneity and evolution of PTCs at spatial and single-cell levels, and propose better diagnostic strategy.

Analysis of Morphologic Classification System for Acute Promyelocytic Leukemia and Its Correlation with Laboratory Tests and FLT3-ITD Mutation

To establish a morphologic classification system for characterizing blast cells in patients with acute promyelocytic leukemia (APL) and analyze the correlation of different APL morphologic characteristics with conventional tests and genetic variants. Based on the morphological characteristics of APL blast cells, a classification system of 14 categories was established to characterize the inter- and intra-individual cellular morphological heterogeneity of patients. The classification system was used for the morphological analysis of 40 APL patients, and the classification results were statistically analyzed with the patients' conventional test indexes and gene variant characteristics to analyze the correlation of different APL blast cell morphological features with conventional test indexes and gene variants. In the FLT3-ITD mutation-positive group, there were significantly fewer cells with regular nuclear shape, hyper granularity, and missing Auer rods (category 1) than in the FLT3 mutation-negative group (P < 0.05). The activated partial thromboplastin (APTT) was significantly longer in the group with regular nucleus compared to the group with irregular nucleus (P < 0.05). In the hypo-granular group, the APTT was also significantly longer compared to the hyper-granular group (P < 0.01), and the proportion of myeloid blast cells was relatively lower (P < 0.05). The peripheral blood white blood cell counts, D-dimer, lactate dehydrogenase and proportion of bone marrow blast cells were significantly higher in the Auer rods (-) group than Auer rods increasing group (all P < 0.05). The newly established morphologic classification system in this study can objectively characterize different types of APL blast cells, which helps to better assess the intra- and inter-individual heterogeneity of APL blast cells, and further use in accurately analyzing the correlation of morphological phenotypes with biological properties of APL.

Neuroma morphology: A macroscopic classification system.

Neuromas come in different shapes and sizes; yet the correlation between neuroma morphology and symptomatology is unknown. Therefore, we aim to investigate macroscopic traits of excised human neuromas and assess the validity of a morphological classification system and its potential clinical implications. End-neuroma specimens were collected from prospectively enrolled patients undergoing symptomatic neuroma surgery. Protocolized images of the specimens were obtained intraoperatively. Pain data (Numeric rating scale, 0-10) were prospectively collected during preoperative interview, patient demographic and comorbidity factors were collected from chart review. A morphological classification is proposed, and the inter-rater reliability (IRR) was assessed. Distribution of neuroma morphology with patient factors, was described. Forty-five terminal neuroma specimens from 27 patients were included. Residual limb patients comprised 93% of the population, of which 2 were upper (8.0%) and 23 (92.0%) were lower extremity residual limb patients. The proposed morphological classification, consisting of three groups (bulbous, fusiform, atypical), demonstrated a strong IRR (Cohen's kappa = 0.8). Atypical neuromas demonstrated higher preoperative pain, compared with bulbous and fusiform. Atypical morphology was more prevalent in patients with diabetes and peripheral vascular disease. A validated morphological classification of neuroma is introduced. These findings may assist surgeons and researchers with better understanding of symptomatic neuroma development and their clinical implications. The potential relationship of neuroma morphology with the vascular and metabolic microenvironment requires further investigation.

NBI Classification Optimization With Morphological Characteristics in Vocal Fold Leukoplakia.

Objectives: To investigate the pathological contribution of vocal fold leukoplakia (VFL) of type II in narrow-band imaging (NBI) classification and morphological characteristics to improve pathological prediction. Material and Methods: The 59 VFL patients with type II in 2019 Ni classification in NBI were included. The pathological reports were collected and divided following 2005 WHO Blue Book. Low-risk VFL contained non-, mild, moderate dysplasia, high-risk VFL included severe dysplasia. The morphological classification and laryngoscopic scoring system were employed to evaluate leukoplakia for pathological prediction. Results: The pathologies contained 1 case of leukoplakia with non-dysplasia, 12 of mild dysplasia, 15 of moderate dysplasia, 8 of severe dysplasia, and 23 of carcinoma. The 30 smooth VFL contained 1 non-dysplasia, 12 mild dysplasia, 14 moderate dysplasia, 2 severe dysplasia, and 1 carcinoma. The 29 rough cases included 1 moderate dysplasia, 6 severe dysplasia, and 22 carcinomas. Laryngoscopic scoring system revealed irregular texture, large size, and thick lesion as factors in relationship with high-risk leukoplakia in univariate (P = .002, <.001, <.001) and multivariate (P = .025, .002, .016) analysis, irregular texture was the most accurate predictor of high-risk VFL pathology. Conclusions and Significance: The pathologies of VFL with type II in NBI classification were hard to be predicted. Morphological irregular/rough texture contributed to predict high-risk pathology in leukoplakia.

Association of Mutant KRAS Alleles With Morphology and Clinical Outcomes in Pancreatic Ductal Adenocarcinoma.

Mutant KRAS is the main oncogenic driver in pancreatic ductal adenocarcinomas (PDACs). However, the clinical and phenotypic implications of harboring different mutant KRAS alleles remain poorly understood. To characterize the potential morphologic and clinical outcome differences in PDACs harboring distinct mutant KRAS alleles. Cohort 1 consisted of 127 primary conventional PDACs with no neoadjuvant therapy, excluding colloid/mucinous, adenosquamous, undifferentiated, and intraductal papillary mucinous neoplasm-associated carcinomas, for which an in-house 42-gene mutational panel had been performed. A morphologic classification system was devised wherein each tumor was assigned as conventional, papillary/large duct (P+LD, defined as neoplastic glands with papillary structure and/or with length ≥0.5 mm), or poorly differentiated (when the aforementioned component was 60% or more of the tumor). Cohort 2 was a cohort of 88 PDACs in The Cancer Genome Atlas, which were similarly analyzed. In both cohorts, there was significant enrichment of P+LD morphology in PDACs with KRAS G12V and G12R compared with G12D. In the entire combined cohort, Kaplan-Meier analyses showed longer overall survival (OS) with KRAS G12R as compared with G12D (median OS of 1255 versus 682 days, P = .03) and in patients whose PDACs displayed P+LD morphology as compared with conventional morphology (median OS of 1175 versus 684 days, P = .04). In the adjuvant-only subset, KRAS G12R had the longest OS compared with G12D, G12V, and other alleles (median OS unreached/undefined versus 1009, 1129, and 1222 days, respectively). PDACs with different mutant KRAS alleles are associated with distinct morphologies and clinical outcomes, with KRAS G12R allele associated with P+LD morphology and longer OS when compared with G12D using Kaplan-Meier studies.

Classification of anatomical morphology of cystic duct and its association with gallstone.

Gallstones are common lesions that often require surgical intervention. Laparoscopic cholecystectomy is the treatment of choice for symptomatic gallstones. Preoperatively, the anatomical morphology of the cystic duct (CD), needs to be accurately recognized, especially when anatomical variations occur in the CD, which is otherwise prone to bile duct injury. However, at present, there is no optimal classification system for CD morphology applicable in clinical practice, and the relationship between anatomical variations in CDs and gallstones remains to be explored. To create a more comprehensive clinically applicable classification of the morphology of CD and to explore the correlations between anatomic variants of CD and gallstones. A total of 300 patients were retrospectively enrolled from October 2021 to January 2022. The patients were divided into two groups: The gallstone group and the nongallstone group. Relevant clinical data and anatomical data of the CD based on magnetic resonance cholangiopancreatography (MRCP) were collected and analyzed to propose a morphological classification system of the CD and to explore its relationship with gallstones. Multivariate analysis was performed using logistic regression analyses to identify the independent risk factors using variables that were significant in the univariate analysis. Of the 300 patients enrolled in this study, 200 (66.7%) had gallstones. The mean age was 48.10 ± 13.30 years, 142 (47.3%) were male, and 158 (52.7%) were female. A total of 55.7% of the patients had a body mass index (BMI) ≥ 24 kg/m2. Based on the MRCP, the CD anatomical typology is divided into four types: Type I: Linear, type II: n-shaped, type III: S-shaped, and type IV: W-shaped. Univariate analysis revealed differences between the gallstone and nongallstone groups in relation to sex, BMI, cholesterol, triglycerides, morphology of CD, site of CD insertion into the extrahepatic bile duct, length of CD, and angle between the common hepatic duct and CD. According to the multivariate analysis, female, BMI (≥ 24 kg/m2), and CD morphology [n-shaped: Odds ratio (OR) = 10.97, 95% confidence interval (95%CI): 5.22-23.07, P < 0.001; S-shaped: OR = 4.43, 95%CI: 1.64-11.95, P = 0.003; W-shaped: OR = 7.74, 95%CI: 1.88-31.78, P = 0.005] were significantly associated with gallstones. The present study details the morphological variation in the CD and confirms that CD tortuosity is an independent risk factor for gallstones.

Molecular phylogeny and ethology of the Family Plagiostomidae (Platyhelminthes, Prolecithophora), with integrative description of a new species, Plagiostomum robusta A. Wang, sp. nov.

The taxon Prolecithophora, which is closely related to the well-known clade Tricladida, is rarely studied, particularly in terms of molecular phylogeny and behavioral characteristics. In this study, we employed an integrative analysis of molecular phylogeny, histology, and ethology to describe a new marine species, Plagiostomum robusta A.Wang, sp. nov. of the order Prolecithophora. Additionally, we obtained its nearly complete mitogenome sequence with annotations of 12 protein-coding genes, two rRNA genes and 22 tRNA genes. P. robusta is characterized by several features, including a pair of short tentacles, a terminal mouth and a terminal gonopore, a large variable pharynx, two extended front ends of the intestine, paired testes located behind the ovaries and outside the vitellaria, a muscular and movable distal sac, and a long tubular penis surrounded by a sheath. The phylogenetic analysis, based on 18S rDNA and 28S rDNA, revealed that the new species formed a clade with six Plagiostomum flatworms, indicating a close kinship with Plagiostomum. Despite contradictions between the traditional morphological classification system and the results of molecular phylogenetics, we chose to assign the new species to Plagiostomum based on comprehensive considerations. Moreover, our study has provided more insights into the behavioral features of Plagiostomidae species, as we found that P. robusta fed on other flatworms and engaged in cannibalism, and unexpectedly it mated via hypodermic inpregnation. This study represents the first comprehensive description of the reproductive behavior of Plagiostomidae species, contributing to the more in-depth understanding of the biological characteristics of this group.

Accuracy and Reliability of Left Atrial Appendage Morphology Assessment by Three-Dimensional Transesophageal Echocardiographic Glass Rendering Modality: A Comparative Study With Computed Tomography

Contrast-enhanced computed tomography is the reference-standard imaging technique to assess left atrial appendage (LAA) morphology. The aim of this study was to evaluate the accuracy and reliability of two-dimensional and new three-dimensional (3D) transesophageal echocardiographic rendering modalities in assessing LAA morphology. Seventy consecutive patients who underwent both computed tomography and transesophageal echocardiography (TEE) were retrospectively enrolled. The traditional LAA morphology classification system (LAAcs; chicken wing, cauliflower, cactus, and windsock) and a new simplified LAAcs based on the LAA bend angle were used for the analysis. LAA morphology was independently assessed by two trained readers using three different modalities: two-dimensional TEE, 3D TEE with multiplanar reconstruction, and a new 3D transesophageal echocardiographic rendering modality with improved transparency (Glass). The new LAAcs and traditional LAAcs were compared in terms of intra- and interrater reliability. With the new LAAcs, two-dimensional TEE was fairly accurate in identifying LAA morphology (κ=0.43, P<.05), with moderate interrater (κ=0.50, P<.05) and substantial intrarater (κ=0.65, P<.005) agreement. Three-dimensional TEE showed higher accuracy and reliability: 3D TEE with multiplanar reconstruction had almost perfect accuracy (κ=0.85, P<.001) and substantial (κ=0.79, P<.001) interrater reliability, while 3D TEE with Glass had substantial accuracy (κ=0.70, P<.001) and almost perfect (κ=0.84, P<.001) interrater reliability. Intrarater agreement was almost perfect for both 3D transesophageal echocardiographic modalities (κ=0.85, P<.001). Accuracy was considerably lower when the traditional LAAcs was used, with 3D TEE with Glass being the most reliable technique (κ=0.75, P<.05). The new LAAcs showed higher inter- and intrarater reliability compared with the traditional LAAcs (interrater, κ=0.85 vs κ=0.49; intrarater, κ=0.94 vs κ=0.68; P<.05). Three-dimensional TEE is an accurate, reliable, and feasible alternative to computed tomography in assessing LAA morphology with the new LAAcs. The new LAAcs shows higher reliability rates than the traditional one.

Classifying the Large Vestibular Aqueduct: Morphometry to Audiometry.

Large vestibular aqueduct (LVA) is the most common inner ear dysplasia identified in patients with hearing loss. Our objective was to systematically quantify LVA morphologies and correlate imaging findings with established audiometric outcomes. Retrospective review. Tertiary referral center. Patients with large vestibular aqueduct identified radiographically, with or without hearing loss. Diagnostic only. Vestibular aqueduct (VA) width at midpoint, width at external aperture, and length were measured on cross-sectional imaging. Morphology was classified as type I (borderline), type II (tubular), or type III (funneled). Audiometric endpoints included air/bone conduction, pure tone averages, and air-bone gaps at 250 and 500 Hz. Statistical associations were evaluated using linear regression models, adjusted for age at first audiogram and sex. One hundred seventeen patients (197 ears) were included, with mean age at first audiogram of 22.2 years (standard deviation, 21.7 yr). Imaging features associated with poor audiometric outcomes were increasing VA width at midpoint and external aperture, decreasing VA length, dilated extraosseous endolymphatic sac, cochleovestibular malformations, and increasing VA type (III > II > I). Quantitative LVA measurements and a standardized morphologic classification system aid in prediction of early audiometric endpoints.

The complete chloroplast genome sequences of three lilies: genome structure, comparative genomic and phylogenetic analyses.

We sequenced and analyzed the complete chloroplast genomes of Lilium amoenum, Lilium souliei, and Nomocharis forrestii in detail, including the first sequence and structural comparison of Nomocharis forrestii. We found that the lengths and nucleotide composition of the three chloroplast genes showed little variation. The chloroplast genomes of the three Lilium species contain 87 protein coding genes (PCGs), 38 tRNAs, and 8 rRNA genes. The only difference is that Nomocharis forrestii had an additional infA pseudogene. In the sequence analysis of the Lilium chloroplast genomes, 216 SSRs, 143 pairs of long repeats, 571 SNPs, and 202 indels were detected. In addition, we identified seven hypervariable regions that can be used as potential molecular markers and DNA barcodes of Lilium through complete sequence alignment. The phylogenetic tree was constructed from the three chloroplast genome sequences of Lilium obtained here and 40 chloroplast genome sequences from the NCBI database (including 35 Lilium species, 4 Fritillaria species, and one species of Smilax). The analysis showed that the species clustering of the genus Lilium essentially conformed to the classical morphological classification system of Comber, but differences in the classification of individual species remained. In our report, we support the reclassification of Lilium henryi and Lilium rosthorniiy in the genus Lilium. In general, this study not only provides genome data for three Lilium species, but also provides a comparative analysis of the Lilium chloroplast genomes. These advances will help to identify Lilium species, clarify the phylogenetic analysis of the Lilium genus, and help to solve and improve the disputes and deficiencies in the traditional morphological classification.

Classification of High-Grade Serous Ovarian Cancer Using Tumor Morphologic Characteristics

Despite similar histologic appearance among high-grade serous ovarian cancers (HGSOCs), clinical observations suggest vast differences in gross appearance. There is currently no systematic framework by which to classify HGSOCs according to their gross morphologic characteristics. To develop and characterize a gross morphologic classification system for HGSOC. This cohort study included patients with suspected advanced-stage ovarian cancer who presented between April 1, 2013, and August 5, 2016, to the University of Texas MD Anderson Cancer Center, a large referral center. Patients underwent laparoscopic assessment of disease burden before treatment and received a histopathologic diagnosis of HGSOC. Researchers assigning morphologic subtype and performing molecular analyses were blinded to clinical outcomes. Data analysis was performed between April 2020 and November 2021. Gross tumor morphologic characteristics. Clinical outcomes and multiomic profiles of representative tumor samples of type I or type II morphologic subtypes were compared. Of 112 women (mean [SD] age 62.7 [9.7] years) included in the study, most patients (84% [94]) exhibited a predominant morphologic subtype and many (63% [71]) had a uniform morphologic subtype at all involved sites. Compared with those with uniform type I morphologic subtype, patients with uniform type II morphologic subtype were more likely to have a favorable Fagotti score (83% [19 of 23] vs 46% [22 of 48]; P = .004) and thus to be triaged to primary tumor reductive surgery. Similarly, patients with uniform type II morphologic subtype also had significantly higher mean (SD) estimated blood loss (639 [559; 95% CI, 391-887] mL vs 415 [527; 95% CI, 253-577] mL; P = .006) and longer mean (SD) operative time (408 [130; 95% CI, 350-466] minutes vs 333 [113; 95% CI, 298-367] minutes; P = .03) during tumor reductive surgery. Type I tumors had enrichment of epithelial-mesenchymal transition (false discovery rate [FDR] q-value, 3.10 × 10-24), hypoxia (FDR q-value, 1.52 × 10-5), and angiogenesis pathways (FDR q-value, 2.11 × 10-2), whereas type II tumors had enrichment of pathways related to MYC signaling (FDR q-value, 2.04 × 10-9) and cell cycle progression (FDR q-value, 1.10 × 10-5) by integrated proteomic and transcriptomic analysis. Abundances of metabolites and lipids also differed between the 2 morphologic subtypes. This study identified 2 novel, gross morphologic subtypes of HGSOC, each with unique clinical features and molecular signatures. The findings may have implications for triaging patients to surgery or chemotherapy, identifying outcomes, and developing tailored therapeutic strategies.

Risk factors of recurrence in chronic subdural hematoma and a proposed extended classification of internal architecture as a predictor of recurrence

Chronic subdural hematomas (cSDHs) constitute one of the most prevalent intracranial disease entities requiring surgical treatment. Although mostly taking a benign course, recurrence after treatment is common and associated with additional morbidity and costs. Aim of this study was to develop hematoma-specific characteristics associated with risk of recurrence. All consecutive patients treated for cSDH in a single university hospital between 2015 and 2019 were retrospectively considered for inclusion. Size, volume, and midline shift were noted alongside relevant patient-specific factors. We applied an extended morphological classification system based on internal architecture in CT imaging consisting of eight hematoma subtypes. A logistic regression model was used to assess the classification’s performance on predicting hematoma recurrence. Recurrence was observed in 122 (32.0%) of 381 included patients. Apart from postoperative depressed brain volume (OR 1.005; 95% CI 1.000 to 1.010; p = 0.048), neither demographic nor factors related to patient comorbidity affected recurrence. The extended hematoma classification was identified as a significant predictor of recurrence (OR 1.518; 95% CI 1.275 to 1.808; p < 0.001). The highest recurrence rates were observed in hematomas of the homogenous (isodense: 41.4%; hypodense: 45.0%) and sedimented (50.0%) types. Our results support that internal architecture subtypes might represent stages in the natural history of chronic subdural hematoma. Detection and treatment at a later stage of spontaneous repair can result in a reduced risk of recurrence. Based on their high risk of recurrence, we advocate follow-up after treatment of sedimented and homogenous hematomas.

A Novel and Automated Approach to Classify Radiation Induced Lung Tissue Damage on CT Scans.

Simple SummaryRadiation-induced lung damage (RILD) is a common side effect of treating lung cancer with radiotherapy (RT). RILD is visible on CT imaging, and its radiological appearance can vary dramatically from patient to patient as well as across different sub-regions of the lung and treatment volumes. A classification system for RILD able to differentiate radiological damage on a local level would allow us to better understand the underlying patterns of RILD, see how they change over time post irradiation, and link it with clinical outcomes. In this work we propose a five-class morphological lung tissue classification system that can describe parenchymal tissue changes at the voxel level. The classifier was implemented in a fully automated manner using an optimised deep-learning method, then trained and tested using data acquired through a multi-centre clinical trial. The proposed method performed well on an unseen testing dataset. The automated segmentation achieved considerable overlap with manual segmentations (ranging between 26% and 98% for the five classes) and was graded as acceptable by a clinical expert in 88% of cases. This demonstrates it to be suitable for application on a large dataset to help uncover different patterns of changes in the population.Radiation-induced lung damage (RILD) is a common side effect of radiotherapy (RT). The ability to automatically segment, classify, and quantify different types of lung parenchymal change is essential to uncover underlying patterns of RILD and their evolution over time. A RILD dedicated tissue classification system was developed to describe lung parenchymal tissue changes on a voxel-wise level. The classification system was automated for segmentation of five lung tissue classes on computed tomography (CT) scans that described incrementally increasing tissue density, ranging from normal lung (Class 1) to consolidation (Class 5). For ground truth data generation, we employed a two-stage data annotation approach, akin to active learning. Manual segmentation was used to train a stage one auto-segmentation method. These results were manually refined and used to train the stage two auto-segmentation algorithm. The stage two auto-segmentation algorithm was an ensemble of six 2D Unets using different loss functions and numbers of input channels. The development dataset used in this study consisted of 40 cases, each with a pre-radiotherapy, 3-, 6-, 12-, and 24-month follow-up CT scans (n = 200 CT scans). The method was assessed on a hold-out test dataset of 6 cases (n = 30 CT scans). The global Dice score coefficients (DSC) achieved for each tissue class were: Class (1) 99% and 98%, Class (2) 71% and 44%, Class (3) 56% and 26%, Class (4) 79% and 47%, and Class (5) 96% and 92%, for development and test subsets, respectively. The lowest values for the test subsets were caused by imaging artefacts or reflected subgroups that occurred infrequently and with smaller overall parenchymal volumes. We performed qualitative evaluation on the test dataset presenting manual and auto-segmentation to a blinded independent radiologist to rate them as ‘acceptable’, ‘minor disagreement’ or ‘major disagreement’. The auto-segmentation ratings were similar to the manual segmentation, both having approximately 90% of cases rated as acceptable. The proposed framework for auto-segmentation of different lung tissue classes produces acceptable results in the majority of cases and has the potential to facilitate future large studies of RILD.

Accuracy and reliability of left atrial appendage morphology assessment by new 3D transesophageal echocardiographic rendering modalities: a comparative study with computed tomography

Abstract Funding Acknowledgements Type of funding sources: None. Background/Introduction. Left atrial appendage (LAA) morphology assessed by contrast-enhanced computed tomography (CT) has been associated to the risk of cardioembolic stroke in non-valvular atrial fibrillation. Subsequent studies with the traditional LAA classification system (CS) into 4 morphologies (Chicken wing, Cauliflower, Cactus and Windsock) yielded mixed results in terms of reliability and stroke risk association. Recently, a simple LAA morphology CS (new-LAAcs) based on the LAA bend angle measurement has been suggested. Three-dimensional transesophageal echocardiography (3D TOE) quality imaging has been improved and new volume rendering modalities developed. Purpose. Aim of this study was to evaluate the accuracy and reliability of 2D and new 3D TOE rendering modalities compared to CT in assessing LAA morphology. We used and validated a new simple LAA morphology classification system (new-LAAcs) based on the LAA bend angle in contrast to the traditional CS. Methods. 50 consecutive patients who underwent both cardiac CT and TOE were enrolled. LAA morphology was assessed by three different TEE modalities: (1) 2D TOE inspective evaluation (2D TOE), (2) 3D TOE multiplanar reconstruction (3D TOE MPR) and (3) 3D TOE Philips TrueVue Glass rendering (3D TOE GLASS). We assessed TOE accuracy compared to CT by sensitivity, specificity, accuracy, and Cohen’s kappa. Two trained readers independently adjudicated LAA morphologies in the new-LAAcs and the inter-rater reliability was obtained by percentage agreement and Cohen’s kappa. The reliability of the new- vs. traditional-LAAcs was assessed by CT in terms of reliability rates and influence on LAA morphology prevalence. Results. CT and TOE imaging analyses were feasible in all patients. 2D TOE was fairly accurate in identifying LAA morphology (κ 0.38, p = 0.022) and had only moderate inter-rater (κ 0.46, p = 0.027) and substantial intra-rater (κ 0.62, p = 0.003) reliability rates. 3D TOE showed high validity: 3D TOE MPR had an almost perfect accuracy (κ 0.84, p &amp;lt; 0.001) and substantial (κ 0.77, p &amp;lt; 0.001) inter-rater reliability; 3D TOE GLASS substantial accuracy (κ 0.67, p &amp;lt; 0.001) and almost perfect (κ 0.82, p &amp;lt; 0.001) inter-rater reliability. Intra-rater agreement was almost perfect for both 3D TOE modalities (κ 0.84, p &amp;lt; 0.001). In the comparison among CS the traditional-LAAcs inter-rater reliability was moderate (κ 0.47, p &amp;lt; 0.001) and the intra-rater reliability substantial (κ 0.68, p &amp;lt; 0.001) while the new-LAAcs yielded an almost perfect reliability level (inter-rater κ 0.84, p &amp;lt; 0.001 and intra-rater κ 0.93, p &amp;lt; 0.001). With the traditional-LAAcs, the prevalence of CW LAA was 30 (60%), while with the new-LAAcs the prevalence of low-risk-LAA was 13 (26%), leading to classify 17 (57%) CW morphologies as high-risk-LAA. Conclusions. 3D TOE is an accurate, reliable, and feasible alternative to CT in assessing LAA morphology with the new-LAAcs. The new-LAAcs shows higher reliability rates than the traditional one. Abstract Figure. Abstract Figure.

Human sperm morphology assessment since 2010: experience of an Australian external quality assurance programme

Research questionWhich classification criteria of sperm normality were used after the publication of the World Health Organization (WHO) 5th Edition manual (WHO5), and how did the laboratories perform? DesignSemen samples were sent to enrolled laboratories over a 10-year period for the determination of the proportion of spermatozoa with normal morphology. The coefficient of variation was used to indicate the level of precision between laboratories. ResultsBefore the publication of WHO5, at least six different classification criteria were in use. After 2010, WHO5 was quickly adopted, with 50% of laboratories using WHO5 criteria after the first 2 years, increasing to 94% after 10 years. Reported normal forms by WHO3 and WHO4 users remained consistent; however, the morphology results for each distribution declined significantly over time for WHO5 users (P < 0.001), suggesting laboratories were becoming stricter in their identification of normal spermatozoa. The precision of WHO5 users improved over time as shown by a steady decline in the coefficients of variation. ConclusionsThe introduction of WHO5 resulted in the effective adoption of its morphology classification system, with laboratories showing improved between-laboratory variation over time; however, the identification of normal forms by WHO5 users over time was inconsistent, as laboratories became stricter. Given the reduction in reported normal forms by WHO5 users, it seems that increased training of laboratory personnel or the consideration of validated objective automated analysers in the assessment of sperm morphology would seem warranted.

Sinus Augmentation—Expect the Unexpected: Diagnostic Anatomical Study

“Big-nose variant” is an anatomical phenomenon defined as the pneumatization of inferior third of the nasal cavity within the alveolar ridge while simultaneously displacing the maxillary sinus laterally. The purpose of the present study was to assess the prevalence of the big-nose variant phenomenon and suggest a morphology classification system. Diagnostic anatomical evaluation was performed in a tertiary medical center on 321 randomly selected maxillary cone beam computerized tomography scans of patients who presented at an oral and maxillofacial department. Two anatomical categories were defined for anatomical identification: classes for horizontal mesiodistal distribution, and divisions for vertical distribution. Class 2, defined as location of the nasal/sinus border between the distal edge of the canine up to the distal edge of second premolar, was found to be the most prevalent (64.6%). Class 3, defined as location of the nasal/sinus border distal to mesial edge of the first molar, was found in 17.9% of cases. Regarding the divisions category, in 96% and 58.2% of teeth examined, nasal cavity alone was found to be superior to the canine and first premolar, respectively, defined as Division A. In 46.9% and 85.6% of teeth examined, maxillary sinus alone was located above the second premolar and first molar, respectively, defined as Division C. Identifying Class 3 on the paraxial reconstruction is the first step in identifying big-nose variant, with further assurance gained from each determining division. The use of the classes and divisions may enable better maxillary treatment planning, alert surgeons for the unexpected, and avoid complications.

Mitochondrial fission and mitophagy are independent mechanisms regulating ischemia/reperfusion injury in primary neurons

Mitochondrial dynamics and mitophagy are constitutive and complex systems that ensure a healthy mitochondrial network through the segregation and subsequent degradation of damaged mitochondria. Disruption of these systems can lead to mitochondrial dysfunction and has been established as a central mechanism of ischemia/reperfusion (I/R) injury. Emerging evidence suggests that mitochondrial dynamics and mitophagy are integrated systems; however, the role of this relationship in the context of I/R injury remains unclear. To investigate this concept, we utilized primary cortical neurons isolated from the novel dual-reporter mitochondrial quality control knockin mice (C57BL/6-Gt(ROSA)26Sortm1(CAG-mCherry/GFP)Ganl/J) with conditional knockout (KO) of Drp1 to investigate changes in mitochondrial dynamics and mitophagic flux during in vitro I/R injury. Mitochondrial dynamics was quantitatively measured in an unbiased manner using a machine learning mitochondrial morphology classification system, which consisted of four different classifications: network, unbranched, swollen, and punctate. Evaluation of mitochondrial morphology and mitophagic flux in primary neurons exposed to oxygen-glucose deprivation (OGD) and reoxygenation (OGD/R) revealed extensive mitochondrial fragmentation and swelling, together with a significant upregulation in mitophagic flux. Furthermore, the primary morphology of mitochondria undergoing mitophagy was classified as punctate. Colocalization using immunofluorescence as well as western blot analysis revealed that the PINK1/Parkin pathway of mitophagy was activated following OGD/R. Conditional KO of Drp1 prevented mitochondrial fragmentation and swelling following OGD/R but did not alter mitophagic flux. These data provide novel evidence that Drp1 plays a causal role in the progression of I/R injury, but mitophagy does not require Drp1-mediated mitochondrial fission.

Ancient Native American bone tattooing tools and pigments: Evidence from central Tennessee

Analyses of archaeological bone tool assemblages from the southeastern United States rely principally on morphological classification systems to delineate typologies and infer artifact function. Under these systems the actual purpose of pointed bone artifacts generically classified as “awls” is frequently overlooked. In this study we move beyond basic morphological classification by combining zooarchaeological analysis, technological assessment, use-wear analysis, and materials science studies to examine an assemblage of bone tools from an ancient Native American site in central Tennessee. Our analysis reveals that approximately 3500–1600 BCE, occupants of the Fernvale site employed sharpened turkey (Meleagris gallopavo) bone tools as tattooing implements, and that both red and black pigment remains are directly associated with these artifacts. These materials comprise the earliest directly-identified tattooing tools to date, and demonstrate the persistence of Native American tattooing in southeastern North America over at least three millennia.

Sonographic Lower Uterine Segment Thickness to Predict Cesarean Scar Defect in Pregnant Women

Objective: To study the validity of sonographic lower uterine segment (LUS) thickness in predicting intraoperative cesarean scar defect (CSD) and thin incision sites in term pregnancy. Methods: This was a cross-sectional study involving 111 full-term pregnant women who were scheduled for repeat cesarean delivery from April, 2019 to January, 2020. The sonographic myometrial LUS thickness was measured prior to surgery. The cesarean scar was assessed using the morphologic classification system as either grade 1 (a normally formed LUS), grade 2 (a thin LUS, but without visible content), or grade 3 (a thin LUS with visible content). Then, the ophthalmic caliper was used to measure the incision site’s uterine-wall thickness. The correlations between the sonographic measurements and intraoperative findings were reported. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated.Results: There were two cases (1.8%) of grade 3 CSD. The overall correlation between the sonographic and intraoperative incision-site thickness showed r=0.559 with p-value &lt; 0.001. The sonographic cut-off value of 1.5 mm could predict CSD and a thin incision-site uterine wall with sensitivity, specificity, PPV, NPV of 50.0%, 90.8%, 9.1%, 99.0%, and 37.5%, 94.6%, 54.5%, 90.0%, respectively. A receiver operating characteristic curve was generated to determine the optimum cut-off value at 2.5 mm with a sensitivity of 76.5% and a specificity of 73.3%. The area under the curve was 0.8 (a 95% confidence interval, 0.718-0.885).Conclusion: Abdominal sonography is a valuable tool for the preoperative prediction of CSD. A myometrial LUS thickness of more than 1.5 mm is associated with a lower likelihood of cesarean scar dehiscence.

&lt;i&gt;Terminalia chebula&lt;/i&gt; (Harar) Characterization by using Morphological Descriptors in Himalayan Region

Terminalia chebula Retz. plays a crucial role in foodstuff, medicine, industry, and environmental protection. The skill of recognizing the variants of the species is very important in some applications, including conservation, strain types identification and performance of strains under different agro-ecological situation. However, it is a difficult task to identify plant species because it requires specialized knowledge. Developing morphological classification system for different genotypes and variants is necessary and valuable since it can help specialists as well as the public to identify and avoid cheating. It is a medicinal tree species which is highly valued in Indian system of medicine viz Ayurveda, Yunani, Sidha etc. Terminalia chebula trees are naturally distributed in the Sub Himalayan tract up to 1400 m above mean sea level in subtropical region, although planted trees can be seen in throughout the Northern Indian region. Research has been conducted to survey, locate the variations, identify the productive strains and also identify the ecological distribution of T. chebula in different agro-ecological regions of Himalayan region. The results indicated a high diversity in fruit and leaf shapes. Nine shapes of fruits were observed in the studied locations (Oblong “Matka type”, Oblong dark colour with short neck, Pyriform, Pyriform type fruit with Medium neck, Narrowly obovate without neck, Clavate with prominent neck, Oval, Ellipsoid and light coloured and Narrowly obovate medium in size with acute tip. Analysis showed that there were significant differences in leaf morphmetric characters, too. Nine shapes of leaves were observed in the region viz. Cuspidate, Elliptic, Aristate, Obtuse, Lanceolate, Ovate, Oblique, Ovoid and Oblong.