Which Picker Fits My Data? A Quantitative Evaluation of Deep Learning Based Seismic Pickers

Seismic event detection and phase picking are the base of many seismological workflows. In recent years, several publications demonstrated that deep learning approaches significantly outperform classical approaches, achieving human-like performance under certain circumstances. However, as studies differ in the datasets and evaluation tasks, it is unclear how the different approaches compare to each other. Furthermore, there are no systematic studies about model performance in cross-domain scenarios, that is, when applied to data with different characteristics. Here, we address these questions by conducting a large-scale benchmark. We compare six previously published deep learning models on eight data sets covering local to teleseismic distances and on three tasks: event detection, phase identification and onset time picking. Furthermore, we compare the results to a classical Baer-Kradolfer picker. Overall, we observe the best performance for EQTransformer, GPD and PhaseNet, with a small advantage for EQTransformer on teleseismic data. Furthermore, we conduct a cross-domain study, analyzing model performance on data sets they were not trained on. We show that trained models can be transferred between regions with only mild performance degradation, but models trained on regional data do not transfer well to teleseismic data. As deep learning for detection and picking is a rapidly evolving field, we ensured extensibility of our benchmark by building our code on standardized frameworks and making it openly accessible. This allows model developers to easily evaluate new models or performance on new data sets. Furthermore, we make all trained models available through the SeisBench framework, giving end-users an easy way to apply these models

Multi-Gene Next-Generation Sequencing Panel for Analysis of BRCA1/BRCA2 and Homologous Recombination Repair Genes Alterations Metastatic Castration-Resistant Prostate Cancer

: Despite significant therapeutic advances, metastatic CRPC (mCRPC) remains a lethal disease. Mutations in homologous recombination repair (HRR) genes are frequent in mCRPC, and tumors harboring these mutations are known to be sensitive to PARP inhibitors. The aim of this study was to verify the technical effectiveness of this panel in the analysis of mCRPC, the frequency and type of mutations in the BRCA1/BRCA2 genes, as well as in the homologous recombination repair (HRR) genes. A total of 50 mCRPC cases were analyzed using a multi-gene next-generation sequencing panel evaluating a total of 1360 amplicons in 24 HRR genes. Of the 50 cases, 23 specimens (46.0%) had an mCRPC harboring a pathogenic variant or a variant of uncertain significance (VUS), whereas in 27 mCRPCs (54.0%), no mutations were detected (wild-type tumors). BRCA2 was the most commonly mutated gene (14.0% of samples), followed by ATM (12.0%), and BRCA1 (6.0%). In conclusion, we have set up an NGS multi-gene panel that is capable of analyzing BRCA1/BRCA2 and HRR alterations in mCRPC. Moreover, our clinical algorithm is currently being used in clinical practice for the management of patients with mCRPC

Integrated clinicopathologic and molecular analysis of endometrial carcinoma: Prognostic impact of the new ESGO-ESTRO-ESP endometrial cancer risk classification and proposal of histopathologic algorithm for its implementation in clinical practice

IntroductionThe European Society of Gynecologic Oncology/European Society of Radiation Therapy and Oncology/European Society of Pathology (ESGO/ESTRO/ESP) committee recently proposed a new risk stratification system for endometrial carcinoma (EC) patients that incorporates clinicopathologic and molecular features. The aim of the study is to compare the new ESGO/ESTRO/ESP risk classification system with the previous 2016 recommendations, evaluating the impact of molecular classification and defining a new algorithm for selecting cases for molecular analysis to assign the appropriate risk class.MethodsThe cohort included 211 consecutive EC patients. Immunohistochemistry and next-generation sequencing were used to assign molecular subgroups of EC: POLE mutant (POLE), mismatch repair deficient (MMRd), p53 mutant (p53abn), and no specific molecular profile (NSMP).ResultsImmuno-molecular analysis was successful in all cases, identifying the four molecular subgroups: 7.6% POLE, 32.2% MMRd, 20.9% p53abn, and 39.3% NSMP. The recent 2020 guidelines showed a 32.7% risk group change compared with the previous 2016 classification system: the reassignment is due to POLE mutations, abnormal p53 expression, and a better definition of lymphovascular space invasion. The 2020 system assigns more patients to lower-risk groups (42.2%) than the 2016 recommendation (25.6%). Considering the 2020 risk classification system that includes the difference between “unknown molecular classification” and “known,” the integration of molecular subgroups allowed 6.6% of patients to be recategorized into a different risk class. In addition, the use of the proposed algorithm based on histopathologic parameters would have resulted in a 62.6% reduction in molecular analysis, compared to applying molecular classification to all patients.ConclusionApplication of the new 2020 risk classification integrating clinicopathologic and molecular parameters provided more accurate identification of low-and high-risk patients, potentially allowing a more specific selection of patients for post-operative adjuvant therapy. The proposed histopathologic algorithm significantly decreases the number of tests needed and could be a promising tool for cost reduction without compromising prognostic stratification

Posttraumatic Pseudoarthrosis of a Clavicle Fracture in an 11-Year-Old Girl: A Case Report and Analysis

Clavicular fractures are some of the most common bone injuries in the paediatric population, yet the rates of nonunion are very low under 18 years. To the best of our knowledge, posttraumatic nonunion of the clavicle in a paediatric population is rarely reported. We report the case of an 11-year-old girl who presented with a nondislocated fracture of the midshaft to the proximal third of the right clavicle. Initial conservative treatment by sling immobilization demonstrated radiologically confirmed healing at 3 months. However, at 1-year follow-up, she presented with painful nonunion. Diagnostic MRI and CT exams confirmed a pseudoarthrosis, requiring elective open reduction and internal fixation with the aid of an ipsilateral iliac crest bone graft

Risk of falls in patients with knee osteoarthritis undergoing total knee arthroplasty: A systematic review and best evidence synthesis

Objectives: Falls occur frequently in patients with impaired ambulation and may dramatically affect the elderly population. Aim was to document the incidence of falls in knee osteoarthritis (OA) patients undergoing total knee arthroplasty (TKA), and to identify factors and treatments that may influence the risk of falls. Methods: A systematic literature search was conducted on three medical electronic databases, PubMed, PeDRO, and Cochrane Collaboration. The Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines were used. Risk of bias analysis and best evidence synthesis were performed. The main aspects related to falls were analyzed: prevalence, risk factors, correlation with clinical outcome, effect of treatments. Results: The systematic review identified 11 papers on 1237 patients. Pre-operative fall prevalence ranged from 23% to 63%, while post-operative values ranged from 12% to 38%. Moderate evidence was found on no influence of clinical scales, no BMI differences between “faller” and “non-faller” and on influence of limited pre-operative range of motion. Conflicting evidence was found for sex, history of previous falls, age, kyphosis, muscle weakness, fear of falling, depression, balance, gait impairment. No evidence was found for the effectiveness of surgical or rehabilitative strategies on falls reduction. Conclusions: OA patients undergoing TKA are at high risk of falls, which is reduced but still present after surgery. Although some risk factors were identified, there are no studies demonstrating the possibility of reducing the incidence of this deleterious event, which warrants further research efforts to better manage this fragile population of elderly patients

Isolated Knee Arthritis as Early and Only Symptom of Whipple’s Disease

We report a case of isolated Whipple’s disease involving the knee of a 64-year-old female patient who presented recurrent monoarthritis whose origin was not clear. Initially, the cause of the gradually invalidating symptoms was related to a meniscal lesion and a diffuse minor grade chondropathy, but pain and functional impairment suggested that more exams were needed. Biopsies were performed during arthroscopy. The histology showed highly inflammatory infiltrates with PAS staining negative for Tropheryma while PCR revealed the infection with Tropheryma whipplei. This, following the recommendation of a rheumatologist and infectious disease specialist, led to biopsies of the gastrointestinal tract and analysis of the cerebrospinal fluid that showed no other organ involvement. This confirms the scientific literature that an isolated monoarthritis without involvement of the gastrointestinal tract caused by this bacterium is rare but can occur as an early manifestation of potentially fatal systemic disease. Moreover, a review of the scientific literature showed the uncertainty about epidemiology of this rare disease, suggesting that more and specific data are required

Genomic Landscape, Clinical Features and Outcomes of Non-Small Cell Lung Cancer Patients Harboring BRAF Alterations of Distinct Functional Classes

Background: In non-small cell lung cancer (NSCLC), BRAF class 1 alterations are effectively targeted by BRAF inhibitors. Conversely, targeted therapies have very low or absent activity in patients carrying class 2 and 3 alterations. The spectrum of BRAF alterations in NSCLC patients, and their accompanying clinical features, genomic landscape and treatment outcomes have been poorly reported. Patients and methods: We identified BRAF alterations of defined functional class across different tumors through a systematic review. Then, we selected NSCLC patients carrying BRAF alterations, according to the systematic review, in the cBioPortal (cBioPortal cohort) to collect and analyze clinical, biomolecular and survival data. Finally, we identified NSCLC patients carrying BRAF non-V600 mutations enrolled in POPLAR and OAK trials (POPLAR/OAK cohort), extracting clinical and survival data for survival analyses. Results: 100 different BRAF non-V600 alterations were identified through the systematic review. In the cBioPortal cohort (n = 139), patients harboring class 2 and 3 alterations were more frequently smokers and had higher tumor mutational burden compared to those carrying class 1 alterations. The spectrum of most frequently co-altered genes was significantly different between BRAF alterations classes, including SETD2, STK11, POM121L12, MUC16, KEAP1, TERT, TP53 and other genes. In the POPLAR/OAK cohort, patients carrying non-V600 BRAF alterations were characterized by poor prognosis compared to BRAF wild-type patients. Conclusions: Different classes of BRAF alterations confer distinctive clinical features, biomolecular signature and disease behavior to NSCLC patients. Non-V600 alterations are characterized by poor prognosis, but key gene co-alterations involved in cancer cell survival and immune pathways may suggest their potential sensitivity to tailored treatments

Chromosome 3p gene alterations as biomarkers for immunocombinations in metastatic renal cell carcinoma: A hypothesis-generating analysis

Background: Identifying biomarkers for metastatic renal cell carcinoma (mRCC) is an unmet need in actual immunotherapy era. Available data regarding chromosome 3p genes (i.e., VHL, PBRM1, SETD2) mutations as potential predictors for therapy response is conflicting. We describe the impact of these mutations on clinical outcomes in mRCC patients treated with immune checkpoint inhibitor (ICI)-doublet or ICI/tyrosine kinase inhibitor (TKI) combinations. Methods: We performed a single-center retrospective analysis on mRCC patients treated with first line ICI/ICI or ICI/TKI. A multi-gene panel was used, allowing the amplification of 841 amplicons (54.93 kb, human reference sequence hg19/GRCh37) in the coding sequences of the following genes: ATM, BAP1, KDM5C, MET, MTOR, NF2, PBRM1, PIK3CA, PTEN, SETD2, SMARCB1, TP53, TSC1, TSC2, VHL. Results: 18 patients undergoing ICI/ICI and ICI/TKI who had tumor tissue adequate for molecular analysis were included. Histology was 100% clear cell. IMDC risk was 50% intermediate, 33.4% good, 16.6% poor. First line therapy was 89% ICI/TKI, 11% ICI/ICI. 83.3% pts (n = 15) carried genomic alterations (GA). Most common GA included VHL in 44% (n = 8; 7 pathogenic - PAT and 1 variant of unknown significance - VUS), PBRM1 in 44% (n = 8; 5 PAT and 3 VUS) and SETD2 in 33% (n = 6; 4 PAT and 2 VUS). With the limit of a small sample that did not allow proper statistical analyses, SETD2-mutated patients had lower median progression free (mPFS) and overall survival (mOS) than non-SETD2 mutated patients. Higher mPFS and mOS were shown with VHL or PBRM1 GA, especially in PBRM1 +VHL mutated pts. Conclusions: Our data shows a possible negative predictive role of SETD2 GA for ICI-based therapy in RCC. Concomitant VHL and PBRM1 GA could act as a predictor for ICI/TKI efficacy. Our hypothesis-generating analysis highlights the need of an integrated evaluation of these genes as promising biomarkers in RCC. Further larger studies are required

A hypothesis-generating analysis on the role of TERT promoter mutation in advanced urothelial carcinoma treated with immunotherapy

Background: The therapeutic scenario of urothelial carcinoma is constantly expanding with the widening of the knowledge on molecular characteristics, thus claiming for the need of prognostic and predictive factors to guide treatment strategy. TERT promoter mutation is one of the most frequent genomic alterations in urothelial car-cinoma and could present several implications, from diagnostic to prognostic or potentially even predictive. Methods: We performed a single-center retrospective analysis on patients with advanced urothelial carcinoma treated with an immune checkpoint inhibitor as second line of therapy to assess the status of the TERT promoter and the potential implication of its mutation on survival outcomes. Results: We analyzed tissue samples from 11 patients with a next-generation sequencing multi-gene panel. The most frequently altered genes were TP53 (54.5%, n = 6) and TERT promoter (36.3%, n = 4). Other mutations found were BRAF, SMAD4, PIK3CA / PDGRFA. The only type of detected TERT promoter mutation was the c 0.124 C > T (n = 4/4, 100%). Of the 4 TERT mutated patients, 2 presented a co-mutation of TP53. Patients with TERT promoter mutation treated with immunotherapy presented a low median overall survival (16.5 months) and progression-free survival (3.8 months). Conclusions: Our hypothesis-generating analysis suggests that the presence of TERT promoter mutation could have a negative prognostic value and should be further evaluated in wider cohorts