julilili42/papers huggingface dataset:
Recognizing but not harming. Borderline B‐cell lymphoid proliferations
2021-06-01

Abstract In the last years several borderline B‐cell lymphoid proliferations have been recognized that lie at the interface between benign and malignant. These lesions can be divided in two groups; those considered precursor lesions of well recognized lymphoid malignancies and the group of indolent lymphomas with limited potential for progression. Precursor lesions are monoclonal and share many genetic features of their malignant counterpart. The first recognized precursor lesion was monoclonal gammopathy of undetermined significance. Thereafter, the widespread use of immunohistochemistry, fluorescence‐activated cell sorting analysis and molecular techniques in lymphoid samples led to the recognition of other precursor lesions such as monoclonal B‐cell lymphocytosis, in situ follicular neoplasia and in situ mantle cell neoplasia. The second group of disorders comprises monoclonal lymphoid proliferations with limited malignant potential without a counterpart among the currently recognized lymphoma entities; these include pediatric‐type follicular lymphoma, pediatric nodal marginal zone lymphoma, and duodenal‐type follicular lymphoma. Despite their clonal nature, a conservative treatment has been shown to be sufficient in most cases. The diagnostic criteria of precursor/indolent B‐cell proliferations, recent advances in the understanding of progression and lymphomagenesis and current recommendations for treatment will be discussed. In order to avoid unnecessary and potentially harmful therapy, these lesions need to be recognized and diagnosed correctly.
Detecting Anomalies in Semantic Segmentation with Prototypes
2021-06-01

Traditional semantic segmentation methods can recognize at test time only the classes that are present in the training set. This is a significant limitation, especially for semantic segmentation algorithms mounted on intelligent autonomous systems, deployed in realistic settings. Regardless of how many classes the system has seen at training time, it is inevitable that unexpected, unknown objects will appear at test time. The failure in identifying such anomalies may lead to incorrect, even dangerous behaviors of the autonomous agent equipped with such segmentation model when deployed in the real world. Current state of the art of anomaly segmentation uses generative models, exploiting their incapability to reconstruct patterns unseen during training. However, training these models is expensive, and their generated artifacts may create false anomalies. In this paper we take a different route and we propose to address anomaly segmentation through prototype learning. Our intuition is that anomalous pixels are those that are dissimilar to all class prototypes known by the model. We extract class prototypes from the training data in a lightweight manner using a cosine similarity-based classifier. Experiments on StreetHazards show that our approach achieves the new state of the art, with a significant margin over previous works, despite the reduced computational overhead. Code is available at https://github.com/DarioFontanel/PAnS.
DOSE‐ADJUSTED EPOCH‐RITUXIMAB OR INTENSIFIED B‐NHL‐BFM‐TYPE THERAPY FOR PEDIATRIC PRIMARY MEDIASTINAL B‐CELL LYMPHOMA
2021-06-01

Introduction: There is no standard therapy for children and adolescents with primary mediastinal large B-cell lymphoma (PMBCL). Relapse rates reach up to 40% with chemotherapy regimen designed for treatment of mature B-NHL in children. Therefore, treatment for children and adolescents was intensified in the B-NHL BFM 04 trial (B 04). Dose-adjusted chemo-immunotherapy with etoposide, prednisone, cyclophosphamide, doxorubicin and rituximab (DA-EPOCH-R) has been reported as an alternative, effective treatment strategy in adults and few children and was subsequently introduced as treatment recommendation by the NHL-BFM study group. Methods: Treatment for PMBCL in the B 04 trial (2004 – 2010) was stratified by initial LDH values and intensified from the previous NHL-BFM 95 trial (N 95) by adding two treatment courses. The infusion time of MTX in B 04 was 24 hours for all patients, while it was 4 hours for 7/20 patients in N 95. From 2010 onward, patients with PMBCL in the B 04 trial and the NHL-BFM registry 2012 received DA-EPOCH-R. The recommendation was modified from the original protocol by the limitation of the cumulative dose of doxorubicin to 360 mg/m2 and the application of at least one dose of intrathecal chemotherapy. We compared the efficacy of DA-EPOCH-R (n = 67, 52 without 1-2 courses BFM-type pretreatment) and intensified BFM-type chemotherapy for mature B-NHL (n = 29) for children and adolescents with PMBCL included in the B 04 trial and the NHL-BFM registry 2012 to the previous treatment strategy of the N 95 trial (n = 20). Results: Two patients were excluded because they received different treatment. The median age of 116 patients was 16.2 years, 53% were female. For treatment with DA-EPOCH-R, B 04 and N 95, event-free (EFS) survival at 5 years was 84% (95%-confidence interval (CI), 72 – 91%), 59% (CI, 39 – 74%), and 39% (CI, 23 – 65%); survival (OS) was 90% (CI, 79 – 95%), 72% (CI, 51 – 88%) and 70% (CI, 45 – 85%), respectively. EFS and OS with DA-EPOCH-R were significant superior to treatment with B 04 (p = .016 for EFS, p = .039 for OS) and N 95 (p < .001 for EFS and p = .026 for OS). The difference in EFS observed between intensified B-NHL-BFM 04 and the previous treatment regimen was not significant (p = .14). EFS for 52 patients receiving DA-EPOCH-R without pretreatment was 87% (CI, 74 – 93%). CNS was involved at relapse in four of 11 patients relapsing after DA-EPOCH-R in contrast to none of 22 after BFM-type B-NHL-therapy (p = .008). Except for younger age at diagnosis, no risk factor for treatment failure with DA-EPOCH-R was identified. EA - previously submitted to regional or national meetings (up to 1000 attendees) Keywords: Non-Hodgkin (Pediatric, Adolescent, and Young Adult), Combination Therapies No conflicts of interests pertinent to the abstract.
A REVIEW OF WRITTEN SOURCES ABOUT OGUZ CITIES IN KAZAKHSTAN’S SECTION OF THE GREAT SILK ROAD
2021-06-01

One of the routes of the Great Silk Road crossed the southern lands of presentday Republic of Kazakhstan. In the southern territories of Kazakhstan, that is, in the middle and lower parts of Syr Darya River, there are cities of the Oghuz period. There are over 50 settlements and towns of Oghuzs along the Syr Darya River. The towns in the lower part of Syr Darya are closely linked to the Great Silk Road, which runs along the caravan routes. During this period, the Oghuz lived in the east, neighboring China. They are mentioned in the inscriptions of the Orkhon. The article presents general information is given about medieval towns such as Sauran (Sabran, Kara Töbe), Signak, Barshinkent (Barçınlığı Kent), Asanas (Aşanas), Zhend (Cend), Zhankent (New Town), which are known as Oghuz towns. The fact that the names of the cities changed not once, but several times, and the opinions of scientists were indicated. The names of historic cities are now widely known among researchers and the population. The article was written in connection with these titles. Moreover, in this study, extensive research was conducted examining the works of notably Russian historians and writers, as well as famous medieval historians. Key words: Great Silk Road, Kazakhstan, Syr Darya River, medieval cities/towns, oghuzes.
WITHDRAWN: A prospective preliminary clinical study on the efficacy of orlistat combined with drospirenone or ethinyl estradiol tablets on overweight or obese PCOS
2021-06-01

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
CYTIDINE DEAMINASES SHAPE THE GENOME OF GERMINAL CENTER B CELL DERIVED LYMPHOMA
2021-06-01

Introduction: Most human lymphomas have their origin in the germinal center (GC) reaction where the cytidine deaminase AID (encoded by the AICDA gene) targets the B cell genome. Although AID's activity at non-immunoglobulin (Ig) genes is reported, this off-target effect is not the only source of tumorigenic mutations in lymphoma patients. Thus, we aimed for a better understanding of AID independent mechanisms of mutagenesis in GC B cell derived lymphomagenesis. Methods: Genetic Aicda knockout was combined in a pre-clinical mouse lymphoma model characterized by GC B cell specific MYC and PI3K co-activation. In-depth characterization of pre-malignant and malignant GC B cells was achieved by flow cytometry, immunohistology and next generation sequencing technologies. The murine findings were confirmed using data derived from human B cells and lymphoma cells provided by the ICGC MMML-seq consortium. Results: In young mice, AID deficiency promoted GC formation, although GC B cell proliferation, survival and differentiation were similar in AID proficient and deficient animals. Upon aging, GC B cell derived lymphomagenesis was unperturbed in the absence of AID. In AID deficient tumors the lack of mutations in Ig genes was in contrast to the increased mutation load in non-Ig genes compared to AID proficient lymphoma. Gene expression profiling and the detection of distinct mutational signatures pointed to the function of the cytidine deaminase APOBEC1 in murine AID deficient lymphoma. The mining of human data uncovered the expression of APOBEC3 family members in human B cells, including APOBEC3B induction in GC B cells, thereby mimicking murine Apobec1 expression kinetics. Although APOBEC3B expression levels were variable across different GC B cell derived lymphoma entities, the positive correlation of its expression and presence of APOBEC related DNA signatures indicates its relevance in human lymphomagenesis. Conclusions: Our research provides experimental evidence of APOBEC mediated DNA mutagenesis in an autochthonous mouse lymphoma model and supports these findings in lymphoma patient data sets. Thus, we unveiled AID independent transformation in lymphoma prone GC B cells and highlight APOBEC enzymes as mutation driver in GC B cell derived lymphomagenesis. The research was funded by: the Deutsche Krebshilfe (Max Eder Program 111349 to S.Sander), the Deutsche Jose Carreras Leukämiestiftung (11/2017 to S.Sander), FOR2674, SFB873 funded by the DFG, the DKTK Joint Funding “RiskY-AML” and the Dietmar Hopp Foundation (to A.Trumpp) and SFB1074 funded by the DFG (to R.Siebert). Keywords: Tumor Biology and Heterogeneity, Aggressive B-cell non-Hodgkin lymphoma No conflicts of interest pertinent to the abstract.
TRIPLE POSITIVE (CD10+BCL6+MUM1+) DIFFUSE LARGE B‐CELL LYMPHOMAS IN ADULTS ARE A HETEROGENEOUS GROUP ENRICHED IN LARGE B‐CELL LYMPHOMAS WITH IRF4 REARRANGEMENT
2021-06-01

Introduction: Gene expression profiling (GEP) divides DLBCL according to the cell of origin (COO) into GCB, ABC and unclassifiable (UNC), exhibiting different mutational profiles. The Hans algorithm (HA), a surrogate of GEP, classifies cases expressing CD10, BCL6 and MUM1 as GCB but it is not clear whether all these cases correspond to GCB-type. Accordingly, LBCL with IRF4 rearrangement (LBCL-IRF4) usually expresses a GCB phenotype (CD10+, BCL6+) together with strong MUM1/IRF4. The aim of this study was to characterize the molecular heterogeneity of DLBCL triple positive (CD10 + BCL6 + MUM1+) in adults. Methods: Fifty-five triple positive DLBCL were investigated with FISH (BCL2, BCL6, MYC, IRF4, IGH, IGL), NGS targeted sequencing (SureSelectXT, 66 genes), COO using Nanostring and/or HTG molecular, and copy number (CN) analysis using Oncoscan platform. The mutational subtype was defined using the algorithm by Wright et al (Cancer Cell 2020). Results: According to GEP, 32/54 (59%) cases were classified as GCB, 17/54 cases (32%) as ABC, and 5/54 (9%) UNC. Based on FISH analyses 3 groups were recognized. Group 1 included 15/55 cases (27%) without translocations. Eight cases (54%) were GCB-, whereas 7 cases ABC-type (46%). The MCD mutational profile predominated in this group (6/12; 50%). Group 2 included 11/55 cases (20%) with isolated IRF4 alterations; 5 cases each were sub-classified either as GCB or ABC. This group was characterized by one or multiple IRF4 mutations (82%) and frequent MYD88, CARD11 and CD79B mutations. In two cases no IRF4 break was identified; however, these two cases had a light chain IG break and multiple IRF4 mutations. Group 3 included 29/55 cases (53%) with one or several translocations in BCL2/BCL6/MYC/IGH. Two of these cases had a complex FISH constellation with BCL2 and/or BCL6 together with IRF4 translocation. In this group predominated the GCB-type (19/29; 66%) and the EZB (8/25; 32%) mutational profile. Oncoscan was performed in 7 cases of LBCL-IRF4. A total of 118 genetic alterations were identified (mean: 17 CNA/case). The comparison between LBCL-IRF4 in adults and previously published data in pediatric population (figure) showed no difference in terms of recurrent CN regions; however, adult cases showed higher genetic complexity (17 vs 6.25 alt/case; P = 0.33) and more often ABC COO (P = 0.05). Mutational comparison showed higher mutational load in adult cases (10.6 vs 4.7 mutation/case; P = 0.004) and higher frequency of KMT2D, MYD88 and BTG2 mutations (P < 0.05). Keywords: Pathology and Classification of Lymphomas No conflicts of interests pertinent to the abstract. SESSION 11: HODGKIN LYMPHOMA
Value of cardiac magnetic resonance imaging derived spectral myocardial strain pattern for non-invasive diagnosis of myocarditis
2021-06-01

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Society of Radiology European Institute for Biomedical Imaging Research Background Traditionally, cardiac function is quantified by measures of peak excursion, for example ejection fraction. However, myocardial strain estimation from cine- cardiac MRI allows quantification of cardiac motion over the whole heart cycle. We propose a spectral decomposition of the strain curves applying Discrete Fourier transformation (DFT). Purpose To evaluate a potential additive diagnostic value of spectral temporal strain curve quantification for non-invasive diagnosis of myocarditis using cardiac MRI. Methods In the single-center prospective study patients with suspected myocarditis underwent comprehensive cardiac MRI followed by biventricular endomyocardial biopsy (EMB) between 2012 and 2014. DFT was applied to myocardial strain curves extracted from cine-Images. As reference model, a L1- and L2-penalized logistic regression model using global native T1 time, T2 time and presence of late-gadolinium enhancement was trained to predict EMB results and compared to two models which additionally include three orders of DFT coefficients and ejection fraction, respectively. Predictive performance was evaluated in a tournament-leave-pair-out cross-validation approach with a bootstrap correction for testing of multiple hyperparameter configurations. Results Out of 100 patients (28 % female, median age 40 [IQR 32 to 56) years) with acute symptom-onset (&amp;lt;30 days) 65 had pathologically proven myocarditis in EMB. The DFT model showed best discrimination (Area under the receiver-operating-curve [AUC] 0.72 [95% CI 52 to 87]). Addition of ejection fraction (AUC 0.60 [95% CI: 0.43 to 0.74]) did not increase AUC compared to the reference (AUC 0.60 [95% CI: 0.43 to 0.74]). Posterior distribution of the bootstrap-corrected AUC difference between DFT and reference model was gaussian (mean 12%, standard deviation 12%) with a posterior probability of 86%, that DFT has a greater AUC. Conclusions Discrimination of myocarditis from similar clinical presentations remains challenging. The results support incremental discriminatory value of DFT-decomposed myocardial strain for non-invasive diagnosis of myocarditis. Future research should address the value of the spectral decomposition of cardiac motion trajectories in larger samples and different disease entities.
Anthropomorphic figurines and miniature beads from the Early Neolithic settlement of Ilindentsi, southwest Bulgaria
2021-06-01

The paper presents two types of small artefacts: anthropomorphic figurines and miniature beads, all of which were acquired during the excavations of the Early Neolithic settlement at Ilindentsi during 2011–2018. The anthropomorphic clay figurines are arranged in three groups: Group 1 – figurines with enlarged hips and buttocks (steatopygia); Group 2 – prism/parallelepiped shaped figurines and Group 3 – figurines with plastic projections on the head (buns or horns). One partially preserved marble figurine was also found. All of these objects show an interesting spatial distribution while being concentrated in two distant houses. All figurines confirm a general trend in the development of these objects in the central Balkans and northern Greece but also emphasise the supraregional contacts with the Pannonian Plain. Miniature beads are very characterisic of the Early Neolithic settlement at Ilindentsi. Forty-one beads have been found, most of them within the boundaries of house No 2. Thirty-six beads were made of clay and only five beads from other raw materials: shell, rock and mother-of-pearl. The collection of miniature clay beads from Ilindnetsi is unique, with no parallels from other contemporary sites in the Balkans. In terms of importance it places Ilindentsi right after emblematic Anatolian sites such as Çatalhöyük and Çukuriçi. The clay beads from Ilindentsi pose a number of questions about their place and role in the so-called Neolithic package; their function, social dimension and last but not least their expression of people’s specialized skills.
The Special, Enviable Role of GWMR
2021-06-01

This column reviews the general features of PHT3D Version 2, a reactive multicomponent transport model that couples the geochemical modeling software PHREEQC-2 (Parkhurst and Appelo 1999) with three-dimensional groundwater flow and transport simulators
New insights into the manual activities of individuals from the Phaleron cemetery (Archaic Athens, Greece)
2021-06-02

Until the early 5th century BC, Phaleron Bay was the main port of ancient Athens (Greece). On its shore, archaeologists have discovered one of the largest known cemeteries in ancient Greece, including a range of burial forms, simple pits, cremations, larnaces (clay tubs), and series of burials of male individuals who appear to have died violent deaths, referred to here as “atypical burials”. Reconstructing the osteobiographies of these individuals will help create a deeper understanding of the socio-political conditions preceding the rise of Classical Athens. Here, we assess the habitual manual behavior of the people of Archaic Phaleron (ca. 7th – 6th cent. BC), relying on a new and precise three-dimensional method for reconstructing physical activity based on hand muscle attachment sites. This approach has been recently validated on laboratory animal samples as well as on recent human skeletons with a detailed level of long-term occupational documentation (i.e., the mid-19th century Basel Spitalfriedhof sample). Our Phaleron sample consists of 48 adequately preserved hand skeletons, of which 14 correspond to atypical burials. Our results identified consistent differences in habitual manual behaviors between atypical burials and the rest. The former present a distinctive power-grasping tendency in most skeletons, which was significantly less represented in the latter (p-values of &lt;0.01 and 0.03). Based on a comparison with the uniquely documented Basel sample (45 individuals), this entheseal pattern of the atypical burials was exclusively found in long-term heavy manual laborers. These findings reveal an important activity difference between burials typical for the Phaleron cemetery and atypical burials, suggesting that the latter were likely involved in distinctive, strenuous manual activities. The results of this pilot study comprise an important first step towards reconstructing the identity of these human skeletal remains. Future research can further elucidate the occupational profiles of these individuals through the discovery of additional well-preserved hand skeletons and by extending our analyses to other anatomical regions.
Empathy in paedophilia and sexual offending against children: a longitudinal extension
2021-06-02

Deficits in cognitive empathy (CE) have been associated with a child sexual offense (CSO) history in paedophilia. However, these results have been obtained in cross-sectional comparison. There are no longitudinal studies yet. We performed a longitudinal study with a 3-year interval and investigated CE and emotional empathy (EE) using the Multifaceted Empathy Test (MET) and the Interpersonal Reactivity Index (IRI) in paedophilic men with a CSO history (P + CSO), paedophilic men without a CSO history (P-CSO), and non-offending teleiophilic male controls (TC). Results were stable and confirmed cross-sectional data with evidence for higher CE as measured by the MET in P-CSO compared to P + CSO. Evidence for more distress in social situations as measured by the IRI was found in P-CSO compared to TC, only. Our results highlight the importance of addressing multiple aspects of empathy in paedophilia and CSO and support the inclusion of CE training in the prevention of CSO.
Alpha2-Adrenoblockers Regulate Development of Oxidative Stress and Cognitive Behaviour of Rats under Chronic Acoustic Stress Conditions
2021-06-02

Noise is a wide-spread stress factor in modern life produced by urbanization, traffic, and an industrialized environment. Noise stress causes dysfunction and neurotransmission impairment in the central nervous system, as well as changes in hormone levels. In this study, we have examined the level of α-Tocopherol (α-T) and malondialdehyde (MDA) in plasma and the erythrocytes’ membrane (EM), as well as the behavioral characteristics of a noise-induced stress model in rats. In addition, the modulating effect of α2-adrenoblockers, beditin, and mesedin on the aforementioned parameters has been investigated. For these purposes, albino male rats were divided into four groups: (1) untreated; (2) noise-exposed, (3) noise-exposed and beditin-treated (2 mg/kg, i.p.), and (4) noise-exposed and mesedin-treated (10 mg/kg, i.p.) animals. Noise-exposed groups were treated with 91dBA noise on 60 days with a daily duration of 8 h. Increased MDA and decreased α-T levels in plasma and EM were observed upon chronic high-level noise exposure. Locomotor and behavioral activity assessed with a Y-maze revealed disorientation and increased anxiety under chronic noise exposure. Prominently, α2-adrenoblockers alleviated both behavioral deficits and oxidative stress, providing evidence for the involvement of α2-adrenoceptor in the pathophysiology of noise-induced stress.