julilili42/papers huggingface dataset:
Guideline: Multiple Hierarchies
2022-01-26

As the title of the Dagstuhl Seminar ``Digital Historical Corpora - Architecture, Annotation, and Retrieval'' already suggests, corpus architecture and corpus annotation is an important topic for representing (historical) texts. Especially the limitation of SGML-based markup languages to tree structured annotations raises a special problems when dealing with manuscripts: How is it possible to represent overlap. This problem was addressed by the Text Encoding Initiative (TEI) and by several scholars. This text gives an overview of several techniques for handling the overlap problem.
The role of the orbitofrontal cortex in creating cognitive maps
2022-01-26

Abstract We use internal models of the external world to guide behavior, but little is known about how these cognitive maps are created . The orbitofrontal cortex (OFC) is typically thought to access these maps to support model-based decision-making, but it has recently been proposed that its critical contribution may be instead to integrate information into existing and new models. We tested between these alternatives using an outcome-specific devaluation task and a high-potency chemogenetic approach. We found that selectively inactivating OFC principal neurons when rats learned distinct cue-outcome associations, but prior to outcome devaluation, disrupted subsequent model-based inference, confirming that the OFC is critical for creating new cognitive maps. However, OFC inactivation surprisingly led to generalized devaluation. Using a novel reinforcement learning framework, we demonstrate that this effect is best explained not by a switch to a model-free system, as would be traditionally assumed, but rather by a circumscribed deficit in defining credit assignment precision during model construction. We conclude that the critical contribution of the OFC to learning is regulating the specificity of associations that comprise cognitive maps. One Sentence Summary OFC inactivation impairs learning of new specific cue-outcome associations without disrupting model-based learning in general.
Bridging today's Internet Heterogeneity with a Content-oriented Approach
2022-01-26

Despite the success of Internet technology and protocols, their deficiencies become apparent with growing and emerging applications like 3G mobile devices or pervasive environments. In these fields, there is a growing demand for additional support of mobility, multi- or anycast communication, or service composition. ...
MicroStone: Exploring the capabilities of the Artec Micro in scanning stone tools v1
2022-01-26

In this protocol, I describe how to scan small-sized lithics with the high-precision desktop 3D scanner Artec Micro. This scanner is particularly efficient when it comes to scan small objects with a 3D resolution of up to 0.029 mm and a 3D accuracy of 0.01 mm. However, a few slight modifications to the common workflow are needed to obtain accurate 3D meshes of small stone tools such as bladelets, microblades, microflakes. Overall, this scanner represents an efficient and reliable alternative to scan artifacts that cannot be successfully captured by other laser or structured light scanners, such as the Artec Space Spider. If several hundreds of artifacts need to be scanned, a less time-consuming alternative is represented by Micro-CT scanners, using a protocol specifically adapted to this task (i.e., the StyroStone Protocol).
Pathology of Tumors Associated With Pathogenic Germline Variants in 9 Breast Cancer Susceptibility Genes
2022-01-27

IMPORTANCE: Rare germline genetic variants in several genes are associated with increased breast cancer (BC) risk, but their precise contributions to different disease subtypes are unclear. This information is relevant to guidelines for gene panel testing and risk prediction. OBJECTIVE: To characterize tumors associated with BC susceptibility genes in large-scale population- or hospital-based studies. DESIGN, SETTING, AND PARTICIPANTS: The multicenter, international case-control analysis of the BRIDGES study included 42 680 patients and 46 387 control participants, comprising women aged 18 to 79 years who were sampled independently of family history from 38 studies. Studies were conducted between 1991 and 2016. Sequencing and analysis took place between 2016 and 2021. EXPOSURES: Protein-truncating variants and likely pathogenic missense variants in ATM, BARD1, BRCA1, BRCA2, CHEK2, PALB2, RAD51C, RAD51D, and TP53. MAIN OUTCOMES AND MEASURES: The intrinsic-like BC subtypes as defined by estrogen receptor, progesterone receptor, and ERBB2 (formerly known as HER2) status, and tumor grade; morphology; size; stage; lymph node involvement; subtype-specific odds ratios (ORs) for carrying protein-truncating variants and pathogenic missense variants in the 9 BC susceptibility genes. RESULTS: The mean (SD) ages at interview (control participants) and diagnosis (cases) were 55.1 (11.9) and 55.8 (10.6) years, respectively; all participants were of European or East Asian ethnicity. There was substantial heterogeneity in the distribution of intrinsic subtypes by gene. RAD51C, RAD51D, and BARD1 variants were associated mainly with triple-negative disease (OR, 6.19 [95% CI, 3.17-12.12]; OR, 6.19 [95% CI, 2.99-12.79]; and OR, 10.05 [95% CI, 5.27-19.19], respectively). CHEK2 variants were associated with all subtypes (with ORs ranging from 2.21-3.17) except for triple-negative disease. For ATM variants, the association was strongest for the hormone receptor (HR)+ERBB2- high-grade subtype (OR, 4.99; 95% CI, 3.68-6.76). BRCA1 was associated with increased risk of all subtypes, but the ORs varied widely, being highest for triple-negative disease (OR, 55.32; 95% CI, 40.51-75.55). BRCA2 and PALB2 variants were also associated with triple-negative disease. TP53 variants were most strongly associated with HR+ERBB2+ and HR-ERBB2+ subtypes. Tumors occurring in pathogenic variant carriers were of higher grade. For most genes and subtypes, a decline in ORs was observed with increasing age. Together, the 9 genes were associated with 27.3% of all triple-negative tumors in women 40 years or younger. CONCLUSIONS AND RELEVANCE: The results of this case-control study suggest that variants in the 9 BC risk genes differ substantially in their associated pathology but are generally associated with triple-negative and/or high-grade disease. Knowing the age and tumor subtype distributions associated with individual BC genes can potentially aid guidelines for gene panel testing, risk prediction, and variant classification and guide targeted screening strategies.
Atezolizumab and Bevacizumab with Transarterial Chemoembolization in Hepatocellular Carcinoma: The DEMAND Trial Protocol
2022-01-27

The combination of the anti-PD-L1 antibody atezolizumab and the anti-VEGF bevacizumab is the first approved immunotherapeutic regimen for first-line therapy in patients with unresectable hepatocellular carcinoma (HCC), currently approved in more than 80 countries. The efficacy and tolerability of this regimen suggest that the use of atezolizumab + bevacizumab could be extended to the treatment of patients with intermediate-stage HCC in combination with transarterial chemoembolization (TACE). The authors describe the rationale and design of the DEMAND study. This investigator-initiated, multicenter, randomized phase II study is the first trial to evaluate the safety and efficacy of atezolizumab + bevacizumab prior to or in combination with TACE in patients with intermediate-stage HCC. The primary end point is the 24-month survival rate; secondary end points include objective response rate, progression-free survival, safety and quality of life. Clinical Trial Registration: NCT04224636 (ClinicalTrials.gov).
Surgery for infective endocarditis following low-intermediate risk transcatheter aortic valve replacement—a multicentre experience
2022-01-27

Abstract OBJECTIVES With the expansion of transcatheter aortic valve replacement (TAVR) into intermediate and low risk, the number of TAVR procedures is bound to rise and along with it the number of cases of infective endocarditis following TAVR (TIE). The aim of this study was to review a multicentre experience of patients undergoing surgical intervention for TIE and to analyse the underlying indications and operative results. METHODS We retrospectively identified and analysed 69 patients who underwent cardiac surgery due to TIE at 9 cardiac surgical departments across Germany. The primary outcome was operative mortality, 6-month and 1-year survival. RESULTS Median age was 78 years (72–81) and 48(69.6%) were male. The median time to surgical aortic valve replacement was 14 months (5–24) after TAVR, with 32 patients (46.4%) being diagnosed with early TIE. Cardiac reoperations were performed in 17% of patients and 33% underwent concomitant mitral valve surgery. The main causative organisms were: Enterococcus faecalis (31.9%), coagulase-negative Staphylococcus spp. (26.1%), Methicillin-sensitive Staphylococcus aureus (15.9%) and viridians group streptococci (14.5%). Extracorporeal life support was required in 2 patients (2.9%) for a median duration of 3 days. Postoperative adverse cerebrovascular events were observed in 13 patients (18.9%). Postoperatively, 9 patients (13.0%) required a pacemaker and 33 patients (47.8%) needed temporary renal replacement therapy. Survival to discharge was 88.4% and survival at 6 months and 1 year was found to be 68% and 53%, respectively. CONCLUSIONS Our results suggest that TIE can be treated according to the guidelines for prosthetic valve endocarditis, namely with early surgery. Surgery for TIE is associated with acceptable morbidity and mortality rates. Surgery should be discussed liberally as a treatment option in patients with TIE by the ‘endocarditis team’ in referral centres.
Patient‐individual phenotypes of glioblastoma stem cells are conserved in culture and associate with radioresistance, brain infiltration and patient prognosis
2022-01-27

Abstract Identification of prognostic or predictive molecular markers in glioblastoma resection specimens may lead to strategies for therapy stratification and personalized treatment planning. Here, we analyzed in primary glioblastoma stem cell (pGSC) cultures the mRNA abundances of seven stem cell (MSI1, Notch1, nestin, Sox2, Oct4, FABP7 and ALDH1A3), and three radioresistance or invasion markers (CXCR4, IK Ca and BK Ca ). From these abundances, an mRNA signature was deduced which describes the mesenchymal‐to‐proneural expression profile of an individual GSC culture. To assess its functional significance, we associated the GSC mRNA signature with the clonogenic survival after irradiation with 4 Gy and the fibrin matrix invasion of the GSC cells. In addition, we compared the molecular pGSC mRNA signature with the tumor recurrence pattern and the overall survival of the glioblastoma patients from whom the pGSC cultures were derived. As a result, the molecular pGSC mRNA signature correlated positively with the pGSC radioresistance and matrix invasion capability in vitro. Moreover, patients with a mesenchymal (&gt;median) mRNA signature in their pGSC cultures exhibited predominantly a multifocal tumor recurrence and a significantly (univariate log rank test) shorter overall survival than patients with proneural (≤median mRNA signature) pGSCs. The tumors of the latter recurred predominately unifocally. We conclude that our pGSC cultures induce/select those cell subpopulations of the heterogeneous brain tumor that determine disease progression and therapy outcome. In addition, we further postulate a clinically relevant prognostic/predictive value for the 10 mRNAs‐based mesenchymal‐to‐proneural signature of the GSC subpopulations in glioblastoma.
Diatoms from the Spring Ecosystems Selected for the Long-Term Monitoring of Climate-Change Effects in the Berchtesgaden National Park (Germany)
2022-01-27

We studied diatoms from the fifteen springs selected in the Berchtesgaden National Park on behalf of the Bavarian State Ministry for the Environment to be sentinel environments of climate-change effects. For three of these springs, diatom data based on samples taken in 1997 were also available. A total of 162 species belonging to 49 genera were found sampling three microhabitat types (lithic materials, bryophytes, surface sediments). The cumulative percentage of all species included in a threat category including endangered species was 43%, confirming previous findings for comparable environments of the Alps. We could find a statistically significant positive association between the Meinzer variability index for discharge and the cumulative relative abundance of aerial diatom species. This study thus highlighted once again the relevance of discharge (and associated water-level) variability as an environmental determinant of diatom assemblages in spring ecosystems. Increased nitrate concentrations in some springs, likely due to diffuse airborne pollution and, locally, to impacts such as forest management, game, and cattle, led to a relevant occurrence of eutraphentic diatom species. Our results show a segregation of the older data in non-parametric diatom-based ordinations, suggesting a strong potential for the use of spring diatoms in studies aiming at tracking the effects of climate and environmental change.
Neoadjuvant Chemotherapy of Patients with Early Breast Cancer Is Associated with Increased Detection of Disseminated Tumor Cells in the Bone Marrow
2022-01-27

Preclinical data suggest that neoadjuvant chemotherapy (NAT) may promote micrometastatic spread. We aimed to compare the detection rate and prognostic relevance of disseminated tumor cells (DTCs) from the bone marrow (BM) of patients with early-stage breast cancer (EBC) after NAT with that of therapy-naive EBC patients. DTCs were identified from BM samples, collected during primary surgery. Patients who received NAT were compared to patients who received chemotherapy after surgery. In total, 809 patients were analyzed. After NAT, 45.4% of patients were DTC-positive as compared to 19.9% of patients in the adjuvant chemotherapy group (p &lt; 0.001). When sampled in patients who had undergone NAT, the detection of DTCs in the BM was significantly increased (OR: 3.1; 95% confidence interval (CI): 2.1–4.4; p &lt; 0.001). After NAT, DTC-positive patients with ≥2 DTCs per 1.5 × 106 mononuclear cells in their BM had an impaired disease-free survival (HR: 4.8, 95% CI: 0.9–26.6; p = 0.050) and overall survival (HR: 4.2; 95% CI: 1.4–12.7; p = 0.005). The higher rate of DTC-positive patients after NAT as compared to a treatment-naive comparable control cohort suggests that NAT supports tumor cell dissemination into the bone marrow. DTC positivity in BM predicted relapse in various distant organs, implying that tumor cell dissemination was not restricted to the bone marrow.
Clinical predictors for a complicated course of disease in an inception cohort of patients with ulcerative colitis: results from the prospective, observational EPICOL study
2022-01-27

Abstract Purpose The clinical course of ulcerative colitis (UC) is highly heterogeneous, with 20 to 30% of patients experiencing chronic disease activity requiring immunosuppressive or biologic therapies. The aim of this study was to identify predictors for a complicated disease course in an inception cohort of patients with UC. Methods EPICOL was a prospective, observational, inception cohort (UC diagnosis, ≤ 6 months) study in 311 patients with UC who were naive to immunosuppressants (IS)/biologics. A complicated course of disease was defined as the need for IS and/or biologic treatment (here therapy with a TNF-α antagonist) and/or UC-related hospitalisation. Patients were followed up for 24 months. Results Of the 307 out of 311 participants (4 patients did not meet the inclusion criteria “confirmed diagnosis of active UC within the last 6 months” ( n = 2) and “immunosuppressive-naïve” ( n = 2), analysis population), 209 (68.1%) versus 98 (31.9%) had an uncomplicated versus a complicated disease course, respectively. In a multivariate regression analysis, prior use of corticosteroids and prior anaemia were associated with a significantly increased risk for a complicated disease course (2.3- and 1.9-fold increase, respectively; p &lt; 0.001 and p = 0.002). Based on these parameters, a risk model for patient stratification was developed. Conclusion Our study identifies anaemia and an early need for corticosteroids as predictors for a complicated course of disease in an inception cohort of patients with UC. By determining these parameters in routine clinical practice, our results may support the identification of patients who might benefit from early escalation of therapy.
Adaptive Whisking in Mice
2022-01-27

Rodents generate rhythmic whisking movements to explore their environment. Whisking trajectories, for one, appear as a fixed pattern of whisk cycles at 5–10 Hz driven by a brain stem central pattern generator. In contrast, whisking behavior is thought to be versatile and adaptable to behavioral goals. To begin to systematically investigate such behavioral adaptation, we established a whisking task, in which mice altered the trajectories of whisking in a goal-oriented fashion to gain rewards. Mice were trained to set the whisker to a defined starting position and generate a protraction movement across a virtual target (no touch-related tactile feedback). By ramping up target distance based on reward history, we observed that mice are able to generate highly specific whisking patterns suited to keep reward probability constant. On a sensorimotor level, the behavioral adaptation was realized by adjusting whisker kinematics: more distant locations were targeted using higher velocities (i.e., pointing to longer force generation), rather than by generating higher acceleration (i.e., pointing to stronger forces). We tested the suitability of the paradigm of tracking subtle alteration in whisking motor commands using small lesions in the rhythmic whisking subfield (RW) of the whisking-related primary motor cortex. Small contralateral RW lesions generated the deterioration of whisking kinematics with a latency of 12 days post-lesion, a change that was readily discriminated from changes in the behavioral adaptation by the paradigm.
Short‐Term Variability of Proton Density Fat Fraction in Pancreas and Liver Assessed by Multiecho Chemical‐Shift Encoding‐Based MRI at 3 T
2022-01-27

Background Quantification of pancreatic fat (PF) and intrahepatic lipids (IHL) is of increasing interest in subjects at risk for metabolic diseases. There is limited data available on short‐ and medium‐term variability of PF/IHL and on their dependence on nutritional status. Purpose To assess short‐term intraday variations of PF/IHL after a high‐fat meal as well as medium‐term changes after 5 days of high‐caloric diet. Study Type Prospective cohort study. Subjects A total of 12 subjects (six males) for intraday variations study, 15 male subjects for medium‐term high‐caloric diet study and 11 age‐ and body mass index (BMI)‐matched controls. Field Strength/Sequence A 3 T; chemical‐shift encoded multiecho gradient echo sequence. Assessment For the intraday study, subjects were scanned after overnight fasting and after a high fat meal on the same day. For the medium‐term study, 26 subjects were scanned after overnight fasting with 15/11 rescanned after 5 days of high‐calorie diet/isocaloric diet. Proton density fat fraction (PDFF) maps were generated inline on the scanner. Regions of interest were manually drawn in head, body, and tail of pancreas and in the liver by a medical physicist and a doctoral student (26/4 years of experience). PF was calculated as the average of the head, body, and tail measurements. Statistical Tests Repeated measurements ANOVA for assessing changes in PF/IHL, linear correlation analyses for assessing relationships of PF/IHL with BMI. Significance level P &lt; 0.05 for all. Results Nonsignificant changes in PF (2.6 ± 1.0 vs. 2.7 ± 0.9% after high‐fat meal, 1.4 ± 0.8 vs. 1.5 ± 0.6% [high‐caloric diet] and 1.5 ± 0.8 vs. 1.8 ± 1.0% [isocaloric control group]), nonsignificant changes in IHL after high‐fat meal (2.6 ± 1.3 vs. 2.5 ± 0.9%) and in the control group (1.1 ± 0.6 vs. 1.2 ± 1.1%), significantly increased IHL after high‐caloric diet (1.7 ± 2.2% vs. 2.7 ± 3.6%). Nonsignificant changes in PF (2.6 ± 1.0 vs. 2.7 ± 0.9% after high‐fat meal, 1.4 ± 0.8 vs. 1.5 ± 0.6% [high‐caloric diet] and 1.5 ± 0.8 vs. 1.8 ± 1.0% [isocaloric control group]), nonsignificant changes in IHL after high‐fat meal (2.6 ± 1.3 vs. 2.5 ± 0.9%) and in the control group (1.1 ± 0.6 vs. 1.2 ± 1.1%), significantly increased IHL after 5‐days of high‐caloric diet (1.7 ± 2.2% vs. 2.7 ± 3.6%). Data Conclusion Time of day and nutritional status have no significant influence on PF/IHL and are therefore not likely to be major confounders in epidemiologic or clinical studies. Evidence Level 2 Technical Efficacy Stage 1
Tracking human skill learning with a hierarchical Bayesian sequence model
2022-01-27

Abstract Humans can implicitly learn complex perceptuo-motor skills over the course of large numbers of trials. This likely depends on our becoming better able to take advantage of ever richer and temporally deeper predictive relationships in the environment. Here, we offer a novel characterization of this process, fitting a non-parametric, hierarchical Bayesian sequence model to the reaction times of human participants’ responses over ten sessions, each comprising thousands of trials, in a serial reaction time task involving higher-order dependencies. The model, adapted from the domain of language, forgetfully updates trial-by-trial, and seamlessly combines predictive information from shorter and longer windows onto past events, weighing the windows proportionally to their predictive power. As the model defines a prior over window depths, we were able to determine the extent to which the internal predictions of individual participant depended on how many previous elements. Already in the first session, the model showed that participants had begun to rely on two previous elements (i.e., trigrams), thereby successfully adapting to the most prominent higher-order structure in the task. The extent to which local statistical fluctuations influenced participants’ responses waned over subsequent sessions, as subjects forgot the trigrams less and evidenced skilled performance. By the eighth session, a subset of participants shifted their prior further to consider a context deeper than two previous elements. Finally, participants showed resistance to interference and slow forgetting of the old sequence when it was changed in the final sessions. Model parameters for individual subjects covaried appropriately with independent measures of working memory. In sum, the model offers the first principled account of the adaptive complexity and nuanced dynamics of humans’ internal sequence representations during long-term implicit skill learning. Author summary A central function of the brain is to predict. One challenge of prediction is that both external events and our own actions can depend on a variably deep temporal context of previous events or actions. For instance, in a short motor routine, like opening a door, our actions only depend on a few previous ones (e.g., push the handle if the key was turned). In longer routines such as coffee making, our actions require a deeper context (e.g., place the moka pot on the hob if coffee is ground, the pot is filled and closed, and the hob is on). We adopted a model from the natural language processing literature that matches humans’ ability to learn variable-length relationships in sequences. This model explained the gradual emergence of more complex sequence knowledge and individual differences in an experiment where humans practiced a perceptual-motor sequence over 10 weekly sessions.