julilili42/papers huggingface dataset:
Laser Ablation – ICP-MS measurements for high resolution chemical ice core analyses with a first application to an ice core from Skytrain Ice Rise (Antarctica)
2024-01-05

Abstract. For many ice core related scientific questions, like the analysis of fast changing climate signals, the depth resolution of conventional methods of analysis is not sufficient. In this study we present a setup of Laser Ablation Inductively Coupled Plasma – Mass Spectrometry (LA-ICP-MS) for high resolution glacier ice impurity analysis to the sub-millimetre scale. This setup enables chemical impurity ice core analysis to a depth resolution of ~ 80 μm while consuming only minimal amounts of ice. The system was used for simultaneous analysis of sodium, magnesium and aluminium incorporated in the ice structure. In a first case study within the framework of the WACSWAIN (WArm Climate Stability of the West Antarctic ice sheet in the last INterglacial) project, the method was applied to a selection of samples from Skytrain ice core (West Antarctica), on a total length of 6.7 m consisting of about 130 single samples. The main goal of this study was to use the new LA-ICP-MS method to extract meaningful climate signals on a depth resolution level beyond the limits of Continuous Flow Analysis (CFA). A comparison between low resolution CFA data and the high resolution LA-ICP-MS data reveals generally good agreement on the decimetre scale. Stacking of parallel laser measurements together with frequency analysis is used to analyse the high resolution LA-ICP-MS data on the millimetre scale. Spectral analysis revealed that despite effects of impurity accumulation in ice crystal grain boundaries, periodic concentration changes in the Skytrain ice core on the millimetre scale can be identified in ice from 26 ka BP (kilo years before present; 1950 CE) and also from the Last Interglacial (LIG). These findings can open new possibilities for climate data interpretation with respect to fast changes in the last glacial and beyond.
Small non-coding RNA content in plasma-derived extracellular vesicles distinguish ataxic SCA3 mutation carriers from pre-ataxic and control subjects
2024-01-05

Abstract Spinocerebellar ataxia type 3 (SCA3), a neurodegenerative disorder caused by a CAG expansion in the ATXN3 gene, is the most common spinocerebellar ataxia subtype worldwide. Currently, there is no therapy to stop or prevent disease progression. Promising therapeutic strategies are emerging, but their translation into clinical practice requires sensitive and reliable biomarkers. Blood circulating extracellular vesicles constitute a promising source of biomarkers with potential to track alterations of the central nervous system due to their ability to cross the blood brain barrier. Here, we perform sequencing analysis of small RNAs from plasma-derived extracellular vesicles from SCA3 mutation carriers (10 pre-ataxic and 10 ataxic) and 12 control subjects to identify potential RNA biomarker candidates for this disease. Data showed that plasma-derived extracellular vesicles from ataxic SCA3 mutation carriers are enriched in mitochondrial, nuclear, and nucleolar RNA biotypes compared to pre-ataxic and control subjects. Moreover, ataxic mutation carriers could be discriminated from control and pre-ataxic subjects based on the miRNAs or piRNAs content, but not tRNA. Furthermore, we identified a subset of differentially expressed miRNAs and piRNAs that clearly differentiate ataxic mutation carriers from pre-ataxic and control subjects. These findings open new avenues for further investigation on the role of these RNAs in the pathogenesis of SCA3 and their potential as biomarkers for this disease.
Aβ38 and Aβ43 do not differentiate between Alzheimer's disease and cerebral amyloid angiopathy
2024-01-07

Abstract Differential diagnosis between Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA) using cerebrospinal fluid (CSF) biomarkers is challenging. A recent study suggested that the addition of Aβ38 and Aβ43 to a standard AD biomarker panel (Aβ40, Aβ42, t‐tau, p‐tau) to improve the differential diagnosis. We tested this hypothesis in an independent German cohort of CAA and AD patients and controls using the same analytical techniques. We found excellent discrimination between AD and controls and between CAA and controls, but not between AD and CAA. Adding Aβ38 and Aβ43 to the panel did not improve the discrimination between AD and CAA.
Local studies provide a global perspective of the impacts of climate change on Indigenous Peoples and local communities
2024-01-08

Abstract Indigenous Peoples and local communities with nature-dependent livelihoods are disproportionately affected by climate change impacts, but their experience, knowledge and needs receive inadequate attention in climate research and policy. Here, we discuss three key findings of a collaborative research consortium arising from the Local Indicators of Climate Change Impacts project. First, reports of environmental change by Indigenous Peoples and local communities provide holistic, relational, placed-based, culturally-grounded and multi-causal understandings of change, largely focused on processes and elements that are relevant to local livelihoods and cultures. These reports demonstrate that the impacts of climate change intersect with and exacerbate historical effects of socioeconomic and political marginalization. Second, drawing on rich bodies of inter-generational knowledge, Indigenous Peoples and local communities have developed context-specific responses to environmental change grounded in local resources and strategies that often absorb the impacts of multiple drivers of change. Indigenous Peoples and local communities adjust in diverse ways to impacts on their livelihoods, but the adoption of responses often comes at a significant cost due to economic, political, and socio-cultural barriers operating at societal, community, household, and individual levels. Finally, divergent understandings of change challenge generalizations in research examining the human dimensions of climate change. Evidence from Indigenous and local knowledge systems is context-dependent and not always aligned with scientific evidence. Exploring divergent understandings of the concept of change derived from different knowledge systems can yield new insights which may help prioritize research and policy actions to address local needs and priorities.
CREST: phase III study of sasanlimab and Bacillus Calmette-Guérin for patients with Bacillus Calmette-Guérin-naïve high-risk non-muscle-invasive bladder cancer
2024-01-08

Bacillus Calmette-Guérin (BCG) is the standard of care for patients with high-risk non-muscle-invasive bladder cancer (NMIBC) after transurethral resection of bladder tumor (TURBT). BCG in combination with programmed cell death-1 (PD-1) inhibitors may yield greater anti-tumor activity compared with either agent alone. CREST is a phase III study evaluating the efficacy and safety of the subcutaneous PD-1 inhibitor sasanlimab in combination with BCG for patients with BCG-naive high-risk NMIBC. Eligible participants are randomized to receive sasanlimab plus BCG (induction ± maintenance) or BCG alone for up to 25 cycles within 12 weeks of TURBT. The primary outcome is event-free survival. Secondary outcomes include additional efficacy end points and safety. The target sample size is around 1000 participants.
Treatment modalities favoring outcome in well-differentiated neuroendocrine tumors G3
2024-01-08

Introduction Neuroendocrine neoplasms (NEN) are a rare and heterogenous group of tumors arising from neuroendocrine cells in multiple organs. Neuroendocrine tumors (NET) G3 encompass a small subgroup accounting for less than 10% of all neuroendocrine neoplasms. In contrast to NET G1 and G2 as well as neuroendocrine carcinomas (NEC), in NET G3 data on treatment and patient outcomes are still limited. Especially in a metastasized tumor stage, the role of surgery, peptide receptor radionucleotide therapy (PRRT), and systemic chemotherapy is not clearly defined. Methods In this real-life cohort, we consecutively analyzed clinical outcome in NET G3 patients receiving different diagnostic and treatment. Results and discussion We found that even metastasized NET G3 patients undergoing surgery, or receiving radiation, somatostatin analogues (SSA), and PRRT showed a clear survival benefit. Interestingly, all treatment regimen were superior to classical chemotherapeutic agents. In addition, somatostatin receptor (SSTR) PET-CT, FDG PET-CT, and repetitive biopsies were shown to be useful diagnostic and prognostic tools in NET G3. Our study demonstrates that patients with highly proliferative NET G3 might benefit from less aggressive treatment modalities commonly used in low proliferative NEN.
Frequency effects in linear discriminative learning
2024-01-08

Word frequency is a strong predictor in most lexical processing tasks. Thus, any model of word recognition needs to account for how word frequency effects arise. The Discriminative Lexicon Model (DLM) models lexical processing with mappings between words' forms and their meanings. Comprehension and production are modeled via linear mappings between the two domains. So far, the mappings within the model can either be obtained incrementally via error-driven learning, a computationally expensive process able to capture frequency effects, or in an efficient, but frequency-agnostic solution modeling the theoretical endstate of learning (EL) where all words are learned optimally. In the present study we show how an efficient, yet frequency-informed mapping between form and meaning can be obtained (Frequency-informed learning; FIL). We find that FIL well approximates an incremental solution while being computationally much cheaper. FIL shows a relatively low type- and high token-accuracy, demonstrating that the model is able to process most word tokens encountered by speakers in daily life correctly. We use FIL to model reaction times in the Dutch Lexicon Project by means of a Gaussian Location Scale Model and find that FIL predicts well the S-shaped relationship between frequency and the mean of reaction times but underestimates the variance of reaction times for low frequency words. FIL is also better able to account for priming effects in an auditory lexical decision task in Mandarin Chinese, compared to EL. Finally, we used ordered data from CHILDES to compare mappings obtained with FIL and incremental learning. We show that the mappings are highly correlated, but that with FIL some nuances based on word ordering effects are lost. Our results show how frequency effects in a learning model can be simulated efficiently, and raise questions about how to best account for low-frequency words in cognitive models.
Protocol for 3D virtual histology of unstained human brain tissue using synchrotron radiation phase-contrast microtomography
2024-01-08

X-ray phase-contrast micro computed tomography using synchrotron radiation (SR PhC-μCT) offers unique 3D imaging capabilities for visualizing microstructure of the human brain. Its applicability for unstained soft tissue is an area of active research. Acquiring images from a tissue block without needing to section it into thin slices, as required in routine histology, allows for investigating the microstructure in its natural 3D space. This paper presents a detailed step-by-step guideline for imaging unstained human brain tissue at resolutions of a few micrometers with SR PhC-μCT implemented at SYRMEP, the hard X-ray imaging beamline of Elettra, the Italian synchrotron facility. We present examples of how blood vessels and neurons appear in the images acquired with isotropic 5 μm and 1 μm voxel sizes. Furthermore, the proposed protocol can be used to investigate important biological substrates such as neuromelanin or corpora amylacea. Their spatial distribution can be studied using specifically tailored segmentation tools that are validated by classical histology methods. In conclusion, SR PhC-μCT using the proposed protocols, including data acquisition and image processing, offers viable means of obtaining information about the anatomy of the human brain at the cellular level in 3D.
Primary Multi-Systemic Metastases in Osteosarcoma: Presentation, Treatment, and Survival of 83 Patients of the Cooperative Osteosarcoma Study Group
2024-01-08

Background: To evaluate patient and tumour characteristics, treatment, and their impact on survival in patients with multi-systemic metastases at initial diagnosis of high-grade osteosarcoma. Precedure: Eighty-three consecutive patients who presented with multi-systemic metastases at initial diagnosis of high-grade osteosarcoma were retrospectively reviewed. In cases of curative intent, the Cooperative Osteosarcoma Study Group recommended surgical removal of all detectable metastases in addition to complete resection of the primary tumour and chemotherapy. Results: Eighty-three eligible patients (1.8%) were identified among a total of 4605 individuals with high-grade osteosarcoma. Nine (10.8%) of these achieved complete surgical remission, of whom seven later had recurrences. The median follow-up time was 12 (range, 1–165) months for all patients. Actuarial event-free survival after 1, 2, and 5 years was 9.6 ± 3.2%, 1.4 ± 1.4%, and 1.4 ± 1.4%, and overall survival was 54.0 ± 5.6%, 23.2 ± 4.9%, and 8.7 ± 3.3%. In univariate analyses, elevated alkaline phosphatase before chemotherapy, pleural effusion, distant bones as metastatic sites, and more than one bone metastasis were negative prognostic factors. Among treatment-related factors, the microscopically complete resection of the primary tumour, a good response to first-line chemotherapy, the macroscopically complete resection of all affected tumour sites, and local treatment (surgery ± radiotherapy) of all bone metastases were associated with better outcomes. Tumour progression under first-line treatment significantly correlated with shorter survival times. Conclusion: The outlook for patients with multi-systemic primary metastases from osteosarcoma remains very poor. The utmost importance of surgical resection of all tumour sites was confirmed. For unresectable bone metastases, radiotherapy might be considered. In the patient group studied, standard chemotherapy was often insufficiently effective. In the case of such advanced disease, alternative treatment options are urgently required.
The High Energy X-ray Probe (HEX-P): probing accretion onto stellar mass black holes
2024-01-08

Accretion is a universal astrophysical process that plays a key role in cosmic history, from the epoch of reionization to galaxy and stellar formation and evolution. Accreting stellar-mass black holes in X-ray binaries are one of the best laboratories to study the accretion process and probe strong gravity—and most importantly, to measure the angular momentum, or spin, of black holes, and its role as a powering mechanism for relativistic astrophysical phenomena. Comprehensive characterization of the disk-corona system of accreting black holes, and their co-evolution, is fundamental to measurements of black hole spin. Here, we use simulated data to demonstrate how key unanswered questions in the study of accreting stellar-mass black holes will be addressed by the High Energy X-ray Probe ( HEX-P ). HEX-P is a probe-class mission concept that will combine high spatial resolution X-ray imaging and broad spectral coverage (0.2–80 keV) with a sensitivity superior to current facilities (including XMM-Newton and NuSTAR ) to enable revolutionary new insights into a variety of important astrophysical problems. We illustrate the capability of HEX-P to: 1) measure the evolving structures of black hole binary accretion flows down to low (≲ 0.1%) Eddington-scaled luminosities via detailed X-ray reflection spectroscopy; 2) provide unprecedented spectral observations of the coronal plasma, probing its elusive geometry and energetics; 3) perform detailed broadband studies of stellar mass black holes in nearby galaxies, thus expanding the repertoire of sources we can use to study accretion physics and determine the fundamental nature of black holes; and 4) act as a complementary observatory to a range of future ground and space-based astronomical observatories, thus providing key spectral measurements of the multi-component emission from the inner accretion flows of black hole X-ray binaries.
Risking your Tail: Modeling Individual Differences in Risk-sensitive Exploration using Bayes Adaptive Markov Decision Processes
2024-01-08

Abstract Novelty is a double-edged sword for agents and animals alike: they might benefit from untapped resources or face unexpected costs or dangers such as predation. The conventional exploration/exploitation tradeoff is thus coloured by risk-sensitivity. A wealth of experiments has shown how animals solve this dilemma, for example using intermittent approach. However, there are large individual differences in the nature of approach, and modeling has yet to elucidate how this might be based on animals’ differing prior expectations about reward and threat, and differing degrees of risk aversion. To capture these factors, we built a Bayes adaptive Markov decision process model with three key components: an adaptive hazard function capturing potential predation, an intrinsic reward function providing the urge to explore, and a conditional value at risk (CVaR) objective, which is a contemporary measure of trait risk-sensitivity. We fit this model to a coarse-grain abstraction of the behaviour of 26 animals who freely explored a novel object in an open-field arena (Akiti et al. Neuron 110, 2022). We show that the model captures both quantitative (frequency, duration of exploratory bouts) and qualitative (with distinguished, cautious, tail-behind approach) features of behavior, including the substantial idiosyncrasies that were observed. Some animals begin with cautious exploration, and quickly transition to confident approach to maximize exploration for reward; we classify them as potentially more risk neutral, and enjoying a flexible hazard prior. By contrast, other animals only ever approach in a cautious manner and display a form of self-censoring; they are characterized by potential risk aversion and high and inflexible hazard priors. Explaining risk-sensitive exploration using factorized parameters of reinforcement learning models could aid in the understanding, diagnosis, and treatment of psychiatric abnormalities such as anxiety disorders.
A conserved cell-pole determinant organizes proper polar flagellum formation
2024-01-08

The coordination of cell cycle progression and flagellar synthesis is a complex process in motile bacteria. In γ-proteobacteria, the localization of the flagellum to the cell pole is mediated by the SRP-type GTPase FlhF. However, the mechanism of action of FlhF, and its relationship with the cell pole landmark protein HubP remain unclear. In this study, we discovered a novel protein called FipA that is required for normal FlhF activity and function in polar flagellar synthesis. We demonstrated that membrane-localized FipA interacts with FlhF and is required for normal flagellar synthesis in Vibrio parahaemolyticus , Pseudomonas putida , and Shewanella putrefaciens , and it does so independently of the polar localization mediated by HubP. FipA exhibits a dynamic localization pattern and is present at the designated pole before flagellar synthesis begins, suggesting its role in licensing flagellar formation. This discovery provides insight into a new pathway for regulating flagellum synthesis and coordinating cellular organization in bacteria that rely on polar flagellation and FlhF-dependent localization.
A psychological network analysis to specify predictions of fraction subtopics on algebra subtopics in an intelligent tutoring system
2024-01-08

Many students face difficulties with algebra. It has been observed that fraction understanding predicts algebra achievements; hence, gaining a better understanding of how algebra understanding builds on fraction understanding is an important goal for research and educational practice. However, a wide range of algebra and fraction subtopics exists, and little is known about which specific fraction subtopics matter most for (i.e., best predict) which specific algebra subtopics. Here, we capitalized on a large data set (3,158 students; 257,321 problem sets) from an intelligent tutoring system (ITS) and employed state-of-the-art psychological network analysis. Using psychological network analysis allowed us to visualize and quantify interdependencies between students’ performance on different fraction and algebra subtopics. We observed relatively high partial correlations between algebra subtopics and between fraction subtopics, respectively. We also found that two fraction subtopics significantly predicted four algebra subtopics. Overall, our study generates differentiated insights into interdependencies in mathematics learning and highlights the potential of psychological network analysis for analyzing learning data from ITSs.
Investigating the effect of nativeness and speaker age on the credibility of spoken sentences
2024-01-08

Previous studies found mixed results regarding a bias in credibility ratings for trivia statements made by L2 speakers in comparison to L1 speakers. Perceptual fluency, social attitudes, and pragmatic lenience have been proposed as underlying causes for the bias. The present study examined credibility ratings for L2 speakers and extended the scope of the investigation by adding the factor age of the speaker. In the present study, German native adult listeners were asked to judge the credibility of trivia statements recorded by L2 adults and L1 children in Experiment 1 and statements by L1 adults and L1 children in Experiment 2. In Experiment 1, the ratings showed no difference in credibility between the L2 adult statements and the L1 child statements. In Experiment 2, listeners rated statements from L1 child speakers as more credible than statements from L1 adult speakers, suggesting a positive bias for the credibility of children. The results are discussed in terms of their relevance for previously suggested causes contributing to a credibility bias.
Tuning the Interfacial Electronic Structure of MoS2 by Adsorption of Cobalt Phthalocyanine Derivatives
2024-01-08

We investigate the interfacial electronic structure of n-type bulk MoS2 upon the adsorption of CoPc and CoPcF16 mono- and few-layers using advanced spectroscopic techniques. These include X-ray photoelectron spectroscopy (XPS), X-ray absorption spectroscopy (XAS), angle-resolved photoelectron spectroscopy (ARPES), and ultraviolet photoelectron spectroscopy (UPS). Our findings indicate that the adsorption of CoPc enhances the degree of n-doping at the interface with MoS2. In contrast, CoPcF16 results in a nearly intrinsic position of the Fermi level. Furthermore, we note the formation of an induced gap state near the valence band maximum for monolayer CoPcF16 on MoS2. These observations underscore the potential to fine-tune the interfacial electronic properties of transition metal dichalcogenides through molecular functionalization for tailored electronic applications.