julilili42/papers huggingface dataset:
Local control and patient reported outcomes after online MR guided stereotactic body radiotherapy of liver metastases
2023-01-16

Introduction Stereotactic body radiotherapy (SBRT) is used to treat liver metastases with the intention of ablation. High local control rates were shown. Magnetic resonance imaging guided radiotherapy (MRgRT) provides the opportunity of a marker-less liver SBRT treatment due to the high soft tissue contrast. We report herein on one of the largest cohorts of patients treated with online MRgRT of liver metastases focusing on oncological outcome, toxicity, patient reported outcome measures (PROMs), quality of life. Material and methods Patients treated for liver metastases with online MR-guided SBRT at a 1,5 T MR-Linac (Unity, Elekta, Crawley, UK) between March 2019 and December 2021 were included in this prospective study. UK SABR guidelines were used for organs at risk constraints. Oncological endpoints such as survival parameters (overall survival, progression-free survival) and local control as well as patient reported acceptance and quality of life data (EORTC QLQ-C30 questionnaire) were assessed. For toxicity scoring the Common Toxicity Criteria Version 5 were used. Results A total of 51 patients with 74 metastases were treated with a median of five fractions. The median applied BED GTV D98 was 84,1 Gy. Median follow-up was 15 months. Local control of the irradiated liver metastasis after 12 months was 89,6%, local control of the liver was 40,3%. Overall survival (OS) after 12 months was 85.1%. Progression free survival (PFS) after 12 months was 22,4%. Local control of the irradiated liver lesion was 100% after three years when a BED ≥100 Gy was reached. The number of treated lesions did not impact local control neither of the treated or of the hepatic control. Patient acceptance of online MRgSBRT was high. There were no acute grade ≥ 3 toxicities. Quality of life data showed no significant difference comparing baseline and follow-up data. Conclusion Online MR guided radiotherapy is a noninvasive, well-tolerated and effective treatment for liver metastases. Further prospective trials with the goal to define patients who actually benefit most from an online adaptive workflow are currently ongoing.
Sustainability of seed harvesting in wild plant populations: an insight from a global database of matrix population models
2023-01-16

Abstract Seed harvesting from wild plant populations is key for ecological restoration, but may threaten the persistence of source populations. Consequently, several countries have set guidelines limiting the proportions of harvestable seeds. However, these guidelines are so far inconsistent, and they lack a solid empirical basis. Here, we use high-resolution data from 298 plant species to model the demographic consequences of seed harvesting. We find that the current guidelines do not protect populations of annuals and short-lived perennials, while they are overly restrictive for long-lived plants. We show that the maximum possible fraction of seed production – what can be harvested without compromising the long-term persistence of populations – is strongly related to the generation time of the target species. When harvesting every year, this safe seed fraction ranges from 80% in long-lived species to 2% in most annuals. Less frequent seed harvesting substantially increases the safe seed fraction: In the most vulnerable annual species, it is safe to harvest 5%, 10% or 30% of population seed production when harvesting every two, five or ten years, respectively. Our results provide a quantitative basis for seed harvesting legislations worldwide, based on species’ generation time and harvesting regime. Significance The UN Decade on Ecosystem Restoration, 2021-2030, foresees upscaling restoration, and the demand for native seed is skyrocketing. Seeds for restoring native vegetation are often harvested in wild, but too intensive harvest can threaten the donor populations. Existing guidelines that set limits to wild seed harvest are mostly based on expert opinions, yet they commonly lack empirical basis and vary among regions in one order of magnitude. We show that the current guidelines urgently need to be reformulated, because they are overly restrictive in long-lived species, while they do not protect annual plants from extinction. Using matrix population models of nearly 300 plant species, we provide a quantitative basis for a new seed harvesting legislation world-wide.
Possessive pronouns in Russian-German language contact: variation or change?
2023-01-16

Abstract The article addresses the question of what happens to internal linguistic variability in a language contact situation by looking at how first-generation Russian immigrants in Germany use two variants of possessive pronouns (reflexive and non-reflexive) for referencing the subject. To what extent does the frequency of the variants, as well as linguistic constraints on their use, remain the same as in the monolingual variety, or change to converge with the structures of the majority language? A forced choice sentence completion task was conducted with 96 adult monolingual Russian and 96 adult bilingual Russian-German speakers to measure the frequency of both variants and the effect of animacy and referentiality of the possessum. The results reveal an increased frequency of the non-reflexive variant in bilingual Russian, indicating convergence with German. At the same time, bilingual speakers observe the same animacy and referentiality constraints on the possessive choice as monolinguals. The effect of linguistic constraints, however, is smaller than the influence of individual speaker-related variables. Overall, our study indicates that convergence in language contact affects the frequency but not the conditioning of the variants and only in some bilingual individuals.
Mobility and kinship in the world’s first village societies
2023-01-17

Around 10,000 y ago in southwest Asia, the cessation of a mobile lifestyle and the emergence of the first village communities during the Neolithic marked a fundamental change in human history. The first communities were small (tens to hundreds of individuals) but remained semisedentary. So-called megasites appeared soon after, occupied by thousands of more sedentary inhabitants. Accompanying this shift, the material culture and ancient ecological data indicate profound changes in economic and social behavior. A shift from residential to logistical mobility and increasing population size are clear and can be explained by either changes in fertility and/or aggregation of local groups. However, as sedentism increased, small early communities likely risked inbreeding without maintaining or establishing exogamous relationships typical of hunter-gatherers. Megasites, where large populations would have made endogamy sustainable, could have avoided this risk. To examine the role of kinship practices in the rise of megasites, we measured strontium and oxygen isotopes in tooth enamel from 99 individuals buried at Pınarbaşı, Boncuklu, and Çatalhöyük (Turkey) over 7,000 y. These sites are geographically proximate and, critically, span both early sedentary behaviors (Pınarbaşı and Boncuklu) and the rise of a local megasite (Çatalhöyük). Our data are consistent with the presence of only local individuals at Pınarbaşı and Boncuklu, whereas at Çatalhöyük, several nonlocals are present. The Çatalhöyük data stand in contrast to other megasites where bioarchaeological evidence has pointed to strict endogamy. These different kinship behaviors suggest that megasites may have arisen by employing unique, community-specific kinship practices.
Clinical-Radiological Mismatch in Multiple Sclerosis Patients during Acute Relapse: Discrepancy between Clinical Symptoms and Active, Topographically Fitting MRI Lesions
2023-01-17

Background: Relapses in multiple sclerosis (MS) patients are usually defined as subacute clinical symptoms that last for at least 24 h. To validate a clinical relapse on magnetic resonance imaging (MRI), an anatomically fitting lesion with gadolinium enhancement in the central nervous system (CNS) would be mandatory. The aim of this study was to validate clinical relapses in regard to the concomitant detection of active, anatomically fitting MRI lesions. Methods: We performed a retrospective analysis of 199 MS patients with acute relapse who had received an MRI scan before the initiation of methylprednisolone (MPS) therapy. Clinical data and MRIs were systematically reanalyzed by correlating clinical symptoms with their anatomical representation in the CNS. Patients were then categorized into subgroups with a clinical-radiological match (group 1) or clinical-radiological mismatch (group 2) between symptoms and active, topographically fitting lesions and further analyzed in regard to clinical characteristics. Results: In 43% of our patients, we observed a clinical-radiological mismatch (group 2). Further analysis of patient characteristics showed that these patients were significantly older at the time of relapse. MS patients in group 2 also showed a significantly longer disease duration and significantly more previous relapses when compared to group 1. Comparing symptom clusters, the appearance of motor dysfunction during the current relapse was significantly more frequent in group 2 than in group 1. The overall dose of MPS treatment was significantly lower in group 2 than in group 1 with a similar treatment response in both groups. Conclusions: The substantial clinical-radiological mismatch during acute relapse in our study could be explained by several factors, including a psychosomatic component or disturbance of network connectivity. Alternatively, secondary progression or a diffuse neuro-inflammatory process might cause clinical symptoms, especially in older patients with a longer disease duration. As a consequence, treatment of clinical relapses and the definition of breakthrough disease should be reconsidered in regard to combined clinical and MRI criteria and/or additional biomarkers. Further studies are necessary to address the contribution of diffuse neuro-inflammation to the clinical presentation of symptoms.
Lexical variation in NPI illusions – A case study of German jemals 'ever' and so recht 'really'
2023-01-17

The illusory licensing of negative polarity items has been an insightful phenomenon for accounts of human sentence processing, as its extreme selectivity has proven problematic to explain in terms of parsing principles that underlie the establishment of other item-to-item dependencies. Using speeded acceptability judgments, I provide novel experimental evidence that the NPI illusion may be restricted to a particular type of NPI—illusory licensing was replicated for German jemals 'ever', but was not confirmed for the attenuating NPI so recht 'really'. I argue that this finding challenges all current accounts of the NPI illusion, and propose an explanation that purports an interaction between a scalar NPI licensing mechanism and scalar properties of the illusory licensing context as the source of the NPI illusion.
Teacher Collaboration and Professional Learning: Examining Professional Development During a National Education Reform
2023-01-17

Teacher collaboration is an important feature of job satisfaction and self-efficacy of teachers. Moreover, the collaboration of teachers is important for adopting professional changes, as professional development (PD) activities that include opportunities for collaboration have been shown to support teachers in improving classroom practice, leading to higher student performance. Situated in the context of the Advanced Placement (AP) reform in the United States, we investigated the perceived importance of opportunities to collaborate with colleagues as a rationale to participate in PD (N = 3,725 teachers). Using descriptive and regression analyses, we found that the opportunity to collaborate with colleagues was a primary rationale why teachers selected PD activities. While this rationale is only slightly related to school and teacher characteristics, we found it to be particularly related to PD characteristics. Specifically, opportunities to collaborate with colleagues were important to teachers in selecting informal face-to-face PD activities. We conclude that collaborative structures benefit all forms of teacher professional development.
New Workflow Predicts Drug Targets Against SARS-CoV-2 via Metabolic Changes in Infected Cells
2023-01-17

COVID-19 is one of the deadliest respiratory diseases, and its emergence caught the pharmaceutical industry off guard. While vaccines have been rapidly developed, treatment options for infected people remain scarce, and COVID-19 poses a substantial global threat. This study presents a novel workflow to predict robust druggable targets against emerging RNA viruses using metabolic networks and information of the viral structure and its genome sequence. For this purpose, we implemented pymCADRE and PREDICATE to create tissue-specific metabolic models, construct viral biomass functions and predict host-based antiviral targets from more than one genome. We observed that pymCADRE reduces the computational time of flux variability analysis for internal optimizations. We applied these tools to create a new metabolic network of primary bronchial epithelial cells infected with SARS-CoV-2 and identified enzymatic reactions with inhibitory effects. The most promising reported targets were from the purine metabolism, while targeting the pyrimidine and carbohydrate metabolisms seemed to be promising approaches to enhance viral inhibition. Finally, we computationally tested the robustness of our targets in all known variants of concern, verifying our targets&amp;rsquo; inhibitory effects. Since laboratory tests are time-consuming and involve complex readouts to track processes, our workflow focuses on metabolic fluxes within infected cells and is applicable for rapid hypothesis-driven identification of potentially exploitable antivirals concerning various viruses and host cell types.
Receptive field sizes and neuronal encoding bandwidth are constrained by axonal conduction delays
2023-01-17

Abstract Studies on population coding implicitly assume that spikes from the presynaptic population arrive simultaneously at the integrating neuron. In natural neuronal populations, this is usually not the case — neuronal signalling takes time and neuronal populations cover a certain space. The spread of spike arrival times depends on population size, cell density and axonal conduction velocity. We here analyze the consequences of population size and axonal conduction delays on the stimulus encoding performance in the electrosensory system of the electric fish Apteronotus leptorhynchus . We experimentally locate p-type electroreceptor afferents along the rostro-caudal body axis and relate locations to neurophysiological response properties. In an information-theoretical approach we analyze the coding performance in homogeneous and heterogeneous populations. As expected, the amount of information increases with population size and, on average, heterogeneous populations encode better than the average same-size homogeneous population if conduction delays are compensated for. The spread of neuronal conduction delays within a receptive field strongly degrades encoding of high-frequency stimulus components. Receptive field sizes typically found in the electrosensory lateral line lobe of A. leptorhynchus appear to be a good compromise between the spread of conduction delays and encoding performance. The limitations imposed by finite axonal conduction velocity are relevant for any converging network as is shown by model populations of LIF neurons. The bandwidth of natural stimuli and the maximum meaningful population sizes are constrained by conduction delays and may thus impact the optimal design of nervous systems. Author summary Reading out the activity of a population of neurons can yield a more complete picture of the stimulus space. Generally, increasing population sizes increases the amount of information. This applies to homogeneous populations of similarly tuned neurons as well as heterogeneous populations. So far studies on population coding assumed the information to reach the integrating neuron simultanously. But neurons are neither disembodied nor does neuronal signalling happen instantaneously; populations cover a certain space and axonal conduction takes time. The interplay of encoding bandwidth, receptive field respectively population size and axonal conduction velocity has not been addressed before. Our results from the electrosensory system and of model simulations show that stimulus dynamics, receptive field sizes, and conduction velocity have to be factored in when we want to understand the design of nervous systems.
Loss or Gain of Function? Effects of Ion Channel Mutations on Neuronal Firing Depend on the Cell Type
2023-01-17

Abstract Clinically relevant mutations to voltage-gated ion channels, called channelopathies, alter ion channel function, properties of ionic current and neuronal firing. The effects of ion channel mutations are routinely assessed and characterized as loss of function (LOF) or gain of function (GOF) at the level of ionic currents. Emerging personalized medicine approaches based on LOF/GOF characterization have limited therapeutic success. Potential reasons are that the translation from this binary characterization to neuronal firing especially when considering different neuronal cell types is currently not well understood. Here we investigate the impact of neuronal cell type on the firing outcome of ion channel mutations with simulations of a diverse collection of neuron models. We systematically analyzed the effects of changes in ion current properties on firing in different neuronal types. Additionally, we simulated the effects of mutations in the KCNA1 gene encoding the K V 1.1 potassium channel subtype associated with episodic ataxia type 1 (EA1). These simulations revealed that the outcome of a given change in ion channel properties on neuronal excitability is cell-type dependent. As a result, cell-type specific effects are vital to a full understanding of the effects of channelopathies on neuronal excitability and present an opportunity to further the efficacy and precision of personalized medicine approaches. Significance Statement Although the genetic nature of ion channel mutations as well as their effects on the biophysical properties of an ion channel are routinely assessed experimentally, determination of their role in altering neuronal firing is more difficult. In particular, cell-type dependency of ion channel mutations on firing has been observed experimentally, and should be accounted for. In this context, computational modelling bridges this gap and demonstrates that the cell type in which a mutation occurs is an important determinant in the effects of neuronal firing. As a result, classification of ion channel mutations as loss or gain of function is useful to describe the ionic current but should not be blindly extend to classification at the level of neuronal firing.
X-SHYNE: X-shooter spectra of young exoplanet analogs
2023-01-18

We present simultaneous 0.65–2.5 μm medium resolution (3300 ≤ R λ ≤ 8100) VLT/X-shooter spectra of the relatively young (150–300 Myr) low-mass (19 ± 5 M Jup ) L–T transition object VHS 1256−1257 b, a known spectroscopic analog of HR8799d. The companion is a prime target for the JWST Early Release Science (ERS) and one of the highest-amplitude variable brown dwarfs known to date. We compare the spectrum to the custom grids of cloudless ATMO models, exploring the atmospheric composition with the Bayesian inference tool ForMoSA . We also reanalyze low-resolution HST/WFC3 1.10–1.67 μm spectra at minimum and maximum variability to contextualize the X-shooter data interpretation. The models reproduce the slope and most molecular absorption from 1.10 to 2.48 μm self-consistently, but they fail to provide a radius and a surface gravity consistent with evolutionary model predictions. They do not reproduce the optical spectrum and the depth of the K I doublets in the J band consistently. We derived T eff = 1380±54 K, log( g ) = 3.97±0.48 dex, [M/H] = 0.21±0.29, and C/O &gt; 0.63. Our inversion of the HST/WFC3 spectra suggests a relative change of K of the disk-integrated T eff correlated with the near-infrared brightness. Our data anchor the characterization of that object in the near-infrared and could be used jointly to the ERS mid-infrared data to provide the most detailed characterization of an ultracool dwarf to date.
Personality, intelligence, and academic achievement: Charting their developmental interplay
2023-01-18

Abstract Objective Although intelligence and personality traits have long been recognized as key predictors of students' academic achievement, little is known about their longitudinal and reciprocal associations. Here, we charted the developmental interplay of intelligence, personality (Big Five) and academic achievement in 3880 German secondary school students, who were assessed four times between the ages 11 and 14 years (i.e., in grades 5, 6, 7, and 8). Method We fitted random intercept cross‐lagged panel models (RI‐CLPs) to investigate reciprocal within‐person associations between (a) academic achievement and intelligence, (b) academic achievement and personality, as well as (c) intelligence and personality. Results The results revealed negative within‐person associations between Conscientiousness and Extraversion assessed at the first wave of measurement and intelligence assessed at the second wave. None of the reciprocal personality–achievement associations attained statistical significance. Academic achievement and intelligence showed reciprocal within‐person relations, with the strongest coefficients found for achievement longitudinally predicting intelligence. Conclusions Our work contributes to developmental theorizing on interrelations between personality, intelligence, and academic achievement, as well as to within‐person conceptualizations in personality research.
Cereblon neo-substrate binding mimics the recognition of the cyclic imide degron
2023-01-18

In targeted protein degradation, immunomodulatory drugs (IMiDs) or cereblon (CRBN) E3 ligase modulatory drugs (CELMoDs) recruit neo-substrate proteins to the E3 ubiquitin ligase receptor CRBN for ubiquitination and subsequent proteasomal degradation. While the structural basis of this mechanism is generally understood, we have only recently described the recognition mode of the natural CRBN degron. In this communication, we reveal that the IMiD- or CELMoD-mediated binding of neo-substrates closely mimics the recognition of natural degrons. In crystal structures, we identify a conserved binding mode for natural degron peptides with an elaborate hydrogen bonding network involving the backbone of each of the six C-terminal degron residues, without the involvement of side chains. In a structural comparison, we show that neo-substrates recruited by IMiDs or CELMoDs emulate every single hydrogen bond of this network and thereby explain the origins of the largely sequence-independent recognition of neo-substrates. Our results imply that the V388I substitution in CRBN does not impair natural degron recognition and complete the structural basis for the rational design of CRBN effectors.