julilili42/papers huggingface dataset:
Tolerability and efficacy of BrECADD versus BEACOPP in advanced stage classical Hodgkin lymphoma: GHSG HD21, a randomized study.
2024-06-05

LBA7000 Background: We hypothesized that therapy with the novel BrECADD regimen (brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, dexamethasone) guided by positron emission tomography after two cycles (PET2) could improve the treatment of advanced-stage classical Hodgkin lymphoma (AS-cHL). The HD21 trial aimed at demonstrating superiority over the intensified BEACOPP regimen (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) in terms of treatment-related morbidity (TRMB) and non-inferiority (NI) in terms of progression-free survival (PFS). This is the first report of the final confirmative analysis of the HD21 trial. Methods: HD21 is an international, open-label, randomized phase III trial including AS-cHL patients 18-60 years at diagnosis. Patients were randomized to receive individualized 4 or 6 cycles of either BEACOPP or BrECADD guided by PET2 results. The co-primary endpoints included TRMB and PFS, which had been successfully established recently. Testing for superiority was planned with mature follow-up of four years. An adjusted alpha level of 0.047 was required to cross the efficacy boundary for superiority. The trial was conducted in accordance with ICH-GCP (NCT02661503) and supported by a research grant from Takeda Oncology. Results: The ITT (intention-to-treat) cohort for the efficacy analysis consisted of 1482 patients, of which 742 were randomized to receive BrECADD and 740 to BEACOPP. Median age was 31.1 years (range 18 to 60), 44% were female. PET2 was negative in 424 (57.5%) and 426 (58.2%) patients for BrECADD or eBEACOPP, respectively, and these were scheduled for 4 treatment cycles. With median follow-up of 48 months, 4y-PFS was 94.3% for BrECADD (95%-CI 92.6-96.1), and 90.9% for BEACOPP (95%-CI 88.7-93.1). The hazard ratio was 0.66 [95% CI 0.45-0.97], p=0.035). PFS benefit of BrECADD was driven by a reduction in early treatment failures, i.e., primary progression within 3 months (5 vs. 15) or early relapse between months 3 and 12 (11 vs. 23) and observed across all investigated subgroups. PET2-negative patients in the BrECADD group showed a 4-year PFS of 96.5%. 4-year OS was 98.5% for BrECADD and 98.2% for BEACOPP. Analyses of gonadal function demonstrated significantly higher follicle stimulating hormone recovery rates after one year in both men (67% vs. 24%) and women (89% vs. 68%) with higher birth-rates in the BrECADD group (n=60 vs. n=43). Conclusions: BrECADD is significantly more effective than BEACOPP and is associated with an unprecedentedly high 4-year PFS, reducing the risk of progression, relapse or death by a third. Together with an abbreviated treatment duration of only 3 months for the majority of patients and a favorable tolerability, treatment with PET2-individualized BrECADD sets a new benchmark for the treatment of adult patients with AS-cHL. Clinical trial information: NCT02661503 .
Virtual reality assessment of a high-calorie food bias: Replication and food-specificity in healthy participants
2024-06-05

A behavioural bias for food was specific to high-calorie food objects. The results confirm the presence of bottom-up advantages in motor-cognitive behaviour for high-calorie food in a non-clinical population. More systematic variations of object fidelity and in clinical populations are outstanding. The utility of VR in assessing approach behaviour is confirmed in this study by exploring manual interactions in a controlled environment.
Ecology of large ungulates in the northeastern Iberian Peninsula during the Upper Palaeolithic through stable isotopes and tooth wear analysis
2024-06-05

The northeastern Iberian Peninsula acted as a refuge zone during the Late Pleistocene where the persistence of terrestrial ecosystems could provide hunter-gatherers with large prey, mainly horse (Equus ferus) and red deer (Cervus elaphus). Isotopic (δ13C, δ18O, δ15N) and dental wear (mesowear and microwear) analyses have been applied on the remains of both species from the archaeological sites of Arbreda and Bora Gran at Serinyà (Girona), where evidence of human occupation from the Mousterian to the Magdalenian has been attested. The incremental enamel analysis on horse teeth revealed seasonal variation in carbonate δ18O but no detectable change in carbonate δ13C values, reflecting a rather stable diet and habitat over the year. Nevertheless, higher inter-individual than intra-individual contrast in carbonate δ13C indicate different environmental conditions from one individual to another for each stratigraphic unit. In red deer teeth, seasonal signals in enamel carbonate δ13C and δ18O demonstrated mirrored trends. Further, red deer show higher δ13C values than those of horses, both in enamel carbonate and bone collagen, as well as higher variability in mesowear and microwear scores, reflecting a mixed-feeding habit. Despite a strong grazing signal in mesowear and microwear, the lower δ13C values for horses suggest a higher dependence on relatively more humid habitats than red deer, which likely foraged in dryer environments with xeric plants during winter. These differences in ecological partitioning are particularly well illustrated in distinct collagen δ13C and δ15N values during the harsh climatic conditions of the Final Gravettian coeval to the GS-3 or Last Glacial Maximum. The capacity of red deer to adapt to fluctuating environmental conditions contrasts with the niche persistence of horse allowed by the availability of mosaic habitat.
High-affinity PQQ import is widespread in Gram-negative bacteria
2024-06-05

ABSTRACT PQQ is a soluble redox cofactor used by diverse bacteria to oxidise fuel compounds as a source of electrons for the respiratory chain. Many Gram-negative bacteria that encode PQQ-dependent enzymes do not possess the biosynthetic machinery for its production and instead obtain it from the environment. To achieve this the bacterium Escherichia coli uses the TonB-dependent transporter PqqU as a high-affinity PQQ importer, allowing it to use PQQ at an external concentration as low as 1 nM. Here, we show that PqqU achieves this by binding PQQ with a very high affinity. Using cryo-electron microscopy we determine the structure of the PqqU-PQQ complex at a resolution of 1.99 Å, revealing that the extracellular loops of PqqU undergo significant conformational changes upon PQQ binding, which captures the cofactor in an internal cavity. This cavity likely facilitates an airlock-style gating mechanism that prevents non-specific import through PqqU. Using structural modelling we show that the change in PqqU structure upon PQQ binding precludes the binding of bacteriophage, which targets it as a cell surface receptor. Guided by the PqqU-PQQ complex structure we use phenotypic analysis to identify the amino acids essential for PQQ import and leverage this information to map the presence of PqqU across Gram-negative bacteria. This reveals that PqqU is encoded by Gram-negative bacteria from at least 22 phyla from diverse habitats, including those found in aquatic, soil, host-associated, and extreme environments. This indicates that PQQ is a ubiquitous nutrient in many environments, and an important cofactor for bacteria that adopt diverse lifestyles and metabolic strategies. Significance Statement Many enzymes form complexes with molecules called cofactors to perform their function. PQQ is a cofactor used by bacterial enzymes that provide energy by breaking down food molecules. While some bacteria make their own PQQ, other bacteria use the transport protein PqqU to bind PQQ from the environment and import it into their cells. We show that PqqU binds PQQ very tightly, allowing bacteria to acquire it at very low concentrations. Using cryo-electron microscopy we image the PqqU-PQQ complex on an atomic level, revealing how PQQ is bound so tightly. Using this the information to analyse microbial genomes, we show that PQQ scavenging is employed by diverse bacteria, implying that PQQ is an important common good of diverse microbiomes.
Word frequency and cognitive effort in turns-at-talk: turn structure affects processing load in natural conversation
2024-06-05

Frequency distributions are known to widely affect psycholinguistic processes. The effects of word frequency in turns-at-talk, the nucleus of social action in conversation, have, by contrast, been largely neglected. This study probes into this gap by applying corpus-linguistic methods on the conversational component of the British National Corpus (BNC) and the Freiburg Multimodal Interaction Corpus (FreMIC). The latter includes continuous pupil size measures of participants of the recorded conversations, allowing for a systematic investigation of patterns in the contained speech and language on the one hand and their relation to concurrent processing costs they may incur in speakers and recipients on the other hand. We test a first hypothesis in this vein, analyzing whether word frequency distributions within turns-at-talk are correlated with interlocutors' processing effort during the production and reception of these turns. Turns are found to generally show a regular distribution pattern of word frequency, with highly frequent words in turn-initial positions, mid-range frequency words in turn-medial positions, and low-frequency words in turn-final positions. Speakers' pupil size is found to tend to increase during the course of a turn at talk, reaching a climax toward the turn end. Notably, the observed decrease in word frequency within turns is inversely correlated with the observed increase in pupil size in speakers, but not in recipients, with steeper decreases in word frequency going along with steeper increases in pupil size in speakers. We discuss the implications of these findings for theories of speech processing, turn structure, and information packaging. Crucially, we propose that the intensification of processing effort in speakers during a turn at talk is owed to an informational climax, which entails a progression from high-frequency, low-information words through intermediate levels to low-frequency, high-information words. At least in English conversation, interlocutors seem to make use of this pattern as one way to achieve efficiency in conversational interaction, creating a regularly recurring distribution of processing load across speaking turns, which aids smooth turn transitions, content prediction, and effective information transfer.
On assessing trait rumination using the Ruminative Response Scale
2024-06-05

Introduction This study explores the stability of scores on psychometrically validated trait questionnaires over time. We illustrate potential pitfalls through a larger study that used the Ruminative Response Scale (RRS) to categorize participants prior to study inclusion into two groups based on their habitual tendency to ruminate. Surprisingly, when we re-administered the RRS at the start of an experimental session, significant score changes occurred, resulting in participants shifting between the two groups. Methods To address this, we modified our recruitment process, aiming to reduce careless responses, including an online RRS assessment a week before the lab appointment. We analyzed the different samples prior to and after changing the recruitment procedure, as well as the total sample regarding the psychometric properties of the RRS. We also explored various indices to identify and predict score changes due to careless responding; however, only a subgroup of participants was successfully identified. Results Our findings suggest that Mahalanobis distances are effective for identifying substantial score changes, with baseline state rumination emerging as a marginally significant predictor. Discussion We discuss the importance of conducting manipulation checks and offer practical implications for research involving psychometrically validated trait questionnaires.
How stimulation intensity affects motor learning
2024-06-05

A recommendation of: Gavin Hsu, Dylan J. Edwards, Leonardo G. Cohen, Lucas C. Parra Dose-response of tDCS effects on motor learning and cortical excitability: a preregistered study https://osf.io/k6abp
A Systematic Methodological Review of Offline Input Processing Research *
2024-06-05

Research on input processing (IP) examines how second language (L2) learners process the language they encounter in oral or written input, seeking to understand the psycholinguistic principles that guide L2 comprehension and their impact on subsequent acquisition processes. Much of this research involves applying insights from VanPatten's IP model for the development of more effective pedagogical interventions (processing instruction [PI]). Here, we systematically review and discuss the methodology used in research that either tested the IP model or assessed the effectiveness of PI. Our analysis includes 108 empirical studies that used offline measures of learning (i.e., measuring comprehension after input exposure). We first present the general characteristics of this type of research and then describe key methodological features of IP studies in depth. We conclude with methodological recommendations and suggestions for future research on IP and PI. We hope to provide readers with a better understanding of the strengths and weaknesses of existing research in the hope of contributing to methodological improvements of future research.
Intact protein barcoding enables one-shot identification of CRISPRi strains and their metabolic state
2024-06-05

Abstract Simultaneous measurements of library barcodes and metabolites can facilitate the screening of metabolically engineered bacterial libraries. Here, we introduce a scalable method for the parallel measurement of protein-based library barcodes and metabolites using flow-injection mass spectrometry (FI-MS). Protein barcodes are based on ubiquitin, a small 76-amino-acid protein, which we labeled with N-terminal tags of six amino acids to identify bacterial strains. We demonstrate that FI-MS effectively detects intact ubiquitin proteins and identifies the N-terminal barcodes. In the same analysis, we semi-quantify relative concentrations of primary metabolites. As a proof of concept, we engineered six ubiquitin-barcoded CRISPRi strains targeting metabolic enzymes, and analyzed their metabolic profiles and ubiquitin barcodes using FI-MS. Our results show distinct metabolome changes within metabolic pathways targeted by CRISPRi. This method enables fast and simultaneously detection of library barcodes and intracellular metabolites, opening up new possibilities to measure metabolomes of engineered bacteria at scale.
Deuterium Isotope Effect in Single Molecule Photophysics and Photochemistry of Hypericin
2024-06-05

Abstract The peripherical protons of the dye molecule hypericin can undergo structural interconversion (tautomerization) between different isomers separated by a low energy barrier with rates that depends sensitively on the interaction with local chemical environment defined by the nature of host material. We investigate the deuterium (D) isotope effect of hypericin tautomerism at the single‐molecule level to avoid ensemble averaging in different polymer matrices by a combined spectroscopic and computational approach. In the ′innocent′ PMMA matrix only intra molecular isotope effects on the internal conversion channel and tautomerization are observed; while PVA specifically interacts with the probe via H‐ and D‐bonding. This establishes a single molecular picture on intra ‐ and inter molecular nano‐environment effects to control chromophore photophysics and ‐chemistry.
Dyskinetic crisis in GNAO1-related disorders: clinical perspectives and management strategies
2024-06-06

Background GNAO1 -related disorders ( GNAO1 -RD) encompass a diverse spectrum of neurodevelopmental and movement disorders arising from variants in the GNAO1 gene. Dyskinetic crises, marked by sudden and intense exacerbations of abnormal involuntary movements, present a significant challenge in GNAO1 -RD. Objectives This study aimed to establish a standardized framework for understanding dyskinetic crises, addressing crucial aspects such as definition, triggers, diagnostic criteria, complications, and management strategies. Methods A Delphi consensus process was conducted involving international experts in GNAO1 -RD. The panel of thirteen experts participated in three voting rounds, discussing 90 statements generated through a literature review and clinical expertise. Results Consensus was achieved on 31 statements, defining dyskinetic crises as abrupt, paroxysmal episodes involving distinct abnormal movements in multiple body regions, triggered by emotional stress or infections. Dyskinetic crises may lead to functional impairment and complications, emphasizing the need for prompt recognition. While individualized pharmacological recommendations were not provided, benzodiazepines and clonidine were suggested for acute crisis management. Chronic treatment options included tetrabenazine, benzodiazepines, gabapentin, and clonidine. Deep brain stimulation should be considered early in the treatment of refractory or prolonged dyskinetic crisis. Conclusion This consensus provides a foundation for understanding and managing dyskinetic crises in GNAO1 -RD for clinicians, caregivers, and researchers. The study emphasizes the importance of targeted parental and caregiver education, which enables early recognition and intervention, thereby potentially minimizing both short- and long-term complications. Future research should concentrate on differentiating dyskinetic crises from other neurological events and investigating potential risk factors that influence their occurrence and nature. The proposed standardized framework improves clinical management, stakeholder communication, and future GNAO1 -RD research.
Assessing Social, Emotional, and Behavioral Skills in Just a Few Minutes: 96-, 45-, and 20-Item Short Forms of the BESSI
2024-06-06

Social, emotional, and behavioral (SEB) skills matter for individuals’ well-being and success. The behavioral, emotional, and social skills inventory (BESSI) uses 192 items to assess 32 specific SEB skills across five broad skill domains. This research developed three short forms of the BESSI-192 and explored their measurement properties, predictive validity, and cross-cultural comparability. We found that BESSI-96, BESSI-45, and BESSI-20 largely captured the psychological content of the BESSI-192 measure, retained a robust multidimensional structure, and demonstrated adequate reliability. At the domain and facet level, the BESSI short forms showed patterns of associations with external criteria that were similar to the BESSI-192 and preserved most of the BESSI-192’s predictive power. The BESSI short forms also demonstrated full or partial measurement invariance between the primarily U.S.-based and German adult samples. We conclude by discussing contexts in which the short forms may be useful for researchers and practitioners.
Radical‐Induced Changes in Transition Metal Interfacial Magnetic Properties: A Blatter Derivative on Polycrystalline Cobalt
2024-06-06

Abstract In this work, we study the interface obtained by depositing a monolayer of a Blatter radical derivative on polycrystalline cobalt. By examining the occupied and unoccupied states at the interface, using soft X‐ray techniques, combined with electronic structure calculations, we could simultaneously determine the electronic structure of both the molecular and ferromagnetic sides of the interface, thus obtaining a full understanding of the interfacial magnetic properties. We found that the molecule is strongly hybridized with the surface. Changes in the core level spectra reflect the modification of the molecule and the cobalt electronic structures inducing a decrease in the magnetic moment of the cobalt atoms bonded to the molecules which, in turn, lose their radical character. Our method allowed us to screen, beforehand, organic/ferromagnetic interfaces given their potential applications in spintronics.
Looks like SNARC spirit: Coexistence of short- and long-term associations between letters and space
2024-06-06

Many studies have demonstrated spatial-numerical associations, but the debate about their origin is still ongoing. Some approaches consider cardinality representations in long-term memory, such as a Mental Number Line, while others suggest ordinality representations, for both numerical and non-numerical stimuli, originating in working or long-term memory. To investigate how long-term memory and working memory influence spatial associations and to disentangle the role of cardinality and ordinality, we ran three preregistered online experiments (N = 515). We assessed spatial response preferences for letters (which only convey ordinal but no cardinal information, in contrast to numbers) in a bimanual go/no go consonant-vowel classification task. Experiment 1 (‘no-go’ trials: non-letter symbols) validated our setup. In Experiments 2 and 3, participants learned an ordinal letter sequence prior to the task, which they recalled afterwards. In Experiment 2, this sequence was merely to be maintained (‘no-go’ trials: non-letter symbols), whereas in Experiment 3, it needed to be retrieved during the task (‘no-go’ trials: letters outside the sequence). We replicated letter-space associations based on the alphabet stored in long-term memory (i.e., letters earlier/later in the alphabet associated with left/right, respectively) in all three experiments. However, letter-space associations based on the working memory sequence (i.e., letters earlier/later in the sequence associated with left/right, respectively) were only detected in Experiment 3, where retrieval occurred during the task. Spatial short- and long-term associations of letters therefore seem to coexist. These findings support a hybrid model that incorporates both short- and long-term representations, which applies similarly to letters as to numbers.