julilili42/papers huggingface dataset:
We are MedChem: The Frontiers in Medicinal Chemistry 2024
2024-09-23

Abstract The Frontiers in Medicinal Chemistry (FiMC) is the largest international Medicinal Chemistry conference in Germany and took place from March 17 th to 20 th 2024 in Munich. Co‐organized by the Division of Medicinal Chemistry of the German Chemical Society (Gesellschaft Deutscher Chemiker; GDCh) and the Division of Pharmaceutical and Medicinal Chemistry of the German Pharmaceutical Society (Deutsche Pharmazeutische Gesellschaft; DPhG), and supported by a local organizing committee from the Ludwigs‐Maximilians‐University Munich headed by Daniel Merk, the meeting brought together approximately 225 participants from 20 countries. The outstanding program of the four‐day conference included 40 lectures by leading scientists from industry and academia as well as early career investigators. Moreover, 100 posters were presented in two highly interactive poster sessions.
Ambiguity in discourse
2024-09-23

Abstract Ambiguity in language and communication has recently come under increasing attention in a number of disciplines, such as linguistics, literary science, psychology, theology, and law. In this paper, we focus on ambiguity in discourse and present an online corpus which contains rich annotations for a variety of examples of ambiguity from different text genres and periods. The corpus features an annotation schema that allows users to specify the multiple attributes of an ambiguity, as well as its interaction with related but distinct phenomena, such as vagueness and underspecification. We discuss how this corpus might foster and enable the interdisciplinary study of ambiguity.
Emergence of community behaviors in the gut microbiota upon drug treatment
2024-09-24

Pharmaceuticals can directly inhibit the growth of gut bacteria, but the degree to which such interactions manifest in complex community settings is an open question. Here, we compared the effects of 30 drugs on a 32-species synthetic community with their effects on each community member in isolation. While most individual drug-species interactions remained the same in the community context, communal behaviors emerged in 26% of all tested cases. Cross-protection during which drug-sensitive species were protected in community was 6 times more frequent than cross-sensitization, the converse phenomenon. Cross-protection decreased and cross-sensitization increased at higher drug concentrations, suggesting that the resilience of microbial communities can collapse when perturbations get stronger. By metabolically profiling drug-treated communities, we showed that both drug biotransformation and bioaccumulation contribute mechanistically to communal protection. As a proof of principle, we molecularly dissected a prominent case: species expressing specific nitroreductases degraded niclosamide, thereby protecting both themselves and sensitive community members.
The Late Early–Middle Pleistocene Mammal Fauna from the Megalopolis Basin (Peloponnese, Greece) and Its Importance for Biostratigraphy and Paleoenvironment
2024-09-24

Recent investigations in the upper Lower–Middle Pleistocene deposits of the Megalopolis Basin (Greece) led to the discovery of several sites/findspots with abundant faunal material. Here, we provide an updated overview including new results on the micro- and macro-mammal fauna. Important new discoveries comprise partial hippopotamus skeletons from Marathousa 1 and the new Lower Pleistocene site Choremi 6, as well as a second partial elephant skeleton from Marathousa 1, including a complete tusk and the rarely found stylohyoideum. Based on the first results from the newly collected micromammals, we discuss age constraints of the sites, and we provide biostratigraphic/biochronologic remarks on key mammal taxa for the Middle Pleistocene of Greece and southeastern Europe. The presence of mammals highly dependent on freshwater for their survival, together with temperate-adapted ones in several stratigraphic layers of the basin, including those correlated with glacial stages, when conditions were colder and/or drier, indicate the capacity of the basin to retain perennial freshwater bodies under milder climatic conditions, even during the harsher glacial periods of the European Middle Pleistocene, and further support its refugial status. Yet, the smaller dimensions of the Megalopolis hippopotamuses may represent a response to the changing environmental conditions of the epoch, not optimal for hippopotamuses. Overall, the Megalopolis Basin comprises a unique fossil record for southeastern Europe and provides valuable insights into the Middle Pleistocene terrestrial ecosystems of Europe, and hominin adaptations in particular.
Impact of Biotransformation on Internal Concentrations and Specificity Classification of Organic Chemicals in the Zebrafish Embryo (Danio rerio)
2024-09-24

Internal concentrations (ICs) are crucial for linking exposure to effects in the development of New Approach Methodologies. ICs of chemicals in aquatic organisms are primarily driven by hydrophobicity and modulated by biotransformation and efflux. Comparing the predicted baseline to observed toxicity enables the estimation of effect specificity, but biological processes can lead to overestimating ICs and bias the specificity assessment. To evaluate the prediction of a mass balance model (MBM) and the impact of biotransformation on ICs, experimental ICs of 63 chemicals in zebrafish embryos were compared to predictions with physicochemical properties as input parameters. Experimental ICs of 79% (50 of 63) of the chemicals deviated less than 10-fold from predictions, and the remaining 13 deviated up to a factor of 90. Using experimental ICs changed the classification for 19 chemicals, with ICs 5 to 90 times lower than predicted, showing the bias of specificity classification. Uptake kinetics of pirinixic acid, genistein, dexamethasone, ethoprophos, atorvastatin, and niflumic acid were studied over a 96 h exposure period, and transformation products (TPs) were elucidated using suspect- and nontarget screening with UPLC-HRMS. 35 TPs (5 to 8 TPs per compound) were tentatively identified and semiquantified based on peak areas, suggesting that biotransformation may partly account for the overpredictions of ICs.
Single-neuron representation of nonsymbolic and symbolic number zero in the human medial temporal lobe
2024-09-24

The number zero holds a special status among numbers, indispensable for developing a comprehensive number theory.<sup>1</sup><sup>,</sup><sup>2</sup><sup>,</sup><sup>3</sup><sup>,</sup><sup>4</sup> Despite its importance in mathematics, the neuronal foundation of zero in the human brain is unknown. We conducted single-neuron recordings in neurosurgical patients<sup>5</sup><sup>,</sup><sup>6</sup><sup>,</sup><sup>7</sup> while they made judgments involving nonsymbolic number representations (dot numerosity), including the empty set, and symbolic numbers (Arabic numerals), including numeral zero. Neurons showed responsiveness to either the empty set or numeral zero, but not both. Neuronal activity to zero in both nonsymbolic and symbolic formats exhibited a numerical distance effect, indicating that zero representations are integrated together with countable numerosities and positive integers at the low end of the number line.<sup>8</sup><sup>,</sup><sup>9</sup> A boundary in neuronal coding existed between the nonsymbolic empty set and small numerosities, correlating with the relative difficulty in discriminating numerosity zero behaviorally. Conversely, no such boundary was found for symbolic zero activity, suggesting that symbolic representations integrate zero with other numerals along the number line, reconciling its outlier role. The status of zero as a special nonsymbolic numerical quantity is reflected in the activity of neurons in the human brain, which seems to serve as a scaffold for more advanced representations of zero as a symbolic number.
Arsenic Reduces Methane Emissions from Paddy Soils: Insights from Continental Investigation and Laboratory Incubations
2024-09-24

Arsenic (As) contamination and methane (CH<sub>4</sub>) emissions co-occur in rice paddies. However, how As impacts CH<sub>4</sub> production, oxidation, and emission dynamics is unknown. Here, we investigated the abundances and activities of CH<sub>4</sub>-cycling microbes from 132 paddy soils with different As concentrations across continental China using metagenomics and the reverse transcription polymerase chain reaction. Our results revealed that As was a crucial factor affecting the abundance and distribution patterns of the <i>mcrA</i> gene, which is responsible for CH<sub>4</sub> production and anaerobic CH<sub>4</sub> oxidation. Laboratory incubation experiments showed that adding 30 mg kg<sup>-1</sup> arsenate increased <sup>13</sup>CO<sub>2</sub> production by 10-fold, ultimately decreasing CH<sub>4</sub> emissions by 68.5%. The inhibition of CH<sub>4</sub> emissions by As was induced through three aspects: (1) the toxicity of As decreased the abundance and activity of the methanogens; (2) the adaptability and response of methanotrophs to As is beneficial for CH<sub>4</sub> oxidation under As stress; and (3) the more robust arsenate reduction would anaerobically consume more CH<sub>4</sub> in paddies. Additionally, significant positive correlations were observed between <i>arsC</i> and <i>pmoA</i> gene abundance in both the observational study and incubation experiment. These findings enhance our understanding of the mechanisms underlying the interactions between As and CH<sub>4</sub> cycling in soils.
Lessons learned from a multimodal sensor-based eHealth approach for treating pediatric obsessive-compulsive disorder
2024-09-24

Introduction The present study investigates the feasibility and usability of a sensor-based eHealth treatment in psychotherapy for pediatric obsessive-compulsive disorder (OCD), and explores the promises and pitfalls of this novel approach. With eHealth interventions, therapy can be delivered in a patient's home environment, leading to a more ecologically valid symptom assessment and access to experts even in rural areas. Furthermore, sensors can help indicate a patient's emotional and physical state during treatment. Finally, using sensors during exposure with response prevention (E/RP) can help individualize therapy and prevent avoidance behavior. Methods In this study, we developed and subsequently evaluated a multimodal sensor-based eHealth intervention during 14 video sessions of cognitive-behavioral therapy (CBT) in 20 patients with OCD aged 12-18. During E/RP, we recorded eye movements and gaze direction via eye trackers, and an ECG chest strap captured heart rate (HR) to identify stress responses. Additionally, motion sensors detected approach and avoidance behavior. Results The results indicate a promising application of sensor-supported therapy for pediatric OCD, such that the technology was well-accepted by the participants, and the therapeutic relationship was successfully established in the context of internet-based treatment. Patients, their parents, and the therapists all showed high levels of satisfaction with this form of therapy and rated the wearable approach in the home environment as helpful, with fewer OCD symptoms perceived at the end of the treatment. Discussion The goal of this study was to gain a better understanding of the psychological and physiological processes that occur in pediatric patients during exposure-based online treatment. In addition, 10 key considerations in preparing and conducting sensor-supported CBT for children and adolescents with OCD are explored at the end of the article. This approach has the potential to overcome limitations in eHealth interventions by allowing the real-time transmission of objective data to therapists, once challenges regarding technical support and hardware and software usability are addressed. Clinical Trial Registration www.ClinicalTrials.gov , identifier (NCT05291611).
Sacsin levels in PBMCs: A diagnostic assay for SACS variants in peripheral blood cells – A PROSPAX study
2024-09-24

Abstract Background Autosomal recessive spastic ataxia of Charlevoix‐Saguenay (ARSACS) is a common recessive ataxia that is still underdiagnosed worldwide. An easily accessible diagnostic biomarker might help to diagnostically confirm patients presenting SACS variants of unknown significance (VUS) or atypical phenotypes. Objectives To detect sacsin in peripheral blood mononuclear cells (PBMCs) and to validate its diagnostic biomarker quality to discriminate biallelic SACS patients (including patients with VUS and/or atypical phenotypes) against healthy controls, non‐ARSACS spastic ataxia patients, and heterozygous SACS carriers. Methods Sacsin protein levels in PBMCs were assessed in patients versus controls and validated in skin‐derived fibroblasts. Results Patients with biallelic SACS variants – including patients with VUS and/or atypical phenotypes – showed loss of sacsin in PBMCs, with discriminative performance against healthy, heterozygous, and non‐ARSACS controls. This included all investigated SACS missense variants. Also, C‐terminal variants escaping nonsense‐mediated decay, while not differing from controls in expression level, showed lower molecular weight in this assay. Conclusions Assessing sacsin levels using PBMCs offers an easy, peripherally accessible diagnostic biomarker for ARSACS, with PBMCs being much less invasive and easier to handle than fibroblasts. Additionally, this might be a potential target‐engagement blood biomarker for sacsin‐increasing therapies.
Staphylococcus aureus thermonuclease NucA is a key virulence factor in septic arthritis
2024-09-24

<title>Abstract</title> Septic arthritis, primarily caused by <italic>Staphylococcus aureus</italic>, poses a significant risk of both mortality and morbidity due to its aggressive nature. The <italic>nuc1</italic>-encoded thermonuclease NucA of <italic>S. aureus</italic> degrades extracellular DNA/RNA, allowing the pathogen to escape neutrophil extracellular traps (NETs) and maintain the infection unabated. Here we show that in the mouse model for hematogenous septic arthritis the Δ<italic>nuc1</italic> mutant was much less pathogenic and the severity of clinical septic arthritis was markedly reduced, including decreased weight loss, lower kidney bacterial loads and much less IL-6 production. In vitro, <italic>S. aureus</italic> genomic DNA induced in macrophages a robust TNF-α response which was abrogated when the DNA was degraded by NucA. NucA induced higher IL-6 production in SAOS-2 and higher TNF-α and IL-10 production in neutrophils and shielded <italic>S. aureus</italic> from phagocyte engulfment and killing. NucA exacerbates septic arthritis possibly by increased internalization by host cells and killing of neutrophiles.
Short sources, islandhood, and pronominal correlates: New experimental support from German and Spanish for a short source approach to apparent exceptions to the clausemate condition on multiple sluicing
2024-09-24

This paper focuses on multiple sluicing (MS) utterances in which the antecedent for sluicing is syntactically complex, insofar as it contains at least one embedded clause. Complex antecedent MS (henceforth caMS) is subject to the clausemate condition (CC). Phrased in sententialist terms, the CC bans sluiced wh-phrases from being base-generated in different finite clauses in the elliptic clause. Under specific conditions, it seems that the CC is obviated. We report results from acceptability judgment experiments on German and Spanish that provide further evidence that elliptic wh-clauses in caMS can be monoclausal in nature and that these monoclausal elliptic clauses (so-called short sources) are judged as significantly more acceptable than their isomorphic, biclausal elliptic clause counterparts. We interpret these results as supporting the view that purported obviations to CC are only apparent, following Cortés Rodríguez (2022a) and Cortés Rodríguez &amp;amp; Griffiths (to appear). Because these experiments are novel in that they focus on caMS configurations involving syntactic islands, their results provide new insights into how putative CC-obviation and islandhood interact and demonstrate that not only personal but also relative pronouns can function as correlates in MS.
Developing a Group-Based Literacy Screening for German Pre-Readers: A Digital, Game-Based Approach
2024-09-24

Early prediction of children's literacy skills is crucial for successful literacy development. However, standardized screenings for pre-readers are mainly paper-based and designed for one-on-one sessions, demanding significant resources. We present the development and feasibility evaluation of a digital, game-based literacy screening for German pre-readers that supports group sessions. The screening comprises five tasks that do not rely on written language skills. We detail critical design decisions and guidelines for the effective implementation of this group-based screening. We evaluated the feasibility and user experience with 34 German second- and third-graders. Results revealed that the screening is suitable for use in group settings and that it was positively perceived by the children. Children found the tasks enganging and straightforward, often perceiving them as games. This study demonstrates that digital game-based screenings can be used effectively in group settings with young children with minimal adult guidance, offering a motivating and engaging assessment method.
Factors beyond Body Mass Index Associated with Cardiometabolic Risk among Children with Severe Obesity
2024-09-25

Background: The increasing prevalence of severe obesity among children and adolescents poses a significant challenge for pediatricians and general practitioners. This study aimed to investigate the relationships between biochemical results, anthropometry, blood pressure measurements, and bioimpedance analysis (BIA)-derived parameters to identify potential cardiometabolic complications associated with severe obesity. Methods: This study included 347 children (162 boys, 185 girls) aged 0–19 years, meeting the criteria for severe obesity based on BMI thresholds for different age groups. The patients were recruited in four pediatric endocrinology centers in Poland (Zabrze, Cracow, Rzeszow, Szczecin). Each participant underwent anthropometric measurements, pubertal stage assessment, blood pressure measurement, biochemical and hormonal tests, and BIA. Results: BMI showed significant associations with fat mass percentage (FM%) and waist-to-height ratio (WHtR) but not waist-to-hip ratio (WHR). The relationship between BMI and FM% was stronger in girls and prepubertal children. The metabolic syndrome (MetS) Z-score showed a strong positive correlation with BMI in the pubertal children. A negative correlation between HDL and triglycerides was observed only in the boys. The prepubertal children exhibited more significant correlations, despite a smaller sample size and shorter duration of obesity. Conclusions: Considering multiple parameters beyond BMI alone provides a better understanding of cardiometabolic risks associated with severe obesity in children. MetS Z-score was not a reliable indicator of increased cardiometabolic risk in younger children. Early-onset severe obesity was associated with a higher risk of metabolic complications. Early intervention is crucial to mitigate metabolic complications in this population.
Sex- specific differences in suspected myocarditis presentations and outcomes
2024-09-25

Significant sex-specific differences in presentations and imaging findings are found in patients with suspected myocarditis. Female sex is associated with a twofold increase in the risk of heart failure hospitalization, which should be considered in risk stratification.
Interesting, oftentimes even trendy! Attitudes of medical students regarding spa medicine
2024-09-25

The popularity of balneology and medical climatology among medical students has scarcely been investigated but may represent a pertinent topic for the field. Methods: A survey was conducted among 53 German medical students (80% female; mean age 22.5 years; 39% pre-clinical stage) on attitudes and interest in spa medicine, their associations with the German terms ‘Kur’ (cure) and ‘Kurortmedizin’ (spa medicine; health resort medicine) and their own health behaviour. Associations with cures were recorded using a visual analogue scale (vas). Results: A majority (72%) of the sample indicated support for the inclusion of more information about spa medicine in university curricula. Spa medicine is associated with older individuals, but with less association to overweight and psychiatric patients. The data for the statements "a spa treatment is up-to-date" and "spa treatment is effective" exhibited a normal distribution in the sample. A significant proportion of respondents reported practicing thermal baths, healthy nutrition, sauna, and Kneipp medicine themselves. Implications: The majority of medical students classified spa medicine as interesting and relevant and do not see it as old-fashioned. This interest should be encouraged in university teaching. Interesting points of reference also arise in relation to predictors of career choice among future physicians.
Longitudinal associations between exercise and biomarkers in autosomal dominant Alzheimer's disease
2024-09-26

Abstract INTRODUCTION We investigated longitudinal associations between self‐reported exercise and Alzheimer's disease (AD)‐related biomarkers in individuals with autosomal dominant AD (ADAD) mutations. METHODS Participants were 308 ADAD mutation carriers aged 39.7 ± 10.8 years from the Dominantly Inherited Alzheimer's Network. Weekly exercise volume was measured via questionnaire and associations with brain volume (magnetic resonance imaging), cerebrospinal fluid biomarkers, and brain amyloid beta (Aβ) measured by positron emission tomography were investigated. RESULTS Greater volume of weekly exercise at baseline was associated with slower accumulation of brain Aβ at preclinical disease stages β = –0.16 [–0.23 to –0.08], and a slower decline in multiple brain regions including hippocampal volume β = 0.06 [0.03 to 0.08]. DISCUSSION Exercise is associated with more favorable profiles of AD‐related biomarkers in individuals with ADAD mutations. Exercise may have therapeutic potential for delaying the onset of AD; however, randomized controlled trials are vital to determine a causal relationship before a clinical recommendation of exercise is implemented. Highlights Greater self‐reported weekly exercise predicts slower declines in brain volume in autosomal dominant Alzheimer's disease (ADAD). Greater self‐reported weekly exercise predicts slower accumulation of brain amyloid beta in ADAD. Associations varied depending on closeness to estimated symptom onset.
Symmetry breaking and non-ergodicity in a driven-dissipative ensemble of multilevel atoms in a cavity
2024-09-26

Dissipative light-matter systems can display emergent collective behavior. Here, we report a <a:math xmlns:a="http://www.w3.org/1998/Math/MathML"><a:msub><a:mi mathvariant="double-struck">Z</a:mi><a:mn>2</a:mn></a:msub></a:math>-symmetry-breaking phase transition in a system of multilevel <c:math xmlns:c="http://www.w3.org/1998/Math/MathML"><c:mmultiscripts><c:mi>Rb</c:mi><c:mprescripts/><c:none/><c:mn>87</c:mn></c:mmultiscripts></c:math> atoms strongly coupled to a weakly driven two-mode optical cavity. In the symmetry-broken phase, nonergodic dynamics manifests in the emergence of multiple stationary states with disjoint basins of attraction. This feature enables the amplification of a small atomic population imbalance into a characteristic macroscopic cavity transmission signal. Our experiment does not only showcase strongly dissipative atom-cavity systems as platforms for probing nontrivial collective many-body phenomena, but also highlights their potential for hosting technological applications in the context of sensing, density classification, and pattern retrieval dynamics within associative memories. Published by the American Physical Society 2024