julilili42/papers huggingface dataset:
LGG-01. PROGNOSTIC UTILITY AND CHARACTERISTICS OF MIB-1 LABELING INDEX AS A PROLIFERATIVE ACTIVITY MARKER IN CHILDHOOD LOW-GRADE GLIOMA: A RETROSPECTIVE OBSERVATIONAL STUDY
2024-06-18

Abstract BACKGROUND The prognostic utility of MIB-1 labeling index (LI) in pediatric low-grade glioma (PLGG) has not yet conclusively been described. We assess the correlation of MIB-1 LI and tumor growth velocity, aiming to contribute to the understanding of clinical implications and the predictive value of MIB-1 LI as an indicator of proliferative activity and progression-free survival (PFS) in pediatric low-grade glioma. METHODS MIB-1 LI of a cohort of 172 pediatric low-grade gliomas were comprehensively characterized. Correlation to tumor growth velocity, assessed by sequential MRI-based three-dimensional volumetric analyses, and PFS was analyzed. RESULTS Mean MIB-1 LI accounted for 2.7 % (range: &amp;lt;1 – 10) and showed a significant decrease to 1.5 % at secondary surgery (p =.0013). A significant difference of MIB-1 LI in different histopathological types and a correlation to tumor volume at diagnosis could be shown. Linear regression analysis showed a correlation between MIB-1 LI and preoperative TGV (R2 =.55, p &amp;lt;.0001), while correlation to tumor growth velocity remarkably decreased after incomplete resection (R2 =.08, p =.013). Log-rank test showed no impact of MIB-1 LI on 5-year PFS after incomplete (MIB-1 LI &amp;gt; 1 vs ≤ 1%: 48 vs 46 %, p =.73) and gross-total resection (MIB-1 LI &amp;gt; 1 vs ≤ 1%: 89 vs 95 %, p =.75). CONCLUSIONS This data confirms a correlation of MIB-1 LI and radiologically detectable tumor growth velocity in PLGG for the first time. Compared to preoperative tumor growth rates, a crucially decreasing correlation of MIB-1 LI and tumor growth velocity after surgery may result in limited prognostic capability of MIB-1 LI in pediatric low-grade glioma.
Reply on RC1
2024-06-18

<strong class="journal-contentHeaderColor">Abstract.</strong> Paleoclimatological field reconstructions are valuable for understanding hydroclimatic variability. While being similarly impactful on societies as temperature variability, hydroclimatic variability has still remained less in focus. However, reconstructing globally complete fields of climate variables lacks adequate proxy data from tropical regions like South America, limiting our understanding of past hydroclimatic changes in these areas. This study addresses this gap using low resolution climate archives, including speleothems, previously omitted from reconstructions. Speleothems record climate variations on decadal to centennial time scales and provide a rich dataset for the otherwise proxy data scarce region of tropical South America. By employing a multi-time scale Paleoclimate Data Assimilation approach, we synthesize climate proxy records and climate model simulations, capable of simulating water isotopologues in the atmosphere, to reconstruct 2000 years of South American climate. This includes surface air temperature, precipitation amount, drought index, isotopic composition of precipitation amount, and the intensity of the South American Summer Monsoon. The reconstruction reveals anomalous climate periods: a wetter and colder phase during the Little Ice Age (1500&ndash;1850 CE) and a drier, warmer period corresponding to the early Medieval Climate Anomaly (600&ndash;900 CE). However, these patterns are not uniform across the continent, with exceptions in northeastern Brazil and the Southern Cone, indicating regional variability. The anomalies are more pronounced than in previous reconstructions, but align with local proxy record studies, thus highlighting the importance of including speleothem proxies. The multi-timescale approach is essential for reconstructing multi-decadal and centennial climate variability. Despite methodological uncertainties regarding climate model biases and proxy record interpretations, this study marks a crucial first step in incorporating speleothems into climate field reconstructions, potentially enhancing insights into past hydroclimatic variability and hydroclimate projections.
Reply on RC2
2024-06-18

<strong class="journal-contentHeaderColor">Abstract.</strong> Paleoclimatological field reconstructions are valuable for understanding hydroclimatic variability. While being similarly impactful on societies as temperature variability, hydroclimatic variability has still remained less in focus. However, reconstructing globally complete fields of climate variables lacks adequate proxy data from tropical regions like South America, limiting our understanding of past hydroclimatic changes in these areas. This study addresses this gap using low resolution climate archives, including speleothems, previously omitted from reconstructions. Speleothems record climate variations on decadal to centennial time scales and provide a rich dataset for the otherwise proxy data scarce region of tropical South America. By employing a multi-time scale Paleoclimate Data Assimilation approach, we synthesize climate proxy records and climate model simulations, capable of simulating water isotopologues in the atmosphere, to reconstruct 2000 years of South American climate. This includes surface air temperature, precipitation amount, drought index, isotopic composition of precipitation amount, and the intensity of the South American Summer Monsoon. The reconstruction reveals anomalous climate periods: a wetter and colder phase during the Little Ice Age (1500&ndash;1850 CE) and a drier, warmer period corresponding to the early Medieval Climate Anomaly (600&ndash;900 CE). However, these patterns are not uniform across the continent, with exceptions in northeastern Brazil and the Southern Cone, indicating regional variability. The anomalies are more pronounced than in previous reconstructions, but align with local proxy record studies, thus highlighting the importance of including speleothem proxies. The multi-timescale approach is essential for reconstructing multi-decadal and centennial climate variability. Despite methodological uncertainties regarding climate model biases and proxy record interpretations, this study marks a crucial first step in incorporating speleothems into climate field reconstructions, potentially enhancing insights into past hydroclimatic variability and hydroclimate projections.
Dynamic pre-structuration of lipid nanodomain-segregating remorin proteins
2024-06-18

<title>Abstract</title> Remorins are multifunctional proteins, regulating immunity, development and symbiosis in plants. When associating to the membrane, remorins sequester specific lipids into functional membrane nanodomains. The multigenic protein family contains six groups, classified upon their protein-domain composition. Membrane targeting of remorins occurs independently from the secretory pathway. Instead, they are directed into different nanodomains depending on their phylogenetic group. All family members contain a C-terminal membrane anchor and a homo-oligomerization domain, flanked by an intrinsically disordered region of variable length at the N-terminal end. We here combined molecular imaging, Nuclear Magnetic Resonance spectroscopy, protein structure calculations and advanced molecular dynamics simulation to unveil a stable pre-structuration of coiled-coil dimers as tunable nanodomain-targeting units, containing a tunable fuzzy coat and a bar code-like positive surface charge before membrane association. These protein characteristics and the differences in structures and dynamics between C-terminal lipid anchors of the remorin groups provide a selective platform for phospholipid binding when encountering the membrane surface. Our data suggest that remorins fold in the cytosol with the N-terminal disordered region as a fuzzy structural ensemble around a dimeric anti-parallel coiled-coil core containing a symmetric interface motif reminiscent of a hydrophobic Leucine zipper. The charge distribution, the intrinsic curvature in dimeric coiled-coil remorins, and their domain geometry would confer distinctive membrane association profiles. The lipid-binding of the C-terminal creates avidity through multivalent electrostatic interactions between anionic lipid headgroups and the positively charged dimer surface suggesting a clip-and-divide mechanism to selectively segregate lipid-protein nanodomains.
Signs of the sacred at the sanctuary of Gravisca, Italy: reconstruction of an Etruscan ritual through a multidisciplinary approach
2024-06-18

Abstract Archaeological campaigns carried out at the emporic sanctuary of Gravisca (Tarquinia, Italy) have revealed extraordinary evidence for ritual depositions and ceremonies linked to the divinities/guarantors of the sanctuary. The ritual of one such deposition was reconstructed using a multidisciplinary approach, comprising an in‐depth analysis of the stratigraphy and archaeobotanical and lipid biomolecular techniques. This approach helped to define the possible sequence of events and human actions that occurred during the ritual, the animal and plant offerings, how these were processed, and the season during which the ceremony took place. Lipid biomolecular analysis also suggested the presence of garum , which to date is the earliest evidence for its use in the Mediterranean area.
A computational approach to understanding effort-based decision-making in depression
2024-06-19

Abstract Background Motivational dysfunction is a core feature of depression, and can have debilitating effects on everyday function. However, it is unclear which disrupted cognitive processes underlie impaired motivation, and whether impairments persist following remission. Decision-making concerning exerting effort to obtain rewards offers a promising framework for understanding motivation, especially when examined with computational tools which can offer precise quantification of latent processes. Methods Effort-based decision-making was assessed using the Apple Gathering Task, where participants decide whether to exert effort via a grip-force device to obtain varying levels of reward; effort levels were individually calibrated and varied parametrically. We present a comprehensive computational analysis of decision-making, initially validating our model in healthy volunteers (N=67), before applying it in a case-control study including current (N=41) and remitted (N=46) unmedicated depressed individuals, and healthy volunteers with (N=36) and without (N=57) a family history of depression. Results Four fundamental computational mechanisms that drive patterns of effort-based decisions, which replicated across samples, were identified: overall bias to accept effort challenges; reward sensitivity; and linear and quadratic effort sensitivity. Traditional model-agnostic analyses showed that both depressed groups showed lower willingness to exert effort. In contrast with previous findings, computational analysis revealed that this difference was primarily driven by lower effort acceptance bias, but not altered effort or reward sensitivity. Conclusions This work provides insight into the computational mechanisms underlying motivational dysfunction in depression. Lower willingness to exert effort could represent a trait-like factor contributing to symptoms, and might represent a fruitful target for treatment and prevention.
Increased Performance in Tutoring Systems During COVID-19 in Uruguay
2024-06-19

Background: COVID-19-related school closures globally disrupted students' education, leading to declines in academic performance. However, some studies also reported performance increases within intelligent tutoring systems (ITSs). Yet, the latter evidence stems exclusively from so-called “Western” countries (e.g., Germany). Hence, whether these findings generalize to other parts of the world remains unclear. Aim: We sought to evaluate whether performance trajectories within ITSs for learning mathematics during COVID-19-related school closures were similar for students from Germany and from Uruguay—a country and cultural context that has not yet received systematic research attention in this line of research.Samples: We analyzed two longitudinal ITS datasets from Uruguay (1,357 students; 38,673 problem sets) and Germany (8,751 students; 328,948 problem sets).Methods: We applied hierarchical linear regressions to evaluate how COVID-19-related school closures affected students' performance in mathematics in both countries.Results: We observed significant performance increases during periods of COVID-19-related school closures relative to students’ performance during the same period in previous years for both samples. These performance increases were associated with increases in relative usage, with students who used the ITS relatively more during COVID-19-related school closures than before also performing better. Conclusions: Our results indicate that previous results of increased academic performance within ITS for learning mathematics during periods of COVID-19-related school closures also pertain to students from Uruguay and highlight the need to diversify research samples. Our findings corroborate the notion that ITSs are a promising and effective tool for distance learning in different regions of the world.
Optical Genome Mapping Reveals Disruption of the RASGRF2 Gene in a Patient with Developmental Delay Carrying a De Novo Balanced Reciprocal Translocation
2024-06-19

While balanced reciprocal translocations are relatively common, they often remain clinically silent unless they lead to the disruption of functional genes. In this study, we present the case of a boy exhibiting developmental delay and mild intellectual disability. Initial karyotyping revealed a translocation t(5;6)(q13;q23) between chromosomes 5 and 6 with limited resolution. Optical genome mapping (OGM) enabled a more precise depiction of the breakpoint regions involved in the reciprocal translocation. While the breakpoint region on chromosome 6 did not encompass any known gene, OGM revealed the disruption of the RASGRF2 (Ras protein-specific guanine nucleotide releasing factor 2) gene on chromosome 5, implicating RASGRF2 as a potential candidate gene contributing to the observed developmental delay in the patient. Variations in RASGRF2 have so far not been reported in developmental delay, but research on the RASGRF2 gene underscores its significance in various aspects of neurodevelopment, including synaptic plasticity, signaling pathways, and behavioral responses. This study highlights the utility of OGM in identifying breakpoint regions, providing possible insights into the understanding of neurodevelopmental disorders. It also helps affected individuals in gaining more knowledge about potential causes of their conditions.
On the Five-Dimensional Non-Extremal Reissner–Nordström Black Hole: Retractions and Scalar Quasibound States
2024-06-19

In this paper, we examine the role played by topology, and some specific boundary conditions as well, on the physics of a higher-dimensional black hole. We analyze the line element of a five-dimensional non-extremal Reissner–Nordström black hole to obtain a new family of subspaces that are types of strong retractions and deformations, and then we extend these results to higher dimensions in order to deduce the relationship between various types of transformations. We also study the scalar field perturbations in the background under consideration and obtain an analytical expression for the quasibound state frequencies by using the Vieira–Bezerra–Kokkotas approach, which uses the polynomial conditions of the general Heun functions, and then we discuss the stability of the system and present the radial eigenfunctions. Our main goal is to discuss the physical meaning of these mathematical applications in such higher-dimensional effective metric.
Novel Small-Molecule Atypical Chemokine Receptor 3 (ACKR3) Agonists: Design, Synthesis, and Pharmacological Evaluation for Antiplatelet Therapy
2024-06-19

Cardiovascular diseases are one of the leading causes of mortality worldwide. Therefore, novel therapeutic measures are urgently needed, and promising new drug targets must be explored. ACKR3, an atypical chemokine receptor, has been associated with prothrombotic events and the development of cardiovascular events. We designed, synthesized, and evaluated a series of novel small molecules ACKR3 agonists. Extensive structure-activity relationship studies resulted in several promising agonists with potencies ranging from low micromolar to nanomolar range, for example, 23 (EC50 = 111 nM, Emax = 95%) and 27 (EC50 = 69 nM, Emax = 82%) in the β-arrestin-recruitment assay. These compounds are selective for ACKR3 versus ACKR2, CXCR3, and CXCR4. Several agonists were subjected to investigations of their P-selectin expression reduction in the flow cytometry experiments. In particular, compounds 23 and 27 showed the highest potency for platelet aggregation inhibition, up to 80% and 97%, respectively. The most promising compounds, especially 27, exhibited good solubility, metabolic stability, and no cytotoxicity, suggesting a potential tool compound for the treatment of platelet-mediated thrombosis.
Comment on egusphere-2024-820
2024-06-19

<strong class="journal-contentHeaderColor">Abstract.</strong> Western disturbances (WDs) are synoptic-scale weather systems embedded within the subtropical westerly jet. Manifesting as upper-level troughs often associated with a lower-tropospheric low over Western India, they share some dynamical features with extratropical cyclones. WDs are most common during the boreal winter (December to March), during which they bring the majority of precipitation &ndash; both rain and snow &ndash; to the Western Himalaya, as well as to surrounding areas of north India, Pakistan and the Tibetan Plateau. WDs are also associated with weather hazards such as heavy snowfall, hailstorms, fog, cloudbursts, avalanches, frost, and coldwaves. In this paper, we review the recent understanding and development on WDs. Recent studies have collectively made use of novel data, novel analysis techniques, and the increasing availability of high-resolution weather and climate models. This review is separated into six main sections &ndash; structure and thermodynamics, precipitation and impacts, teleconnections, modelling experiments, forecasting at a range of scales, and paleoclimate and climate change &ndash; each motivated with a brief discussion of the accomplishments and limitations of previous research. A number of step changes in understanding are synthesised. Use of new modelling frameworks and tracking algorithms has significantly improved knowledge of WD structure and variability, and a more frequentist approach can now be taken. Improved observation systems have helped quantification of water security over the Western Himalaya. Convection-permitting models have improved our understanding of how WDs interact with the Himalayas to trigger natural hazards. Improvements in paleoclimate and future climate modelling experiments have helped to explain how WDs and their impacts over the Himalaya respond to large-scale natural and anthropogenic forcings. We end by summarising unresolved questions and outlining key future WD research topics.
Gender and circadian preferences influence emotions and motivation in secondary mathematics classrooms
2024-06-19

Many studies have reported poor school achievement in evening persons and general circadian fluctuations in cognition. The aim of this study was to analyze circadian fluctuations in a cross-sectional design and examine the effects of chronotype on situational emotions and intrinsic motivation. A cross-sectional survey study was conducted in three Turkish secondary schools with a total sample of 599 students (283 females and 316 males). Data were collected at the end of specific math lessons of the same grade level and content, using a form combining three scales. We found no gender-related differences in intrinsic motivation, while there were some differences in situational motivation. In math classes, female students exhibited higher level of interest, while boys scored higher on boredom. In addition, students who scored high on morning affect reported higher levels of interest, well-being, and less boredom. Students with higher stability (and lower fluctuations in mood and cognition during the day) reported a higher degree of enjoyment, perceived competence, perceived choice, and less pressure/tension in their math lessons. A positive association was observed between distinctness, interest, and well-being, while negative correlations existed between distinctness and boredom. This suggests that students with higher diurnal stability reported a higher level of interest, well-being, and a lower level of boredom. Additionally, the results of the analyses showed that morningness, distinctness, and eveningness were significant predictors of intrinsic motivation. Conversely, gender, time of application, morningness, and distinctness emerged as predictors for situational emotions in mathematics classes.
A history of olive and grape cultivation in Southwest Asia using charcoal and seed remains
2024-06-20

Evaluating archaeobotanical data from over 3.9 million seeds and 124,300 charcoal fragments across 330 archaeological site phases in Southwest Asia, we reconstruct the history of olive and grape cultivation spanning a period of 6,000 years. Combining charcoal and seed data enables investigation into both the production and consumption of olive and grape. The earliest indication for olive and grape cultivation appears in the southern Levant around ca. 5000 BC and 4 th millennium BC respectively, although cultivation may have been practiced prior to these dates. Olive and grape cultivation in Southwest Asia was regionally concentrated within the Levant until 600 BC, although there were periodic pushes to the East. Several indications for climate influencing the history of olive and grape cultivation were found, as well as a correlation between periods of high population density and high proportions of olive and grape remains in archaeological sites. While temporal uncertainty prevents a detailed understanding of the causal mechanisms behind these correlations, we suggest that long distance trade in olives, grapes and their associated products was integral to the economic, social, and demographic trajectories of the region.
Variants in the proteasome regulator PSMF1 cause a phenotypic spectrum from early-onset Parkinson’s disease to perinatal lethality and disrupt mitochondrial function
2024-06-20

Abstract Dissecting biological pathways highlighted by Mendelian gene discovery has provided critical insights into the pathogenesis of Parkinson’s disease (PD) and neurodegeneration. This approach ultimately catalyzes the identification of potential biomarkers and therapeutic targets. Here, we identify PSMF1 as a novel gene implicated in parkinsonism and childhood neurodegeneration. We find that biallelic PSMF1 missense and loss-of-function variants co-segregate with phenotypes from early-onset PD to perinatal lethality with neurological manifestations across 17 pedigrees with 24 affected subjects, showing clear genotype-phenotype correlation. PSMF1 encodes the proteasome regulator PSMF1/PI31, a highly conserved, ubiquitously expressed partner of the 20S proteasome and neurodegeneration-associated F-box-O 7 and valosin-containing proteins. We demonstrate that PSMF1 variants impair mitochondrial membrane potential, dynamics and mitophagy, and may affect proteasomal abundance and assembly in patient-derived fibroblasts. Furthermore, Drosophila and mouse models of PSMF1 loss of function exhibit age-dependent motor impairment, as well as brain-wide mitochondrial membrane depolarization and dopaminergic neurodegeneration in aged flies, and diffuse gliosis in mice. Collectively, our findings unequivocally link defective PSMF1 to early-onset parkinsonism and neurodegeneration, and suggest proteasomal and mitochondrial dysfunction as mechanistic contributors.