julilili42/papers huggingface dataset:
Increased mRNA expression of CDKN2A is a transcriptomic marker of clinically aggressive meningiomas
2022-12-10

Abstract Background Homozygous loss of CDKN2A/B is a genetic alteration found in many cancer types including meningiomas, where it is associated with poor clinical outcome. It is now also a diagnostic criterion for grade 3 meningiomas in the 2021 WHO classification for central nervous system tumors. However, as in other cancers, the relationship between copy number loss of CDKN2A/B and expression of its gene product is unclear and may be either commensurate or paradoxical in nature. Therefore, we aimed to investigate the association of CDKN2A mRNA expression with clinical prognosis, WHO grade, and other molecular biomarkers in meningiomas such as DNA methylation, molecular group, and proteomics. Methods We used multidimensional molecular data of 490 meningioma samples from 4 independent cohorts to examine the relationship between mRNA expression of CDKN2A and copy number status, its correlation to clinical outcome, the transcriptomic pathways altered in differential CDKN2A expression, and its relationship with DNA methylation, and proteomics using an integrated molecular approach. Results Meningiomas without any copy number loss were dichotomized into high (CDKN2A high ) and low (CDKN2A low ) CDKN2A mRNA expression groups. Patients with CDKN2A high meningiomas had poorer progression free survival (PFS) compared to those with CDKN2A low meningiomas. CDKN2A mRNA expression was increased in more aggressive molecular groups, and in higher WHO grade meningiomas across all cohorts. CDKN2A high meningiomas and meningiomas with CDKN2A copy number loss shared common up-regulated cell cycling pathways. CDK4 mRNA expression was increased in CDKN2A high meningiomas and both p16 and CDK4 protein were more abundant in CDKN2A high meningiomas. CDKN2A high meningiomas were frequently hypermethylated at the gene body and UTR compared to CDKN2A low meningiomas and found be more commonly Rb-deficient. Conclusions An intermediate level of CDKN2A mRNA expression appears to be optimal as significantly low (CDKN2A deleted) or high expression (CDKN2A high ) are associated with poorer outcomes clinically. Though CDK4 is elevated in CDKN2A high meningiomas, Rb-deficiency may be more common in this group, leading to lack of response to CDK inhibitors.
Anomalous weathering records in the Cleveland Basin (Yorkshire, UK) during the T‐OAE global warming
2022-12-10

Abstract Early Toarcian (~183 Ma) was marked by a global warming event which accelerated continental chemical weathering. To constrain the early Toarcian weathering intensity of a Cleveland Basin (Yorkshire, UK) region, this study employed its sediment chemical weathering proxies (potassium/aluminium (K/Al) and K/rubidium (K/Rb)). The K/Al and K/Rb exhibit an anomalous chemical weathering intensity signal from the contemporaneous warm, moist world. Variations in weathering intensity for the Yorkshire section inversely comply with detrital grain size changes (indicated by Al/silicon (Al/Si)). This finding implies that continental chemical weathering did not play a major role in changing detrital grain sizes in the Yorkshire sediments. Instead, short‐term sea‐level changes in the Cleveland Basin can explain the stratigraphic variations in detrital grain sizes. Anomalies of geochemical proxies for chemical weathering and eustatic sea‐level changes do exist at local scales possibly driven by Milankovitch cycle, which reminds us to be more careful when reconstructing palaeoclimate states.
How to support learning with multimedia instruction: Implementation intentions help even when load is high
2022-12-11

Abstract There is ample evidence that multimedia learning is challenging, and learners often underutilize appropriate cognitive processes. Previous research has applied prompts to promote the use of helpful cognitive processing. However, prompts still require learners to regulate their learning, which may interfere with learning, especially in situations where cognitive demands are already high. As an alternative, implementation intentions (i.e. if‐then plans) are expected to help regulate behaviour automatically due to their specific wording, thereby offloading demands. Accordingly, this study aimed at investigating whether implementation intentions compared with prompts improve learning performance, especially under high cognitive load. Students ( N = 120) learned either in a control condition without instructional support, with prompts, or with implementation intentions. Within each condition, half of the participants studied the multimedia instruction under conditions of either high or low cognitive load, which was experimentally manipulated by instructing them to perform one of two secondary tasks. In line with our hypotheses, the results showed that under low cognitive load, both prompts and implementation intentions led to better learning than the control condition. By contrast, under high cognitive load, only implementation intentions promoted learning. Thus, implementation intentions are an efficient means to promote learning even under challenging circumstances.
Anticipating and defusing the role of conspiracy beliefs in shaping opposition to wind farms
2022-12-12

Abstract Reaching net-zero targets requires massive increases in wind energy production, but efforts to build wind farms can meet stern local opposition. Here, inspired by related work on vaccinations, we examine whether opposition to wind farms is associated with a world view that conspiracies are common (‘conspiracy mentality’). In eight pre-registered studies (collective N = 4,170), we found moderate-to-large relationships between various indices of conspiracy beliefs and wind farm opposition. Indeed, the relationship between wind farm opposition and conspiracy beliefs was many times greater than its relationship with age, gender, education and political orientation. Information provision increased support, even among those high in conspiracy mentality. However, information provision was less effective when it was presented as a debate (that is, including negative arguments) and among participants who endorsed specific conspiracy theories about wind farms. Thus, the data suggest preventive measures are more realistic than informational interventions to curb the potentially negative impact of conspiracy beliefs.
Geochemical Characterization of Insoluble Particle Clusters in Ice Cores Using Two‐Dimensional Impurity Imaging
2022-12-12

Abstract Understanding post‐depositional processes altering the layer sequence in ice cores is especially needed to avoid misinterpretation of the oldest and most highly thinned layers. The record of soluble and insoluble impurities represents an important part of the paleoclimate proxies in ice cores but is known to be affected through interaction with the ice matrix, diffusion, and chemical reactions. Laser ablation inductively coupled plasma mass spectrometry (LA‐ICP‐MS) has been recognized for its micron‐scale resolution and micro‐destructiveness in ice core impurity analysis. Employing LA‐ICP‐MS for 2D chemical imaging has already revealed a close relationship between the ice grain boundary network and impurity signals with a significant soluble component, such as Na and Mg. Here we show the latest improvements in chemical imaging with LA‐ICP‐MS, by increasing the spatial resolution to 20 μm and extending the simultaneous analysis to also mostly insoluble impurities, such as Al and Fe. All analytes reveal signals of dispersed spots in a sample of an East Greenland ice core. Based on their average size around 50–60 times larger than an average particle and their heterogeneous elemental ratios these spots are interpreted as particle clusters. To distinguish their origin, a simple colocalization classification reveals elemental ratios consistent with marine and mineral dust aerosol. Based on already existing data from cryo‐Raman spectroscopy, we discuss potential ways to integrate the two methods in a future comparison. Such a combined approach may help constraining post‐depositional changes to the dust‐related insoluble impurity components, such as cluster formation and chemical reactions at grain boundaries.
Risk factors and prevalence of human African trypanosomiasis in individuals living in remote areas of the republic of Congo
2022-12-12

Abstract Background Human African trypanosomiasis (HAT) is one of the world’s classical neglected tropical diseases representing a major public health threat in sub-Saharan Africa. Although the parasitic disease is in decline in the Republic of Congo, the better understanding of the epidemiological situation of active foci is required to reduce the risk of disease resurgence which could impede progress registered so far. The aim of this study was to determine the prevalence of HAT and the associated risk factors in individuals living in remote areas of the Republic of Congo. Methods A cross-sectional survey was carried out in volunteers living in rural settings from June 2020 to January 2021. Socio-demographic and Clinical parameters of the participants were recorded. The presence of HAT-specific antibodies was assessed in whole blood, and then confirmed in serial diluted plasma samples using Card-Agglutination Trypanosomiasis Test (CATT)/ T.b. gambiense CATT. The Capillary Tube Centrifugation (CTC) and Lymph nodes (LN) examination were done for detecting trypanosome parasites in CATT-serum positive cases. The staging of positive participants was determined by cerebrospinal fluid (CSF) examination. Results Out of 8556 enrolled participants, 48.5% were more than 15 years old, 57.7% were unschooled and 67.2% practiced peasant activities. The prevalence of HAT infection was 0.3% with the predominance of patients at stage 1 of the disease (84.0%). The districts of Mindouli (OR: 25.9 (5.2–468); p = 0.0016) and Mpouya (OR: 13.3 (2.5–246); p = 0.0140) was revealed as the foci of high risk of HAT infection. Several factors were associated with an increased risk of HAT infection mainly including the non-schooling (OR: 5.1 (1.2–21.9); p = 0.0268), the life in couple or married (OR: 3.3 (1.0–11.3); p = 0.0545) and the practice of peasant activities (OR: 6.9 (2.4–29.3); p = 0.0017). Conclusion This study highlights the need of revising and strengthening the strategies of HAT control in Republic of Congo, using an approach which will take into account the education level, the marital status and the occupation of the population at risk.
It takes neurons to understand neurons: Digital twins of visual cortex synthesize neural metamers
2022-12-12

ABSTRACT Metamers, images that are perceived as equal, are a useful tool to study representations of natural images in biological and artificial vision systems. We synthesized metamers for the mouse visual system by inverting a deep encoding model to find an image that matched the observed neural activity to the original presented image. When testing the resulting images in physiological experiments we found that they most closely reproduced the neural activity of the original image when compared to other decoding methods, even when tested in a different animal whose neural activity was not used to produce the metamer. This demonstrates that deep encoding models do capture general characteristic properties of biological visual systems and can be used to define a meaningful perceptual loss for the visual system.
Planetary Line-to-accretion Luminosity Scaling Relations: Extrapolating to Higher-order Hydrogen Lines
2022-12-12

Abstract Aoyama et al. provided scaling relations between hydrogen-line luminosities and the accretion luminosity for planetary-mass objects. These fits should be an improvement over blind extrapolations of stellar relations. The fits go up only to the n = 8 electron energy level, but higher- n Balmer lines have been observed in the near-UV with UVES. We extend the scaling relations to higher- n levels for the Balmer and other series by fitting the fit coefficients ( a , b ) themselves and extrapolating them. Within the assumption of an accretion shock as the source of line emission, these fits should be robust for accreting planetary-mass objects.
Sinonasal Outcome After Endoscopic Transnasal Surgery—A Prospective Rhinological Study
2022-12-12

BACKGROUND: The sinonasal outcome after transnasal skull base surgery has often been neglected aside from major outcome criteria as extent of tumor resection, ophthalmological, and endocrinological parameters. OBJECTIVE: To analyze rhinological outcome after endoscopic transnasal neurosurgery. METHODS: Patients were treated using a middle turbinate–preserving transnasal endoscopic approach for sellar/parasellar lesions. As major variables, olfactory function and nose breathing ability were assessed. The study participants were investigated by odor testing (“Sniffin’ sticks”), rhinomanometry, and endoscopic inspection of the nasal cavity before and 6 months after surgery. Furthermore, sinonasal-associated quality of life was measured before, immediately and 6 months after surgery with a standardized questionnaire (SNOT-20-GAV). RESULTS: Eighty-two patients (47 male, 35 female, median age 55 years) matched the inclusion criteria. Before surgery, the average odor was found to be 30.75 (≥31 = normosmia); in the postinterventional examination at 6 months, the average increased to 33.08 (n.s.). Rhinomanometric examination of binostril nasal airflow showed an average of 590.42 mL/s on inspiration before and an increase to 729.78 mL/s at 6 months after surgery. SNOT-20 symptom scores had a maximum score right after and no difference at 6 months after surgery (scores 23.76 and 14.91 vs 15.53 before surgery). CONCLUSION: Based on the study, the endoscopic transnasal technique preserving the middle turbinate has no significant negative effects on the rhinological outcome.
Establishment of a novel method to assess MEK1/2 inhibition in PBMCs for clinical drug development
2022-12-12

The Raf/MEK/ERK signaling pathway plays a key role in regulating cellular proliferation, differentiation, apoptosis, cytokine production, and immune responses. However, it is also involved in diseases such as cancer, and numerous viruses rely on an active Raf/MEK/ERK pathway for propagation. This pathway, and particularly MEK1/2, are therefore promising therapeutic targets. Assessment of target engagement is crucial to determine pharmacodynamics or the efficacy of a MEK1/2 inhibitor. In the field of infectious diseases, this is usually first determined in clinical trials with healthy volunteers. One method to detect MEK1/2 inhibitor target engagement is to assess the degree of ERK1/2 phosphorylation, as ERK1/2 is the only known substrate of MEK1/2. As healthy subjects, however, only feature a low baseline MEK1/2 activation and therefore low ERK1/2 phosphorylation in most tissues, assessing target engagement is challenging, and robust methods are urgently needed. We hence developed a method using PBMCs isolated from whole blood of healthy blood donors, followed by ex vivo treatment with the MEK1/2 inhibitor zapnometinib and stimulation with PMA to first inhibit and then induce MEK1/2 activation. As PMA cannot activate MEK1/2 upon MEK1/2 inhibition, MEK1/2 inhibition results in impaired MEK1/2 activation. In contrast, PMA stimulation without MEK1/2 inhibition results in high MEK1/2 activation. We demonstrated that, without MEK1/2 inhibitor treatment, MEK1/2 stimulation with PMA induces high MEK1/2 activation, which is clearly distinguishable from baseline MEK1/2 activation in human PBMCs. Furthermore, we showed that treatment with the MEK1/2 inhibitor zapnometinib maintains the MEK1/2 activation at approximately baseline level despite subsequent stimulation with PMA. As our protocol is easy to follow and preserves the cells in an in vivo -like condition throughout the whole handling process, this approach can be a major advance for the easy assessment of MEK1/2 inhibitor target engagement in healthy probands for clinical drug development.
How Salome Seduced Constantius II on Stage
2022-12-12

Abstract Athanasius, the bishop of Alexandria, was a master of invective. In this paper, I want to take a closer look at the negative representation of Arian bishops and emperor Constantius II in the Historia Arianorum through a close reading of a key passage that is often quoted, but rarely discussed in detail (chapter 52). I want to highlight how Athanasius supercharges his representation with references to the past, to drama and to the bible. This topic is indebted to recent scholarship on Athanasius and his polemics, which it hopes to enrich by highlighting Athanasius’ allusiveness and influence. Occasionally I will draw on Athanasius’ earlier works to show how his line of argument developed and refer to other authors who either took over his image or held different views. This paper contributes to the ongoing study of invective, which was so prominent in the religious sphere.
CINWA (database of terminology for cultivated plants in indigenous languages of northwestern South America): introducing a resource for research in ethnobiology, anthropology, historical linguistics, and interdisciplinary research on the neolithic transition in South America
2022-12-13

Abstract This article introduces CINWA, a freely accessible online database of terminology for cultivated plants in indigenous languages of South America based on FAIR principles for scientific data management and stewardship. In the pre-release version we present here, CINWA assembles more than 2700 terms from more than 60 indigenous languages of northwestern South America, and coverage will be continuously expanded. CINWA is primarily designed for use in historical linguistics to explore patterns of lexical borrowing that might be used as a proxy for tracing the pathways by which knowledge of individual cultivated plants and the associated know-how spread from speech community to speech community in pre-Columbian South America. In spite of intensifying research, this is still unclear for most cultivars as the locales of initial cultivation are heterogeneous and spatially diffuse. However, possible uses of the CINWA database are manifold and go beyond this research question. The database can be used as a resource for ethnobiological and comparative anthropological research on South American communities, South American agricultural ecosystems and practices, and for studies in lexical borrowing, language contact, and historical linguistics broadly.
The consequences of debris flows in Brazil: a historical analysis based on recorded events in the last 100 years
2022-12-13

Abstract This study aims at providing an overview of the socioeconomic consequences that debris-flow events have caused in Brazil, positioning the country in the international scenario and identifying areas where targeted actions are necessary. The analysis is conducted by calculating the debris-flow mortality rate (MR) and by using the so-called F-N plots (frequency of events that have caused N or more fatalities vs. the number of fatalities), based on a compilation of debris-flow-related disasters from 1920 to 2021. In total, 45 debris-flow events were documented in the considered period, responsible for 5771 fatalities and more than 5.5 billion USD in economic losses. The Serra do Mar Mountain Range is the main site of reported debris-flow occurrences (64.5%), followed by Serra da Mantiqueira (13.3%), and Serra Geral (13.3%). Southeast Brazil (SEB) is the region most affected by debris-flow events, due to the highest population density and the development of several cities in hilly areas, such as Petrópolis (Rio de Janeiro state) and Cubatão (São Paulo state). The debris-flow MR of SEB is higher than any other region in Brazil, pushing the national debris-flow MR upwards, and the F-N curve of SEB consolidates the region as the one with the highest risk to the phenomenon, indicating a higher probability of fatal events. The F-N plots further show that debris-flow events in Brazil represent a higher societal risk than in countries such as China, Japan and Italy. While there are differences in country size and the scale effect should be considered, these results highlight the urgent need for investments in disaster prevention and preparedness programs.
Understanding Daily, Emotional, and Physical Burdens and Needs of Parents Caring for Children with Type 1 Diabetes
2022-12-13

Aims. To investigate (1) daily, emotional, and physical caregiving burdens in parents of children with type 1 diabetes, (2) the sociodemographic and clinical predictors of three burdens, and (3) support measures that parents wish to receive. Methods. The study was a multicenter cross-sectional survey conducted in nine German pediatric diabetes centers. A questionnaire assessing three types of burdens and wishes for support was distributed to parents with a child with type 1 diabetes visiting one of the pediatric centers for a routine check-up. Results. Data from 1,107 parents (83% mothers) were analyzed. Parents reported significantly higher emotional burdens compared to daily and physical burdens ( <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" id="M1"> <a:mi>p</a:mi> <a:mo>&lt;</a:mo> <a:mn>0.0001</a:mn> </a:math> ). Mothers felt more burdened than fathers did. Parents of younger children reported higher daily and physical burdens compared to the parents of older children, and similarly, parents of technology users reported higher daily and physical burdens compared to the parents of nontechnology users. However, emotional burdens did not differ in both comparisons. Other demographic factors (i.e., parent’s age, migration status, and single-parent family status) predicted high levels of daily or physical burdens, but only HbA1c level and the parent’s gender (mother) predicted a high emotional burden. Independent of the level of burden, 78% of parents wanted additional diabetes training. Conclusion. Despite parents reporting high emotional burdens in connection with diabetes care, HbA1c and the gender of the reporting parent were the only risk factors. As the child gets older, parents’ daily and physical distress decrease but not the emotional burden. Diabetes training including regularly offered booster sessions as well as low-threshold interventions for mental health issues and practical self-care skills is recommended to provide continuous support for parents.
The association of perceived leadership style and subjective well-being of employees in a tertiary hospital in Germany
2022-12-13

Background Professionals in the healthcare sector are a particularly vulnerable group for occupational strain due to high work-related psychological stress. For the implementation of targeted stress-prevention interventions as an important part of a workplace health management programme for all occupational groups and hierarchy levels, information about the current state of their mental health is mandatory. Hence, this study investigated the association of general well-being and different leadership styles among employees in a German tertiary hospital. Methods Via an online survey, 10,101 employees were contacted. The final sample consisted of 1137 employees. Of these, 27.7% described themselves as leaders and 72.3% as followers. Most participants were female (74.8%), more than half were under 41 years old. Besides control variables, general well-being (WHO-5) and leadership style (transactional and transformational, laissez-faire and destructive leadership) were assessed. Results Leaders reported higher well-being scores than followers. Physicians without leadership responsibilities had the lowest scores for well-being. Practitioners of both transformational and transactional leadership were associated with higher well-being scores, while those practicing laissez-faire and destructive leadership had lower scores for almost every professional group. Conclusion Results highlight the necessity for future multimodal health-preventive leadership interventions feature behavioural and organizational intervention modules specifically tailored to hospital professionals at different hierarchical and functional levels to foster the mental health of employees.