Miracle-dz/UniFAR-FTUs huggingface dataset:
Separate and Combined Effects of Geometrical and Mechanical Properties Changes Due to Aging on the Femoral Strength in Men and Women

Aging, from 40 to +80 years old, causes geometrical and mechanical properties changes in the proximal femur. The subperiosteal width expands faster in men compared to women during aging, while the cortical thickness varies unequally in each sector and differently between men and women. Another change which occurs during aging is bone mechanical properties such as stiffness and ultimate strains. Numerical analysis allows us to study the potential effects of each of the age-dependent changes on the fracture forces separately and combined. We investigated the effects of the geometrical and bone mechanical properties changes due to aging on the femoral strength during a common falling scenario using a transverse isotropic continuum damage model. First, the femur model was adapted from a previously developed human body model named THUMS v4.02. Then, three sets of models were developed to address each of the changes separately and combined for both sexes. We found that the fracture forces in women are on average 1500 N less than in men of the same age. The age-dependent geometrical changes increased the fracture forces in men (25 N/decade), whereas it reduced the fracture forces by 116 N/decade in women. The mechanical properties changes reduced the fracture forces in men more than in women (354.5 N/ decade vs. 225.4 N/decade). When accounting for both geometrical and mechanical properties changes due to aging, the fracture forces decreased by 10.7% of the baseline in women per decade compared to 7.2% per decade in men.
Social Integrating Robots Suggest Mitigation Strategies for Ecosystem Decay

We develop here a novel hypothesis that may generate a general research framework of how autonomous robots may act as a future contingency to counteract the ongoing ecological mass extinction process. We showcase several research projects that have undertaken first steps to generate the required prerequisites for such a technology-based conservation biology approach. Our main idea is to stabilise and support broken ecosystems by introducing artificial members, robots, that are able to blend into the ecosystem’s regulatory feedback loops and can modulate natural organisms’ local densities through participation in those feedback loops. These robots are able to inject information that can be gathered using technology and to help the system in processing available information with technology. In order to understand the key principles of how these robots are capable of modulating the behaviour of large populations of living organisms based on interacting with just a few individuals, we develop novel mathematical models that focus on important behavioural feedback loops. These loops produce relevant group-level effects, allowing for robotic modulation of collective decision making in social organisms. A general understanding of such systems through mathematical models is necessary for designing future organism-interacting robots in an informed and structured way, which maximises the desired output from a minimum of intervention. Such models also help to unveil the commonalities and specificities of the individual implementations and allow predicting the outcomes of microscopic behavioural mechanisms on the ultimate macroscopic-level effects. We found that very similar models of interaction can be successfully used in multiple very different organism groups and behaviour types (honeybee aggregation, fish shoaling, and plant growth). Here we also report experimental data from biohybrid systems of robots and living organisms. Our mathematical models serve as building blocks for a deep understanding of these biohybrid systems. Only if the effects of autonomous robots onto the environment can be sufficiently well predicted can such robotic systems leave the safe space of the lab and can be applied in the wild to be able to unfold their ecosystem-stabilising potential.
Sirtuin 2 (SIRT2): Confusing Roles in the Pathophysiology of Neurological Disorders

As a type of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases, sirtuin 2 (SIRT2) is predominantly found in the cytoplasm of cells in the central nervous system (CNS), suggesting its potential role in neurological disorders. Though SIRT2 is generally acknowledged to accelerate the development of neurological pathologies, it protects the brain from deterioration in certain circumstances. This review summarized the complex roles SIRT2 plays in the pathophysiology of diverse neurological disorders, compared and analyzed the discrete roles of SIRT2 in different conditions, and provided possible explanations for its paradoxical functions. In the future, the rapid growth in SIRT2 research may clarify its impacts on neurological disorders and develop therapeutic strategies targeting this protein.
Age at Nomination Among Soccer Players Nominated for Major International Individual Awards: A Better Proxy for the Age of Peak Individual Soccer Performance?

Individual soccer performance is notoriously difficult to measure due to the many contributing sub-variables and the variety of contexts within which skills must be utilised. Furthermore, performance differs across rather specialised playing positions. In research, soccer performance is often measured using combinations of, or even single, sub-variables. All too often these variables have not been validated against actual performance. Another approach is the use of proxies. In sports research, the age of athletes when winning championship medals has been used as a proxy for determining their age of peak performance. In soccer, studies have used the average age of players in top European leagues or in the Champions League to determine the age of individual peak performance. Such approaches have methodological shortcomings and may underestimate the peak. We explore the use of a new proxy, the age at nomination for major individual awards, to determine the average age at peak individual soccer performance. A total of 1,981 players nominated for major awards from 1956 to 2019 were included, and a subset of 653 retired players was extracted, thus including players’ complete careers. Players’ average ages at nomination, at their first nomination, and at their last ever nomination were calculated, and differences across playing positions were calculated together with changes over time in the average age at peak. Based on our proxy, the age of individual peak soccer performance occurs around 27–28 years, varying across playing positions from 26 to 31 years. A player’s first peak, on average, seems to coincide with known peaks of physiological variables; their last-ever peak occurs long after physiological performance has started to decline, indicating that the decline can be compensated for by other variables. The peak age is higher than previously reported for soccer; however, it is similar to those in other team ball sports. The average age at peak performance has increased over time, especially in the last decade. Our approach of using proxies for unearthing information about hidden features of otherwise immeasurable complex performance appears to be viable, and such proxies may be used to validate sub-variables that measure complex behaviour.
Build Your Own Mushroom Soil: Microbiota Succession and Nutritional Accumulation in Semi-Synthetic Substratum Drive the Fructification of a Soil-Saprotrophic Morel

Black morel, a widely prized culinary delicacy, was once an uncultivable soil-saprotrophic ascomycete mushroom that can now be cultivated routinely in farmland soils. It acquires carbon nutrients from an aboveground nutritional supplementation, while it remains unknown how the morel mycelium together with associated microbiota in the substratum metabolizes and accumulates specific nutrients to support the fructification. In this study, a semi-synthetic substratum of quartz particles mixed with compost was used as a replacement and mimic of the soil. Two types of composts (C1 and C2) were used, respectively, plus a bare-quartz substratum (NC) as a blank reference. Microbiota succession, substrate transformation as well as the activity level of key enzymes were compared between the three types of substrata that produced quite divergent yields of morel fruiting bodies. The C1 substratum, with the highest yield, possessed higher abundances of Actinobacteria and Chloroflexi. In comparison with C2 and NC, the microbiota in C1 could limit over-expansion of microorganisms harboring N-fixing genes, such as Cyanobacteria, during the fructification period. Driven by the microbiota, the C1 substratum had advantages in accumulating lipids to supply morel fructification and maintaining appropriate forms of nitrogenous substances. Our findings contribute to an increasingly detailed portrait of microbial ecological mechanisms triggering morel fructification.
Case Report: Abomasum Impaction in Beef Cattle Due to High Intake of Distillers' Grain and Treatment Options in Southwest China

In Southern China, distillers' grain is the main feed ingredient for small beef cattle farms. High intake of distillers' grain may lead to abomasum impaction, a disorder caused by the accumulation of solid content within the organ. For treatment, there are non-surgical and surgical options. In this study, we aimed to describe the clinical presentation, diagnosis, and treatment of beef cattle with abomasum impaction due to high intake of distillers' grain. Forty-nine Simmental beef cattle from 13 farms in Chongqing, China, were diagnosed with abomasum impaction. Animals were male, aged ≤2 years, and weighed between 200 and 350 kg. In this retrospective study, information on distillers' grain intake and clinical data were collected for 49 beef cattle diagnosed with abomasum impaction. The animals were treated between 2011 and 2019 with either non-surgical therapy or surgery. Animals diagnosed with mild abomasum impaction (n = 14) fully recovered after non-surgical treatment. Among moderate cases (n = 19), 12 cattle recovered after non-surgical treatment (63%), while the remaining seven did not respond well and underwent surgery. Three of those animals were subsequently cured (3/7). Among the severe cases (n = 16), four cattle were cured after non-surgical treatment (25%) (4/16). Of the remaining 12 cattle, six were slaughtered, and six died after surgery. Non-surgical treatment is efficient for mild abomasum impaction caused by a high intake of distillers' grain and may be considered for both moderate and severe cases. However, the treatment success rate for more severe cases decreases as the disease severity worsens.
Repurposing of Anti-Diabetic Agents as a New Opportunity to Alleviate Cognitive Impairment in Neurodegenerative and Neuropsychiatric Disorders

Cognitive impairment is a shared abnormality between type 2 diabetes mellitus (T2DM) and many neurodegenerative and neuropsychiatric disorders, such as Alzheimer’s disease (AD) and schizophrenia. Emerging evidence suggests that brain insulin resistance plays a significant role in cognitive deficits, which provides the possibility of anti-diabetic agents repositioning to alleviate cognitive deficits. Both preclinical and clinical studies have evaluated the potential cognitive enhancement effects of anti-diabetic agents targeting the insulin pathway. Repurposing of anti-diabetic agents is considered to be promising for cognitive deficits prevention or control in these neurodegenerative and neuropsychiatric disorders. This article reviewed the possible relationship between brain insulin resistance and cognitive deficits. In addition, promising therapeutic interventions, especially current advances in anti-diabetic agents targeting the insulin pathway to alleviate cognitive impairment in AD and schizophrenia were also summarized.
An Antisense Circular RNA Regulates Expression of RuBisCO Small Subunit Genes in Arabidopsis

Circular RNA (circRNA) is a novel class of endogenous long non-coding RNA (lncRNA) and participates in diverse physiological process in plants. From the dataset obtained by high-throughput RNA sequencing, we identified a circRNA encoded by the sense strand of the exon regions spanning two RuBisCO small subunit genes, RBCS2B and RBCS3B, in Arabidopsis thaliana. We further applied the single specific primer-polymerase chain reaction (PCR) and Sanger sequencing techniques to verify this circRNA and named it ag-circRBCS (antisense and across genic-circular RNA RBCS). Using quantitative real-time PCR (qRT-PCR), we found that ag-circRBCS shares a similar rhythmic expression pattern with other RBCS genes. The expression level of ag-circRBCS is 10–40 times lower than the expression levels of RBCS genes in the photosynthetic organs in Arabidopsis, whereas the Arabidopsis root lacked ag-circRBCS expression. Furthermore, we used the delaminated layered double hydroxide lactate nanosheets (LDH-lactate-NS) to deliver in vitro synthesized ag-circRBCS into Arabidopsis seedlings. Our results indicate that ag-circRBCS could significantly depress the expression of RBCS. Given that ag-circRBCS was expressed at low concentration in vivo, we suggest that ag-circRBCS may represent a fine-tuning mechanism to regulating the expression of RBCS genes and protein content in Arabidopsis.
Phenotypic Trait Variation in Populations of a Global Invader Mayweed Chamomile (Anthemis cotula): Implications for Weed Management

Mayweed chamomile (Anthemis cotula L.) is an annual crop weed that has become a substantial impediment to diversify traditional wheat-based cropping systems such as in the Pacific Northwest (PNW), USA. Some of the broadleaf rotational crops are vulnerable to the weed as they are less competitive or lack compatible herbicides for A. cotula management. Although A. cotula has been present in the PNW for more than a century, traits that contribute to invasiveness and how these vary among the weed populations have not been investigated. We assessed trait variation with a common garden greenhouse experiment by comparing 19 A. cotula populations from the PNW and Kashmir Valley, India. Seeds from individual plants from each population were used to grow plants through their senescence. We measured phenological (e.g., flowering duration), morphological (e.g., plant biomass), reproductive fitness (e.g., number of flower heads), and physiological (floral scent VOCs: volatile organic compounds) traits on individual plants and analyzed the data using mixed-effects models. We found high inter-population variation in most of the traits measured, but the variation was not associated with the geographical distance. Seedling emergence within 30 days of planting ranged from 2 to 49% for PNW populations to 55 to 72% for Indian populations. Flowering duration ranged from 2 to 3 months among populations. Other traits such as initial and final flowering dates, the total number of flower heads, and floral scent VOCs also differed among populations. These trait patterns may indicate a localized adaptation of A. cotula populations to environmental or management regimes, variation arising from anthropogenic or natural dispersal, multiple introductions, genetic drift, or combinations of these. Regardless of the processes, the trait variation suggests that weed management plan for A. cotula may need to be tailored to specific locations instead of a uniformly adopted plan across the region.
The CNS-Penetrant Soluble Guanylate Cyclase Stimulator CY6463 Reveals its Therapeutic Potential in Neurodegenerative Diseases

Effective treatments for neurodegenerative diseases remain elusive and are critically needed since the burden of these diseases increases across an aging global population. Nitric oxide (NO) is a gasotransmitter that binds to soluble guanylate cyclase (sGC) to produce cyclic guanosine monophosphate (cGMP). Impairment of this pathway has been demonstrated in neurodegenerative diseases. Normalizing deficient NO-cGMP signaling could address multiple pathophysiological features of neurodegenerative diseases. sGC stimulators are small molecules that synergize with NO, activate sGC, and increase cGMP production. Many systemic sGC stimulators have been characterized and advanced into clinical development for a variety of non-central nervous system (CNS) pathologies. Here, we disclose the discovery of CY6463, the first brain-penetrant sGC stimulator in clinical development for the treatment of neurodegenerative diseases, and demonstrate its ability to improve neuronal activity, mediate neuroprotection, and increase cognitive performance in preclinical models. In several cellular assays, CY6463 was demonstrated to be a potent stimulator of sGC. In agreement with the known effects of sGC stimulation in the vasculature, CY6463 elicits decreases in blood pressure in both rats and mice. Relative to a non-CNS penetrant sGC stimulator, rodents treated with CY6463 had higher cGMP levels in cerebrospinal fluid (CSF), functional-magnetic-resonance-imaging-blood-oxygen-level-dependent (fMRI-BOLD) signals, and cortical electroencephalographic (EEG) gamma-band oscillatory power. Additionally, CY6463 improved cognitive performance in a model of cognitive disruption induced by the administration of a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. In models of neurodegeneration, CY6463 treatment increased long-term potentiation (LTP) in hippocampal slices from a Huntington’s disease mouse model and decreased the loss of dendritic spines in aged and Alzheimer’s disease mouse models. In a model of diet-induced obesity, CY6463 reduced markers of inflammation in the plasma. Furthermore, CY6463 elicited an additive increase in cortical gamma-band oscillatory power when co-administered with donepezil: the standard of care in Alzheimer’s disease. Together, these data support the clinical development of CY6463 as a novel treatment for neurodegenerative disorders.
Regulation of Th1 T Cell Differentiation by Iron via Upregulation of T Cell Immunoglobulin and Mucin Containing Protein-3 (TIM-3)

Iron plays an important role in host–pathogen interactions, in being an essential element for both pathogen and host metabolism, but also by impacting immune cell differentiation and anti-microbial effector pathways. Iron has been implicated to affect the differentiation of T lymphocytes during inflammation, however, so far the underlying mechanism remained elusive. In order to study the role of iron in T cell differentiation we here investigated how dietary iron supplementation affects T cell function and outcome in a model of chronic infection with the intracellular bacterium Salmonella enterica serovar typhimurium (S. Typhimurium). Iron loading prior to infection fostered bacterial burden and, unexpectedly, reduced differentiation of CD4+ T helper cells type 1 (Th1) and expression of interferon-gamma (IFNγ), a key cytokine to control infections with intracellular pathogens. This effect could be traced back to iron-mediated induction of the negative immune checkpoint regulator T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), expressed on the surface of this T cell subset. In vitro experiments demonstrated that iron supplementation specifically upregulated mRNA and protein expression of TIM-3 in naïve Th cells in a dose-depdendent manner and hindered priming of those T cells towards Th1 differentiation. Importantly, administration of TIM-3 blocking antibodies to iron-loaded mice infected with S. Typhimurium virtually restored Th1 cell differentiation and significantly improved bacterial control. Our data uncover a novel mechanism by which iron modulates CD4+ cell differentiation and functionality and hence impacts infection control with intracellular pathogens. Specifically, iron inhibits the differentiation of naive CD4+ T cells to protective IFNγ producing Th1 lymphocytes via stimulation of TIM-3 expression. Finally, TIM-3 may serve as a novel drug target for the treatment of chronic infections with intracellular pathogens, specifically in iron loading diseases.
Anxiety and Social Support as Predictors of Student Academic Motivation During the COVID-19

In this study we examined whether parents’ perceptions of students’ anxiety as well as perceived support from both teachers and classmates were predictive of changes in students’ academic motivation during the first wave of COVID-19. To this end, we used a retrospective pretest-posttest design together with a latent change score model to analyze our data. From April to May of 2020, 394 Portuguese parents of students in grades 1–9 participated in this study. Our results showed that students’ anxiety and teachers’ social support, as perceived by parents, were highly significant predictors of academic motivation changes. Specifically, we found a negative effect of anxiety and a positive effect of teachers’ social support on students’ academic motivation. Our results did not show, however, a significant predictive role of classmates’ social support. This study provides an important contribution to further understand the intrapersonal and interpersonal factors that are associated with the decline of students’ academic motivation during the COVID-19 pandemic. The pivotal role of teachers in sustaining students’ academic motivation and other relevant educational implications for the ongoing pandemic are discussed.
Economic Inequality Increases Status Anxiety Through Perceived Contextual Competitiveness

Status anxiety, the constant concern about individuals’ position on the social ladder, negatively affects social cohesion, health, and wellbeing (e.g., chronic stress). Given previous findings showing that status anxiety is associated with economic inequality, we aimed in this research to test this association experimentally. A cross-sectional study (Study 1) was run in order to discard confounding effects of the relationship between perceived economic inequality (PEI) and status anxiety, and to explore the mediating role of a competitive climate (N = 297). Then we predicted that people assigned to a condition of high inequality would perceive more status anxiety in their social context, and they would themselves report higher status anxiety. Thus, in an experimental study (Study 2) PEI was manipulated (N = 200). In Study 1, PEI uniquely predicted status anxiety, and perceived competitiveness mediated the relationship. In Study 2 PEI increased perceived contextual status anxiety, a specific form of perceived competitiveness based on socioeconomic status (SES). Moreover, preliminary evidence of an indirect effect was found from PEI to personal status anxiety, through (higher) perceived contextual status anxiety. These preliminary findings provide experimental evidence for the effects of economic inequality on status anxiety and the mechanism involved. Economic inequality makes people feel that they live in a society where they are constantly concerned and competing with each other for their SES. These results could have important implications as health and wellbeing could be promoted by reducing economic inequalities and the competitive and materialistic environments of our societies.