Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential drug response in pulmonary arterial hypertension: The potential for precision medicine

Abstract Pulmonary arterial hypertension (PAH) is a rare, complex, and deadly cardiopulmonary disease. It is characterized by changes in endothelial cell function and smooth muscle cell proliferation in the pulmonary arteries, causing persistent vasoconstriction, resulting in right heart hypertrophy and failure. There are multiple drug classes specific to PAH treatment, but variation between patients may impact treatment response. A small subset of patients is responsive to pulmonary vasodilators and can be treated with calcium channel blockers, which would be deleterious if prescribed to a typical PAH patient. Little is known about the underlying cause of this important difference in vasoresponsive PAH patients. Sex, race/ethnicity, and pharmacogenomics may also factor into efficacy and safety of PAH‐specific drugs. Research has indicated that endothelin receptor antagonists may be more effective in women and there have been some minor differences found in certain races and ethnicities, but these findings are muddled by the impact of socioeconomic factors and a lack of representation of non‐White patients in clinical trials. Genetic variants in genes such as CYP3A5, CYP2C9, PTGIS, PTGIR, GNG2, CHST3, and CHST13 may influence the efficacy and safety of certain PAH‐specific drugs. PAH research faces many challenges, but there is potential for new methodologies to glean new insights into PAH development and treatment.
Influence of social lifestyles on host–microbe symbioses in the bees

Abstract Microbiomes are increasingly recognised as critical for the health of an organism. In eusocial insect societies, frequent social interactions allow for high‐fidelity transmission of microbes across generations, leading to closer host–microbe coevolution. The microbial communities of bees with other social lifestyles are less studied, and few comparisons have been made between taxa that vary in social structure. To address this gap, we leveraged a cloud‐computing resource and publicly available transcriptomic data to conduct a survey of microbial diversity in bee samples from a variety of social lifestyles and taxa. We consistently recover the core microbes of well‐studied corbiculate bees, supporting this method's ability to accurately characterise microbial communities. We find that the bacterial communities of bees are influenced by host location, phylogeny and social lifestyle, although no clear effect was found for fungal or viral microbial communities. Bee genera with more complex societies tend to harbour more diverse microbes, with Wolbachia detected more commonly in solitary tribes. We present a description of the microbiota of Euglossine bees and find that they do not share the “corbiculate core” microbiome. Notably, we find that bacteria with known anti‐pathogenic properties are present across social bee genera, suggesting that symbioses that enhance host immunity are important with higher sociality. Our approach provides an inexpensive means of exploring microbiomes of a given taxa and identifying avenues for further research. These findings contribute to our understanding of the relationships between bees and their associated microbial communities, highlighting the importance of considering microbiome dynamics in investigations of bee health.
Non-linear association between aspartate aminotransferase to alanine aminotransferase ratio and mortality in critically ill older patients: A retrospective cohort study

Background The aspartate aminotransferase to alanine aminotransferase (AST/ALT) ratio has been shown to be associated with poor clinical outcomes across various patient groups. However, little is unclear about the association between the two in critically ill older patients. Therefore, we aim to investigate the association of the AST/ALT ratio with hospital mortality in this special population. Methods In this retrospective cohort study, we extracted elderly patients (age ≥ 65 years) from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The primary outcome was in-hospital mortality. The association between the AST/ALT ratio and hospital mortality was studied using univariable and multivariable Cox regression analysis, as well as restricted cubic splines (RCS). Survival analysis was performed using the Kaplan-Meier (KM) method according to the AST/ALT ratio. Results Among the 13,358 eligible patients, the mean age was 77.6 years, 7,077 patients (52.9%) were male, and 2,511 patients (18.8%) died in hospital. The AST/ALT ratio was found to be independently associated with in-hospital mortality (HR = 1.05, 95% CI: 1.01–1.09, P = 0.022) after adjusting for potential confounders. Furthermore, a non-linear relationship and saturation effect were observed between them, with the inflection point being 1.80. When the AST/ALT ratio was less than 1.80, we found that every 1 unit increase in the AST/ALT ratio resulted in a 39% increased risk of in-hospital mortality (HR = 1.39, 95% CI: 1.18–1.64, P < 0.001). However, when the AST/ALT ratio was greater than 1.80, the association became saturated (HR = 1.01, 95% CI: 0.96–1.07, P = 0.609). Sensitivity and subgroup analyses showed the results were robust. Conclusion In critically ill older patients, the association between the AST/ALT ratio and in-hospital mortality was non-linear and showed a saturation effect. An elevated AST/ALT ratio was significantly associated with increased in-hospital mortality when the AST/ALT ratio was less than 1.80.
The structural-demographic theory revisited: An empirical test for industrialized societies

The structural demographic theory for industrialized societies generates three testable predictions. The first prediction is that labor oversupply leads to declining (relative) wages. The second prediction is that labor oversupply leads to elite overproduction: as relative wages fall, elite incomes display a hump-shaped pattern while elite numbers increase. The third prediction is that elite overproduction leads to political instability. I test these predictions on US data by combining evidence from existing studies with empirical proxies for elite numbers and elite income. The predictions are not supported by the data. First, labor oversupply cannot explain the polarization of wages and the decline in relative wages. The largest share in wage variance is explained by automation. Second, the data shows that as relative wages fall, elite incomes increase, in contrast to the hump-shaped pattern displayed by the model. Third, elite overproduction did not predict political instability in the last decades. Political instability is modelled by the Political Stress Index (PSI). The reviewed evidence shows that the increase in the model based PSI in the last decades is driven by the increase in inequality. The rise in inequality was caused by technological change, globalisation and to a lesser extent by the erosion of labor market institutions. Attributing the rise in inequality and the resulting increase in political instability to labor oversupply rather than to the lost race between education and technology may weaken incentives to design effective policies addressing the inefficiencies in the US education system.
A Retrospective Comparison of Toxicity, Response and Survival of Intensity-Modulated Radiotherapy Versus Three-Dimensional Conformal Radiation Therapy in the Treatment of Rectal Carcinoma

Introduction: The main target of neoadjuvant treatment in rectal cancer is to downstage and downsize large tumours to increase the chance of complete surgical resection, and therefore decrease the chances of local recurrence. With or without the addition of chemotherapy, until recently, three-dimensional conformal radiotherapy (3D-CRT) used to be the radiotherapy treatment modality of choice. However, intensity-modulated radiotherapy (IMRT) is being increasingly adopted by many radiotherapy centres as a more modern, conformal technique due to its ability to minimize radiation dose to nearby organs. The aim of our analysis was to assess the difference in toxicity, response to treatment, and survival between the patients treated with these two different treatment modalities in our institution. Methods: We performed a retrospective analysis of data and compared two groups of patients with locally advanced rectal cancer who were treated with either 3D-CRT or IMRT. The main outcomes were radiation toxicity and response to treatment. Overall survival was a secondary outcome. Results: One hundred and thirty-six patients were included in the study: 71 patients treated with 3D-CRT and 65 patients treated with IMRT. With regard to toxicity, there was no significant difference between the groups for bladder and skin toxicity, but there was a significant reduction in acute grade 2 bowel toxicity in patients treated with a long course of IMRT [3D-CRT 77% (48/62) vs IMRT 64% (30/47) p=0.042]. There was no statistically significant difference in the treatment response rates of these two radiotherapy treatment modalities, as well as in overall survival between the groups (p=0.604). Conclusion: Our study showed that IMRT can significantly reduce acute bowel side effects for patients undergoing neoadjuvant radiotherapy for locally advanced rectal cancers. Further studies are needed to confirm the clinical advantage of IMRT in rectal carcinoma.
Chimpanzees make tactical use of high elevation in territorial contexts

Tactical warfare is considered a driver of the evolution of human cognition. One such tactic, considered unique to humans, is collective use of high elevation in territorial conflicts. This enables early detection of rivals and low-risk maneuvers, based on information gathered. Whether other animals use such tactics is unknown. With a unique dataset of 3 years of simultaneous behavioral and ranging data on 2 neighboring groups of western chimpanzees, from the Taï National Park, Côte d’Ivoire, we tested whether chimpanzees make decisions consistent with tactical use of topography to gain an advantage over rivals. We show that chimpanzees are more likely to use high hills when traveling to, rather than away from, the border where conflict typically takes place. Once on border hills, chimpanzees favor activities that facilitate information gathering about rivals. Upon leaving hills, movement decisions conformed with lowest risk engagement, indicating that higher elevation facilitates the detection of rivals presence or absence. Our results support the idea that elevation use facilitated rival information gathering and appropriate tactical maneuvers. Landscape use during territorial maneuvers in natural contexts suggests chimpanzees seek otherwise inaccessible information to adjust their behavior and points to the use of sophisticated cognitive abilities, commensurate with selection for cognition in species where individuals gain benefits from coordinated territorial defense. We advocate territorial contexts as a key paradigm for unpicking complex animal cognition.
Evaluating TCFD reporting—A new application of zero-shot analysis to climate-related financial disclosures

We examine climate-related disclosures in a large sample of reports published by banks that officially endorsed the recommendations of the Task Force for Climate-related Financial Disclosures (TCFD). In doing so, we introduce a new application of the zero-shot text classification. By developing a set of fine-grained TCFD labels, we show that zero-shot analysis is a useful tool for classifying climate-related disclosures without further model training. Overall, our findings indicate that corporate climate-related disclosures increased after the launch of the TCFD recommendations and following individual endorsements. However, there are marked differences in the extent of reporting by recommended disclosure topic, suggesting that some recommendations have not yet been fully met. Our findings yield important conclusions for the design of climate-related disclosure frameworks.
Environmental variables serve as predictors of the invasive Asian longhorned tick (Haemaphysalis longicornis Neumann): An approach for targeted tick surveillance

Since the 2017 discovery of established populations of the Asian longhorned tick, (Haemaphysalis longicornis Neumann) in the United States, populations continue to be detected in new areas. For this exotic and invasive species, capable of transmitting a diverse repertoire of pathogens and blood feeding on a variety of host species, there remains a lack of targeted information on how to best prepare for this tick and understand when and where it occurs. To fill this gap, we conducted two years of weekly tick surveillance at four farms in Tennessee (three H. longicornis-infested and one without) to identify environmental factors associated with each questing life stage, to investigate predictors of abundance, and to determine the likelihood of not collecting ticks at different life stages. A total of 46,770 ticks were collected, of which 12,607 H. longicornis and five other tick species were identified. Overall, abundance of H. longicornis were associated with spring and summer seasons, forested environments, relative humidity and barometric pressure, sunny conditions, and in relation with other tick species. The likelihood of not collecting H. longicornis was associated with day length and barometric pressure. Additional associations for different life stages were also identified and included other tick species, climatic variables, and environmental conditions. Here, we demonstrated that environmental variables can be useful to predict the presence of questing H. longicornis and provide ideas on how to use this information to develop a surveillance plan for different southeastern areas with and without infestations.
Physical activity at work may not be health enhancing. A systematic review with meta-analysis on the association between occupational physical activity and cardiovascular disease mortality covering 23 studies with 655 892 participants

Objectives Emerging evidence suggests contrasting health effects for leisure-time and occupational physical activity. In this systematic review, we synthesized and described the epidemiological evidence regarding the association between occupational physical activity and cardiovascular disease (CVD) mortality. Methods A literature search was performed in PubMed, Embase, CINAHL, PsycINFO and Evidence-Based Medicine Reviews, from database inception to 17 April 2020. Articles were included if they described original observational prospective research, assessing the association between occupational physical activity and CVD mortality among adult workers. Reviews were included if they controlled for age and gender and at least one other relevant variable. We performed meta-analyses on the associations between occupational physical activity and CVD mortality. Results We screened 3345 unique articles, and 31 articles (from 23 studies) were described in this review. In the meta-analysis, occupational physical activity showed no significant association with overall CVD mortality for both males [hazard ratio (HR) 0.97, 95% confidence interval (CI) 0.84–1.12] and females (HR 0.97, 95% CI 0.82–1.15). Additional analysis showed that higher levels of occupational physical activity were non-significantly associated with a 9% increase in studies reporting on the outcome ischemic heart disease mortality (HR 1.09, 95% CI 0.82–1.43). Conclusions While the beneficial association between leisure-time physical activity and CVD mortality has been widely documented, occupational physical activity was not found to have a beneficial association with CVD mortality. This observation may have implications for our appreciation of the association between physical activity and health for workers in physically demanding jobs, as occupational physical activity may not be health enhancing.
Validating the Unmind Index as a measure of mental health and wellbeing among adults in USA, Australia, and New Zealand

Background The Unmind Index is a 26-item, 7-subscale measure of mental health and wellbeing designed for use on the Unmind digital workplace mental health platform. The Unmind Index was developed and validated in the UK but is used internationally. This paper reports further psychometric validation of this measure for use in USA, Australia, and New Zealand (ANZ). Methods Participants in four countries completed the Unmind Index and a battery of existing measures. In Study 1 (N = 770), we validated the Unmind Index separately in USA and in ANZ. In Study 2 (N = 600), we used multiple group confirmatory factor analysis to test the measurement invariance of the Unmind Index across the UK, USA, and ANZ. Results Study 1 establishes the factor structure, reliability, convergent and discriminant validity, and measurement invariance by age and gender of the Unmind Index separately for USA and for ANZ. Study 2 further demonstrates measurement invariance across locations, and establishes benchmark scores by location, age, and gender. Conclusions We conclude that the Unmind Index is valid and reliable as a measure of mental health and wellbeing in these locations.
Risk-sensitivity in sensorimotor control

Consider, for example, that you have the choice between a 50:50 gamble of winning either $0 or $100 and a sure-bet of $50. Most people prefer the sure-bet, because it is devoid of risk, even though both choices have the same expected payoff. In fact, most people would even prefer the sure-bet if it had a slightly lower payoff, say $45 – the $5 difference in expected payoff is called a risk-premium that risk-averse decision-makers are prepared to pay in order to avoid risk, thereby providing a livelihood to insurance companies (Samuelson and Nordhaus, 2009). In contrast, risk-seeking individuals that are obsessed by the possibility of winning $100 might prefer the gamble over even a sure-bet of $55, ultimately providing a livelihood for casino owners. How can such risk-sensitive behavior be explained? The theory of risk in decision-making goes back to the eighteenth century (Bernoulli, 1954/1738) and has since developed into a host of different models of decision-making under uncer-Here we will briefly review different models of risk and then discuss their relevance for the study of sensorimotor control. A first quantitative model of risk was developed by Daniel Bernoulli in the eighteenth century in response to the famous St. Petersburg paradox (Bernoulli, 1954/1738). In this paradox a fair coin is tossed repeatedly and every time a head comes up the value of the jackpot is doubled, but the game ends as soon as a tail appears. Therefore, if the jackpot is initialized with $1 and tail appears in the first toss you win $1, if it appears in the second toss you win $2, in the third toss it is $4, and so forth. The question was how much a gambler should be prepared to pay to enter such a game of chance. Since the expected payoff E[$] (/)$ (/)$ (/)$ (/)$ = + + + = + = ∞ ∑ 1 2 1 1 4 2 1 8 4 12 2 1 0  k k k is infinity, the apparent answer seemed to be that one should be prepared
The interaction of seasonal rainfall and nitrogen fertiliser rate on soil N2O emission, total N loss and crop yield of dryland sorghum and sunflower grown on sub-tropical Vertosols

Summer crop production on slow-draining Vertosols in a sub-tropical climate has the potential for large emissions of soil nitrous oxide (N2O) from denitrification of applied nitrogen (N) fertiliser. While it is well established that applying N fertiliser will increase N2O emissions above background levels, previous research in temperate climates has shown that increasing N fertiliser rates can increase N2O emissions linearly, exponentially or not at all. Little such data exists for summer cropping in sub-tropical regions. In four field experiments at two locations across two summers, we assessed the impact of increasing N fertiliser rate on both soil N2O emissions and crop yield of grain sorghum (Sorghum bicolor L.) or sunflower (Helianthus annuus L.) in Vertosols of sub-tropical Australia. Rates of N fertiliser, applied as urea at sowing, included a nil application, an optimum N rate and a double-optimum rate. Daily N2O fluxes ranged from –3.8 to 2734g N2O-Nha–1day–1 and cumulative N2O emissions ranged from 96 to 6659g N2O-Nha–1 during crop growth. Emissions of N2O increased with increased N fertiliser rates at all experimental sites, but the rate of N loss was five times greater in wetter-than-average seasons than in drier conditions. For two of the four experiments, periods of intense rainfall resulted in N2O emission factors (EF, percent of applied N emitted) in the range of 1.2–3.2%. In contrast, the EFs for the two drier experiments were 0.41–0.56% with no effect of N fertiliser rate. Additional 15N mini-plots aimed to determine whether N fertiliser rate affected total N lost from the soil–plant system between sowing and harvest. Total 15N unaccounted was in the range of 28–45% of applied N and was presumed to be emitted as N2O+N2. At the drier site, the ratio of N2 (estimated by difference)to N2O (measured) lost was a constant 43%, whereas the ratio declined from 29% to 12% with increased N fertiliser rate for the wetter experiment. Choosing an N fertiliser rate aimed at optimum crop production mitigates potentially high environmental (N2O) and agronomic (N2+N2O) gaseous N losses from over-application, particularly in seasons with high intensity rainfall occurring soon after fertiliser application.
Electrophysiological Signatures of Visual Recognition Memory across All Layers of Mouse V1

In mouse primary visual cortex (V1), familiar stimuli evoke significantly altered responses when compared with novel stimuli. This stimulus-selective response plasticity (SRP) was described originally as an increase in the magnitude of visual evoked potentials (VEPs) elicited in layer 4 (L4) by familiar phase-reversing grating stimuli. SRP is dependent on NMDA receptors (NMDARs) and has been hypothesized to reflect potentiation of thalamocortical (TC) synapses in L4. However, recent evidence indicates that the synaptic modifications that manifest as SRP do not occur on L4 principal cells. To shed light on where and how SRP is induced and expressed in male and female mice, the present study had three related aims: (1) to confirm that NMDAR are required specifically in glutamatergic principal neurons of V1, (2) to investigate the consequences of deleting NMDAR specifically in L6, and (3) to use translaminar electrophysiological recordings to characterize SRP expression in different layers of V1. We find that knock-out (KO) of NMDAR in L6 principal neurons disrupts SRP. Current-source density (CSD) analysis of the VEP depth profile shows augmentation of short latency current sinks in layers 3, 4, and 6 in response to phase reversals of familiar stimuli. Multiunit recordings demonstrate that increased peak firing occurs in response to phase reversals of familiar stimuli across all layers, but that activity between phase reversals is suppressed. Together, these data reveal important aspects of the underlying phenomenology of SRP and generate new hypotheses for the expression of experience-dependent plasticity in V1. SIGNIFICANCE STATEMENT Repeated exposure to stimuli that portend neither reward nor punishment leads to behavioral habituation, enabling organisms to dedicate attention to novel or otherwise significant features of the environment. The neural basis of this process, which is so often dysregulated in neurologic and psychiatric disorders, remains poorly understood. Learning and memory of stimulus familiarity can be studied in mouse visual cortex by measuring electrophysiological responses to simple phase-reversing grating stimuli. The current study advances knowledge of this process by documenting changes in visual evoked potentials (VEPs), neuronal spiking activity, and oscillations in the local field potentials (LFPs) across all layers of mouse visual cortex. In addition, we identify a key contribution of a specific population of neurons in layer 6 (L6) of visual cortex.