Miracle-dz/UniFAR-FTUs huggingface dataset:
An alternative resource allocation strategy in the chemolithoautotrophic archaeon Methanococcus maripaludis

Significance Most of our knowledge about microbial physiology originates from studying fast-growing, heterotrophic bacteria. Yet, microorganisms are energy-limited in many natural environments and grow slowly or persist in a nongrowing state. Microorganisms adapted to oligotrophic lifestyles are phylogenetically diverse and often possess biochemically unique and highly niche-specialized metabolisms. In a systems-level study, we discovered a strategy for acclimation to slow growth in a chemolithoautotrophic archaeon. In contrast to relying on gene regulation like metabolically versatile, heterotrophic model bacteria such as Escherichia coli, Methanococcus maripaludis responds to energy limitation by redistributing energy for cellular maintenance and changing catabolic and ribosomal activities. The alternative resource allocation strategy presented here does not follow the canonical growth rate–dependent physiological regulations. Most microorganisms in nature spend the majority of time in a state of slow or zero growth and slow metabolism under limited energy or nutrient flux rather than growing at maximum rates. Yet, most of our knowledge has been derived from studies on fast-growing bacteria. Here, we systematically characterized the physiology of the methanogenic archaeon Methanococcus maripaludis during slow growth. M. maripaludis was grown in continuous culture under energy (formate)-limiting conditions at different dilution rates ranging from 0.09 to 0.002 h−1, the latter corresponding to 1% of its maximum growth rate under laboratory conditions (0.23 h−1). While the specific rate of methanogenesis correlated with growth rate as expected, the fraction of cellular energy used for maintenance increased and the maintenance energy per biomass decreased at slower growth. Notably, proteome allocation between catabolic and anabolic pathways was invariant with growth rate. Unexpectedly, cells maintained their maximum methanogenesis capacity over a wide range of growth rates, except for the lowest rates tested. Cell size, cellular DNA, RNA, and protein content as well as ribosome numbers also were largely invariant with growth rate. A reduced protein synthesis rate during slow growth was achieved by a reduction in ribosome activity rather than via the number of cellular ribosomes. Our data revealed a resource allocation strategy of a methanogenic archaeon during energy limitation that is fundamentally different from commonly studied versatile chemoheterotrophic bacteria such as E. coli.
Mendelian randomization identifies blood metabolites previously linked to midlife cognition as causal candidates in Alzheimer’s disease

Significance The absence of disease-modifying therapeutics for Alzheimer’s disease (AD) continues, and an understanding of early, easily accessible biomarkers to inform treatment strategies remains elusive. This study uses knowledge of blood metabolites previously associated with midlife cognition—a preclinical predictor of AD—to systematically investigate causal associations with later AD status. Given that the pathological changes underlying AD are thought to develop years before clinical manifestations of the disease, developing these findings further could hold special utility in informing early treatment intervention. There are currently no disease-modifying treatments for Alzheimer’s disease (AD), and an understanding of preclinical causal biomarkers to help target disease pathogenesis in the earliest phases remains elusive. Here, we investigated whether 19 metabolites previously associated with midlife cognition—a preclinical predictor of AD—translate to later clinical risk, using Mendelian randomization (MR) to tease out AD-specific causal relationships. Summary statistics from the largest genome-wide association studies (GWASs) for AD and metabolites were used to perform bidirectional univariable MR. Bayesian model averaging (BMA) was additionally performed to address high correlation between metabolites and identify metabolite combinations that may be on the AD causal pathway. Univariable MR indicated four extra-large high-density lipoproteins (XL.HDL) on the causal pathway to AD: free cholesterol (XL.HDL.FC: 95% CI = 0.78 to 0.94), total lipids (XL.HDL.L: 95% CI = 0.80 to 0.97), phospholipids (XL.HDL.PL: 95% CI = 0.81 to 0.97), and concentration of XL.HDL particles (95% CI = 0.79 to 0.96), significant at an adjusted P < 0.009. MR–BMA corroborated XL.HDL. FC to be among the top three causal metabolites, in addition to total cholesterol in XL.HDL (XL.HDL.C) and glycoprotein acetyls (GP). Both XL.HDL. C and GP demonstrated suggestive univariable evidence of causality (P < 0.05), and GP successfully replicated within an independent dataset. This study offers insight into the causal relationship between metabolites demonstrating association with midlife cognition and AD. It highlights GP in addition to several XL.HDLs—particularly XL.HDL. FC—as causal candidates warranting further investigation. As AD pathology is thought to develop decades prior to symptom onset, expanding on these findings could inform risk reduction strategies.
Climatic and anthropogenic influences on vegetation changes during the last 5000 years in a seasonal dry tropical forest at the northern limits of the Neotropics

Seasonal dry tropical forest (STDF) is a widespread vegetation type in western Mexico. Generally, this type of forest develops in semihumid habitats where lacustrine basins are scarce, preventing documentation of the vegetation history and forest dynamics using a paleoecological approach. Here, we present a palynological record from the Santa Maria del Oro crater lake, located within the distribution area of the STDF and the adjacent dry oak forest which gives insight into the changes in diversity and human impact at this tropical site. Pollen data, in combination with geochemical analysis and microcharcoal data from a lacustrine sequence, are used to discuss vegetation change and diversity in the plant assemblages related to drought or anthropogenic activity over the last 5000 years. Our results show three distinct periods of drought in the basin, from 4200 to 3850, 3100 to 2300, 1570 to 1100 and 300 cal year BP, with changes in vegetation composition mainly related to a decrease in taxa diversity during these periods. Based on the presence of maize pollen, two periods of human activity (3790–2160 and 280 cal year BP to present) were detected with an increase in herbaceous pollen used as a surrogate for deforestation. These two disturbance periods, pre-Columbian and postcolonial, occurred during wet conditions in the basin. Our results highlight the correlation between El Niño events, drought and fire with changes in the composition and diversity of STDF.
Creating Loyal Prosocial Transformative Service Consumers: A Proposed Model With Direct and Indirect Effects

Understanding transformative services, where the consumer is not the primary well-being beneficiary, is fundamental to furthering the transformative service research (TSR) paradigm. Furthermore, it is imperative to understand the co-creation behaviors consumers can partake in during prosocial transformative services to improve their service experience and, ultimately, their repeat usage of the service. This study is one of the first to develop a model drawing together three key service frameworks (co-creation behavior, service quality, and consumer value), which is empirically validated using real consumers of a prosocial transformative service, namely blood donation. In addition, a key strength of the study is the objective measurement of behavioral loyalty using organizational records, which is an important extension to prior TSR studies that often measure attitudinal loyalty (behavioral intentions) as a proxy. The findings have important implications for furthering transformative scholars’ and practitioners’ understanding of how services can improve individual and societal well-being.
Holocene fire history reconstruction of a mid-elevation mixed-conifer forest in the Eastern Cascades, Washington, USA

Fire histories of mid-elevation mixed-conifer forests are uncommon in the eastern Cascades, limiting our understanding of long-term fire dynamics in these environments. The purpose of this study was to reconstruct the fire and vegetation history for a moist mid-elevation mixed-conifer site, and to determine whether Holocene fire activity in this watershed was intermediate to fire regimes observed at higher and lower elevations in the eastern Cascades. Fire activity and vegetation change was reconstructed using macroscopic charcoal and pollen analysis of sediment core from Long Lake. This site is located ~45 km west of Yakima, WA, and exists in a grand fir-dominated, mixed-conifer forest. Results show low fire activity from ca. 9870 to 6000 cal yr BP, after which time fire increased and remained frequent until ca. 500 cal yr BP. A woodland environment existed at the site in the early Holocene, with the modern coniferous forest establishing ca. 6000–5500 cal yr BP. A mixed-severity fire regime has existed at the site for the past ~6000 years, with both higher- and lower-severity fire episodes occurring on average every ~80–100 years. However, only one fire episode occurred in the Long Lake watershed during the past 500 years, and none within the past ~150 years. Based on a comparison with other eastern Cascade sites, Holocene fire regimes at Long Lake, particularly during the late Holocene, appear to be intermediate between those observed at higher- and lower elevation sites, both in terms of fire severity and frequency.
Coming Together in the Fight Against Intimate Partner Violence: Lessons Learned From a Researcher–Practitioner Collaboration Evaluating Cincinnati’s Domestic Violence Enhanced Response Team (DVERT)

Intimate partner violence (IPV) is an insidious public health concern that affects people of all demographic backgrounds. In the city of Cincinnati, Ohio there has been a significant increase in IPV-related homicides over the past 5 years. Women Helping Women (WHW), a nonprofit organization that works to prevent gender-based violence, collaborated with Cincinnati Police Department (CPD) to create the Domestic Violence Enhanced Response Team (DVERT). Researchers from the University of Cincinnati School of Criminal Justice were invited to work with WHW to evaluate the program. This article discusses the history of the DVERT program and collaboration, obstacles that ensued, lessons learned, and successes of the relationship between the researchers, WHW, and CPD. Implications for other researchers and practitioners looking to form partnerships are discussed.
Antimicrobial stewardship in Northern Ireland during COVID‐19

This article provides an overview of the antimicrobial stewardship measures and prescribing trends in primary care in Northern Ireland (NI) over recent years. It discusses the impact of the COVID‐19 pandemic on antibacterial prescribing in primary care (including by dentists), and the measures being taken to improve antimicrobial stewardship and reduce antimicrobial resistance in the future.
Electron density and electron temperature measurements in nanosecond pulse discharges over liquid water surface

Time-resolved electron density, electron temperature, and gas temperature in nanosecond pulse discharges in helium and O2–He mixtures near liquid water surface are measured using Thomson/pure rotational Raman scattering, in two different geometries, (a) ‘diffuse filament’ discharge between a spherical high-voltage electrode and a grounded pin electrode placed in a reservoir filled with distilled water, with the tip exposed, and (b) dielectric barrier discharge between the high-voltage electrode and the liquid water surface. A diffuse plasma filament generated between the electrodes in helium during the primary discharge pulse exhibits noticeable constriction during the secondary discharge pulse several hundred ns later. Adding oxygen to the mixture reduces the plasma filament diameter and enhances constriction during the secondary pulse. In the dielectric barrier discharge, diffuse volumetric plasma occupies nearly the entire space between the high voltage electrode and the liquid surface, and extends radially along the surface. In the filament discharge in helium, adding water to the container results in considerable reduction of plasma lifetime compared to the discharge in dry helium, by about an order of magnitude, indicating rapid electron recombination with water cluster ions. Peak electron density during the pulse is also reduced, by about a factor of two, likely due to dissociative attachment to water vapor during the discharge pulse. These trends become more pronounced as oxygen is added to the mixture, which increases net rate of dissociative attachment. Gas temperature during the primary discharge pulse remains near room temperature, after which it increases up to T ~ 500 K over 5 µs and decays back to near room temperature before the next discharge pulse several tens of ms later. As expected, electron density and electron temperature in diffuse DBD plasmas are considerably lower compared to peak values in the filament discharge. Use of Thomson scattering for measurements of electron density and electron temperature in near-surface plasmas is hindered by strong light scattering off the surface.
Elevated Atmospheric CO2 and Nitrogen Fertilization Affect the Abundance and Community Structure of Rice Root-Associated Nitrogen-Fixing Bacteria

Elevated atmospheric CO2 (eCO2) results in plant growth and N limitation, yet how root-associated nitrogen-fixing bacterial communities respond to increasing atmospheric CO2 and nitrogen fertilization (eN) during the growth stages of rice is unclear. Using the nifH gene as a molecular marker, we studied the combined effect of eCO2 and eN on the diazotrophic community and abundance at two growth stages in rice (tillering, TI and heading, HI). Quantitative polymerase chain reaction (qPCR) showed that eN had no obvious effect on nifH abundance in rice roots under either ambient CO2 (aCO2) or eCO2 treatment at the TI stage; in contrast, at the HI, nifH copy numbers were increased under eCO2 and decreased under aCO2. For rhizosphere soils, eN significantly reduced the abundance of nifH under both aCO2 and eCO2 treatment at the HI stage. Elevated CO2 significantly increased the nifH abundance in rice roots and rhizosphere soils with nitrogen fertilization, but had no obvious effect without N addition at the HI stage. There was a significant interaction [CO2 × N fertilization] effect on nifH abundance in rice zone at the HI stage. In addition, the nifH copy numbers in rice roots were significantly higher at the HI stage than at the TI stage. Sequencing analysis indicated that the root-associated diazotrophic community structure tended to cluster according to the nitrogen fertilization treatment and that Rhizobiales were the dominant diazotrophs in all root samples at the HI stage. Additionally, nitrogen fertilization significantly increased the relative abundance of Methylosinus (Methylocystaceae) under eCO2 treatment, but significantly decreased the relative abundance of Rhizobium (Rhizobiaceae) under aCO2 treatment. Overall, the combined effect of eN and eCO2 stimulates root-associated diazotrophic methane-oxidizing bacteria while inhibits heterotrophic diazotrophs.
Epigenetic Regulation of Cardiac Neural Crest Cells

The cardiac neural crest cells (cNCCs) is a transient, migratory cell population that contribute to the formation of major arteries and the septa and valves of the heart. Abnormal development of cNCCs leads to a spectrum of congenital heart defects that mainly affect the outflow region of the hearts. Signaling molecules and transcription factors are the best studied regulatory events controlling cNCC development. In recent years, however, accumulated evidence supports that epigenetic regulation also plays an important role in cNCC development. Here, we summarize the functions of epigenetic regulators during cNCC development as well as cNCC related cardiovascular defects. These factors include ATP-dependent chromatin remodeling factors, histone modifiers and DNA methylation modulators. In many cases, mutations in the genes encoding these factors are known to cause inborn heart diseases. A better understanding of epigenetic regulators, their activities and their roles during heart development will ultimately contribute to the development of new clinical applications for patients with congenital heart disease.
The Psychological Impact of COVID-19 Among Pakistani Adults in Lahore

Background: In the wake of the worldwide spread of the novel coronavirus and the resultant restrictive measures, mental health has become a crucial issue. Physical health is not the only aspect of humans that is at risk. Globally, the rates and severity of mental illness are being significantly impacted by this pandemic. Two scales have been validated to measure the impact of coronavirus disease 2019 (COVID-19) on the levels of anxiety and obsessional thinking in clinical and non-clinical populations. The present study was designed to investigate the levels of anxiety and obsessions related to COVID-19 in the general public of Lahore, Pakistan. Materials and Methods: Data were collected via snowball sampling from May 9 to May 19. An online survey consisting of a demographic profile and two scales, Coronavirus Anxiety Scale (CAS) and Obsession with COVID-19 Scale (OCS), was sent through email, WhatsApp, and Facebook groups to adults (18 years and above) of Lahore, Pakistan. Results: A total of 240 individuals (20% men and 80% women) recorded their responses. The majority belonged to a nuclear family system (60%), and their education level ranged from high school to Ph.D. The cut-off score for probable dysfunctional coronavirus anxiety and obsession levels was not met within this sample (CAS, M = 3.24, SD = 4.21; OCS, M = 4.14, SD = 3.15), suggesting that the general population of Lahore, Pakistan is not suffering from dysfunctional anxiety or obsessions related to COVID-19. Forty-seven participants' score on OCS and 35 participants' scores on CAS were above the cut-off, i.e., ≥7 and ≥9, respectively. The results of the correlation analysis showed a significant positive relationship (**p < 0.619) between anxiety and obsessions related to COVID-19. Conclusion: One important, yet surprising, conclusion of this study is that the average adult in Lahore does not show much anxiety or obsessions related to COVID-19. Other studies around the world using these measurement tools have indicated significantly high levels of both anxiety and obsessions related to COVID-19. These findings may demonstrate the resilience of Pakistanis or perhaps the lack of understanding of the seriousness of the situation.
Inflammation-Mediated Angiogenesis in Ischemic Stroke

Stroke is the leading cause of disability and mortality in the world, but the pathogenesis of ischemic stroke (IS) is not completely clear and treatments are limited. Mounting evidence indicate that neovascularization is a critical defensive reaction to hypoxia that modulates the process of long-term neurologic recovery after IS. Angiogenesis is a complex process in which the original endothelial cells in blood vessels are differentiated, proliferated, migrated, and finally remolded into new blood vessels. Many immune cells and cytokines, as well as growth factors, are directly or indirectly involved in the regulation of angiogenesis. Inflammatory cells can affect endothelial cell proliferation, migration, and activation by secreting a variety of cytokines via various inflammation-relative signaling pathways and thus participate in the process of angiogenesis. However, the mechanism of inflammation-mediated angiogenesis has not been fully elucidated. Hence, this review aimed to discuss the mechanism of inflammation-mediated angiogenesis in IS and to provide new ideas for clinical treatment of IS.
Development and Validation a Nomogram Incorporating CT Radiomics Signatures and Radiological Features for Differentiating Invasive Adenocarcinoma From Adenocarcinoma In Situ and Minimally Invasive Adenocarcinoma Presenting as Ground-Glass Nodules Measuring 5-10mm in Diameter

Purpose To develop and validate a nomogram for differentiating invasive adenocarcinoma (IAC) from adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) presenting as ground-glass nodules (GGNs) measuring 5-10mm in diameter. Materials and Methods This retrospective study included 446 patients with 478 GGNs histopathologically confirmed AIS, MIA or IAC. These patients were assigned to a primary cohort, an internal validation cohort and an external validation cohort. The segmentation of these GGNs on thin-slice computed tomography (CT) were performed semi-automatically with in-house software. Radiomics features were then extracted from unenhanced CT images with PyRadiomics. Radiological features of these GGNs were also collected. Radiomics features were investigated for usefulness in building radiomics signatures by spearman correlation analysis, minimum redundancy maximum relevance (mRMR) feature ranking method and least absolute shrinkage and selection operator (LASSO) classifier. Multivariable logistic regression analysis was used to develop a nomogram incorporating the radiomics signature and radiological features. The performance of the nomogram was assessed with discrimination, calibration, clinical usefulness and evaluated on the validation cohorts. Results Five radiomics features remained after features selection. The model incorporating radiomics signatures and four radiological features (bubble-like appearance, tumor-lung interface, mean CT value, average diameter) showed good calibration and good discrimination with AUC of 0.831(95%CI, 0.772~0.890). Application of the nomogram in the internal validation cohort with AUC of 0.792 (95%CI, 0.712~0.871) and in the external validation cohort with AUC of 0.833 (95%CI, 0.729-0.938) also indicated good calibration and good discrimination. The decision curve analysis demonstrated that the nomogram was clinically useful. Conclusion This study presents a nomogram incorporating the radiomics signatures and radiological features, which can be used to predict the risk of IAC in patients with GGNs measuring 5-10mm in diameter individually.