Miracle-dz/UniFAR-FTUs huggingface dataset:
Inflammation, Cognition, and White Matter in Older Adults: An Examination by Race

Objectives Non-Latino Black adults have greater risk for Alzheimer’s dementia compared to non-Latino White adults, possibly due to factors disproportionally affecting Black adults including cardiovascular disease (CVD). Chronic peripheral inflammation is implicated in both Alzheimer’s dementia and CVD and is known to impact cognition and cerebral white matter, yet little work has examined these associations by race. This study examined associations between inflammation, cognition, and cerebral white matter generally, and by race. Methods Eighty-six non-demented older Black and White participants (age = 69.03; 50% female; 45% Black participants) underwent fasting venipuncture, cognitive testing, and MRI. Serum was assayed for interleukin-6 (IL-6), C-reactive protein (CRP), and interleukin 1-beta. Cognitive domains included memory, executive function, and attention/information processing. MRI measures included white matter hyperintensity volumes (WMH) and quantification of white matter integrity in areas outside WMHs via DTI-derived fractional anisotropy (FA) and mean diffusivity, as well as multi-component relaxometry derived myelin water fraction (MWF). Results Black and White participants did not differ on age, sex, or CVD risk. Separate linear regression models adjusting for relevant confounders revealed that higher IL-6 associated with lower executive function and higher CRP levels associated with lower FA and MWF. Stratified analyses revealed that these association were significant for Black participants only. Discussion These findings suggest that peripheral inflammation is inversely associated with select cognitive domains and white matter integrity (but not WMHs), particularly in older Black adults. It is important to consider race when investigating inflammatory associates of brain and behavior.
Value beyond function: analyzing the perception of wheelchair innovations in Kenya

Innovations in the field of assistive technology are usually evaluated based on practical considerations related to their ability to perform certain functions. However, social and emotional aspects play a huge role in how people with disabilities interact with assistive products and services. Over a five months period, we tested an innovative wheelchair service provision model that leverages 3D printing and Computer Aided Design to provide bespoke wheelchairs in Kenya. The study involved eight expert wheelchair users and five healthcare professionals who routinely provide wheelchair services in their community. Results from the study show that both users and providers attributed great value to both the novel service delivery model and the wheelchairs produced as part of the study. The reasons for their appreciation went far beyond the practical considerations and were rooted in the fact that the service delivery model and the wheelchairs promoted core values of agency, empowerment and self-expression.
Changes in Sensitivity of Tree-Ring Widths to Climate in a Tropical Moist Forest Tree in Bangladesh

Tree growth in the tropics is strongly influenced by climate. However, reported tree growth responses to climate are largely inconsistent, varying with geographic location, forest type, and tree species. It is thus important to study the growth responses of tropical trees in sites and species that are under-represented so far. Bangladesh, a country influenced by the Asian monsoon climate, is understudied in terms of tree growth response to climate. In the present study, we developed a 121-year-long regional ring-width index chronology of Chukrasia tabularis A. Juss. sampled in two moist forest sites in Bangladesh to investigate tree growth responses to climate in monsoon South Asia. Standard dendrochronological methods were used to produce the ring-width chronologies. The climate sensitivity of C. tabularis was assessed through bootstrap correlation analysis and the stationarity and consistency of climate–growth relationships was evaluated using moving correlation functions and comparing the regression slopes of two sub-periods (1950–1985 and 1986–2015). Tree growth was negatively correlated with the mean, minimum, and maximum temperatures, particularly during the early growing season (March). Likewise, precipitation negatively influenced tree growth in the later growing season (October). Besides, radial growth of Chukrasia sharply ceased in years following strong and moderate El Niño events. In parallel with a significant positive trend in local temperatures, tree growth sensitivity to early growing season (March–April) mean temperatures and July minimum temperatures increased in recent decades. Tree growth sensitivity to October precipitation and April vapor pressure deficit also increased. Overall, climate–growth relationships were stronger during the period 1986–2015 than during 1950–1985. Changes in climate sensitivity might be linked to a warming trend that induced an increase in the dry season length during recent decades. With a further predicted temperature increase at our study sites, our results suggest that radial growth of C. tabularis will further decline in response to climate warming.
Evolution of Antibiotic Resistance in Surrogates of Francisella tularensis (LVS and Francisella novicida): Effects on Biofilm Formation and Fitness

Francisella tularensis, the causative agent of tularemia, is capable of causing disease in a multitude of mammals and remains a formidable human pathogen due to a high morbidity, low infectious dose, lack of a FDA approved vaccine, and ease of aerosolization. For these reasons, there is concern over the use of F. tularensis as a biological weapon, and, therefore, it has been classified as a Tier 1 select agent. Fluoroquinolones and aminoglycosides often serve as the first line of defense for treatment of tularemia. However, high levels of resistance to these antibiotics has been observed in gram-negative bacteria in recent years, and naturally derived resistant Francisella strains have been described in the literature. The acquisition of antibiotic resistance, either natural or engineered, presents a challenge for the development of medical countermeasures. In this study, we generated a surrogate panel of antibiotic resistant F. novicida and Live Vaccine Strain (LVS) by selection in the presence of antibiotics and characterized their growth, biofilm capacity, and fitness. These experiments were carried out in an effort to (1) assess the fitness of resistant strains; and (2) identify new targets to investigate for the development of vaccines or therapeutics. All strains exhibited a high level of resistance to either ciprofloxacin or streptomycin, a fluoroquinolone and aminoglycoside, respectively. Whole genome sequencing of this panel revealed both on-pathway and off-pathway mutations, with more mutations arising in LVS. For F. novicida, we observed decreased biofilm formation for all ciprofloxacin resistant strains compared to wild-type, while streptomycin resistant isolates were unaffected in biofilm capacity. The fitness of representative antibiotic resistant strains was assessed in vitro in murine macrophage-like cell lines, and also in vivo in a murine model of pneumonic infection. These experiments revealed that mutations obtained by these methods led to nearly all ciprofloxacin resistant Francisella strains tested being completely attenuated while mild attenuation was observed in streptomycin resistant strains. This study is one of the few to examine the link between acquired antibiotic resistance and fitness in Francisella spp. , as well as enable the discovery of new targets for medical countermeasure development.
Glycolysis Inhibition Regulates Endothelial Junctions by Perturbing Actin and Focal Adhesions

One of the central functions of the endothelium is to maintain a vascular barrier that prevents fluid leakiness and immune cell influx from the circulating blood into the tissue. The barrier integrity of the endothelium is largely controlled by adherens junctions (AJs) and the key AJ molecule VE-cadherin, which maintains cell cohesion via homotypic trans-interaction with VE-cadherin molecules on neighboring endothelial cells. Tension is required to maintain junction homeostasis, but little is known about the role of endothelial metabolism and bioenergetics in regulating junctional forces. Because glycolysis is the main source of ATP generation in endothelial cells, we examined the bioenergetic control of the mechanics of VE-cadherin junctions, by focusing on the glycolysis regulatory enzyme 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3). Results from traction force imbalance measurements and a VE-cadherin tension sensor revealed that inhibiting PFKFB3 significantly reduced the average junctional tension and the force on VE-cadherin complexes. The decrease in tension was largely due to mechanical changes distal from the cell-cell contacts. Specifically, inhibiting glycolysis perturbs focal adhesions and disrupts actin organization, directly impacting the net force on intercellular contacts. These findings identify a critical role of cellular metabolism for the mechanics and integrity of vascular endothelial junctions, by maintaining global cell mechanics. Statement of Significance This study examines how forces at intercellular junctions are bioenergetically regulated. Results reveal altered mechanical force generation and transmission due to the breakdown of stress-transmitting fibers during lung injury. These junctions control the barrier function of the vascular endothelium, which requires tight inter cellular adhesions to prevent fluid and macromolecules from passing through the endothelial barrier. We determined how the availability of ATP affects the tension between human endothelial cells, by regulating forces produced remotely from the junctions. These global changes alter both the force at the junctions themselves, and the force transmitted across the entire cell through actin fibers.
Iron Regulation in Elderly Asian Elephants (Elephas maximus) Chronically Infected With Mycobacterium tuberculosis

Restriction of nutrients to pathogens (nutritional immunity) is a critical innate immune response mechanism that operates when pathogens such as Mycobacterium tuberculosis have the potential to evade humoral immunity. Tuberculosis is of growing concern for zoological collections worldwide and is well-illustrated by infections of Asian and African elephants, where tuberculosis is difficult to diagnose. Here, we investigated hematological parameters and iron deposition in liver, lung, and spleen of three Asian elephants (Elephas maximus) infected with Mycobacterium tuberculosis. For reference purposes, we analyzed tissue samples from control M. tuberculosis-negative elephants with and without evidence of inflammation and/or chronic disease. Molecular analyses of bacterial lesions of post mortally collected tissues confirmed M. tuberculosis infection in three elephants. DNA sequencing of the bacterial cultures demonstrated a single source of infection, most likely of human origin. In these elephants, we observed moderate microcytic anemia as well as liver (mild), lung (moderate) and spleen (severe) iron accumulation, the latter mainly occurring in macrophages. Macrophage iron sequestration in response to infection and inflammation is caused by inhibition of iron export via hepcidin-dependent and independent mechanisms. The hepatic mRNA levels of the iron-regulating hormone hepcidin were increased in only one control elephant suffering from chronic inflammation without mycobacterial infection. By contrast, all three tuberculosis-infected elephants showed low hepcidin mRNA levels in the liver and low serum hepcidin concentrations. In addition, hepatic ferroportin mRNA expression was high. This suggests that the hepcidin/ferroportin regulatory system aims to counteract iron restriction in splenic macrophages in M. tuberculosis infected elephants to provide iron for erythropoiesis and to limit iron availability for a pathogen that predominantly proliferates in macrophages. Tuberculosis infections appear to have lingered for more than 30 years in the three infected elephants, and decreased iron availability for mycobacterial proliferation may have forced the bacteria into a persistent, non-proliferative state. As a result, therapeutic iron substitution may not have been beneficial in these elephants, as this therapy may have enhanced progression of the infection.
Clinical Outcome of Septic Patients With Heart Failure With Preserved Ejection Fraction Presenting to the Emergency Department of a Tertiary Hospital: A Retrospective Cohort Study

Background: Patients with heart failure with preserved ejection fraction (HFpEF) may be at a higher risk of mortality from sepsis than patients without heart failure. Objective: The aim of this study is to compare sepsis-related morbidity and mortality between patients with HFpEF and patients without heart failure presenting to the emergency department (ED) of a tertiary medical center. Design: Single-center retrospective cohort study conducted at an academic ED between January 1, 2015 and December 31, 2018. Patients: Patients with a diagnosis of sepsis were included. Main Measures: Bivariate and multivariate analyses were performed to look at differences in demographics, infection, and treatment parameters as well as outcomes of patients with sepsis. The primary outcome of the study was in-hospital mortality. Secondary outcomes included ED mortality, lengths of stay, and treatment differences between both groups. Key Results: A total of 1,092 patients presented with sepsis to the ED, of which 305 (27.93%) had HFpEF. There was no significant difference in in-hospital mortality between the two groups (40.7% vs. 37.4%; p = 0.314). However, there was a significant increase in ED mortality for septic HFpEF patients compared to non-heart failure patients (2.4 vs. 0.4%; p = 0.003). Septic HFpEF patients presenting to the ED were older than non-heart failure patients (76.84 vs. 68.44 years old; p < 0.0001). On the other hand, there was no significant increase in the use of vasopressors in the first 24 h between both groups. There was a significantly higher rate of intubation in the first 48 h for septic HFpEF patients (17.5 vs. 8.9%; p < 0.0001). Finally, there was significantly less intravenous fluid requirement at 6 h (1.94 L vs. 2.41L; p < 0.0001) and 24 h (3.11 L vs. 3.54L; p = 0.004) for septic patients with HFpEF compared to non-heart failure patients. Conclusion: Septic HFpEF patients experienced an increase in ED mortality, intubation, and steroid use compared to septic non-heart failure patients.
Calcium-driven regulation of voltage-sensing domains in BK channels

Allosteric interplays between voltage-sensing domains (VSD), Ca2+-binding sites, and the pore domain govern the Ca2+- and voltage-activated K+ (BK) channel opening. However, the functional relevance of the Ca2+- and voltage-sensing mechanisms crosstalk on BK channel gating is still debated. We examined the energetic interaction between Ca2+ binding and VSD activation measuring and analyzing the effects of internal Ca2+ on BK channels gating currents. Our results indicate that the Ca2+ sensors occupancy has a strong impact on the VSD activation through a coordinated interaction mechanism in which Ca2+ binding to a single α-subunit affects all VSDs equally. Moreover, the two distinct high-affinity Ca2+-binding sites contained in the C-terminus domains, RCK1 and RCK2, appear to contribute equally to decrease the free energy necessary to activate the VSD. We conclude that voltage-dependent gating and pore opening in BK channels is modulated to a great extent by the interaction between Ca2+ sensors and VSDs.
A new Miocene skate from the Central Paratethys (Upper Austria): the first unambiguous skeletal record for the Rajiformes (Chondrichthyes: Batomorphii)

A new fossil skate, Ostarriraja parva gen. et sp. nov., represented by a single partial articulated skeleton collected from the early Miocene fish-bearing strata of Upper Austria, is described here in detail. This taxon exhibits a unique combination of skeletal and dental features (e.g. nasal capsules broad and oval; presence of pectoral arch; compound radial articulated with single radial segments in serial fashion; separated pelvic girdle condyles; reduced catenated calcification of radials; about 86 pectoral radials; 20–21 pelvic-fin radials; 65–70 predorsal vertebrae) that clearly support its assignment to a new genus of the order Rajiformes, and the phylogenetic analyses reveal its basal position within the group. The comparison between Ostarriraja and the holomorphic batoids from Late Cretaceous of Lebanon traditionally aligned with skates concurs to suggest that this Neogene occurrence represents unquestionably the first known skeletal record for the group. The morphological and phylogenetic affinities of Ostarriraja with the living skates suggest a close association of this taxon with the temperate-cold water environments hypothesized for the Central Paratethys during the early Miocene. http://zoobank.org/urn:lsid:zoobank.org:pub:8BB8F0F3-35C5-47FA-AE3C-2CBF445C4BCA
KONSEP PEMBANGUNAN BERKELANJUTAN DALAM PERENCANAAN PEMBANGUNAN NASIONAL DAN REGIONAL

Tujuan dari penelitian ini adalah untuk mengetahui konsep pemangunan berkelanjutan beserta prinsipnya. Untuk menyusun perencanaan pembangunan yang berbasis konsep pembangunan berkelanjutan, perlu dipahami unsur apa saja yang diperlukan serta faktor dan piranti apa saja yang diperlukan untuk membangun secara berkelanjutan. Adapun pilar-pilar pembangunan berkelanjutan berupa berkelanjutan ekonomi, berkelanjutan sosial dan berkelanjutan lingkungan, yang ketiganya harus berkembang secara seimbang; kalau tidak pembangunan akan terjebak pada model pembangunan konvensional yang menekankan pertumbuhan ekonomi saja dan meninggalkan perkembangan sosial dan lingkungan. Disamping itu, untuk keberhasilan pembangunan berkelanjutan, disyaratkan pula perlunya modal sosial yang mampu memelihara hubungan kerja sama yang baik antar berbagai lembaga pemerintahan baik secara vertikal maupun horisontal, serta diperlukan pula sinergi antara pemerintah, pihak swasta dan masyarakat dengan pendekatan multi pihak dari ketiga kelompok tersebut dalam penyusunan rencana dan kebijakan pembangunan yang berwawasan lingkungan.
Phosphate Fertilization Reduces the Severity of Asian Soybean Rust Under High Disease Pressure

Mineral nutrition of plants is a strategy that can be used in the management of plant diseases. Therefore, the objective of this work is to determine which phosphorus dose reduces the severity of Asian soybean rust (Phakopsora pachyrhizi) with or without chemical control. Two trials were conducted under field conditions with six P doses (0, 25, 50, 100, 200 and 400 mg/dm³), and two trials in 100 L pots at P doses 0, 100, 200 and 400 mg/dm3. The inoculation of border rows and inoculation directly on plants in pots was performed with 105/mL of fungus urediniospores 15 days before the application of fungicide to increase the disease pressure. The application of fungicide (azoxystrobin + ciproconazole) was carried out at the R1 stage, and afterwards the mixture was reapplied three times in chemical control treatments. The results showed that the application of triazol + strobilurin fungicides in the presence of P decreased the severity of the disease (area under disease progress curve and disease infection rate) greater than in the absence of the fungicides. The productivity and levels of chlorophyll a, b and total also increased with chemical control in the presence of P. The dose 400 mg/dm3 of P was the most efficient in a soil with a low fertility, and 200 mg/dm³ was efficient in a soil with a high fertility. In conclusion the application of the fungicides triazol + strobilurin was very important to get good control of Asian soybean rust; phosphate fertilization contributed to the amelioration of Asian soybean rust.
Precision Medicine in Neonates: Future Perspectives for the Lung

Bronchopulmonary dysplasia (BPD) is the most common complication of pre-term birth with long lasting sequelae. Since its first description more than 50 years ago, many large randomized controlled trials have been conducted, aiming to improve evidence-based knowledge on the optimal strategies to prevent and treat BPD. However, most of these intervention studies have been performed on a population level without regard for the variation in clinical and biological diversity (e.g., gestational age, ethnicity, gender, or disease progression) between patients that is driven by the complex interaction of genetic pre-disposition and environmental exposures. Nevertheless, clinicians provide daily care such as lung protective interventions on an individual basis every day despite the fact that research supporting individualized or precision medicine for monitoring or treating pre-term lungs is immature. This narrative review summarizes four potential developments in pulmonary research that might facilitate the process of individualizing lung protective interventions to prevent development of BPD. Electrical impedance tomography and electromyography of the diaphragm are bedside monitoring tools to assess regional changes in lung volume and ventilation and spontaneous breathing effort, respectively. These non-invasive tools allow a more individualized optimization of invasive and non-invasive respiratory support. Investigation of the genomic variation in caffeine metabolism in pre-term infants can be used to optimize and individualize caffeine dosing regimens. Finally, volatile organic compound analysis in exhaled breath might accurately predict BPD at an early stage of the disease, enabling clinicians to initiate preventive strategies for BPD on an individual basis. Before these suggested diagnostic or monitoring tools can be implemented in daily practice and improve individualized patient care, future research should address and overcome their technical difficulties, perform extensive external validation and show their additional value in preventing BPD.
Study of PEG-6000 effect on growth and physiological parameters of China aster (Callistephus chinensis) and strawflower (Helichrysum bracteatum) in in vivo conditions

Drought stress is one of the most important environmental factors in reduction of growth, development and production of plants. In our study, in order to simulate water deficit induced by osmotic stress, different concentrations of polyethylene glycol (PEG) 6000 were used: 10 %, 20 % and 40 %. The goal of the investigation is to establish the growth and physiological response of annual flowers (Callistephus chinensis L. and Helichrysum bracteatum) to drought. Seedlings from Callistephus chinensis L. and Helichrysum bracteatum react individually on the simulated drought stress, using PEG in controlled (in vivo) conditions – the detected water deficit varies between 49.9 % to 63.12 % – at 40 % PEG. Changes were identified in the seedling growth, cell membrane stability and the RWC in plant tissues, corresponding to the stress duration and increase of the PEG concentration. The usage of 40 % for 6 days was the maximum admissible for the seedlings from Callistephus chinensis L. and Helichrysum bracteatum, based on the low percentage of plants which regained their development.