Miracle-dz/UniFAR-FTUs huggingface dataset:
Adenosine, caffeine, and sleep–wake regulation: state of the science and perspectives

For hundreds of years, mankind has been influencing its sleep and waking state through the adenosinergic system. For ~100 years now, systematic research has been performed, first started by testing the effects of different dosages of caffeine on sleep and waking behaviour. About 70 years ago, adenosine itself entered the picture as a possible ligand of the receptors where caffeine hooks on as an antagonist to reduce sleepiness. Since the scientific demonstration that this is indeed the case, progress has been fast. Today, adenosine is widely accepted as an endogenous sleep‐regulatory substance. In this review, we discuss the current state of the science in model organisms and humans on the working mechanisms of adenosine and caffeine on sleep. We critically investigate the evidence for a direct involvement in sleep homeostatic mechanisms and whether the effects of caffeine on sleep differ between acute intake and chronic consumption. In addition, we review the more recent evidence that adenosine levels may also influence the functioning of the circadian clock and address the question of whether sleep homeostasis and the circadian clock may interact through adenosinergic signalling. In the final section, we discuss the perspectives of possible clinical applications of the accumulated knowledge over the last century that may improve sleep‐related disorders. We conclude our review by highlighting some open questions that need to be answered, to better understand how adenosine and caffeine exactly regulate and influence sleep.
One Full or Two Fractional Doses of Inactivated Poliovirus Vaccine for Catch-up Vaccination in Older Infants: A Randomized Clinical Trial in Bangladesh

Abstract Background The polio eradication endgame called for the removal of trivalent oral poliovirus vaccine (OPV) and introduction of bivalent (types 1 and 3) OPV and inactivated poliovirus vaccine (IPV). However, supply shortages have delayed IPV administration to tens of millions of infants, and immunogenicity data are currently lacking to guide catch-up vaccination policies. Methods We conducted an open-label randomized clinical trial assessing 2 interventions, full or fractional-dose IPV (fIPV, one-fifth of IPV), administered at age 9–13 months with a second dose given 2 months later. Serum was collected at days 0, 60, 67, and 90 to assess seroconversion, priming, and antibody titer. None received IPV or poliovirus type 2-containing vaccines before enrolment. Results A single fIPV dose at age 9–13 months yielded 75% (95% confidence interval [CI], 6%–82%) seroconversion against type 2, whereas 2 fIPV doses resulted in 100% seroconversion compared with 94% (95% CI, 89%–97%) after a single full dose (P < .001). Two doses of IPV resulted in 100% seroconversion. Conclusions Our study confirmed increased IPV immunogenicity when administered at an older age, likely due to reduced interference from maternally derived antibodies. Either 1 full dose of IPV or 2 doses of fIPV could be used to vaccinate missed cohorts, 2 fIPV doses being antigen sparing and more immunogenic. Clinical Trial Registration NCT03890497.
Complex Ecotype Dynamics Evolve in Response to Fluctuating Resources

Despite regular feast and famine conditions representing an environmental pressure that is commonly encountered by microbial communities, the evolutionary outcomes of repeated cycles of feast and famine have been less studied. By experimentally evolving initially isogenic Escherichia coli populations to 10-day feast/famine cycles, we observed rapid diversification into ecotypes with evidence of bidirectional cross-feeding on costly resources and frequency-dependent fitness. ABSTRACT Ecotypic diversification and its associated cooperative behaviors are frequently observed in natural microbial populations whose access to resources is often sporadic. However, the extent to which fluctuations in resource availability influence the emergence of cooperative ecotypes is not fully understood. To determine how exposure to repeated resource limitation affects the establishment and long-term maintenance of ecotypes in a structured environment, we followed 32 populations of Escherichia coli evolving to either 1-day or 10-day feast/famine cycles for 900 days. Population-level analysis revealed that compared to populations evolving to 1-day cycles, 10-day populations evolved increased biofilm density, higher parallelism in mutational targets, and increased mutation rates. As previous investigations of evolution in structured environments have identified biofilm formation as the earliest observable phenotype associated with diversification of ecotypes, we revived cultures midway through the evolutionary process and conducted additional genomic, transcriptional, and phenotypic analyses of clones isolated from these evolving populations. We found not only that 10-day feast/famine cycles support multiple ecotypes but also that these ecotypes exhibit cooperative behavior. Consistent with the black queen hypothesis, or evolution of cooperation by gene loss, transcriptomic evidence suggests the evolution of bidirectional cross-feeding behaviors based on essential resources. These results provide insight into how analogous cooperative relationships may emerge in natural microbial communities. IMPORTANCE Despite regular feast and famine conditions representing an environmental pressure that is commonly encountered by microbial communities, the evolutionary outcomes of repeated cycles of feast and famine have been less studied. By experimentally evolving initially isogenic Escherichia coli populations to 10-day feast/famine cycles, we observed rapid diversification into ecotypes with evidence of bidirectional cross-feeding on costly resources and frequency-dependent fitness. Although unidirectional cross-feeding has been repeatedly observed to evolve in laboratory culture, most investigations of bidirectional cooperative behaviors in microbial populations have been conducted in engineered communities. This work demonstrates the de novo evolution of black queen relationships in a microbial population originating from a single ancestor, providing a model for investigation of the eco-evolutionary processes leading to mutualistic cooperation.
A feasibility randomized controlled trial of a multi-process action control web-based intervention that targets physical activity in mothers

ABSTRACT The onset of motherhood is associated with a decline in moderate- to vigorous-physical activity (MVPA) and this deficit can remain for years to come. This study explored the feasibility of a web-based intervention, informed by the multi-process action control (M-PAC) framework, to promote PA in mothers. Forty-one inactive mothers of children <16 were randomized to a 10-week web-intervention (n = 20) or wait-list control (n = 21). Primary outcomes of recruitment and retention were measured with frequency counts; usability and satisfaction were measured via self-report questionnaires and qualitative interviews; secondary outcomes of MVPA and M-PAC constructs were assessed via self-report. Recruitment was 41%, retention was 88%, and satisfaction and usability were high. Participants logged in 7.94 (SD = 3.87) times and spent 37.71 (SD = 20.21) minutes per week on the web-intervention. Suggestions for intervention improvement included additional content targeting mothers, reminders, and optimized navigation. Intervention participants trended toward improved MVPA and M-PAC constructs, particularly action control processes of habit, self-identity, and behavioral regulation. The high feasibility ratings of recruitment, retention, satisfaction, and usability demonstrated that the study can be extended to a full-scale RCT with minor additions to the intervention such as content targeting mothers, reminders, and optimized navigation.
Personally Generated Quality of Life Outcomes in Adults With Juvenile Idiopathic Arthritis

Objective To explore quality of life (QOL) using the individualized Patient Generated Index (PGI) in young adults who were diagnosed with juvenile idiopathic arthritis (JIA) in childhood, and to examine associations between PGI ratings and standardized health-related outcome measures. Methods Patients (N = 79, mean age 25.1 [SD 4.2] yrs, 72% female) completed the PGI and the standardized measures: Health Assessment Questionnaire–Disability Index, 12-item Short Form Health Survey (SF-12; physical and mental health-related QOL [HRQOL]), Brief Pain Inventory (pain severity and interference), 5-item Hopkins Symptom Checklist, and visual analog scale for fatigue. Information on morning stiffness, medications, and demographics was also collected. Patients were compared to 79 matched controls. Results The most frequently nominated areas of importance for patients’ personally generated QOL (assessed by PGI) were physical activity (n = 38, 48%), work/school (n = 31, 39%), fatigue (n = 29, 37%) and self-image (n = 26, 33%). Nomination of physical activity was associated with older age, morning stiffness, and more pain interference. Nomination of fatigue was associated with current use of disease-modifying antirheumatic drugs, whereas nomination of self-image was associated with polyarticular course JIA and pain interference. Nomination of work/school was not associated with other factors. Higher PGI scores (indicating better QOL) correlated positively with all SF-12 subscales except role emotional, and negatively with disability, pain severity, pain interference, and morning stiffness. Compared to controls, patients had more pain, poorer physical HRQOL, and less participation in full-time work or school. Conclusion Physical activity, work/school, fatigue, and self-image were frequently nominated areas affecting QOL in young adults with JIA. The PGI included aspects of QOL not covered in standardized measures.
Targeted mutagenesis in Anaplasma marginale to define virulence and vaccine development against bovine anaplasmosis

Tick-borne Anaplasma species are obligate, intracellular, bacterial pathogens that cause important diseases globally in people, agricultural animals, and dogs. Targeted mutagenesis methods are yet to be developed to define genes essential for these pathogens. In addition, vaccines conferring protection against diseases caused by Anaplasma species are not available. Here, we describe a targeted mutagenesis method for deletion of the phage head-to-tail connector protein (phtcp) gene in Anaplasma marginale. The mutant did not cause disease and exhibited attenuated growth in its natural host (cattle). We then assessed its ability to confer protection against wild-type A. marginale infection challenge. Additionally, we compared vaccine protection with the mutant to that of whole cell A. marginale inactivated antigens as a vaccine (WCAV) candidate. Upon infection challenge, non-vaccinated control cattle developed severe disease, with an average 57% drop in packed cell volume (PCV) between days 26–31 post infection, an 11% peak in erythrocytic infection, and apparent anisocytosis. Conversely, following challenge, all animals receiving the live mutant did not develop clinical signs or anemia, or erythrocyte infection. In contrast, the WCAV vaccinees developed similar disease as the non-vaccinees following A. marginale infection, though the peak erythrocyte infection reduced to 6% and the PCV dropped 43%. This is the first study describing targeted mutagenesis and its application in determining in vivo virulence and vaccine development for an Anaplasma species pathogen. This study will pave the way for similar research in related Anaplasma pathogens impacting multiple hosts.
Aerothermodynamics of a hypersonic projectile with a double-disk aerospike

Abstract The use of aerospikes at the nose of a hypersonic vehicle can substantially reduce its drag; however, the associated heat flux at the reattachment point is very high for turbulent flows. In this paper, the aerothermodynamics of a generic projectile model represented by a hemisphere- cylinder, fitted axisymmetrically with an aerospike at the nose is investigated numerically with a commercially available Navier Stokes Solver. The base model is a hemisphere-cylinder with a diameter of 40mm and an overall length of 70mm. An aerospike protrudes axisymmetrically at the nose of the base model and has a hemispherical cap from which another aerospike protrudes which again has a hemispherical cap, thus forming a double-disk aerospike. Compressible, axisymmetric Navier-Stokes Equations are solved for turbulent hypersonic flow of thermally perfect air with free stream conditions of Mach No 6·2 at standard sea level atmospheric conditions. The results for the model with double-disk aerospikes are compared with those of hemisphere-cylinder without aerospike. The results suggest that the use of double-disk aerospike can favourably reduce the turbulent reattachment heat flux along with suitable drag reduction of the main body.
The NaHCO3-Responsive Phenotype in Methicillin-Resistant Staphylococcus aureus (MRSA) Is Influenced by mecA Genotype

Methicillin-resistant Staphylococcus aureus (MRSA) strains are a leading cause of many invasive clinical syndromes, and pose treatment difficulties due to their in vitro resistance to most β-lactams on standard laboratory testing. A novel phenotype frequently identified in MRSA strains, termed ‘NaHCO3-responsiveness’, is a property whereby strains are susceptible in vitro to many β-lactams in the presence of NaHCO3. ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) strains are a leading cause of many invasive clinical syndromes, and pose treatment difficulties due to their in vitro resistance to most β-lactams on standard laboratory testing. A novel phenotype frequently identified in MRSA strains, termed ‘NaHCO3-responsiveness’, is a property whereby strains are susceptible in vitro to many β-lactams in the presence of NaHCO3. Specific mecA genotypes, repression of mecA/PBP2a expression and perturbed maturation of PBP2a by NaHCO3 have all been associated with this phenotype. The aim of this study was to define the relationship between specific mecA genotypes and PBP2a substitutions, on the one hand, with NaHCO3-responsiveness in vitro. Mutations were made in the mecA ribosomal binding site (RBS -7) and at amino acid position 246 of its coding region in parental strains MW2 (NaHCO3-responsive) and C36 (NaHCO3- nonresponsive) to generate ‘swap’ variants, each harboring the other’s mecA-RBS/coding region genotypes. Successful swaps were confirmed by both sequencing, as well as predicted swap of in vitro penicillin-clavulanate susceptibility phenotypes. MW2 swap variants harboring the nonresponsive mecA genotypes became NaHCO3-nonresponsive (resistant to the β-lactam, oxacillin [OXA]), in the presence of NaHCO3. Moreover, these swap variants had lost NaHCO3-mediated repression of mecA/PBP2a expression. In contrast, C36 swap variants harboring the NaHCO3-responsive mecA genotypes remained NaHCO3-nonresponsive phenotypically, and still exhibited nonrepressible mecA/PBP2a expression. These data demonstrate that in addition to the mecA genotype, NaHCO3-responsiveness may also depend on strain-specific genetic backgrounds.
Sexual and Gender Minorities Facing the Coronavirus Pandemic: A Systematic Review of the Distinctive Psychosocial and Health-Related Impact

ABSTRACT Sexual and gender minorities (SGM) constitute vulnerable groups in many countries. Thus, they might be affected to a different extent than heterosexual and cisgender individuals by the Coronavirus pandemic. This systematic review aimed to summarize the state of international research on the mental and physical health-related as well as socioeconomic effects of the Coronavirus pandemic on SGM individuals. Following the PRISMA protocol, we identified 35 publications, including different article formats. We considered minority stress theory and intersectionality in synthesizing the reviewed literature. Our key finding implicates that both minority- and pandemic-specific adversities have increased the vulnerabilities of SGM individuals during the Coronavirus pandemic. Minority-specific stressors include discrimination experiences, poorer mental and physical health, and fewer socioeconomic resources. Pandemic-specific challenges such as the deferral and delay of medication or school closing have exposed certain SGM subgroups (transgender individuals, young SGM) to particularly high risk. Moreover, the reviewed evidence suggests distinctive interactive effects of minority-specific stressors with pandemic-specific challenges (e.g., being forced to stay close to rejecting others during lockdown periods). A significant share of the included literature was US-based, while research from other countries remained scarce. The specific mechanisms still deserve to be better understood to protect SGM in future crises, especially during pandemics.
Chronic, increasing, and decreasing peer victimization trajectories and the development of externalizing and internalizing problems in middle childhood.

Children's peer victimization trajectories and their longitudinal associations with externalizing and internalizing problems were investigated from Grades 2 to 5. Secondary data analysis was performed with the Early Childhood Longitudinal Study (ECLS-K-2011; n = 13,860, Mage = 8.1 years old in the spring of Grade 2; 51.1% male, 46.7% White, 13.2% African-American, 25.3% Hispanic or Latino, 8.5% Asian, and 6.1% other or biracial). Children who experienced high and persistent levels of peer victimization (high-chronic victims) exhibited co-occurring externalizing and internalizing problems. Moreover, among high-chronic victims, boys had a more pronounced increase in their externalizing trajectories, and girls had greater increases in their social anxiety trajectories. In contrast, those with decreasing peer victimization across time exhibited signs of recovery, particularly with respect to their social anxiety. These findings elucidated how chronic, increasing, and decreasing victims exhibited distinct patterns in the co-occurring development of their externalizing and internalizing problems, and how findings varied depending on the form of problem behavior and by child sex.
Disruptive technologies in health care disenchanted: a systematic review of concepts and examples

Abstract Objectives To clarify the concept of disruptive technologies in health care, provide examples and consider implications of potentially disruptive technologies for health technology assessment (HTA). Methods We conducted a systematic review of conceptual and empirical papers on healthcare technologies that are described as “disruptive. ” We searched MEDLINE and Embase from 2013 to April 2019 (updated in December 2021). Data extraction was done in duplicate by pairs of reviewers utilizing a data extraction form. A qualitative data analysis was undertaken based on an analytic framework for analysis of the concept and examples. Key arguments and a number of potential predictors of disruptive technologies were derived and implications for HTA organizations were discussed. Results Of 4,107 records, 28 were included in the review. Most of the papers included conceptual discussions and business models for disruptive technologies; only few papers presented empirical evidence. The majority of the evidence is related to the US healthcare system. Key arguments for describing a technology as disruptive include improvement of outcomes for patients, improved access to health care, reduction of costs and better affordability, shift in responsibilities between providers, and change in the organization of health care. A number of possible predictors for disruption were identified to distinguish these from “sustaining” innovations. Conclusions Since truly disruptive technologies could radically change technology uptake and may modify provision of care patterns or treatment paths, they require a thorough evaluation of the consequences of using these technologies, including economic and organizational impact assessment and careful monitoring.
Exploration of animal models to study the life cycle of Fasciola hepatica

Abstract Abstract The parasite Fasciola hepatica is an important zoonotic parasite. The development of an animal model of F. hepatica's life cycle is critical for studying the biological characteristics of the parasite in snails and mammals. Eggs of F. hepatica of bovine origin were cultured, and metacercariae were obtained after infection of Galba pervia snails. The life cycle system of F. hepatica was initiated in 2 different animals by orally infecting rabbits, SD rats and Kunming mice with the metacercariae. The animals' survival after infection, parasite migration in the animals and pathological damage to the liver were observed. We discovered that rabbits died due to acute suppurative hepatitis 60–69 days after infection, and eggs were found in the feces on day 63 of infection. The liver of SD rats showed punctate lesions on day 3 of infection, and further changes occurred as the infection progressed. However, liver repair was observed at week 9. SD rats survived for more than a year after infection and continued the F. hepatica life cycle. The liver lesions in Kunming mice after infection were similar but more severe than those in SD rats. Death was observed on the 31st post-infection day. We discovered that while rabbits, SD rats and Kunming mice can all be used as animal models of F. hepatica, SD rats are more suitable experimental animals in terms of tolerance and pathological response.
Probabilistic estimation and statuses of total, bioaccessible and inorganic arsenic accumulation in commercial white and brown rice in Thailand

ABSTRACT Arsenic (As) in rice is a crucial public health concern because it is a human carcinogen. This study was conducted to determine the actual As concentrations and estimate the probable range of As in rice. The status of As accumulation in rice was also determined. White (n=154) and brown (n=54) rice samples were collected over three crop years. The concentrations of As (total, bioaccessible and inorganic) were determined. The total As concentrations in white (0.088–0.295 mg/kg) and brown (0.119–0.517 mg/kg) rice were approximately 58.8% and 57.4% higher than the Codex standards, respectively. However, the bioaccessible and inorganic As in both types of rice were lower than the standards for both rice types. Regarding the classifications of As accumulation (low, normal, high and unusually high), the actual As concentrations found in the rice samples were either in the normal range or a high concentration of As.