Miracle-dz/UniFAR-FTUs huggingface dataset:
Quantifying the impact of a periodic presence of antimicrobial on resistance evolution in a homogeneous microbial population of fixed size

The evolution of antimicrobial resistance often occurs in a variable environment, as antimicrobial is given periodically to a patient or added and removed from a medium. This environmental variability has a huge impact on the microorganisms’ fitness landscape, and thus on the evolution of resistance. Indeed, mutations conferring resistance often carry a fitness cost in the absence of antimicrobial, which may be compensated by subsequent mutations. As antimicrobial is added or removed, the relevant fitness landscape thus switches from a fitness valley to an ascending landscape or vice-versa. Here, we investigate the effect of these time-varying patterns of selection within a stochastic model. We focus on a homogeneous microbial population of fixed size subjected to a periodic alternation of phases of absence and presence of an antimicrobial that stops growth. Combining analytical approaches and stochastic simulations, we quantify how the time necessary for fit resistant bacteria to take over the microbial population depends on the period of the alternations. We demonstrate that fast alternations strongly accelerate the evolution of resistance, and that a plateau is reached once the period gets sufficiently small. Besides, the acceleration of resistance evolution is stronger for larger populations. For asymmetric alternations, featuring a different duration of the phases with and without antimicrobial, we shed light on the existence of a broad minimum of the time taken by the population to fully evolve resistance. At this minimum, if the alternations are sufficiently fast, the very first resistant mutant that appears ultimately leads to full resistance evolution within the population. This dramatic acceleration of the evolution of antimicrobial resistance likely occurs in realistic situations, and can have an important impact both in clinical and experimental situations.
Ecological pressures and milk metabolic hormones of ethnic Tibetans living at different altitudes

Abstract Background: Very little is known about how milk hormones, shown to influence growth during infancy, may contribute to patterns of altered growth in high altitude living infants. Aim: This study investigated the association between maternal BMI, the metabolic hormones adiponectin and leptin in human milk and infant weight for age z-scores (WAZ) in Tibetans. Subjects and methods: A sample of 116 mothers and infants (aged 0–36 months) were recruited from two locations: the Nubri Valley, Nepal (rural; altitude = 2400–3900 m) and Kathmandu, Nepal (urban, 1400 m). Milk samples, anthropometrics, biological data and environmental information were collected on mothers and infants. Milk was analysed for leptin and adiponectin. Results: Maternal BMI was significantly associated with milk leptin content, but not adiponectin in either group. In the rural high altitude sample, child WAZ declined with age, but no such decline was seen in the urban sample. Conclusions: Milk leptin and adiponectin were not associated with infant growth in the rural Nubri sample, but were both inversely associated with infant WAZ in the Kathmandu sample. It appears that, in ecologically stressful environments, associations between milk hormones and growth during infancy may not be detectable in cross-sectional studies.
Association of intraoperative cerebral and muscular tissue oxygen saturation with postoperative complications and length of hospital stay after major spine surgery: an observational study

Background. Compromised tissue oxygenation is one of the root causes of dysfunction of various organs and postoperative complications. Oxygenation of different tissue beds may follow different patterns of change during physiological derangement. Methods. Patients undergoing elective major posterior spine surgery participated in this prospective observational study. Cerebral tissue oxygen saturation (SctO 2 ) was monitored on the upper forehead and muscular tissue oxygen saturation (SmtO 2 ) on the lower leg. The associations of various oxygenation indices with postoperative composite complications and length of hospital stay (LOH) were investigated. Results. The number of composite complications per patient was 3 (2) while the LOH was 6 (3) days (n = 102). Multiple SmtO 2 indices (maximum, minimum, mean, median, and area under curve (AUC)) were associated with composite complications (univariate analysis, P < 0.05). No SctO 2 indices were associated with complications. Multiple SmtO 2 indices (maximum, mean, median, and AUC) showed differences ( P < 0.05) between patients with composite complications ≤3 and >3, respectively. SmtO 2 standard deviation, AUC, and AUC weighted, and SctO 2 standard deviation, were associated with LOH (univariate analysis, P < 0.05). Two SmtO 2 indices (AUC and AUC weighted), showed differences ( P < 0.05) between the patients with an LOH ≤6 and >6 days, respectively. SmtO 2 , but not SctO 2 , indices improved the adjusted R 2 for composite complications (+54.0%, P = 0.0001) and LOH (+19.0%, P = 0.02) based on multiple linear models. Conclusions. Muscular tissue oxygenation has a stronger association with postoperative complications and length of hospital stay than cerebral tissue oxygenation after major spine surgery.
A clinical risk score of myocardial fibrosis predicts adverse outcomes in aortic stenosis

Abstract Aims Midwall myocardial fibrosis on cardiovascular magnetic resonance (CMR) is a marker of early ventricular decompensation and adverse outcomes in aortic stenosis (AS). We aimed to develop and validate a novel clinical score using variables associated with midwall fibrosis. Methods and results One hundred forty-seven patients (peak aortic velocity (Vmax) 3.9 [3.2,4.4] m/s) underwent CMR to determine midwall fibrosis (CMR cohort). Routine clinical variables that demonstrated significant association with midwall fibrosis were included in a multivariate logistic score. We validated the prognostic value of the score in two separate outcome cohorts of asymptomatic patients (internal: n = 127, follow-up 10.3 [5.7,11.2] years; external: n = 289, follow-up 2.6 [1.6,4.5] years). Primary outcome was a composite of AS-related events (cardiovascular death, heart failure, and new angina, dyspnoea, or syncope). The final score consisted of age, sex, Vmax, high-sensitivity troponin I concentration, and electrocardiographic strain pattern [c-statistic 0.85 (95% confidence interval 0.78–0.91), P < 0.001; Hosmer–Lemeshow χ2 = 7.33, P = 0.50]. Patients in the outcome cohorts were classified according to the sensitivity and specificity of this score (both at 98%): low risk (probability score <7%), intermediate risk (7–57%), and high risk (>57%). In the internal outcome cohort, AS-related event rates were >10-fold higher in high-risk patients compared with those at low risk (23.9 vs. 2.1 events/100 patient-years, respectively; log rank P < 0.001). Similar findings were observed in the external outcome cohort (31.6 vs. 4.6 events/100 patient-years, respectively; log rank P < 0.001). Conclusion We propose a clinical score that predicts adverse outcomes in asymptomatic AS patients and potentially identifies high-risk patients who may benefit from early valve replacement.
Flexible mate choice may contribute to ecotype assortative mating in pumpkinseed sunfish (Lepomis gibbosus)

Gene flow is expected to limit adaptive divergence, but the ecological and behavioural factors that govern gene flow are still poorly understood, particularly at the earliest stages of population divergence. Reduced gene flow through mate choice (sexual isolation) can evolve even under conditions of subtle population divergence if intermediate phenotypes have reduced fitness. We indirectly tested the hypothesis that mate choice has evolved between coexisting littoral and pelagic ecotypes of polyphenic pumpkinseed sunfish (Lepomis gibbosus) that have diverged in morphology and resource use and where intermediate phenotypes have reduced performance. We assessed the ecotype of nesting males and females using stable isotope estimates of diet and a divergent male morphological trait, oral jaw width. We found positive assortative mating between ecotypes in a common spawning habitat along exposed lake shorelines, but contrary to expectations, assortative mating was variably expressed between two sampling years. Although the factors that influence variable assortative mating remain unclear, our results are consistent with mate choice being expressed by ecotypes. Despite being variably expressed, mate choice will reduce gene flow between ecotypes and could contribute to further adaptive divergence depending on its frequency and strength in the population. Our findings add to a growing body of evidence indicating mate choice behaviour can be a plastic trait, an idea that should be more explicitly considered in empirical studies of mate choice as well as conceptual frameworks of mate choice evolution and adaptive divergence.
Chemical evolution of secondary organic aerosol from OH-initiated heterogeneous oxidation

Abstract. The heterogeneous oxidation of laboratory Secondary Organic Aerosol (SOA) particles by OH radicals was investigated. SOA particles, produced by reaction of α-pinene and O3, were exposed to OH radicals in a flow tube, and particle chemical composition, size, and hygroscopicity were measured to assess modifications due to oxidative aging. Aerosol Mass Spectrometer (AMS) mass spectra indicated that the degree of oxidation of 200 nm diameter SOA particles was significantly enhanced due to OH-initiated oxidation, as evidenced by the increase in the fraction of m/z 44 fragment of total organic mass concentration (F44). F44 values of the SOA particles, initially in the range F44=0.04–0.07, increased by up to ΔF44~0.01 under equivalent atmospheric aging timescales of 2 weeks, assuming a 24-h average OH concentration of 106 cm−3. Particle O/C ratios calculated from F44 values, initially in the range O/C=0.25–0.35, rose by a maximum of ΔO/C~0.04 units for 2 weeks of aging. Particle densities also increased with heterogeneous oxidation, consistent with the observed increase in the degree of oxidation. Minor reductions in particle size, with volume losses of up to 10%, were observed due to volatilization of oxidation products. The SOA particles activated more readily to form cloud droplets with an increase in the κ hygroscopicity parameter of up to a factor of two for the equivalent of 2 weeks of OH atmospheric exposure. These results indicate that OH heterogeneous oxidation of typical SOA needs to be considered as an atmospheric organic aerosol aging mechanism, most likely of higher relative importance away from VOC source regions, where other aging mechanisms are less dominant.
Radiation induced pulmonary fibrosis as a model of progressive fibrosis: Contributions of DNA damage, inflammatory response and cellular senescence genes

ABSTRACT Purpose/Aim of Study: Studies of pulmonary fibrosis (PF) have resulted in DNA damage, inflammatory response, and cellular senescence being widely hypothesized to play a role in the progression of the disease. Utilizing these aforementioned terms, genomics databases were interrogated along with the term, “pulmonary fibrosis,” to identify genes common among all 4 search terms. Findings were compared to data derived from a model of radiation-induced progressive pulmonary fibrosis (RIPF) to verify that these genes are similarly expressed, supporting the use of radiation as a model for diseases involving PF, such as human idiopathic pulmonary fibrosis (IPF). Materials and Methods: In an established model of RIPF, C57BL/6J mice were exposed to 12.5 Gy thorax irradiation and sacrificed at 24 hours, 1, 4, 12, and 32 weeks following exposure, and lung tissue was compared to age-matched controls by RNA sequencing. Results: Of 176 PF associated gene transcripts identified by database interrogation, 146 (>82%) were present in our experimental model, throughout the progression of RIPF. Analysis revealed that nearly 85% of PF gene transcripts were associated with at least 1 other search term. Furthermore, of 22 genes common to all four terms, 16 were present experimentally in RIPF. Conclusions: This illustrates the validity of RIPF as a model of progressive PF/IPF based on the numbers of transcripts reported in both literature and observed experimentally. Well characterized genes and proteins are implicated in this model, supporting the hypotheses that DNA damage, inflammatory response and cellular senescence are associated with the pathogenesis of PF.
High preoperative monocyte count/high-density lipoprotein ratio is associated with postoperative atrial fibrillation and mortality in coronary artery bypass grafting.

Objectives The monocyte to high-density lipoprotein ratio has recently emerged as an indicator of inflammation and oxidative stress. The aim of this study was to evaluate the association of the monocyte to high-density lipoprotein ratio with postoperative atrial fibrillation and mortality in coronary artery bypass grafting. Methods Six hundred and sixty-two patients who were in sinus rhythm preoperatively and who had isolated coronary artery bypass grafting were retrospectively included in the study. Patients who had atrial fibrillation in the early postoperative period were enrolled in group 1 ( n = 153); patients who remained in sinus rhythm in the early postoperative period were included in group 2 ( n = 509). The clinical and demographic data of the patients, biochemical and complete blood count parameters, preoperative monocyte count/high-density lipoprotein cholesterol ratio, and operative and postoperative data were recorded. Results Preoperative monocyte counts ( P = 0.0001), monocyte count/high-density lipoprotein cholesterol ratio ( P = 0.0001) and C-reactive protein levels ( P = 0.0001) were significantly increased in group 1. In the first month, 8 patients in group 1 (5.2%) and 5 patients in group 2 (1.0%) died, which was statistically significant ( P = 0.003). In univariate and multivariate logistic regression analyses, an elevated preoperative monocyte count/high-density lipoprotein cholesterol ratio ( P = 0.03) and C-reactive protein levels ( P = 0.0001) were predictors of postoperative atrial fibrillation. Preoperative monocyte counts ( P = 0.001), monocyte count/high-density lipoprotein cholesterol ratio ( P = 0.0001) and the use of inotropic support ( P = 0.0001) were also predictors of mortality in the early postoperative period. Conclusions We have observed that high preoperative monocyte count/ high-density lipoprotein ratio was associated with postoperative atrial fibrillation and mortality after coronary artery bypass grafting operation.
Performance optimization of amplify-and-forward relaying schemes for uplink OFDMA communications

Cooperative communication is a promising technique to enhance the system performance by exploiting the spatial diversity provided by the relay use. Incremental relaying techniques are proposed to limit the resources use to only bad channel conditions. In this paper, we deal with AF and IAF performance optimization for uplink Orthogonal Frequency Division Multiple Access (OFDMA) communications, carried on a packet-per-packet basis. For OFDMA cellular system, we define a cost that reliably quantifies the additional multiple-access interference (MAI) inherent to the relaying use. This MAI cost expression depends highly on the adopted frequency reuse pattern. The optimization, in terms of Packet-Error-Rate (PER), is carried out while keeping this MAI cost constant, for regular and fractional frequency reuse patterns. For FFR, different frequency reuse factors are applied to cell-center and cell-edge areas. Simulation results are showing that IAF relaying outperforms the direct transmission scheme by more than 15 dB gain, in terms of the reduction of the MAI. Additionally, IAF seems to be usually more powerful than AF.
Impact of sedation vs. general anaesthesia on percutaneous epicardial access safety and procedural outcomes

Aims Patient movement while under moderate/deep sedation may complicate percutaneous epicardial access (EpiAcc), mapping and ablation. We sought to compare procedural outcomes in patients undergoing EpiAcc under sedation vs. general anaesthesia (GA) for ablation. Methods and results Patients undergoing EpiAcc between January 2004 and July 2014 were included. Safety, procedural, and clinical outcomes were compared between patients undergoing EpiAcc under sedation or GA for ventricular tachycardia or premature ventricular complex ablation. Between January 2004 and July 2014, 170 patients underwent EpiAcc (mean age, 53.2 ± 15.8 years; average ejection fraction, 44.3 ± 15.3%). The majority (122 [72%] patients) were male. GA was used in 69 (40.6%). There was no difference in route of access (more often anterior, 53.0%) or the rate of successful access (96% overall) between groups. Similarly, the site of ablation (endocardial vs. epicardial vs. combined endocardial/epicardial) was similar between groups. Complications were equally seen between groups-the most frequent event/complication was pericardial effusion, occurring in 10.6% of patients. Finally, procedural and clinical success rates between GA and sedation groups were comparable (93 vs. 91% and 44 vs. 51%, respectively, P > 0.05). Conclusions Choice of anaesthesia for EpiAcc does not appear to significantly affect safety and procedural or clinical outcomes. For patients in whom anaesthesia may pose increased risk, it is reasonable to obtain epicardial access under sedation.
Prime time: sexual health outcomes at 24 months for a clinic-linked intervention to prevent pregnancy risk behaviors.

IMPORTANCE Preventing early pregnancy among vulnerable adolescents requires innovative and sustained approaches. Prime Time, a youth development intervention, aims to reduce pregnancy risk among adolescent girls seeking clinic services who are at high risk for pregnancy. OBJECTIVE To evaluate sexual risk behaviors and related outcomes with a 24-month postbaseline survey, 6 months after the conclusion of the Prime Time intervention. DESIGN Randomized controlled trial. SETTING Community and school-based primary care clinics. PARTICIPANTS Of 253 sexually active 13- to 17-year-old girls meeting specified risk criteria, 236 (93.3%) completed the 24-month follow-up survey. INTERVENTION Offered during an 18-month period, Prime Time includes case management and youth leadership programs. MAIN OUTCOME MEASURES Self-reported consistency of condom, hormonal, and dual-method contraceptive use with most recent male sex partner and number of male sex partners in the past 6 months. RESULTS At 24-month follow-up, the intervention group reported significantly more consistent use of condoms, hormonal contraception, and dual-method contraception than the control group. Intervention participants also reported improvements in family connectedness and self-efficacy to refuse unwanted sex, and reductions in the perceived importance of having sex. No between-group differences were found in the number of recent male sex partners. CONCLUSIONS AND RELEVANCE This study contributes to what has been a dearth of evidence regarding youth development interventions offered through clinic settings, where access to high-risk adolescents is plentiful but few efforts have emphasized a dual approach of strengthening sexual and nonsexual protective factors while addressing risk. Findings suggest that health services grounded in a youth development framework can lead to long-term reductions in sexual risk among vulnerable youth.
Fitness and eco-physiological response of a chytrid fungal parasite infecting planktonic cyanobacteria to thermal and host genotype variation

Abstract Understanding how individual parasite traits contribute to overall fitness, and how they are modulated by both external and host environment, is crucial for predicting disease outcome. Fungal (chytrid) parasites of phytoplankton are important yet poorly studied pathogens with the potential to modulate the abundance and composition of phytoplankton communities and to drive their evolution. Here, we studied life-history traits of a chytrid parasite infecting the planktonic, bloom-forming cyanobacterium Planktothrix spp. under host genotype and thermal variation. When expressing parasite fitness in terms of transmission success, disease outcome was largely modulated by temperature alone. Yet, a closer examination of individual parasite traits linked to different infection phases, such as (i) the establishment of the infection (i.e. intensity of infection) and (ii) the exploitation of host resources (i.e. size of reproductive structures and propagules), revealed differential host genotype and temperature × host genotype modulation, respectively. This illustrates how parasite fitness results from the interplay of individual parasite traits that are differentially controlled by host and external environment, and stresses the importance of combining multiple traits to gain insights into underlying infection mechanisms.
Inferring cell state by quantitative motility analysis reveals a dynamic state system and broken detailed balance

Cell populations display heterogeneous phenotypic states at multiple scales. Similar to molecular features commonly used to explore cell heterogeneity, cell behavior is a rich phenotypic space that may allow for identification of relevant cell states. Inference of cell state from cell behavior across a time course may enable the investigation of dynamics of transitions between heterogeneous cell states, a task difficult to perform with destructive molecular observations. Cell motility is one such easily observed cell behavior with known biomedical relevance. To investigate cell heterogeneity through the lens of cell behavior, we developed Heteromotility, a software tool to extract quantitative motility features from timelapse cell images. In mouse embryonic fibroblasts (MEFs), myoblasts, and muscle stem cells (MuSCs), Heteromotility analysis identifies multiple motility phenotypes within the population. In all three systems, the motility state identity of individual cells is dynamic. Quantification of state transitions reveals that MuSCs undergoing activation transition through progressive motility states toward the myoblast phenotype. By probability flux analysis, we find that this MuSC motility state system breaks detailed balance, while the MEF and myoblast systems do not. Our data indicate that the system regulating cell behavior can be decomposed into a set of attractor states which depend on the identity of the cell, together with a set of transitions between states governed by inputs from signaling pathways such as oncogenes and growth factors. Within one state, equilibrium formalisms can capture variation in behavior, while switching between states violates equilibrium conditions and would require an external driving force. These results support a conceptual view of the cell as a non-deterministic state automaton, responding to inputs from signaling pathways and generating outputs in the form of observable motile behaviors.