Miracle-dz/UniFAR-FTUs huggingface dataset:
Dynamics and Fate of Beneficial Mutations Under Lineage Contamination by Linked Deleterious Mutations

Beneficial mutations drive adaptive evolution, yet their selective advantage does not ensure their fixation. Haldane’s application of single-type branching process theory showed that genetic drift alone could cause the extinction of newly arising beneficial mutations with high probability. With linkage, deleterious mutations will affect the dynamics of beneficial mutations and might further increase their extinction probability. Here, we model the lineage dynamics of a newly arising beneficial mutation as a multitype branching process. Our approach accounts for the combined effects of drift and the stochastic accumulation of linked deleterious mutations, which we call lineage contamination. We first study the lineage-contamination phenomenon in isolation, deriving dynamics and survival probabilities (the complement of extinction probabilities) of beneficial lineages. We find that survival probability is zero when U≳sb, where U is deleterious mutation rate and sb is the selective advantage of the beneficial mutation in question, and is otherwise depressed below classical predictions by a factor bounded from below by ∼1−U/sb. We then put the lineage contamination phenomenon into the context of an evolving population by incorporating the effects of background selection. We find that, under the combined effects of lineage contamination and background selection, ensemble survival probability is never zero but is depressed below classical predictions by a factor bounded from below by e−εU/s¯b, where s¯b is mean selective advantage of beneficial mutations, and ε=1−e−1≈0.63. This factor, and other bounds derived from it, are independent of the fitness effects of deleterious mutations. At high enough mutation rates, lineage contamination can depress fixation probabilities to values that approach zero. This fact suggests that high mutation rates can, perhaps paradoxically, (1) alleviate competition among beneficial mutations, or (2) potentially even shut down the adaptive process. We derive critical mutation rates above which these two events become likely.
Preventing cardiovascular disease in older adults: One size does not fit all

Frailty and cardiovascular disease are highly interconnected and increase in prevalence with age. Identifying frailty allows for a personalized cardiovascular risk prescription and individualized management of hypertension, hyperlipidemia, diabetes, and lifestyle in the aging population. The balance of risk and benefit may differ considerably for 2 patients of the same age if one is fi t and the other is frail.
Efficacy of Dexmedetomidine as a Sole Sedative Agent in Small Diagnostic and Therapeutic Procedures: A Systematic Review

Dexmedetomidine is an upcoming agent with sedative, anxiolytic, and analgesic properties. This review summarizes empirical evidence for the efficacy of dexmedetomidine as a sole sedative agent, and its effectiveness for small diagnostic and therapeutic procedure, in comparison with other frequently used sedatives. All randomized controlled trials on the effect of dexmedetomidine were reviewed. Pain level, patient satisfaction, operator satisfaction, procedure duration, recovery time, and hemodynamic and respiratory characteristics were examined. A total of 1993 patients (1,621 adults; 372 children) from 35 studies were included. In the adult studies, dexmedetomidine yielded significantly lower pain levels compared to the other sedatives (in 31.25% of the included studies) and significantly more patient satisfaction (68.2%). In studies on children, more favorable results concerning respiratory safety and the level of adequate sedation were found compared to the control sedatives. Implications for future studies are discussed.
Incidence and Risk Factors of Mastitis in Shiraz, Iran: Results of a Cohort Study.

BACKGROUND Approximately one in five Western women who breastfeed are likely to experience acute mastitis. This study investigated the incidence and risk factors of acute mastitis in a cohort of Iranian women. SUBJECTS AND METHODS Subjects were 672 participants of the Shiraz Infant Feeding Study conducted between June 2014 and March 2015. Mothers were recruited from the maternity ward and followed up at 1, 3, 4, and 6 months postpartum to obtain information on their breastfeeding practices and experiences. The occurrence of acute mastitis in the first 26 weeks postpartum was self-reported and the occurrence of acute mastitis in the first 4 weeks and between 5 and 12 weeks postpartum was treated as separate outcomes. The risk factors for acute mastitis were explored using multivariable logistic regression analysis. RESULTS In total, 130 mothers (19.3%, 95% confidence interval: 16.3-22.3%) experienced at least one episode of acute mastitis. Having expressed breast milk and use of a pacifier were significantly associated with acute mastitis in both the first 4 weeks and between 5 and 12 weeks postpartum. Persistent problems with cracked or sore nipples, or engorged breasts, and a reduction in breastfeeding were associated with acute mastitis between 5 and 12 weeks. CONCLUSIONS The incidence of acute mastitis experienced by this cohort of Iranian women is similar to that reported for women in Western countries. The risk factors of acute mastitis identified in this study are potentially modifiable and could be prevented or ameliorated with adequate support and anticipatory guidance provided in the early postpartum period.
Annual variation in semen characteristics of pigeons (Columba livia).

The purpose of this study was to evaluate annual semen characteristics of pigeons (Columba livia). Ten selected male pigeons, aged 2 to 5 yr were housed under natural environmental conditions, and semen collection was conducted via a digital massage twice weekly throughout the year. The success rate of semen collection in a total of 920 attempts was 40% (371/920) over the whole year. The highest success rate was 69% (55/80) in March followed by 66% (53/80) in November, whereas the lowest rates were in August (13%,10/80) and September (13%, 8/60) (P < 0.01). Volume of the ejaculate averaged 11.0 +/- 0.9 microL (mean +/- SEM). The greatest volume was obtained in November (13.5 +/- 1.0 microL), whereas the least was obtained in August (7.0 +/- 1.0 microL). The average sperm motility was 72 +/- 2% of all ejaculates, of which the highest motility (82 +/- 2%) was observed in March, whereas the least motility (48 +/- 3%) was in August. Sperm viability and sperm motility were positively correlated (r = 0.91; P < 0.01). Maximum sperm concentration was 4.9 +/- 0.4 x 10(9) sperm/mL noted in March, whereas the minimum was 3.8 +/- 0.2 x 10(9) sperm/mL observed in October. Donors generally exhibited susceptible (54%) or dull submission (43%), whereas resistance to handling was rarely observed (3%). During collections, a red (47%) or pink (44%) cloacal membrane was often observed, whereas during only 9% of the collections, the cloacal membrane was pale. When the ambient temperature decreased below 15 C, semen could not be obtained (0/80). A high amount of semen (>10 microL) was obtained when the temperature ranged between 19 and 24 C. Optimal sperm motility (approximately 80%) and viability (>85%) was observed when the temperature was between 18 and 24 C. At temperatures greater than 28 C, sperm motility and viability decreased. Sperm concentration was not significantly influenced by temperature fluctuations. In summary, annual variation in semen characteristics exhibited two peaks per year with mean motility and viability reaching peak annual values in March and November. Both of these months had mean ambient temperatures between 19 and 24 C, a range associated with maximal ejaculatory volumes.
Influence of supplemental fat on weights of eggs and yolks during early egg production.

An experiment was conducted to determine the influence of dietary fat on weight of eggs and egg yolks of White Leghorn hens from 24 to 38 wk of age. Beginning at 24 wk of age, nine experimental units of eight hens each were fed one of five diet treatments. Treatments consisted of a corn-soybean meal diet containing no added fat, diets containing 3 or 6% animal-vegetable fats (A-V fat) formulated to be isocaloric and equinitrogenous with the no added fat diet, and diets containing 3 or 6% A-V fat in which the metabolizable energy (ME) concentration increased 105 kcal/kg with each 3% increment of A-V fat. Weights of eggs, yolks, and whites were measured biweekly. Supplemental A-V fat did not affect rate of egg production, but feed efficiency was improved significantly as ME increased from diets of increasing ME. No effect of A-V fat on egg or yolk weight was observed until after 4 wk of treatment (28 wk of age). From this time through 12 wk of treatment, a linear increase in yolk weight with increments of A-V fat (P less than .01) occurred, irrespective of diet series (isocaloric or increasing ME). Concurrently, there was a nonsignificant (P less than .10) trend for increased egg weight as A-V fat level increased, but weights of egg whites were not affected significantly. Average increases in yolk and egg weights during the period when hens were 28 through 36 wk of age were approximately . 5 and 1 g, respectively, when 6% A-V fat was used, irrespective of diet series. (ABSTRACT TRUNCATED AT 250 WORDS)
Effect of varying calcium and phosphorus level on manganese utilization.

Two experiments were conducted to evaluate the effect of varying levels of excess Ca and P on manganese (Mn) utilization. The criterion used to study the Mn-antagonizing effects of excess Ca and P was the regression of total tibia Mn on supplemental Mn intake. In Experiment 1, high supplemental levels of Mn were fed (0, 500, and 1,000 mg Mn per kg); in Experiment 2, lower Mn levels were fed (0, 50, and 100 mg Mn per kg). Supplements were added to a corn-soybean meal diet containing 1.1% Ca, . 7% (.5% available) P, and 37 mg Mn per kg. In Experiment 1, a 3 x 3 x 3 factorial arrangement of treatments (four replicates) was used. Treatments were as follows: 0, . 5, and 1.0% excess Ca as feed-grade ground limestone; 0, . 4, and . 8% excess P as KH2PO4; and 0, 500, and 1,000 mg Mn per kg as MnSO4.H2O. Total tibia Mn was depressed by P (P less than .0001) but not by Ca (P greater than .05). Compared with the standard (no added P), . 4% P reduced Mn utilization by 22%, whereas . 8% P reduced it by 38%. Manganese supplementation was found to ameliorate the growth-depressing effect of . 8% supplemental P. Results of Experiment 2 agreed with the results in Experiment 1, providing evidence that bioavailability estimates obtained from experiments containing high levels of Mn can be extrapolated to diets containing lower levels. Results from Experiment 2 indicated that, relative to the standard (no added P), . 22, . 44 and . 88% excess P reduced Mn utilization by 16, 22 and 31%, respectively.
Historical changes in northeastern US bee pollinators related to shared ecological traits

Pollinators such as bees are essential to the functioning of terrestrial ecosystems. However, despite concerns about a global pollinator crisis, long-term data on the status of bee species are limited. We present a long-term study of relative rates of change for an entire regional bee fauna in the northeastern United States, based on >30,000 museum records representing 438 species. Over a 140-y period, aggregate native species richness weakly decreased, but richness declines were significant only for the genus Bombus. Of 187 native species analyzed individually, only three declined steeply, all of these in the genus Bombus. However, there were large shifts in community composition, as indicated by 56% of species showing significant changes in relative abundance over time. Traits associated with a declining relative abundance include small dietary and phenological breadth and large body size. In addition, species with lower latitudinal range boundaries are increasing in relative abundance, a finding that may represent a response to climate change. We show that despite marked increases in human population density and large changes in anthropogenic land use, aggregate native species richness declines were modest outside of the genus Bombus. At the same time, we find that certain ecological traits are associated with declines in relative abundance. These results should help target conservation efforts focused on maintaining native bee abundance and diversity and therefore the important ecosystems services that they provide.
Aspirin or Rivaroxaban for VTE Prophylaxis after Hip or Knee Arthroplasty

Background Clinical trials and meta‐analyses have suggested that aspirin may be effective for the prevention of venous thromboembolism (proximal deep‐vein thrombosis or pulmonary embolism) after total hip or total knee arthroplasty, but comparisons with direct oral anticoagulants are lacking for prophylaxis beyond hospital discharge. Methods We performed a multicenter, double‐blind, randomized, controlled trial involving patients who were undergoing total hip or knee arthroplasty. All the patients received once‐daily oral rivaroxaban (10 mg) until postoperative day 5 and then were randomly assigned to continue rivaroxaban or switch to aspirin (81 mg daily) for an additional 9 days after total knee arthroplasty or for 30 days after total hip arthroplasty. Patients were followed for 90 days for symptomatic venous thromboembolism (the primary effectiveness outcome) and bleeding complications, including major or clinically relevant nonmajor bleeding (the primary safety outcome). Results A total of 3424 patients (1804 undergoing total hip arthroplasty and 1620 undergoing total knee arthroplasty) were enrolled in the trial. Venous thromboembolism occurred in 11 of 1707 patients (0.64%) in the aspirin group and in 12 of 1717 patients (0.70%) in the rivaroxaban group (difference, 0.06 percentage points; 95% confidence interval [CI], ‐0.55 to 0.66; P<0.001 for noninferiority and P=0.84 for superiority). Major bleeding complications occurred in 8 patients (0.47%) in the aspirin group and in 5 (0.29%) in the rivaroxaban group (difference, 0.18 percentage points; 95% CI, ‐0.65 to 0.29; P=0.42). Clinically important bleeding occurred in 22 patients (1.29%) in the aspirin group and in 17 (0.99%) in the rivaroxaban group (difference, 0.30 percentage points; 95% CI, ‐1.07 to 0.47; P=0.43). Conclusions Among patients who received 5 days of rivaroxaban prophylaxis after total hip or total knee arthroplasty, extended prophylaxis with aspirin was not significantly different from rivaroxaban in the prevention of symptomatic venous thromboembolism. (Funded by the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT01720108.)
National survey of Japanese patients with mevalonate kinase deficiency reveals distinctive genetic and clinical characteristics

Abstract Objectives: Mevalonate kinase deficiency (MKD), a rare autosomal recessive autoinflammatory syndrome, is caused by disease-causing variants of the mevalonate kinase (MVK) gene. A national survey was undertaken to investigate clinical and genetic features of MKD patients in Japan. Methods: The survey identified ten patients with MKD. Clinical information and laboratory data were collected from medical records and by direct interviews with patients, their families, and their attending physicians. Genetic analysis and measurement of MVK activity and urinary excretion of mevalonic acid were performed. Results: None of the 10 patients harbored MVK disease-causing variants that are common in European patients. However, overall symptoms were in line with previous European reports. Continuous fever was observed in half of the patients. Elevated transaminase was observed in four of the 10 patients, two of whom fulfilled the diagnostic criteria for hemophagocytic lymphohistiocytosis. About half of the patients responded to temporary administration of glucocorticoids and NSAIDs; the others required biologics such as anti-IL-1 drugs. Conclusion: This is the first national survey of MKD patients in a non-European country. Although clinical symptoms were similar to those reported in Europe, the incidence of continuous fever and elevated transaminase was higher, probably due to differences in disease-causing variants.
Trained Innate Immunity as a Novel Mechanism Linking Infection and the Development of Atherosclerosis

Rationale: There is strong epidemiological evidence for an association between acute and chronic infections and the occurrence of atherosclerotic cardiovascular disease. The underlying pathophysiological mechanisms remain unclear. Monocyte-derived macrophages are the most abundant immune cells in atherosclerotic plaques. It has recently been established that monocytes/macrophages can develop a long-lasting proinflammatory phenotype after brief stimulation with micro-organisms or microbial products, which has been termed trained immunity. Objective: The aim of this study is to assess whether trained immunity mediates the link between infections and atherosclerotic cardiovascular disease. Methods and Results: Brief exposure of monocytes to various micro-organisms results in the development of macrophages with a persistent proinflammatory phenotype: this represents a de facto nonspecific innate immune memory, which has been termed trained immunity. This is mediated by epigenetic reprogramming at the level of histone methylation and a profound rewiring of intracellular metabolism. Although this mechanism offers powerful protection against reinfection, trained macrophages display an atherogenic phenotype in terms of cytokine production and foam cell formation. Trained monocytes are present up to 3 months after experimental infection in humans. Moreover, a trained immunity phenotype is present in patients with established atherosclerosis. Conclusions: We propose that trained immunity provides the missing mechanistic link that explains the association between infections and atherosclerosis. Therefore, pharmacological modulation of trained immunity has the potential to prevent infection-related atherosclerotic cardiovascular disease in the future.
Post-stroke psychosis: how long should we treat?

Objective: To describe a rare case of a patient who developed psychotic symptoms after a right stroke that disappeared with antipsychotic treatment, but appears to need low-dose maintenance antipsychotic therapy. Case description: A 65-year-old man presented at the psychiatric emergency service with a history of persistent delusional jealousy, visual illusions and agitation with onset about 1 month after a right posterior cerebral artery ischemic stroke. These symptoms only disappeared with therapeutic dosages of an antipsychotic drug (3 mg/day of risperidone). At 2-year follow-up, he no longer had delusional activity and the antipsychotic treatment was gradually discontinued over the following year. However, 1 week after full cessation, the patient once more became agitated and suspicious and was put back on risperidone at 0.25 mg/day, resulting in rapid clinical remission. One year after the return to low-dose risperidone, the patient's psychopathology is still under control and he is free from psychotic symptoms. Comments: Psychosis is a relatively rare complication after stroke. To our knowledge, no cases of post-stroke psychosis that apparently require continuous low-dose antipsychotic treatment have been reported to date. Our case suggests that low-dose maintenance antipsychotic therapy may be needed for certain patients with post-stroke psychosis, especially for those with risk factors and non-acute onset.
The gaseous environment of the chick embryo in relation to its development and hatchability. 5. Effect of carbon dioxide and oxygen levels during the terminal days of incubation.

Abstract TESTING an assumption that the developing chick embryo may have different requirements at different stages of incubation, four previous reports of this series (Taylor et al., 1956; Taylor and Kreutziger, 1965; 1966; 1969) have demonstrated a progressive increase in tolerance to higher levels of CO2 to the end of the 16th day of incubation. A fluctuating response to high O2 levels was observed. An early tolerance was followed by a decreased resistance, then by a reversal of trend toward a very high resistance in the 13-16 day period. Responses to low O 2 levels were within a very narrow range and without a significant trend. The final days of incubation are normally characterized by the highest levels of mortality of chick embryos. The present report involves results of various gassing levels for the two 4-day periods of 17-20 and 18-21 days respectively. During these days the chick embryo undergoes critical…
Examining tRNA 3′-ends in Escherichia coli: teamwork between CCA-adding enzyme, RNase T, and RNase R

tRNA maturation and quality control are crucial for proper functioning of these transcripts in translation. In several organisms, defective tRNAs were shown to be tagged by poly(A) or CCACCA tails and subsequently degraded by 3′-exonucleases. In a deep-sequencing analysis of tRNA 3′-ends, we detected the CCACCA tag also in Escherichia coli. However, this tag closely resembles several 3′-trailers of tRNA precursors targeted for maturation and not for degradation. Here, we investigate the ability of two important exonucleases, RNase R and RNase T, to distinguish tRNA precursors with a native 3′-trailer from tRNAs with a CCACCA tag. Our results show that the degrading enzyme RNase R breaks down both tRNAs primed for degradation as well as precursor transcripts, indicating that it is a rather nonspecific RNase. RNase T, a main processing exonuclease involved in trimming of 3′-trailers, is very inefficient in converting the CCACCA-tagged tRNA into a mature transcript. Hence, while both RNases compete for trailer-containing tRNA precursors, the inability of RNase T to process CCACCA tails ensures that defective tRNAs cannot reenter the functional tRNA pool, representing a safeguard to avoid detrimental effects of tRNAs with erroneous integrity on protein synthesis. Furthermore, these data indicate that the RNase T-mediated end turnover of the CCA sequence represents a means to deliver a tRNA to a repeated quality control performed by the CCA-adding enzyme. Hence, originally described as a futile side reaction, the tRNA end turnover seems to fulfill an important function in the maintenance of the tRNA pool in the cell.
Load Balanced GANs for Multi-view Face Image Synthesis

Multi-view face synthesis from a single image is an ill-posed problem and often suffers from serious appearance distortion. Producing photo-realistic and identity preserving multi-view results is still a not well defined synthesis problem. This paper proposes Load Balanced Generative Adversarial Networks (LB-GAN) to precisely rotate the yaw angle of an input face image to any specified angle. LB-GAN decomposes the challenging synthesis problem into two well constrained subtasks that correspond to a face normalizer and a face editor respectively. The normalizer first frontalizes an input image, and then the editor rotates the frontalized image to a desired pose guided by a remote code. In order to generate photo-realistic local details, the normalizer and the editor are trained in a two-stage manner and regulated by a conditional self-cycle loss and an attention based L2 loss. Exhaustive experiments on controlled and uncontrolled environments demonstrate that the proposed method not only improves the visual realism of multi-view synthetic images, but also preserves identity information well.