Miracle-dz/UniFAR-FTUs huggingface dataset:
MicroRNAs: Small molecules with big impacts in liver injury

A type of small noncoding RNAs known as microRNAs (miRNAs) fine‐tune gene expression posttranscriptionally by binding to certain messenger RNA targets. Numerous physiological processes in the liver, such as differentiation, proliferation, and apoptosis, are regulated by miRNAs. Additionally, there is growing evidence that miRNAs contribute to liver pathology. Extracellular vesicles like exosomes, which contain secreted miRNAs, may facilitate paracrine and endocrine communication between various tissues by changing the gene expression and function of distal cells. The use of stable miRNAs as noninvasive biomarkers was made possible by the discovery of these molecules in body fluids. Circulating miRNAs reflect the conditions of the liver that are abnormal and may serve as new biomarkers for the early detection, prognosis, and evaluation of liver pathological states. miRNAs are appealing therapeutic targets for a range of liver disease states because altered miRNA expression is associated with deregulation of the liver's metabolism, liver damage, liver fibrosis, and tumor formation. This review provides a comprehensive review and update on miRNAs biogenesis pathways and mechanisms of miRNA‐mediated gene silencing. It also outlines how miRNAs affect hepatic cell proliferation, death, and regeneration as well as hepatic detoxification. Additionally, it highlights the diverse functions that miRNAs play in the onset and progression of various liver diseases, including nonalcoholic fatty liver disease, alcoholic liver disease, fibrosis, hepatitis C virus infection, and hepatocellular carcinoma. Further, it summarizes the diverse liver‐specific miRNAs, illustrating the potential merits and possible caveats of their utilization as noninvasive biomarkers and appealing therapeutic targets for liver illnesses.
Early Career Training in Addiction Medicine: A Qualitative Study with Health Professions Trainees Following a Specialized Training Program in a Canadian Setting

Abstract Background: There has been a notable deficiency in the implementation of addiction science in clinical practice and many healthcare providers feel unprepared to treat patients with substance use disorders (SUD) following training. However, the perceptions of addiction medicine training by learners in health professions have not been fully investigated. This qualitative study explored perceptions of prior training in SUD care among early-career trainees enrolled in Addiction Medicine fellowships and electives in Vancouver, Canada. Methods: From April 2015 – August 2018, we interviewed 45 early-career physicians, social workers, nurses, and 17 medical students participating in training in addiction medicine. We coded transcripts inductively using qualitative data analysis software (NVivo 11.4.3). Results: Findings revealed six key themes related to early-career training in addiction medicine: (1) Insufficient time spent on addiction education, (2) A need for more structured addictions training, (3) Insufficient hands-on clinical training and skill development, (4) Lack of patient-centeredness and empathy in the training environment, (5) Insufficient implementation of evidence-based medicine, and (6) Prevailing stigmas toward addiction medicine. Conclusion: Early clinical training in addiction medicine appears insufficient and largely focused on symptoms, rather than etiology or evidence. Early career learners in health professions perceived benefit to expanding access to quality education and reported positive learning outcomes after completing structured training programs.
The First Copernican Astrologer: Andreas Aurifaber's Practica for 1541

One of the perennial products of German printing presses from the 1470s into the seventeenth century were ‘practicas’, small quarto booklets typically consisting of no more than 8 or 12 leaves, in which astrologers of lesser or greater renown and ability rendered their judgement on the configuration of the heavens in the upcoming year and the effect of cosmic influences on the weather, agricultural productivity, and human fortunes. Practicas often appeared together with a broadside almanac or calendar, but where the almanacs primarily presented factual information, practicas were more interpretive, argumentative, and persuasive in nature. While practicas appeared throughout Europe, they were particularly popular and common in the German-speaking lands. Although variation and experimentation were not uncommon, German practicas were highly stereotyped in their format and contents. Following a title-page woodcut with an anthropomorphic representation of the planet or planets that would dominate the coming year, practicas usually included a dedicatory epistle, a chapter or two that described prominent astronomical phenomena such as eclipses and justified the choice of the year’s ruling planet, and then chapters on war, illness, and agricultural productivity. After further chapters on the fortunes of various social classes and geographic regions, a final, lengthy chapter treated the moon phases for each month and their significance. The German practicas developed quickly during the late 1480s, and the characteristic format that would persist for over a century began to appear already in the mid-1490s. As practicas were relatively inexpensive and were printed predominantly in German rather than Latin by 1500, and overwhelmingly so by 1520, practicas have rightly been regarded as the means of communicating cosmological and other kinds of knowledge to a broad and modestly educated audience. Therefore the German humanist Achilles Gasser’s practica for 1546, in which Gasser mentioned Nicolas Copernicus by name and described a heliocentric cosmos, represented a significant step in transmitting Copernican ideas to a broader public. Gasser’s practica for 1546 was likely published late in 1545 for sale around the time of the New Year, and thus just a few years after first publication of Copernicus’s De revolutionibus. Karl Heinz Burmeister has described Gasser’s tract, which had theretofore escaped the notice of bibliographers, and emphasized that it represents the first appearance of Copernicus’s name in a German-language book, rather than in Latin technical literature. Richard Kremer identifies Gasser as the first to mention Copernicus in an annual practica, with the second occurrence of Copernicus’s name to be found in Joachim Heller’s practica for 1549. Recent publications by JHA, xli (2010)
All‐cause and liver‐related mortality risk factors in excessive drinkers: Analysis of data from the UK biobank

Abstract Background High alcohol intake is associated with increased mortality. We aimed to identify factors affecting mortality in people drinking extreme amounts of alcohol. Methods We obtained information from the UK Biobank on approximately 500,000 participants aged 40–70 years at baseline assessment in 2006–2010. Habitual alcohol intake, lifestyle and physiological data, laboratory test results, and hospital diagnoses and death certificate data (to June 2020) for 5136 men (2.20% of male participants) and 1504 women (0.60%) who reported consuming ≥80 or ≥50 g/day, respectively, were used in survival analysis. Results Mortality hazard ratios for these excessive drinkers, compared to all other participants, were 2.02 (95% CI 1.89–2.17) for all causes, 1.89 (1.69–2.12) for any cancer, 1.87 (1.61–2.17) for any circulatory disease, and 9.40 (7.00–12.64) for any liver disease. Liver disease diagnosis or abnormal liver function tests predicted not only deaths attributed to liver disease but also those from cancers or circulatory diseases. Mortality among excessive drinkers was also associated with quantitative alcohol intake; diagnosed alcohol dependence, harmful use, or withdrawal syndrome; and current smoking at assessment. Conclusions People with chronic excessive alcohol intake experience decreased average survival, but there is substantial variation in their mortality, with liver abnormality and alcohol dependence or other alcohol use disorders associated with a worse prognosis. Clinically, patients with these risk factors and high alcohol intake should be considered for early or intensive management. Research can usefully focus on the factors predisposing to dependence or liver abnormality.
An improved algorithm for crossing curved light surfaces: rapidly rotating pulsar magnetospheres in curved space–time

The structure of force-free, steady and axisymmetric magnetosphere of a neutron star (NS) is governed by the Grad-Shafranov (GS) equation, which is a second-order differential equation but degrades to first-order on the light surface (LS). The key to numerically solving the GS equation is to enable magnetic field lines smoothly cross the LS, and crossing a straight LS in flat spacetime has been a well-studied problem. But the numerical algorithm implementation becomes complicate in the presence of a bent LS, e.g. in curved spacetime, since there is no suitable computation grid adapted to it. We propose to circumvent this grid-LS mismatch problem by introducing a new coordinate frame designed such that the LS in it is a straight line. As an application, we investigate the general relativistic (GR) effect in magnetosphere structure of rapidly rotating pulsars in detail, where the LS is bent towards the central NS. We split the GR effect into two parts, curvature and frame-dragging; measure each of them and examine their dependence on the NS mass and the angular velocity for pulsars embedded in aligned dipole and multipole magnetic fields. Qualitatively speaking, we find that the curvature effect compactifies the magnetic field lines near the NS, therefore reduces the open magnetic flux and the Poynting luminosity, while the frame-dragging effect contributes a minor part in shaping the magnetosphere structure but plays a role in enhancing the spacelike current generation.
Combined radiation burn injuries: A note

Combined radiation injury occurs when radiation is accompanied by any other form of trauma. The past experiences of Hiroshima, Nagasaki, and Chernobyl have revealed that a large number of victims of such nuclear accidents or attacks suffer from combined radiation injuries. The possibility of a nuclear attack seems very far-fetched, but the destruction that would occur in such an event would be massive, with a huge lossof lives. Therefore, preparedness for the same should be done beforehand. The severity of combined radiation depends upon various factors, such as radiation dose, type, tissues affected, and traumas. The article focuses on combined radiation burn injury (CRBI) which may arise due to the combination of ionising radiation with thermal burns. CRBI can have varied effects on different organs like the hematopoietic, digestive, lymphatic, cardiovascular, and respiratory systems. Some of the most profound lethal effects are hematopoietic dysfunction, gastrointestinal leakage, bacterial translocation to other organ sites, pulmonary fibrosis, and pneumonitis. In this article, we have attempted to accumulate the knowledge of ongoing research on the functioning of different organ systems, which are affected due to CRBI and possible countermeasures to minimize the effects, thus improving survival.
PHOTOEVAPORATION AS A TRUNCATION MECHANISM FOR CIRCUMPLANETARY DISKS

We investigate the conditions under which the regular satellites of Jupiter and Saturn formed. The final stage of giant planet accretion is thought to occur slowly over a relatively long, 10 Myr, timescale. Gas accretion during this stage, through a completely or partially opened gap in the solar nebula, occurs slowly, allowing for the condensation of ices and incomplete differentiation seen in the regular satellites of the giant planets. Furthermore, the dichotomy seen in the Jovian and Saturnian systems may be explained as this infall wanes or is completely shutoff as a result of gaps opening or global depletion of gas in the solar nebula. We present one-dimensional simulations of circumplanetary disks that couple the viscous transport of material with the loss of mass at the disk outer edge by ultraviolet photoevaporation as well as the infall of material from the solar nebula. We find that the circumplanetary disks of these protoplanets are truncated as a result of photoevaporation at a range of values with the mean corresponding to ≈0.16 Hill radii. These truncation radii are broadly consistent with the current locations of the regular satellite systems of Jupiter and Saturn. We also find that photoevaporation can successfully act as a clearing mechanism for circumplanetary nebulae on the potentially short timescales, 102–104 yr, over which mass accretion from the solar nebula wanes as a result of a gap opening. Such a rapid clearing of the circum-Jovian disk may be required to explain the survival of the Galilean satellites.
Ultrahigh-energy neutrinos from gamma-ray bursts

Protons accelerated to high energies in the relativistic shocks that generate gamma ray bursts photoproduce pions, and then neutrinos in situ. I show that ultra high energy neutrinos (> 10^19 eV) are produced during the burst and the afterglow. A larger flux, also from bursts, is generated via photoproduction off CMBR photons in flight but is not correlated with currently observable bursts, appearing as a bright background. Adiabatic/synchrotron losses from protons/pions/muons are negligible. Temporal and directional coincidences with bursts detected by satellites can separate correlated neutrinos from the background.
Inference of Gene Flow between Species under Misspecified Models

Abstract Genomic sequence data provide a rich source of information about the history of species divergence and interspecific hybridization or introgression. Despite recent advances in genomics and statistical methods, it remains challenging to infer gene flow, and as a result, one may have to estimate introgression rates and times under misspecified models. Here we use mathematical analysis and computer simulation to examine estimation bias and issues of interpretation when the model of gene flow is misspecified in analysis of genomic datasets, for example, if introgression is assigned to the wrong lineages. In the case of two species, we establish a correspondence between the migration rate in the continuous migration model and the introgression probability in the introgression model. When gene flow occurs continuously through time but in the analysis is assumed to occur at a fixed time point, common evolutionary parameters such as species divergence times are surprisingly well estimated. However, the time of introgression tends to be estimated towards the recent end of the period of continuous gene flow. When introgression events are assigned incorrectly to the parental or daughter lineages, introgression times tend to collapse onto species divergence times, with introgression probabilities underestimated. Overall, our analyses suggest that the simple introgression model is useful for extracting information concerning between-specific gene flow and divergence even when the model may be misspecified. However, for reliable inference of gene flow it is important to include multiple samples per species, in particular, from hybridizing species.
Association of congenital Zika syndrome with dental alterations in children with microcephaly

The effects of congenital Zika syndrome (CZS) on the tooth development of infected children are not well known. The aim of this study was to analyze the association of CZS with dental alterations in children with microcephaly seen at a referral hospital in Rio Grande do Norte, Brazil. The chronology and sequence of tooth eruption and the presence of dental alterations were evaluated by a single calibrated examiner (kappa > 0.80) in 62 children aged 7 to 35 months with microcephaly associated with CZS and other congenital infections. Medical data of the mother and child were collected from the records and the parents responded to a socioeconomic questionnaire. Descriptive analysis and Fisher’s exact test were used (5% significance level). The mean age of the children was 26.4 months (SD = 7.52). The mean weight and head circumference at birth were 2,593 g (SD = 0.60) and 29.6 cm (SD = 2.48), respectively. Microcephaly was associated with congenital Zika virus infection in 79% of cases and with other congenital infections in 21%. No significant association was found between CZS and alterations in the chronology (p = 1.00) or sequence of tooth eruption (p = 0.16) or changes in enamel development (p = 1.00). In conclusion, children with microcephaly exhibit a delay and alterations in the sequence of tooth eruption of primary teeth, as well as developmental defects of enamel, which are not associated with Zika virus infection.
Absence of ULK1 decreases AMPK activity in the kidney, leading to chronic kidney disease progression

AMP‐activated protein kinase (AMPK) inactivation in chronic kidney disease (CKD) leads to energy status deterioration in the kidney, constituting the vicious cycle of CKD exacerbation. Unc‐51‐like kinase 1 (ULK1) is considered a downstream molecule of AMPK; however, it was recently reported that the activity of AMPK could be regulated by ULK1 conversely. We demonstrated that AMPK and ULK1 activities were decreased in the kidneys of CKD mice. However, whether and how ULK1 is involved in the underlying mechanism of CKD exacerbation remains unknown. In this study, we investigated the ULK1 involvement in CKD, using ULK1 knockout mice. The CKD model of Ulk1−/− mice exhibited significantly exacerbated renal function and worsening renal fibrosis. In the kidneys of the CKD model of Ulk1−/− mice, reduced AMPK and its downstream β‐oxidation could be observed, leading to an energy deficit of increased AMP/ATP ratio. In addition, AMPK signaling in the kidney was reduced in control Ulk1−/− mice with normal renal function compared to control wild‐type mice, suggesting that ULK1 deficiency suppressed AMPK activity in the kidney. This study is the first to present ULK1 as a novel therapeutic target for CKD treatment, which regulates AMPK activity in the kidney.
Asymptotic safety of gravity with matter

We study the asymptotic safety conjecture for quantum gravity in the presence of matter fields. A general line of reasoning is put forward explaining why gravitons dominate the high-energy behaviour, largely independently of the matter fields as long as these remain sufficiently weakly coupled. Our considerations are put to work for gravity coupled to Yang-Mills theories with the help of the functional renormalisation group. In an expansion about flat backgrounds, explicit results for beta functions, fixed points, universal exponents, and scaling solutions are given in systematic approximations exploiting running propagators, vertices, and background couplings. Invariably, we find that the gauge coupling becomes asymptotically free while the gravitational sector becomes asymptotically safe. The dependence on matter field multiplicities is weak. We also explain how the scheme dependence, which is more pronounced, can be handled without changing the physics. Our findings offer a new interpretation of many earlier results, which is explained in detail. The results generalise to theories with minimally coupled scalar and fermionic matter. Some implications for the ultraviolet closure of the Standard Model or its extensions are given.
Reduction of Missed Diagnosis of G6PD Deficiency in Heterozygous Females by G6PD/6PGD Ratio Assay Combined with Amplification Refractory Mutation System PCR

Objective: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked genetic disorder that results in impaired enzyme activity. The G6PD/6PGD ratio assay was routinely used for G6PD deficiency screening in China, but there is an apparent defect of missed diagnosis in heterozygous females. The study aims to explore the means to improve its accuracy. Methods: A total of 4,161 Chinese females of childbearing age were collected in this retrospective study. All samples were first subjected to G6PD/6PGD ratio assay and then screened by amplification refractory mutation system PCR (ARMS-PCR) for six hotspot mutants in Chinese population (c.1376G>T, c.1388G>A, c.95A>G, c.1024C>T, c.392G>T, and c.871G>A). For the samples with G6PD/6PGD ratio<1.0 and no mutations were found by ARMS-PCR, next-generation sequencing (NGS) was performed. Sanger sequencing was finally used to verify all the variants. Results: The prevalence of G6PD deficiency in Shenzhen females of childbearing age was 7.31%. The proportion of the six hotspot mutations accounted for 98.03% of all 304 G6PD variants carriers. Taking the ARMS-PCR/NGS results as a reference, the missed diagnosis rate of the G6PD/6PGD ratio assay was 33.88%. Using ARMS-PCR to retest the samples with a G6PD/6PGD ratio between 1.00 and ∼1.10 or 1.00 and ∼1.15 could reduce the missed diagnosis rate from the original 33.88% to 18.09% or 12.05% separately. Conclusion: ARMS-PCR is an appropriate supplementary method for discovering most carriers missed by the G6PD/6PGD ratio assay.
3C 273 variability at 7 mm: evidence of shocks and precession in the jet

We report 4 years of observations of 3C273 at 7 mm obtained with the Itapetinga Radiotelescope, in Brazil, between 2009 and 2013. We detected a flare in 2010 March, when the flux density increased by 50% and reached 35 Jy. After the flare, the flux density started to decrease and reached values lower than 10 Jy. We suggest that the 7 mm flare is the radio counterpart of the $\gamma$-ray flare observed by Fermi/LAT in 2009 September, in which the flux density at high energies reached a factor of fifty of its average value. A delay of 170 days between the radio and $\gamma$-ray flares was revealed using the Discrete Correlation Function (DCF) that can be interpreted in the context of a shock model, in which each flare corresponds to the formation of a compact superluminal component that expands and becomes optically thin at radio frequencies at latter epochs. The difference in flare intensity between frequencies and at a different times, is explained as a consequence of an increase in the Doppler factor $\delta$, as predicted by the 16 year precession model proposed by Abraham & Romero, which has a large effect on boosting at high frequencies while does not affect too much the observed optically thick radio emission. We discuss other observable effects of the variation in $\delta$, as the increase in the formation rate of superluminal components, the variations in the time delay between flares and the periodic behaviour of the radio light curve that we found compatible with changes in the Doppler factor.