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Osteopathy and morphometric vertebral fractures (VFs) are emerging complications in acromegaly. However, the prediction of VFs in this clinical setting is still a matter of uncertainty, and it is debated whether they are an early event in the natural history of the disease.<br /><br /> We aimed to evaluate the prevalence and determinants of morphometric VFs in patients with recently diagnosed acromegaly.<br /><br /> We enrolled 92 patients (43 men/49 women) on admission to the neurosurgery unit before transsphenoidal surgery, and compared them with control individuals without secondary forms of osteoporosis and pituitary disorders. We performed a VF assessment on preoperative chest x-ray images and collected biochemical, demographic, and clinical data.<br /><br /> We detected a significantly higher prevalence of VFs (33.7%) in patients with acromegaly than in controls (P = .001). Among the patients with acromegaly and VFs, 12 (38.7%) showed multiple VFs, and 5 (16.1%) showed moderate/severe VFs. Patients with VFs had higher random serumd in the workup at the diagnosis of acromegaly.Folate metabolism plays an essential role in tumor development. Various cancers display therapeutic response to reagents targeting key enzymes of the folate cycle, but obtain chemoresistance later. Therefore, novel targets in folate metabolism are highly demanded. Methylenetetrahydrofolate dehydrogenase/methylenetetrahydrofolate cyclohydrolase 2 (MTHFD2) is one of the key enzymes in folate metabolism and its expression is highly increased in multiple human cancers. However, the underlying mechanism that regulates MTHFD2 expression remains unknown. Here, we elucidate that SIRT4 deacetylates the conserved lysine 50 (K50) residue in MTHFD2. K50 deacetylation destabilizes MTHFD2 by elevating cullin 3 E3 ligase-mediated proteasomal degradation in response to stressful stimuli of folate deprivation, leading to suppression of nicotinamide adenine dinucleotide phosphate production in tumor cells and accumulation of intracellular reactive oxygen species, which in turn inhibits the growth of breast cancer cells. [https://www.selleckchem.com/products/Rolipram.html Rolipram nmr] Collectively, our study reveals that SIRT4 senses folate availability to control MTHFD2 K50 acetylation and its protein stability, bridging nutrient/folate stress and cellular redox to act on cancer cell growth.There are many problems in biology and related disciplines involving stochasticity, where a signal can only be detected when it lies above a threshold level, while signals lying below threshold are simply not detected. A consequence is that the detected signal is conditioned to lie above threshold, and is not representative of the actual signal. In this work, we present some general results for the conditioning that occurs due to the existence of such an observational threshold. We show that this conditioning is relevant, for example, to gene-frequency trajectories, where many loci in the genome are simultaneously measured in a given generation. Such a threshold can lead to severe biases of allele frequency estimates under purifying selection. In the analysis presented, within the context of Markov chains such as the Wright-Fisher model, we address two key questions (1) "What is a natural measure of the strength of the conditioning associated with an observation threshold?" (2) "What is a principled way to correct for the effects of the conditioning?". We answer the first question in terms of a proportion. Starting with a large number of trajectories, the relevant quantity is the proportion of these trajectories that are above threshold at a later time and hence are detected. The smaller the value of this proportion, the stronger the effects of conditioning. We provide an approximate analytical answer to the second question, that corrects the bias produced by an observation threshold, and performs to reasonable accuracy in the Wright-Fisher model for biologically plausible parameter values.We investigated the effect of aging on the basement membrane (BM) during postinjury muscle recovery. Using a rat model, we found that aging delayed muscle fiber and BM recovery. In addition, expression of BM-related factors peaked 7 days after muscle injury among both young and older rats. Peak expression of collagen IV synthetic factors decreased with age, whereas expression of the degradative factor was unaffected by age. These results suggest that age-related delays in postinjury muscle fiber and BM recovery may be related to the suppression of collagen IV synthetic factors.<br /><br /> Our goal was to investigate the accuracy of the two-dimensional and three-dimensional computed tomography imaging features in predicting the progression of acute uncomplicated type B aortic intramural haematoma (IMH).<br /><br /> This study retrospectively screened 140 patients diagnosed with acute uncomplicated type B IMH in our institution from January 2015 to December 2020. Patients were classified as exhibiting progression (aortic dissection, aortic rupture, aneurysm formation, ulcer-like projection depth &gt;10 mm or &gt;10% increase in the initial thickness of the aortic wall) and regression (completely or partially reabsorbed haematoma) based on follow-up computed tomography.<br /><br /> During the 11.4-month follow-up [interquartile range (IQR), 2.6-17.8], 55 patients had haematoma progression. The progression group had higher haematoma volume (HV) and total lesion volume [94.8 (IQR, 80.0-108.2) cm3 vs 40.3 (IQR, 30.8-57.9) cm3; 278.0 (IQR, 238.6-369.3) cm3 vs 197.3 (IQR, 152.8-235.9) cm3, both P &lt; 0.001) and longer lesion length [43.2 (IQR, 37.5-46.7) cm vs 30.4 (IQR, 28.1-37.6) cm, P &lt; 0.001)] than the regression group. According to the area under the curve, HV &gt; 66 cm3 is the greatest risk factor for haematoma progression. In multivariable analysis, HV was a powerful independent predictive factor for type B IMH progression, with a hazard ratio of 17.9 (95% confidence interval, 5.5-58.7; P &lt; 0.001).<br /><br /> Volumetric parameters may help to predict disease progression more precisely for patients with acute uncomplicated type B IMH compared to standard axial measurements, which might optimize the initial treatment and follow-up protocol.<br /><br />Volumetric parameters may help to predict disease progression more precisely for patients with acute uncomplicated type B IMH compared to standard axial measurements, which might optimize the initial treatment and follow-up protocol.<br /><br /> Monitoring countries' progress toward the achievement of their nutrition targets is an important task, but data sparsity makes monitoring trends challenging. Childhood stunting and overweight data in the European region over the last 30 y have had low coverage and frequency, with most data only covering a portion of the complete age interval of 0-59 mo.<br /><br /> We implemented a statistical method to extract useful information on child malnutrition trends from sparse longitudinal data for these indicators.<br /><br /> Heteroscedastic penalized longitudinal mixed models were used to accommodate data sparsity and predict region-wide, country-level trends over time. We leveraged prevalence estimates stratified by sex and partial age intervals (i.e., intervals that do not cover the complete 0-59 mo), which expanded the available data (for stunting from 84 sources and 428 prevalence estimates to 99 sources and 1786 estimates), improving the robustness of our analysis.<br /><br /> Results indicated a generally decreasing trend in stunting and a stable, slightly diminishing rate for overweight, with large differences in trends between low- and middle-income countries compared with high-income countries. No differences were found between age groups and between sexes. Cross-validation results indicated that both stunting and overweight models were robust in estimating the indicators for our data (root mean squared error 0.061 and 0.056; median absolute deviation 0.045 and 0.042; for stunting and overweight, respectively).<br /><br /> These statistical methods can provide useful and robust information on child malnutrition trends over time, even when data are sparse.<br /><br />These statistical methods can provide useful and robust information on child malnutrition trends over time, even when data are sparse.<br /><br /> COVID-19 has disproportionately impacted older adults and Black individuals. Research has focused on physical outcomes, with less attention to the psychological effects of COVID-19. The objective of this study was to examine the interplay between perceptions of the COVID-19 outbreak as a threat to one's day-to-day life, race, and psychological distress among middle-aged and older men and women.<br /><br /> Analyses were conducted on a subsample of self-identified non-Latino Whites and Black individuals aged 50 and older (N = 3,834) from the American Trends Panel. Psychological distress was assessed with 5 items adapted from the Center for Epidemiologic Studies Depression Scale and Generalized Anxiety Disorder-7. Perceived COVID-19 day-to-day threat was assessed with a single question. Negative binomial regressions tested the study aim.<br /><br /> Perceptions of COVID-19 day-to-day threat were positively associated with psychological distress. Black individuals reported lower distress than Whites. Regardless of gender, greater should consider coexisting intersections in marginalized identities and mental health during COVID-19.CRISPR base editing techniques tend to edit multiple bases in the targeted region, which is a limitation for precisely reverting disease-associated single-nucleotide polymorphisms (SNPs). We designed an imperfect gRNA (igRNA) editing methodology, which utilized a gRNA with one or more bases that were not complementary to the target locus to direct base editing toward the generation of a single-base edited product. Base editing experiments illustrated that igRNA editing with CBEs greatly increased the single-base editing fraction relative to normal gRNA editing with increased editing efficiencies. Similar results were obtained with an adenine base editor (ABE). At loci such as DNMT3B, NSD1, PSMB2, VIATA hs267 and ANO5, near-perfect single-base editing was achieved. Normally an igRNA with good single-base editing efficiency could be selected from a set of a few igRNAs, with a simple protocol. As a proof-of-concept, igRNAs were used in the research to construct cell lines of disease-associated SNP causing primary hyperoxaluria construction research. This work provides a simple strategy to achieve single-base base editing with both ABEs and CBEs and overcomes a key obstacle that limits the use of base editors in treating SNP-associated diseases or creating disease-associated SNP-harboring cell lines and animal models.The bioluminescent symbiosis involving the sea urchin cardinalfish Siphamia tubifer and the luminous bacterium Photobacterium mandapamensis is an emerging vertebrate model for the study of microbial symbiosis. However, little genetic data are available for the host, limiting the scope of research that can be implemented with this association. We present a chromosome-level genome assembly for S. tubifer using a combination of PacBio HiFi sequencing and Hi-C technologies. The final assembly was 1.2 Gb distributed on 23 chromosomes and contained 32,365 protein coding genes with a BUSCO score of 99%. A comparison of the S. tubifer genome to that of another nonluminous species of cardinalfish revealed a high degree of synteny, whereas a comparison to a more distant relative in the sister order Gobiiformes revealed the fusion of two chromosomes in the cardinalfish genomes. The complete mitogenome of S. tubifer was also assembled, and an inversion in the vertebrate WANCY tRNA genes as well as heteroplasmy in the length of the control region were discovered.