Power-law scaling indicates that large-scale training with uniform sampling is prohibitively slow. Active learning methods aim to increase data efficiency by prioritizing learning on the most relevant examples. Despite their appeal, these methods have yet to be widely adopted since no one algorithm has been shown to a) generalize across models and tasks b) scale to large datasets and c) yield overall FLOP savings when accounting for the overhead of data selection. In this work we propose a method which satisfies these three properties, leveraging small, cheap proxy models to estimate"learnability"scores for datapoints, which are used to prioritize data for the training of much larger models. As a result, our models require 46% and 51% fewer training updates and up to 25% less total computation to reach the same performance as uniformly trained visual classifiers on JFT and multimodal models on ALIGN. Finally, we find our data-prioritization scheme to be complementary with recent data-curation and learning objectives, yielding a new state-of-the-art in several multimodal transfer tasks.

Glucagon like peptide-1 (GLP-1) receptor agonists are well established drugs for the treatment of type 2 diabetes (T2D). In addition to glycemic control, GLP-1 receptor agonists have beneficial other effects. They act by binding to GLP-1 receptors, which are widely distributed in the body, including cardiomyocytes and blood vessels. The aim of this article is to provide a comprehensive review of GLP-1 receptor agonists impact on cardiovascular outcomes and risk reduction. In the last decade, several cardiovascular outcomes trials (CVOT) have been conducted in order to explore cardiovascular benefit of GLP-1 receptor agonists. CVOTs primarily proved cardiovascular safety and tolerability of different GLP-1 receptor agonists, but also showed cardiovascular benefit of specific drugs. CVOTs have shown that GLP-1 receptor agonists reduce MACE in patients with T2D compared to placebo. In addition, they have positive impact on several cardiovascular risk factors such as obesity by promoting weight loss, blood pressure and blood lipid levels. Also, they stimulate the endothelium to produce nitric oxide, reduce oxidative stress, and have antiatherogenic and antiinflammatory effects. Studies have shown their positive impact on kidney outcomes in patients with T2D compared to placebo. The results of previous trials are encouraging in terms of multiple positive effects of GLP-1 receptor agonists. However, further research is needed to understand their full potential and all details of their mechanism of action, which will enable to expand the therapeutic indications and to determine their optimal use in clinical practice.

Cobalt’s pivotal role in global development, especially in lithium-ion batteries, entails driving increased demand and strengthening global trading networks. The production of different waste solutions in metallurgical operations requires the development of an environmentally friendly research strategy. The ultrasonic spray pyrolysis and hydrogen reduction method were chosen to produce nanosized magnetic powders from waste solution based on iron and cobalt obtained during the purification process of used polycrystalline diamond blanks. With specific objectives focused on investigating the impact of reaction temperature and residence time on the morphology, chemical composition, and crystal structure of synthesized nanosized cobalt powders, our research involved 15 experimental runs using two reactors with varying residence times (7.19 s and 23 s) and distinct precursors (A, B, and C). Aerosol droplets were reduced at 600 to 900 °C with a flow rate of 3 L/min of argon and hydrogen (1:2). Characterization via scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and X-ray diffraction revealed that higher temperatures influenced the spherical particle morphology. Altering cobalt concentration in the solution impacted the particle size, with higher concentrations yielding larger particles. A short residence time (7.9 s) at 900 °C proved optimal for cobalt submicron synthesis, producing spherical particles ranging from 191.1 nm to 1222 nm. This research addresses the environmental significance of recovering magnetic particles from waste solutions, contributing to sustainable nanomaterial applications.

The utmost importance of high voltage circuit breakers in the electrical power grid highlights the essential need for their reliability. To ensure this, accurate condition assessment methods for core components like the main contact system are crucial. Dynamic resistance measurement plays a key role as it assesses arcing contacts' condition without contact chamber disassembly. This paper endeavors to meticulously investigate and illuminate the pertinent indices derived from dynamic resistance measurements and motion trajectory waveforms, showcasing their efficacy through two real-world case studies conducted under varied testing scenarios. The analysis underscores the proposed indices' effectiveness, enhancing comprehension of the arcing contact assessment method.

The reliable and steady operation of the electrical power system relies heavily on the correct operational status and condition of the high voltage air break disconnector switch. If these switches experience any malfunction, it could result in considerable damage, leading to financial consequences and potential hazards for maintenance staff. This paper presents a design for the acquisition and data analysis to evaluate the state of electric motor drives responsible for activating disconnectors. The approach involves capturing relevant time series of the voltage of the motor power supply and current and deriving meaningful indices to assess their condition. The viability of these concepts is showcased through case studies conducted on a real disconnector switch situated within a substation.

BACKGROUND Cirrus is an automated risk predictor for breast cancer that comprises texture-based mammographic features and is mostly independent of mammographic density. We investigated genetic and environmental variance of variation in Cirrus. METHODS We measured Cirrus for 3195 breast-cancer-free participants, including 527 pairs of monozygotic (MZ) twins, 271 pairs of dizygotic (DZ) twins, and 1599 siblings of twins. Multivariate normal models were used to estimate the variance and familial correlations of age-adjusted Cirrus as a function of age. The classic twin model was expanded to allow the shared environment effects to differ by zygosity. The single-nucleotide polymorphism (SNP)-based heritability was estimated for a subset of 2356 participants. RESULTS There was no evidence that the variance or familial correlations depended on age. The familial correlations were 0.52(standard error[SE]=0.03) for MZ pairs and 0.16(SE=0.03) for DZ and non-twin sister pairs combined. Shared environmental factors specific to MZ pairs accounted for 20% of the variance. Additive genetic factors accounted for 32%(SE=5%) of the variance, consistent with the SNP-based heritability of 36%(SE=16%). CONCLUSIONS Cirrus is substantially familial due to genetic factors and an influence of shared environmental factors that was evident for MZ twin pairs only. The latter could be due to non-genetic factors operating in utero or in early life that are shared by MZ twins. IMPACT Early-life factors shared more by MZ pairs than DZ/non-twin sister pairs, could play a role in the variation in Cirrus, consistent with early life being recognised as a critical window of vulnerability to breast carcinogens.

Ovim radom obuhvaćen je prikaz nastanka i razvoja stećaka, zatim tehničko i foto snimanje stećaka i nišana na lokalitetu Mramorje u naselju Sućeska, općina Srebrenica. Analiza nadgrobnika na terenu omogućila je prikupljanje osnovnih podataka o spomenicima. Groblja sa stećcima i nišanima, njihov arheološki i historijski kontekst, raznolikost tipova nadgrobnih spomenika te ukrasa kao i sadržaj natpisa predstavljaju cjelokupne aspekte njihove pojave i proučavanja. Integritet nadgrobnih spomenika ogleda se u njihovoj fizičkoj cjelovitosti, homogenosti i kompletnosti kao grobljanskih cjelina i autentičnosti.

ABSTRACT Eight long-COVID patients with moderate fatigue that had lasted for ≥3 months were recruited. All patients were allocated in a double-blind parallel-group design to receive either 4 g of creatine per day plus breathing exercises (study group) or breathing exercises only (control group) for 3 months. Creatine induced a significant increase in tissue total creatine levels for all 14 locations evaluated in the present study (P < 0.05), while its levels significantly dropped in the right frontal gray matter and left parietal mesial gray matter at follow-up in the control group (P < 0.05). No change in time to exhaustion was demonstrated in the control group (P > 0.05), while the mean time to exhaustion was significantly improved for 54 s in the study group post-administration (P = 0.05). These preliminary findings suggest that creatine is as an effective adjuvant therapeutic to breathing exercises for tackling the clinical features in long-COVID.

This study conducted an initial investigation into the association between ACE gene insertion/deletion (I/D) polymorphisms (rs1799752) and hypertension in the Republic of Srpska, Bosnia and Herzegovina. The study featured two distinct groups, each with 100 subjects, systematically categorized based on hypertension status and gender. DNA was extracted, PCR-amplified, and analyzed by gel electrophoresis. Results revealed a higher prevalence of the DD genotype and the D allele in the hypertensive group, although statistical significance was not observed. The II genotype occurred in 18% of the hypertension group and 21% in the control group. A significant difference was found in allele I frequencies between the two groups (p=0.004), with no gender-related variations in ACE alleles. The limited sample size may have constrained the ability to detect statistically significant differences. The odds ratio for the (DD + ID) genotype compared to II was 1.2110 (95% CI: 0.6006 to 2.4418; p=0.5927), indicating no statistical significance. Furthermore, no significant associations were identified between ACE genotypes and alleles and gender. In summary, this preliminary study suggests a potential trend towards a higher prevalence of the ACE gene D allele and DD genotype in hypertensive individuals. However, due to the small sample size, these associations did not achieve statistical significance in this population. Larger-scale investigations are needed for more definitive insights into the relationship between ACE gene polymorphisms and hypertension.

Future self-perceptions seem to promote far-sighted decisions in intertemporal choices. Previous work suggested that future self-relatedness, the extent to which we feel similar and connected to our future self, is associated with moral concerns. We aimed to extend these findings to everyday moral judgments and behavior using experience sampling methods. In addition, we assessed how moral foundation concerns mediate the relationship between future self-relatedness and moral behavior. Participants (N = 151) reported their state-levels of future self-relatedness, individualizing, and binding moral foundations and answered whether they performed a moral action five times a day for seven days. Within- and between-participants future self-relatedness predicted daily fluctuations in individualizing and binding moral foundations concerns. On the behavioral level, only within-participants future self-relatedness predicted individualizing moral actions with individualizing moral foundations mediating this effect. Our findings suggest that within- and between-person changes in future self-relatedness might be used to predict everyday moral concerns and behavior.

Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer, but a comprehensive description of its genomic landscape is lacking. We report the whole genome sequencing of 778 ccRCC patients enrolled in the 100,000 Genomes Project, providing the most detailed somatic mutational landscape to date. We identify new driver genes, which as well as emphasising the major role of epigenetic regulation in ccRCC highlight additional biological pathways extending opportunities for drug repurposing. Genomic characterisation identified patients with divergent clinical outcome; higher number of structural copy number alterations associated with poorer prognosis, whereas VHL mutations were independently associated with a better prognosis. The twin observations that higher T-cell infiltration is associated with better outcome and that genetically predicted immune evasion is not common supports the rationale for immunotherapy. These findings should inform personalised surveillance and treatment strategies for ccRCC patients.

Despite the increasing number of GPCR structures and recent advances in peptide design, the development of efficient technologies allowing rational design of high-affinity peptide ligands for single GPCRs remains an unmet challenge. Here, we develop a computational approach for designing conjugates of lariat-shaped macrocyclized peptides and a small molecule opioid ligand. We demonstrate its feasibility by discovering chemical scaffolds for the kappa-opioid receptor (KOR) with desired pharmacological activities. The designed De Novo Cyclic Peptide (DNCP)-β-naloxamine (NalA) exhibit in vitro potent mixed KOR agonism/mu-opioid receptor (MOR) antagonism, nanomolar binding affinity, selectivity, and efficacy bias at KOR. Proof-of-concept in vivo efficacy studies demonstrate that DNCP-β-NalA(1) induces a potent KOR-mediated antinociception in male mice. The high-resolution cryo-EM structure (2.6 Å) of the DNCP-β-NalA–KOR–Gi1 complex and molecular dynamics simulations are harnessed to validate the computational design model. This reveals a network of residues in ECL2/3 and TM6/7 controlling the intrinsic efficacy of KOR. In general, our computational de novo platform overcomes extensive lead optimization encountered in ultra-large library docking and virtual small molecule screening campaigns and offers innovation for GPCR ligand discovery. This may drive the development of next-generation therapeutics for medical applications such as pain conditions.

In the literature, auditory attention is explored through neural speech tracking, primarily entailing modeling and analyzing electroencephalography (EEG) responses to natural speech via linear filtering. Our study takes a novel approach, introducing an enhanced coherence estimation technique that employs multitapers to assess the strength of neural speech tracking. This enables effective discrimination between attended and ignored speech. To mitigate the impact of colored noise in EEG, we address two biases – overall coherence-level bias and spectral peak-shifting bias. In a listening study involving 32 participants with hearing impairment, tasked with attending to competing talkers in background noise, our coherence-based method effectively discerns EEG representations of attended and ignored speech. We comprehensively analyze frequency bands, individual frequencies, and EEG channels. Frequency bands of importance are shown to be delta, theta and alpha, as well as the central EEG channels. Lastly, we showcase coherence differences across different noise reduction settings implemented in hearing aids, underscoring our method’s potential to objectively assess auditory attention and enhance hearing aid efficacy.

Background/Aim: Most scoring systems in healthcare take into account the physical condition and pain status of a patient, but the impact of society on the individual is ignored. The aim of our study was to evaluate the social media posts made by patients regarding lumbar discectomy surgery. The objective was to identify and explore concerns and issues that may not be immediately evident during clinical evaluations but are significant to the patients themselves. Methods: Public posts with the hashtags #discectomy, #lumbardisectomy, and #discectomyrecovery were examined on the Instagram application. The tone of the post, return to sports (RTS), rehabilitation or physical therapy (PT), return to work (RTW), incision site (e.g., scarring, sutures, and dressing), pain, activities of daily living (ADL), and X-ray/magnetic resonance imaging (MRI) data were evaluated. The "Instagram likes ratio" was determined by dividing the total number of likes received for each post by the number of followers. Results: 272 posts were assessed, and 77.9% of them exhibited a positive tone. The topic that was most frequently discussed was ADL, which was discussed in 24.6% of the posts. Statistical analysis demonstrated a significant association between positive tone and ADL, as well as positive tone and RTS (P<0.001). A statistically significant correlation was observed between negative tone and neurological deficits, pain, and X-ray/MRI findings (P<0.001). Conclusion: Our study offers a unique perspective on the experience and satisfaction of patients who have undergone lumbar discectomy. Neurologic deficits and pain were notably significant in the negative posts. However, in general, the majority of the posts maintained a positive tone. The results could provide insights into patients' experiences and perspectives that can potentially inform healthcare professionals in providing more comprehensive and patient-centered care.

Traditional dairy products, especially cheeses, represent part of the cultural food heritage of many countries. In addition, these cheeses constitute microbiological “reservoirs”, of which many have been lost due to the introduction of the pasteurization of milk in the dairy industry. Increased awareness of the importance of microorganisms that make up the biodiversity of traditional cheeses, as well as the development of molecular methods in recent decades, have enabled efforts to identify and preserve them. Traditional Livno cheese is a full-fat hard cheese, considered one of the most famous traditional cheeses of Bosnia and Herzegovina and is seasonally produced from a mixture of raw sheep’s milk supplemented with cow’s milk. Often, Livno cheese has variable quality, due to microbial contamination and poor milk quality. In this study, traditional Livno cheese was studied during the ripening of cheeses produced by different producers during two seasons. Culture-dependent analyses were made during ripening using microbiological plating on suitable media. Likewise, culture-independent methods Denaturing Gradient Gel Electrophoresis (DGGE) and Automated Ribosomal Intergenic Spacer Analysis (ARISA) were used to elucidate the cheese microbiota. Results of analysis showed Lactococcus spp., Streptococcus spp., Lactobacillus spp., Pediococcus spp. and Leuconostoc spp. to be dominant species in traditional Livno cheese. However, when comparing the use of culture-dependent and culture-independent methods in the evaluation of Livno cheese microbiota, Enterococcus was not detected by culture-independent DGGE methods. The microbial population of both the milk and the environment determines the fermentation processes during cheese production and ripening, and thereby defines the quality of this cheese. The numbers of bacteria in the cheese were shown to be dependent on the manufacturer, the degree of ripening and the production season.