Miracle-dz/UniFAR-FTUs huggingface dataset:
Epigenetic Silencing of BMP6 by the SIN3A–HDAC1/2 Repressor Complex Drives Melanoma Metastasis via FAM83G/PAWS1

Aberrant epigenetic transcriptional regulation is linked to metastasis, a primary cause of cancer-related death. Dissecting the epigenetic mechanisms controlling metastatic progression may uncover important insights to tumor biology and potential therapeutic targets. Here, we investigated the role of the SIN3A histone deacetylase 1 and 2 (SIN3A–HDAC1/2) complex in cancer metastasis. Using a mouse model of melanoma metastasis, we found that the SIN3A–HDAC1/2 transcription repressor complex silences BMP6 expression, causing increased metastatic dissemination and tumor growth via suppression of BMP6-activated SMAD5 signaling. We further discovered that FAM83G/PAWS1, a downstream effector of BMP6–SMAD5 signaling, contributes critically to metastatic progression by promoting actin-dependent cytoskeletal dynamics and cell migration. Pharmacologic inhibition of the SIN3A–HDAC1/2 complex reduced the numbers of melanoma cells in the circulation and inhibited metastatic tumor growth by inducing disseminated cell dormancy, highlighting the SIN3A–HDAC1/2 repressor complex as a potential therapeutic target for blocking cancer metastasis. Implications: This study identifies the novel molecular links in the metastatic progression to target cytoskeletal dynamics in melanoma and identifies the SIN3A–HDAC1/2 complex and FAM83G/PAWS1 as potential targets for melanoma adjuvant therapy.
Enhanced hyaluronic acid production in Streptococcus zooepidemicus by an optimized culture medium containing hyaluronidase inhibitor

Abstract This study describes the hyaluronic acid (HA) production by S. zooepidemicus ATCC 43079, and the effect of the hyaluronidase enzyme on HA levels. The hyaluronidase production, glucose consumption, and lactate formation were recorded during fermentation. The HA production, and productivity at different amounts of glucose, yeast extract and pH were evaluated by response surface statistical approach in presence of 6-O-palmytoil-l-ascorbic acid as a chemical inhibitor for biocatalyst hyaluronidase. Under optimum conditions, HA production was increased two-fold from 190 ± 17 mg L−1 in basal medium to 384.6 ± 7.5 mg L−1 in the optimized medium containing enzyme inhibitor. Furthermore, the results indicated that the chemical inhibitor could suppress the biocatalyst activity and prevent the HA loss at the end of the exponential phase of S. zooepidemicus ATCC 43079.
Aging impairs human bone marrow function and cardiac repair following myocardial infarction in a humanized chimeric mouse

Ventricular remodeling following myocardial infarction (MI) is a major cause of heart failure, a condition prevalent in older individuals. Following MI, immune cells are mobilized to the myocardium from peripheral lymphoid organs and play an active role in orchestrating repair. While the effect of aging on mouse bone marrow (BM) has been studied, less is known about how aging affects human BM cells and their ability to regulate repair processes. In this study, we investigate the effect aging has on human BM cell responses post‐MI using a humanized chimeric mouse model. BM samples were collected from middle aged (mean age 56.4 ± 0.97) and old (mean age 72.7 ± 0.59) patients undergoing cardiac surgery, CD34+/− cells were isolated, and NOD‐scid‐IL2rγnull (NSG) mice were reconstituted. Three months following reconstitution, the animals were examined at baseline or subjected to coronary artery ligation (MI). Younger patient cells exhibited greater repopulation capacity in the BM, blood, and spleen as well as greater lymphoid cell production. Following MI, CD34+ cell age impacted donor and host cellular responses. Mice reconstituted with younger CD34+ cells exhibited greater human CD45+ recruitment to the heart compared to mice reconstituted with old cells. Increased cellular responses were primarily driven by T‐cell recruitment, and these changes corresponded with greater human IFNy levels and reduced mouse IL‐1β in the heart. Age‐dependent changes in BM function led to significantly lower survival, increased infarct expansion, impaired host cell responses, and reduced function by 4w post‐MI. In contrast, younger CD34+ cells helped to limit remodeling and preserve function post‐MI.
Triangulation of pharmacoepidemiology and laboratory science to tackle otic quinolone safety

The scientific method requires studies with high internal and external validity. Though both are necessary, they do not go hand‐in‐hand: The more controlled a study is to enhance internal validity, the less applicable to real‐world clinical care, and vice versa. In the many instances where evidence from clinical trials is not available, scientific inference must rely on more extreme approaches on this spectrum, such as mechanistic (limited generalizability/strong bias control) and real‐world evidence (RWE) studies (higher generalizability/lesser bias control).
The Role of Interaural Differences, Head Shadow, and Binaural Redundancy in Binaural Intelligibility Benefits Among School-Aged Children

In complex listening environments, children can benefit from auditory spatial cues to understand speech in noise. When a spatial separation is introduced between the target and masker and/or listening with two ears versus one ear, children can gain intelligibility benefits with access to one or more auditory cues for unmasking: monaural head shadow, binaural redundancy, and interaural differences. This study systematically quantified the contribution of individual auditory cues in providing binaural speech intelligibility benefits for children with normal hearing between 6 and 15 years old. In virtual auditory space, target speech was presented from + 90° azimuth (i.e., listener's right), and two-talker babble maskers were either co-located (+ 90° azimuth) or separated by 180° (–90° azimuth, listener's left). Testing was conducted over headphones in monaural (i.e., right ear) or binaural (i.e., both ears) conditions. Results showed continuous improvement of speech reception threshold (SRT) between 6 and 15 years old and immature performance at 15 years of age for both SRTs and intelligibility benefits from more than one auditory cue. With early maturation of head shadow, the prolonged maturation of unmasking was likely driven by children's poorer ability to gain full benefits from interaural difference cues. In addition, children demonstrated a trade-off between the benefits from head shadow versus interaural differences, suggesting an important aspect of individual differences in accessing auditory cues for binaural intelligibility benefits during development.
Trends in climatically driven extreme growth reductions of Picea abies and Pinus sylvestris in Central Europe

Extreme tree growth reductions represent events of abrupt forest productivity decline and carbon sequestration reduction. An increase in their magnitude can represent an early warning signal of impending tree mortality. Yet the long‐term trends in extreme growth reductions remain largely unknown. We analyzed the trends in the proportion of trees exhibiting extreme growth reductions in two Central‐European conifer species—Pinus sylvestris (PISY) and Picea abies (PCAB)—between 1901 and 2018. We used a novel approach for extreme growth reduction quantification by relating their size to their mean recurrence interval. Twenty‐eight sites throughout Czechia and Slovakia with 1120 ring width series representing high‐ and low‐elevation forests were inspected for extreme growth reductions with recurrence intervals of 15 and 50 years along with their link to climatic drivers. Our results show the greatest growth reductions at low‐elevation PCAB sites, indicating high vulnerability of PCAB to drought. The proportions of trees exhibiting extreme growth reductions increased over time at low‐elevation PCAB, decreased recently following an abrupt increase in the 1970–1980s at high‐elevation PCAB, and showed nonsignificant trends in high‐ and low‐elevation PISY. Climatic drivers of extreme growth reductions, however, shifted over time for all site categories as the proportion of low‐temperature‐induced extreme growth reductions declined since the 1990s, whereas events caused by drought consistently increased in frequency during the same period. We observed higher growth volatility at the lower range of distribution compared with the upper range margin of PISY and PCAB. This will undoubtedly considerably impact tree growth and vitality as temperatures and incidence of drought in Central Europe are expected to further increase with ongoing climate change.
Spatial distribution of fine high-sulfur lean coal in enhanced gravity field

ABSTRACT The spatial distribution of fine high-sulfur lean coal under different backwash water pressures and rotational frequencies in enhanced gravity field using the Falcon concentrator was investigated. It deals with the distribution characteristics of products, including yield, ash content, sulfur content, and pyritic sulfur content, in overflow, upper groove, and lower groove from the top to the bottom in space. Backwash water pressure had coarse adjustment while rotational frequency had fine adjustment on the Falcon concentration process; meanwhile, the desulfurization and de-ashing results were discussed by combining them. The extensive migration characteristic of pyritic sulfur in space was also studied.
Availability, content and quality of commercially available smartphone applications for the self-management of low back pain: a systematic assessment

Abstract Purpose Explore smartphone apps that may be recommended by clinicians for the self-management of low back pain. Methods Prospectively registered systematic assessment of self-contained apps for self-management of low back pain on the Google Play and Apple App stores (Oceania), including ≥1 NICE low back pain and sciatica clinical guideline-recommended component and functioning without health professional input. Outcomes were quality (Mobile App Rating Scale; MARS), and self-management (Self-Management Support Checklist; SMS-14) and behaviour change potential (App Behaviour Change Scale; ABACUS). Results 25 apps were included. The average quality of included apps was acceptable (Mean MARS score of 3.9 out of a maximum possible 5). The self-management support and behaviour change potential of included apps appeared low (mean SMS-14 score was 3.4/14; mean ABACUS score was 5.4/21). The apps showed no significant correlation between app consumer ratings and MARS scores. App quality was significantly correlated with app price (p = 0.049) but not consumer ratings, however, these findings were based on a small number of studies and the overall model was not significant. Conclusions Smartphone apps for the self-management of low back pain are of average to good quality, with questionable potential for self-management and behaviour change. Clinicians should consider that few apps were designed to specifically incorporate self-management support and behaviour change potential when recommending apps to clients. Further development in these areas of app design would be of benefit. Implications for Rehabilitation Smartphone apps have the potential to improve LBP self-management outcomes, however, apps are not well regulated and the quality of information and advice provided is often low quality. The findings from this systematic assessment indicate that LBP self-management apps have limited self-management support and behaviour change potential features. Recommendation of current smartphone apps for LBP should take into consideration that although apps are of acceptable quality they are not specifically designed with self-management support and behaviour change principles. App quality does not appear to be associated with consumer ratings, however, there may be a positive association between app price and quality which requires further investigation.
Phenology of Lycorma delicatula (Hemiptera: Fulgoridae) in Virginia, USA

Abstract The spotted lanternfly, Lycorma delicatula (White), is an invasive planthopper that was first discovered in North America in Berks County, Pennsylvania in 2014. Currently, L. delicatula has spread to eight additional states and threatens agricultural, ornamental, and timber commodities throughout the United States.The timing of insect life events is very important in the development of pest management tools and strategies. In 2019 and 2020, L. delicatula phenology was successfully documented in Winchester, Virginia using weekly 5-min observational surveys at established monitoring plots. Each year, L. delicatula were active in the environment from May to November with initial detections of first, second, third, fourth, and adults occurring in May, May, June, June, and July, respectively. Cumulative average growing degree days were also calculated for the onset of each L. delicatula life stage using local weather data and a lower developmental threshold of 10°C. First-instar L. delicatula were initially observed at 135 and 111.5, adults at 835 and 887, and egg masses at 1673.5 and 1611.5 in 2019 and 2020, respectively. Combined, these data can be used by growers and land managers to facilitate timing of effective pest management strategies.
Global colistin use: a review of the emergence of resistant Enterobacterales and the impact on their genetic basis

Abstract The dramatic global rise of MDR and XDR Enterobacterales in human medicine forced clinicians to the reintroduction of colistin as last-resort drug. Meanwhile, colistin is used in the veterinary medicine since its discovery, leading to a steadily increasing prevalence of resistant isolates in the livestock and meat-based food sector. Consequently, transmission of resistant isolates from animals to humans, acquisition via food and exposure to colistin in the clinic are reasons for the increased prevalence of colistin-resistant Enterobacterales in humans in the last decades. Initially, resistance mechanisms were caused by mutations in chromosomal genes. However, since the discovery in 2015, the focus has shifted exclusively to mobile colistin resistances (mcr). This review will advance the understanding of chromosomal-mediated resistance mechanisms in Enterobacterales. We provide an overview about genes involved in colistin resistance and the current global situation of colistin-resistant Enterobacterales. A comparison of the global colistin use in veterinary and human medicine highlights the effort to reduce colistin sales in veterinary medicine under the One Health approach. In contrast, it uncovers the alarming rise in colistin consumption in human medicine due to the emergence of MDR Enterobacterales, which might be an important driver for the increasing emergence of chromosome-mediated colistin resistance.
Antimicrobial resistance: progress and challenges in antibiotic discovery and anti‐infective therapy

The alarming rise in the emergence of antimicrobial resistance in human, animal and plant pathogens is challenging global health and food production. Traditional strategies used for antibiotic discovery persistently result in the re‐isolation of known compounds, calling for the need to develop more rational strategies to identify new antibiotics. Additionally, anti‐infective therapy approaches targeting bacterial signalling pathways related to virulence is emerging as an alternative to the use of antibiotics. In this perspective article, we critically analyse approaches aimed at revitalizing the identification of new antibiotics and to advance antivirulence therapies. The development of high‐throughput in vivo, in vitro and in silico platforms, together with the progress in chemical synthesis, analytical chemistry and structural biology, are reviving a research area that is of tremendous relevance for global health.
Label-free cell viability assay using lens-free microscopy

We introduce a label-free technique based on lens-free microscopy to perform cell counting and cell viability assay. Without the use of any labelling, the discrimination between alive and dead cells is obtained by analyzing the cells on the basis of their holographic signature. We have assessed this novel technique by comparing the obtained results in terms of viability and cell counting against automatic optical counting and trypan blue staining as reference methods. The lensfree measurements agree very well with the reference techniques up to ~30.106 cells/ml. We found a coefficient of determination R2 of 0.99 and a slope of 1.01 for the viability measurements (N=84 CHO cell samples).
Calcium transport in male reproduction is possibly influenced by vitamin D and CaSR.

Vitamin D is important for gonadal function in rodents, and improvement of vitamin D status in men with low sperm counts increases live birth rate. Vitamin D is a regulator of transcellular calcium transport in the intestine and kidney and may influence the dramatic changes in the luminal calcium concentration in epididymis. Here, we show spatial expression in the male reproductive tract of vitamin D receptor (VDR)-regulated factors involved in calcium transport: Transient receptor potential vanilloid 5/6 (TRPV5/6), sodium/calcium exchanger 1 (NCX1), plasma membrane calcium ATPase 1 (PMCA1), calbindin D9k, calcium-sensing receptor (CaSR), and parathyroid hormone-related peptide (PTHrP) in mouse and human testis and epididymis. Testicular Casr expression was lower in Vdr ablated mice compared with controls. Moreover, expression levels of Casr and Pthrp were strongly correlated in both testis and epididymis and Pthrp was suppressed by 1,25(OH)2D3 in a spermatogonial cell line. The expression of CaSR in epididymis may be of greater importance than in the gonad in mice as germ cell-specific Casr deficient mice had no major reproductive phenotype, and coincubation with a CaSR-agonist had no effect on human sperm-oocyte binding. In humans, seminal calcium concentration between 5-10 mM was associated with a higher fraction of motile and morphologically normal sperm cells and the seminal calcium concentration was not associated with serum calcium levels. In conclusion, VDR regulates CaSR and PTHrP, and both factors may be involved in the regulation of calcium transport in the male reproductive tract with possible implications for sperm function and storage.
Prevalence of pre-sarcopenia among postmenopausal women younger than 65 years

Abstract Objective: Sarcopenia is associated with high morbidity and mortality in older women. Early detection and intervention during the postmenopausal period were hypothesized to help maintain muscle mass and performance. Although the Asian Working Group has developed guidelines for sarcopenia management, the condition has not been sufficiently investigated in the middle-aged cohort of the Asian population. This study aimed to measure the prevalence of pre-sarcopenia and sarcopenia in middle-aged postmenopausal women and to determine the factors associated with low muscle mass. Methods: In this cross-sectional study conducted in the Menopause Clinic, King Chulalongkorn Memorial Hospital, we used the bioelectrical impedance analysis method to determine the appendicular muscle mass using a body composition analyzer (TANITA MC980 Plus). Appendicular muscle mass index, handgrip strength, and 6-m gait speed were measured in 340 women aged 45 to 65 years. Hormonal profiles, anthropometric data, and relevant history were recorded. Results: The mean age of the study participants and time since menopause were 57.8 ± 4.5 years and 9.4 ± 5.5 years, respectively. The proportion of pre-sarcopenic, sarcopenic, and nonsarcopenic women were 11.8%, 2.7%, and 85.6%, respectively. A body mass index ≤ 20 kg/m2 had the strongest correlation with low muscle mass (odds ratio 7.1; 95% confidence interval 3.0-16.8, P < 0.001). Conclusion: Nearly 12% of Thai middle-aged postmenopausal women were pre-sarcopenic. Early detection of symptoms of pre-sarcopenia and maintenance of a healthy body mass index may reduce the burden of this condition for middle-aged and older women.
The Short-Chain Fatty Acids Propionate and Butyrate Augment Adherent-Invasive Escherichia coli Virulence but Repress Inflammation in a Human Intestinal Enteroid Model of Infection

The human terminal ileum and colon are colonized by a community of microbes known as the microbiota. Short-chain fatty acids (SCFAs) excreted by bacterial members of the microbiota define the intestinal environment. ABSTRACT Short-chain fatty acids (SCFAs), which consist of six or fewer carbons, are fermentation products of the bacterial community that inhabits the intestine. Due to an immunosuppressive effect on intestinal tissue, they have been touted as a therapeutic for inflammatory conditions of the bowel. Here, we study the impact of acetate, propionate, and butyrate, the three most abundant SCFAs in the intestine, on gene expression in the intestinal pathobiont adherent-invasive Escherichia coli. We pair this with adherence, invasion, and inflammation in Caco-2 and human intestinal enteroid (HIE)-derived monolayer models of the intestinal epithelium. We report that propionate and butyrate upregulate transcription of adherent-invasive Escherichia coli (AIEC) flagellar synthesis genes and decrease expression of capsule assembly and transport genes. These changes are predicted to augment AIEC invasiveness. In fact, SCFA supplementation increases AIEC adherence to and invasion of the Caco-2 monolayer but has no effect on these parameters in the HIE model. We attribute this to the anti-inflammatory effect of propionate and butyrate on HIEs but not on Caco-2 cells. We conclude that the potential of SCFAs to increase the virulence of intestinal pathogens should be considered in their use as anti-inflammatory agents. IMPORTANCE The human terminal ileum and colon are colonized by a community of microbes known as the microbiota. Short-chain fatty acids (SCFAs) excreted by bacterial members of the microbiota define the intestinal environment. These constitute an important line of communication within the microbiota and between the microbiota and the host epithelium. In inflammatory conditions of the bowel, SCFAs are often low and there is a preponderance of a conditionally virulent bacterium termed adherent-invasive Escherichia coli (AIEC). A connection between SCFA abundance and AIEC has been suggested. Here, we study AIEC in monoculture and in coculture with human intestinal enteroid-derived monolayers and show that the SCFAs propionate and butyrate increase expression of AIEC virulence genes while concurrently bolstering the intestinal epithelial barrier and reducing intestinal inflammation. While these SCFAs have been promoted as a therapy for inflammatory bowel conditions, our findings demonstrate that their effect on bacterial virulence must be considered.