bluuebunny/crossref_metadata_2025 huggingface dataset:
‘I thought they would do it on the spot’: why do people with non-traumatic musculoskeletal pain present to emergency departments?
Authors: French Grace , Richards Karen , Waller Robert , Lin Ivan
Published: March 2023

Objective To investigate the reasons patients with non-traumatic musculoskeletal pain (NTMSP) present to an emergency department (ED), their experience of care and perceptions about managing their condition in the future. Methods A qualitative study using semi-structured interviews with patients with NTMSP presenting to a suburban ED. A purposive sampling strategy included participants with different pain characteristics, demographics and psychological factors. Results Eleven patients with NTMSP who presented to an ED were interviewed, reaching saturation of major themes. Seven reasons for ED presentation were identified: (1) desire for pain relief, (2) inability to access other healthcare, (3) expecting comprehensive care at the ED, (4) fear of serious pathology/outcome, (5) influence of a third party, (6) desire/expecting radiological imaging for diagnosis and (7) desire for ‘ED specific’ interventions. Participants were influenced by a unique combination of these reasons. Some expectations were underpinned by misconceptions about health services and care. While most participants were satisfied with their ED care, they would prefer to self-manage and seek care elsewhere in the future. Conclusions The reasons for ED presentation in patients with NTMSP are varied and often influenced by misconceptions about ED care. Most participants reported that, in future, they were satisfied to access care elsewhere. Clinicians should assess patient expectations so misconceptions about ED care can be addressed.
An organisational approach to improving diagnostic safety
Authors: Scott Ian A. , Crock Carmel
Published: March 2023

Diagnostic error affects up to 10% of clinical encounters and is a major contributing factor to 1 in 100 hospital deaths. Most errors involve cognitive failures from clinicians but organisational shortcomings also act as predisposing factors. There has been considerable focus on profiling causes for incorrect reasoning intrinsic to individual clinicians and identifying strategies that may help to prevent such errors. Much less focus has been given to what healthcare organisations can do to improve diagnostic safety. A framework modelled on the US Safer Diagnosis approach and adapted for the Australian context is proposed, which includes practical strategies actionable within individual clinical departments. Organisations adopting this framework could become centres of diagnostic excellence. This framework could act as a starting point for formulating standards of diagnostic performance that may be considered as part of accreditation programs for hospitals and other healthcare organisations.
Deep learning method for rapidly estimating pig body size
Authors: Wang Yue , Sun Gang , Seng Xiaoyue , Zheng Haibo , Zhang Hang , Liu Tonghai
Published: March 2023

Context During pig breeding, a change in a pig’s body size is an important indicator that reflects its health. However, it is difficult to extract the necessary features from images to estimate pig body size without contact. Aims It is crucial to develop a fast and accurate body size estimation algorithm to meet the practical needs of farms, i.e., numerous body size detections. Methods This report presents a rapid pig body size estimation technique based on deep learning. The YOLOv5 model is enhanced by integrating MobilenetV3, and a lightweight object detection network is introduced as the feature extraction network. An attention mechanism is also added to this system. Following these improvements, the proposed YOLOv5_Mobilenet_SE model is more suitable for the small-target detection of key parts of live pigs. A depth camera was used at a fixed height to capture the pig’s back information, which enables calculations of the critical height, i.e., the body height, of live pigs. Other key measuring points on the pig are generated according to the detection frame of the key parts located by the model. A gradient boosting regression algorithm is used to establish the body size prediction model based on the Euclidean distance between the key measuring points and the actual body size data. Key results The upgraded YOLOv5_Mobilenet_SE model achieves a mean average precision of 3.9%, which is higher than that obtained using the original YOLOv5 model. The model size is reduced from 91.2 to 10.2 M, and the average detection time for each image is 4.4 ms. The mean absolute percent errors in terms of body size, body width, and body height are 2.02%, 1.95%, and 1.84%, respectively, relative to manual measurements. Conclusions This method greatly reduces the model size and detection time while ensuring accuracy, and therefore, this method can cut costs for farms performing pig body size measurements. Implications The results of this study can provide technical support for automated and digital monitoring in the pig breeding industry.
Trends in testing of sexually transmissible infections (STIs), sexual health knowledge and behaviours, and pornography use in cross-sectional samples of young people in Victoria, Australia, 2015–21
Authors: Eddy Sarah , Douglass Caitlin , Raggatt Michelle , Thomas Alexander , Lim Megan
Published: March 2023

Background Sexually transmissible infections (STI) are prevalent and increasing among young Australians. This study examined trends in STI testing, sexual health knowledge/behaviours, and pornography use in young people aged 15–29 years in Victoria, Australia between 2015 and 2021. Methods Seven online cross-sectional surveys were conducted in a convenience sample of young people, recruiting a total of 7014 participants (67% female). Logistic regression analyses determined trends over time in binary outcomes. Results There was a decrease in reports of lifetime vaginal sex over time, while lifetime anal sex remained stable. Among those who had ever had vaginal sex, results showed an increase in the use of long-acting reversible contraceptives on the last occasion of vaginal sex. There was no change in STI testing or condom use with all partner types. Knowledge of STIs and sexual health changed over time: the proportion knowing that chlamydia can make women infertile decreased over time, while knowledge that taking the pill does not reduce fertility increased. There was no change in pornography use after adjusting for demographic variables. Conclusions Although uptake of long-acting contraceptives increased, STI knowledge and testing, as well as consistent condom use, remained low. Public health interventions should continue to address these critical components of STI prevention.
Discussion on interface deformation and liquid breakup mechanism in vapor–liquid two-phase flow
Authors: An 安 Xiang 祥 , Dong 董 Bo 波 , Zhang 张 Ya-Jin 雅瑾 , Zhou 周 Xun 训
Published: March 2023

The interface deformation and liquid breakup in vapor–liquid two-phase flow are ubiquitous in natural phenomena and industrial applications. It is crucial to understand the corresponding mechanism correctly. The droplet and liquid ligament dynamic behaviors are investigated in this work by simulating three benchmark cases through adopting a three-dimensional (3D) phase-field-based lattice Boltzmann model, and vapor–liquid phase interface deformation and liquid breakup mechanisms including the capillary instability and end-pinching mechanism are analyzed. The analysis results show that the capillary instability is the driving mechanism of the liquid breakup and the secondary droplet production at a large Weber number, which is different from the Rayleigh–Taylor instability and Kelvin–Helmholtz instability characterizing the vapor–liquid interface deformation. In addition, as another liquid breakup mechanism, the end-pinching mechanism, which describes the back-flow phenomenon of the liquid phase, works at each breakup point, thus resulting in capillary instability on the liquid phase structure. In essence, it is the fundamental mechanism for the liquid breakup and the immanent cause of capillary instability.
Time of Day Effects in the Relationships Between Daytime Sleepiness, Current Arousal, and Cognitive Performance
Authors: Do Cardinal , Suhr Julie A
Published: March 2023

Objective

Daytime sleepiness is commonly reported among older adults. Additionally, aging is associated with a shift toward greater alertness in the morning that wanes throughout the day. The impact of time of day of testing on the relationships between daytime sleepiness and cognition is unknown.

Methods

We explored the effects of time of testing in relation to self-reported daytime sleepiness/current arousal and cognition among 133 older adults.

Results

Time of testing moderated the relationship between daytime sleepiness and immediate learning/memory, with greater sleepiness being associated with poorer performance in the afternoon, but not morning. Time of testing also moderated the relationship between current arousal and processing speed, with lower arousal being associated with worse performance in the afternoon.

Conclusions

These findings suggest that time of testing is important to account for when assessing sleepiness and cognition in older adults and that consideration should be given to how sleepiness is measured.
Varying benefits of generalist and specialist camouflage in two versus four background environments
Authors: Hughes Anna E , Briolat Emmanuelle S , Arenas Lina María , Liggins Eric , Stevens Martin
Published: March 2023

Background-matching camouflage is a well-established strategy to reduce detection, but implementing this on heterogeneous backgrounds is challenging. For prey with fixed color patterns, solutions include specializing on a particular visual microhabitat, or adopting a compromise or generalist appearance, matching multiple backgrounds less well. Existing studies suggest both approaches can succeed, but most consider relatively simple scenarios, where artificial prey appear against two backgrounds differing in a single visual characteristic. Here, we used computer-based search tasks with human participants to test the relative benefits of specializing and generalizing for complex targets, displayed on either two or four types of naturalistic backgrounds. Across two background types, specialization was beneficial on average. However, the success of this strategy varied with search duration, such that generalist targets could outperform specialists over short search durations due to the presence of poorly matched specialists. Over longer searches, the remaining well-matched specialists had greater success than generalists, leading to an overall benefit of specialization at longer search durations. Against four different backgrounds, the initial cost to specialization was greater, so specialists and generalists ultimately experienced similar survival. Generalists performed better when their patterning was a compromise between backgrounds that were more similar to each other than when backgrounds were more different, with similarity in luminance more relevant than pattern differences. Time dependence in the relative success of these strategies suggests that predator search behavior may affect optimal camouflage in real-world situations.
Social network differences and phenotypic divergence between stickleback ecotypes
Authors: Neumann Kevin M , Bell Alison M
Published: March 2023

Elucidating the mechanisms underlying differentiation between populations is essential to our understanding of ecological and evolutionary processes. While social network analysis has yielded numerous insights in behavioral ecology in recent years, it has rarely been applied to questions about population differentiation. Here, we use social network analysis to assess the potential role of social behavior in the recent divergence between two three-spined stickleback ecotypes, “whites” and “commons”. These ecotypes differ significantly in their social behavior and mating systems as adults, but it is unknown when or how differences in social behavior develop. We found that as juveniles, the white ecotype was bolder and more active than the common ecotype. Furthermore, while there was no evidence for assortative shoaling preferences, the two ecotypes differed in social network structure. Specifically, groups of the white ecotype had a lower clustering coefficient than groups of the common ecotype, suggesting that groups of the white ecotype were characterized by the formation of smaller subgroups, or “cliques”. Interestingly, ecotypic differences in the clustering coefficient were not apparent in mixed groups composed of whites and commons. The formation of cliques could contribute to population divergence by restricting the social environment that individuals experience, potentially influencing future mating opportunities and preferences. These findings highlight the insights that social network analysis can offer into our understanding of population divergence and reproductive isolation.
Antinuclear antibody (ANA) status predicts immune-related adverse events in liver cancer patients undergoing anti-PD-1 therapy
Authors: Hsu Shu-Jung , Chao Yen-Cheng , Lin Xia-Hui , Liu Hua-Hua , Zhang Yang , Hong Wei-Feng , Chen Mao-Pei , Xu Xin , Zhang Lan , Ren Zheng-Gang , Du Shi-Suo , Chen Rong-Xin
Published: March 2023

Immune-related adverse events (irAEs) clinically resemble autoimmune diseases, indicating autoantibodies could be potential biomarkers for the prediction of irAEs. This study aimed to assess the predictive value of peripheral blood antinuclear antibody (ANA) status for irAEs, considering the time and severity of irAEs, as well as treatment outcome in liver cancer patients administered anti-PD-1 therapy. Ninety-three patients with advanced primary liver cancer administered anti-PD-1 treatment were analyzed retrospectively. They were divided into the ANA positive (ANA+, titer ≥ 1:100) and negative (ANA-, titer < 1:100) groups. Development of irAEs, progression-free survival (PFS), and overall survival (OS) were assessed. Compared with ANA- patients, ANA+ cases were more prone to develop irAEs (43.3% vs. 19.2%, P = 0.031). With the increase of ANA titers, the frequency of irAEs increased. The time interval between anti-PD-1 therapy and the onset of irAEs was significantly shorter in ANA+ patients compared with the ANA- group (median, 1.7 months vs. 5.0 months, P = 0.022). Moreover, the time between anti-PD-1 therapy and irAE occurrence decreased with increasing ANA titer. In addition, PFS and OS were decreased in ANA+ patients compared with the ANA− group (median PFS, 2.8 months vs. 4.2 months, P = 0.043; median OS, 21.1 months vs. not reached, P = 0.041). IrAEs occur at higher frequency in ANA+ liver cancer patients undergoing anti-PD-1 therapy. ANA titer could help predict irAE development and treatment outcome in these patients.
The effects of a physical exercise program in Chinese kidney transplant recipients: a prospective randomised controlled trial
Authors: Zhang Pengpeng , Liu Shan , Zhu Xiao , Liu Huan , Zeng Le , Yan Jin , Liu Jia
Published: March 2023

Background

Kidney transplant has become the preferred therapy for end-stage renal disease. However, kidney transplant recipients (KTRs) still face several challenges, such as physical inactivity. The purpose of this study was to explore the effects of a nurse-led physical exercise program in Chinese KTRs.

Methods

A total of 106 participants were enrolled from the Third Xiangya Hospital of Central South University between July 2021 and June 2022 and randomly assigned to the control or intervention groups. Participants in the control group were provided with routine nursing care and participants in the intervention group received a nurse-led rigorous physical exercise program that was divided into two stages: the pre-discharge stage and the post-discharge stage. The pre-discharge stage included the non-ambulatory and ambulatory stages. The Chinese traditional exercise Baduanjin was incorporated into the physical exercise during the ambulatory stage. The post-discharge stage continued the same exercise as the ambulatory stage at home. After 3 months of intervention, both groups received the same follow-up for 3 months. The primary and secondary outcomes of all participants were collected. The data were analysed with repeated measures analysis of variance to examine the effectiveness of the intervention.

Results

Compared with the control group, the intervention group had less fatigue and more motivation to be active in primary outcomes. Moreover, patients in the intervention group had a higher phase angle, a longer 6-minute walk distance, more 30-second chair stand times and decreased anxiety and depression levels in secondary outcomes. No adverse events were observed during the intervention. There were no significant differences in all dimensions of the quality-of-life questionnaire between the intervention and the control group.

Conclusion

Chinese KTRs could benefit from the nurse-led physical exercise program post-operatively.

Trial registration

ChiCTR2100048755
Benedicamus Domino tropes in the monastery of Benedictine nuns at St George’s, Prague
Authors: Vlhová-Wörner Hana
Published: March 2023

Within the rich spectrum of musical documents from medieval Bohemia, the corpus of tropes that survives in manuscripts from St George’s convent at Prague Castle is perhaps the most important. Forty-two Benedicamus Domino tropes appear in manuscripts from the monastery—one of the richest and most important female foundations in Central Europe, with a small community of nuns from noble families—most of them compiled at the end of the 13th and the first decades of the 14th centuries. The collection includes Benedicamus tropes that were circulating in the wider Central European territory, tropes that had their origins in the west and for which Prague constituted one of the furthest destinations within their dissemination, and a significant number of chants survive only in manuscripts from St George’s and may have had their origins in this milieu. These Benedicamus tropes exhibit a striking variety of forms and richness in their melodic material: a number of polyphonic tropes employ a Stimmtausch technique, others are wholly structured as strophic songs with or without refrains. Many of the trope texts indicate that they were meant to be sung by both male and female communities at St George’s, and their appearance in books with private prayers suggests that they may also have served an educational purpose.
Cost-effectiveness of early rhythm control vs. usual care in atrial fibrillation care: an analysis based on data from the EAST-AFNET 4 trial
Authors: Gottschalk Sophie , Kany Shinwan , König Hans-Helmut , Crijns Harry JGM , Vardas Panos , Camm A John , Wegscheider Karl , Metzner Andreas , Rillig Andreas , Kirchhof Paulus , Dams Judith
Published: March 2023

Aims

The randomized, controlled EAST-AFNET 4 trial showed that early rhythm control (ERC) reduces the rate of a composite primary outcome (cardiovascular death, stroke, or hospitalization for worsening heart failure or acute coronary syndrome) by ∼20%. The current study examined the cost-effectiveness of ERC compared to usual care.

Methods and results

This within-trial cost-effectiveness analysis was based on data from the German subsample of the EAST-AFNET 4 trial (n = 1664/2789 patients). Over a 6-year time horizon and from a healthcare payer’s perspective, ERC was compared to usual care regarding costs (hospitalization and medication) and effects (time to primary outcome; years survived). Incremental cost-effectiveness ratios (ICERs) were calculated. Cost-effectiveness acceptability curves were constructed to visualize uncertainty. Early rhythm control was associated with higher costs [+€1924, 95% CI (−€399, €4246)], resulting in ICERs of €10 638 per additional year without a primary outcome and €22 536 per life year gained. The probability of ERC being cost-effective compared to usual care was ≥95% or ≥80% at a willingness-to-pay value of ≥€55 000 per additional year without a primary outcome or life year gained, respectively.

Conclusion

From a German healthcare payer’s perspective, health benefits of ERC may come at reasonable costs as indicated by the ICER point estimates. Taking statistical uncertainty into account, cost-effectiveness of ERC is highly probable at a willingness-to-pay value of ≥€55 000 per additional life year or year without a primary outcome. Future studies examining the cost-effectiveness of ERC in other countries, subgroups with higher benefit from rhythm control therapy, or cost-effectiveness of different modes of ERC are warranted.
Grf10 regulates the response to copper, iron, and phosphate in Candida albicans
Authors: Wangsanut Tanaporn , Arnold Sylvia J Y , Jilani Safia Z , Marzec Sarah , Monsour Robert C , Rolfes Ronda J
Published: March 2023

The pathogenic yeast, Candida albicans, and other microbes must be able to handle drastic changes in nutrient availability within the human host. Copper, iron, and phosphate are essential micronutrients for microbes that are sequestered by the human host as nutritional immunity; yet high copper levels are employed by macrophages to induce toxic oxidative stress. Grf10 is a transcription factor important for regulating genes involved in morphogenesis (filamentation, chlamydospore formation) and metabolism (adenylate biosynthesis, 1-carbon metabolism). The grf10Δ mutant exhibited resistance to excess copper in a gene dosage-dependent manner but grew the same as the wild type in response to other metals (calcium, cobalt, iron, manganese, and zinc). Point mutations in the conserved residues D302 and E305, within a protein interaction region, conferred resistance to high copper and induced hyphal formation similar to strains with the null allele. The grf10Δ mutant misregulated genes involved with copper, iron, and phosphate uptake in YPD medium and mounted a normal transcriptional response to high copper. The mutant accumulated lower levels of magnesium and phosphorus, suggesting that copper resistance is linked to phosphate metabolism. Our results highlight new roles for Grf10 in copper and phosphate homeostasis in C. albicans and underscore the fundamental role of Grf10 in connecting these with cell survival.
Reduced Epigenetic Age in Older Adults With High Sense of Purpose in Life
Authors: Kim Eric S , Nakamura Julia S , Strecher Victor J , Cole Steven W
Published: March 2023

Psychosocial risk factors have been linked with accelerated epigenetic aging, but little is known about whether psychosocial resilience factors (eg, Sense of Purpose in Life) might reduce epigenetic age acceleration. In this study, we tested if older adults who experience high levels of Purpose might show reduced epigenetic age acceleration. We evaluated the relationship between Purpose and epigenetic age acceleration as measured by 13 DNA methylation (DNAm) “epigenetic clocks” assessed in 1 572 older adults from the Health and Retirement Study (mean age 70 years). We quantified the total association between Purpose and DNAm age acceleration as well as the extent to which that total association might be attributable to demographic factors, chronic disease, other psychosocial variables (eg, positive affect), and health-related behaviors (heavy drinking, smoking, physical activity, and body mass index [BMI]). Purpose in Life was associated with reduced epigenetic age acceleration across 4 “second-generation” DNAm clocks optimized for predicting health and longevity (false discovery rate [FDR] q < 0.0001: PhenoAge, GrimAge, Zhang epigenetic mortality index; FDR q < 0.05: DunedinPoAm). These associations were independent of demographic and psychosocial factors, but substantially attenuated after adjusting for health-related behaviors (drinking, smoking, physical activity, and BMI). Purpose showed no significant association with 9 “first-generation” DNAm epigenetic clocks trained on chronological age. Older adults with greater Purpose in Life show “younger” DNAm epigenetic age acceleration. These results may be due in part to associated differences in health-related behaviors. Results suggest new opportunities to reduce biological age acceleration by enhancing Purpose and its behavioral sequelae in late adulthood.
Modifications of epidemic-type-aftershock-sequence models for characterizing diffusive shear slips of deep long-period earthquakes
Authors: Aso Naofumi , Terai Nozomi
Published: March 2023

Deep long-period earthquakes (DLPs) are the major seismic events in the lower crust and can provide important information on the evolution of the Earth. To capture any fluid-related diffusive phenomena, we attempted to translate the swarm-like nature of DLPs into a diffusive one by modifying the epidemic-type aftershock sequence (ETAS) model, which is a standard tool for evaluating seismicity. The modified ETAS model explained the seismicity of DLPs in eastern Shimane, Japan successfully. The diffusional migration rate may not be as high as the rupture velocity of ordinary earthquakes, but it is still sufficient to associate slow deformation with low-frequency seismic radiation. The principal mechanical process of DLPs is likely shear slip, since the observed diffusivity (103–105 m2/s) is much larger than estimates for shallow volcanic events (100–101 m2/s), but close to those of tectonic tremors (104–105 m2/s). While the areal extent of aseismic slips is greater on the plate interface than in a less-mature system at volcanic roots, tectonic low-frequency earthquakes tend to be smaller than volcanic DLPs. The concept that seismic patches cause these earthquakes via universal diffusive shear slips can independently explain this paradox.
Melittin treatment prevents colorectal cancer from progressing in mice through ER stress-mediated apoptosis
Authors: Luo Yan , Xu Chong-ming , Luo Bo , Liang Gai , Zhang Qu
Published: March 2023

Objectives

The primary goal of the current study was to investigate the effect of melittin on colorectal cancer (CRC).

Methods

The viability of cancer cells was tested using the MTT assay, and the apoptosis of tumour cells was assayed using Annexin V/PI staining in vitro or TUNEL staining in vivo. The in vivo toxicity and efficacy of melittin were assessed in a xenograft mouse model.

Results

Melittin inhibited the viability of CRC cell lines and induced apoptosis in SW480 cells by regulating apoptosis-related proteins. Melittin triggered endoplasmic reticulum (ER) stress and caused an imbalance in calcium homeostasis in SW480 cells. An absence of melittin triggered ER stress via the calcium chelating agent BAPTA/AM, and the IP3R inhibitor 2-aminoethoxydiphenyl borate (2-APB) impaired melittin-induced apoptosis in SW480 cells. Melittin treatment suppressed tumour growth but did not affect the body weight of SW480 tumour-bearing mice. Unlike cisplatin and 5-fluorouracil, melittin treatment did not change the biochemical and haematological parameters of the tumour-bearing mice. Finally, in these mice, melittin treatment induced ER stress, which was then blocked by BAPTA/AM, whilst 2-APB impaired the growth inhibitory effect of melittin.

Conclusion

Melittin treatment inhibits CRC progression by inducing ER stress and an imbalance in calcium homeostasis.
The dual inhibitor Sacubitril-valsartan ameliorate high-fat high-fructose-induced metabolic disorders in rats superiorly compared to valsartan only
Authors: Abo-khookh Ahmed M , Ghoneim Hamdy A , Abdelaziz Rania R , Nader Manar A , Shawky Noha M
Published: March 2023

Objectives

Sacubitril-valsartan, a recently approved treatment for heart failure, has shown some promise as a possible therapeutic option for diabetes mellitus. It is still not clear whether those beneficial effects are comparable to valsartan effects. In this work, we aimed at investigating Sacubitril-valsartan effect on metabolic changes in a model of high-fat high fructose diet-induced diabetes mellitus, in comparison to the metabolic changes induced by valsartan only.

Methods

Rats were ad libitum fed with either standard chow plus tap water for drinking (controls) or 60% beef tallow and 10% fructose drinking water (diseased) for 11 weeks. Starting in week 9, each group was subdivided into four, namely vehicle, pioglitazone, Sacubitril-valsartan and valsartan. Treatments were administered from weeks 9 to 11, while rats were maintained in their respective diet groups.

Key findings

Sacubitril-valsartan treatment significantly decreased daily food intake, body weight and epididymal white adipose weight, and normalized insulin and glycosylated haemoglobin in high-fat high fructose. Both valsartan and Sacubitril-valsartan only attenuated the elevated fasting blood glucose levels, glucose, insulin and pyruvate tolerance and increased protein kinase B phosphorylation in diseased rats.

Conclusions

Sacubitril-valsartan may be an effective modulator of diabetes mellitus-associated metabolic aberration, superiorly compared to valsartan only.
Compound shougong powder inhibits the malignant phenotype of hepatocellular carcinoma cells by targeting the DNA damage repair pathway
Authors: Zhu Yong-fu , Xu Jing , Wu Jian , Ma Jia , Zhang Dong-wei , Xia Li-ming , Wang Tian-ming , Huo Xing-xing , Song Hang
Published: March 2023

Objectives

Compound Shougong Powder (SGS), a traditional Chinese medicine formulation, has been used to treat cancer for many years with remarkable efficacy. However, the mechanisms underlying the therapeutic effect of SGS in Hepatocellular carcinoma (HCC) are not completely clear.

Methods

The survival and metastasis of HCC cells were examined by CCK-8 assay, EdU assay, Wound-healing and Transwell assay. The anti-tumour effect of SGS was studied using hoechst 33258 staining and flow cytometry. RNA sequencing was applied to detect the underlying mechanism. Comet DNA, qRT-PCR and WB experiments were performed for validation. In addition, HCC nude mouse model was constructed to detect SGS effect in vivo.

Key findings

SGS inhibited the proliferation, migration and invasion of HCC cells and induced apoptosis in vitro. In addition, SGS also suppressed tumour growth in a nude mouse model of HCC in a dose-dependent manner. RNA sequencing of the suitably treated HCC cells revealed significant changes in the expression levels of genes involved in the DNA damage repair pathway. The sequencing results were verified by Comet DNA, qRT-PCR, WB assays and molecular docking.

Conclusions

Taken together, SGS inhibits the malignant phenotype of HCC cells by down-regulating DNA repair genes and consequently inducing DNA damage.
The complex interplay of AGN jet-inflated bubbles and the intracluster medium
Authors: Huško Filip , Lacey Cedric G
Published: March 2023

We use SWIFT, a smoothed particle hydrodynamics code, to simulate the evolution of bubbles inflated by active galactic nuclei (AGNs) jets, as well as their interactions with the ambient intracluster medium (ICM). These jets inflate lobes that turn into bubbles after the jets are turned off (at t = 50 Myr). Almost all of the energy injected into the jets is transferred to the ICM very quickly after they are turned off, with roughly 70 per cent of it in thermal form and the rest in kinetic. At late times (t > 500 Myr) we find the following: (1) the bubbles draw out trailing filaments of low-entropy gas, similar to those recently observed, (2) the action of buoyancy and the uplift of the filaments dominates the energetics of both the bubbles and the ICM, and (3) almost all of the originally injected energy is in the form of gravitational potential energy, with the bubbles containing 15 per cent of it, and the rest contained in the ICM. These findings indicate that feedback proceeds mainly through the displacement of gas to larger radii. We find that the uplift of these filaments permanently changes the thermodynamic properties of the ICM by reducing the central density and increasing the central temperature (within 30 kpc). We propose that jet feedback proceeds not only through the heating of the ICM (which can delay cooling), but also through the uplift-related reduction of the central gas density. The latter also delays cooling, on top of reducing the amount of gas available to cool.
Thez≲ 1 drop of cosmic dust abundance in a semi-analytic framework
Authors: Parente Massimiliano , Ragone-Figueroa Cinthia , Granato Gian Luigi , Lapi Andrea
Published: March 2023

Observations suggest that the amount of galactic dust in the Universe decreased by a factor of ∼2–3 during the last ∼8 Gyr. However, cosmological models of galaxy evolution usually struggle to explain this decrease. Here, we use the semi-analytic model (SAM) L-Galaxies2020 to show that this drop may be reproduced assuming standard prescriptions for dust production and evolution. We extend the SAM with (i) a state-of-the-art dust model that adopts the two-size approximation and (ii) a new disc instability criterion that triggers bulge and central black hole growth. The model reproduces some fundamental properties of the local galaxy population, such as the fraction of spheroid-dominated galaxies and some scaling relations involving dust. Moreover, the model predicts a galactic dust drop from z ∼ 1 → 0, which becomes closer to the observed one when adopting the new treatment of disc instabilities. This result is related to the newly implemented supermassive black hole growth during disc instabilities, which enhances the quenching of massive galaxies. Consequently, these objects feature a lower gas and dust content. We provide a census of the contribution of all the processes affecting the galactic dust content. Accretion is the dominant dust mass growth process. Destruction by supernovae, astration and ejection by winds have all a non-negligible role in decreasing the overall dust content in galaxies below z ∼ 1. We also discuss predictions concerning extra-galactic dust, confirming that a sputtering efficiency lower than the canonical one is required to match the few available observations.
On the dearth of C-enhanced metal-poor stars in the galactic bulge
Authors: Pagnini G , Salvadori S , Rossi M , Aguado D , Koutsouridou I , Skúladóttir Á
Published: March 2023

The chemical fingerprints of the first stars are retained within the photospheres of ancient unevolved metal-poor stars. A significant fraction of these stellar fossils is represented by stars known as Carbon-Enhanced Metal-Poor (CEMP), $\mathrm{[C/Fe]} \gt +0.7$ and $\mathrm{[Fe/H]} \lt -2$, which are likely imprinted by low-energy primordial supernovae. These CEMP stars are largely observed in the Galactic halo and ultrafaint dwarf galaxies, with values reaching $\rm [C/Fe]=+4.5$. The Galactic bulge is predicted to host the oldest stars, but it shows a striking dearth of CEMP stars with $\rm [C/Fe]\gtrsim +2.0$. Here, we explore the possible reasons for this anomaly by performing a statistical analysis of the observations of metal-poor stars in combination with the predictions of Lambda cold dark matter models. We suggest that the dearth of CEMP stars with high $\mathrm{[C/Fe]}$ is not due to the low statistics of observed metal-poor stars but is the result of the different formation process of the bulge. N-body simulations show that the first star-forming haloes which end up in the bulge are characterized by the highest star formation rates. These rates enable the formation of rare massive first stars exploding as pair-instability supernovae (PISNe), which wash out the signature of primordial faint supernovae. We demonstrate that the mean $\mathrm{[C/Fe]}$ of first stars polluted environments decreases with the increasing contribution of PISNe. We conclude that the dearth of CEMP stars in the Galactic bulge indirectly probes the existence of elusive PISNe, and propose a novel method which exploits this lack to constrain the mass distribution of the first stars.
Extragalactic science with the experiment for cryogenic large-aperture intensity mapping
Authors: Pullen Anthony R , Breysse Patrick C , Oxholm Trevor , Switzer Eric R , Anderson Christopher J , Barrentine Emily , Bolatto Alberto D , Cataldo Giuseppe , Essinger-Hileman Thomas , Maniyar Abhishek S , Stevenson Thomas , Somerville Rachel S , Volpert Carrie , Wollack Edward J , Yang Shengqi , Yung L Y Aaron , Zhou Zilu
Published: March 2023

The EXperiment for Cryogenic Large-Aperture Intensity Mapping (EXCLAIM) is a balloon-borne cryogenic telescope that will survey the spectrum of diffuse emission from both the Milky Way and the cosmic web to probe star formation, the interstellar medium, and galaxy evolution across cosmic time. EXCLAIM’s primary extragalactic science survey maps 305 deg2 along the celestial equator with an R = 512 spectrometer over the frequency range ν = 420 − 540 GHz, targeting emission of the [C ii] line over redshifts 2.5 < z < 3.5 and several CO lines for z < 1. Cross-correlation with galaxy redshift catalogues isolates line emission from the large-scale structure at target redshifts. In this paper, we forecast the sensitivity for both the two-point and conditional one-point cross-correlation. We predict that EXCLAIM will detect both the [C ii]-QSO cross-power spectrum and the conditional voxel intensity distribution (CVID) at various redshifts under a broad range of [C ii] intensity models, allowing it to differentiate among these models in the literature. These forecasts for the power spectra include the effects of line interlopers and continuum foreground contamination. We then convert the joint [C ii] constraints from both the cross-power spectrum and the CVID into constraints on the [C ii] halo luminosity–mass relation $L_\mathrm{[C\, \small {II}]}(M)$ model parameters and the star formation rate density (SFRD) from [C ii] emission. We also develop sensitivity estimates for CO, showing the ability to differentiate between models.
Joint HST, VLT/MUSE, and XMM−Newton observations to constrain the mass distribution of the two strong lensing galaxy clusters: MACS J0242.5-2132 and MACS J0949.8+1708
Authors: Allingham Joseph F V , Jauzac Mathilde , Lagattuta David J , Mahler Guillaume , Bœhm Céline , Lewis Geraint F , Eckert Dominique , Edge Alastair , Ettori Stefano
Published: March 2023

We present the strong lensing analysis of two galaxy clusters: MACS J0242.5-2132 (MACS J0242, z = 0.313) and MACS J0949.8+1708 (MACS J0949, z = 0.383). Their total matter distributions are constrained, thanks to the powerful combination of observations with the Hubble Space Telescope (HST) and the Multi-Unit Spectroscopic Explorer instrument. Using these observations, we precisely measure the redshift of six multiple image systems in MACS J0242 and two in MACS J0949. We also include four multiple image systems in the latter cluster identified in HST imaging without MUSE redshift measurements. For each cluster, our best-fit mass model consists of a single cluster-scale halo and 57 (170) galaxy-scale halos for MACS J0242 (MACS J0949). Multiple images positions are predicted with a rms 0.39 arcsec and 0.15 arcsec for MACS J0242 and MACS J0949 models, respectively. From these mass models, we derive aperture masses of M(R <200 kpc$) = 1.67_{-0.05}^{+0.03}\times 10^{14}\, {\rm M}_{\odot }$ and M(R <200 kpc$) = 2.00_{-0.20}^{+0.05}\times 10^{14}\, {\rm M}_{\odot }$. Combining our analysis with X-ray observations from the XMM−Newton Observatory, we show that MACS J0242 appears to be a relatively relaxed cluster, whereas conversely, MACS J0949 shows a relaxing post-merger state. At 200 kpc, X-ray observations suggest the hot gas fraction to be, respectively, $f_g = 0.115^{+0.003}_{-0.004}$ and $0.053^{+0.007}_{-0.006}$ for MACS J0242 and MACS J0949. MACS J0242 being relaxed, its density profile is very well fitted by a Navarro−Frenk−White distribution, in agreement with X-ray observations. Finally, the strong lensing analysis of MACS J0949 suggests a flat dark matter density distribution in the core, between 10 and 100 kpc. This appears consistent with X-ray observations.
Refining the OJ 287 2022 impact flare arrival epoch
Authors: Valtonen Mauri J , Zola Staszek , Gopakumar A , Lähteenmäki Anne , Tornikoski Merja , Dey Lankeswar , Gupta Alok C , Pursimo Tapio , Knudstrup Emil , Gomez Jose L , Hudec Rene , Jelínek Martin , Štrobl Jan , Berdyugin Andrei V , Ciprini Stefano , Reichart Daniel E , Kouprianov Vladimir V , Matsumoto Katsura , Drozdz Marek , Mugrauer Markus , Sadun Alberto , Zejmo Michal , Sillanpää Aimo , Lehto Harry J , Nilsson Kari , Imazawa Ryo , Uemura Makoto
Published: March 2023

The bright blazar OJ 287 routinely parades high brightness bremsstrahlung flares, which are explained as being a result of a secondary supermassive black hole (SMBH) impacting the accretion disc of a more massive primary SMBH in a binary system. The accretion disc is not rigid but rather bends in a calculable way due to the tidal influence of the secondary. Next, we refer to this phenomenon as a variable disc level. We begin by showing that these flares occur at times predicted by a simple analytical formula, based on general relativity inspired modified Kepler equation, which explains impact flares since 1888. The 2022 impact flare, namely flare number 26, is rather peculiar as it breaks the typical pattern of two impact flares per 12-yr cycle. This is the third bremsstrahlung flare of the current cycle that follows the already observed 2015 and 2019 impact flares from OJ 287. It turns out that the arrival epoch of flare number 26 is sensitive to the level of primary SMBH’s accretion disc relative to its mean level in our model. We incorporate these tidally induced changes in the level of the accretion disc to infer that the thermal flare should have occurred during 2022 July–August, when it was not possible to observe it from the Earth. Thereafter, we explore possible observational evidence for certain pre-flare activity by employing spectral and polarimetric data from our campaigns in 2004/05 and 2021/22. We point out theoretical and observational implications of two observed mini-flares during 2022 January–February.
Anisotropic correlation functions as tracers of central galaxy alignments in simulations
Authors: Rodriguez Facundo , Merchán Manuel , Artale M Celeste , Andrews Moira
Published: March 2023

Motivated by observational results, we use IllustrisTNG hydrodynamical numerical simulations to study the alignment of the central galaxies in groups with the surrounding structures. This approach allows us to analyse galaxy and group properties not available in observations. To perform this analysis, we use a modified version of the two-point cross-correlation function and a measure of the angle between the semimajor axes of the central galaxies and the larger structures. Overall, our results reproduce observational ones, as we find large-scale anisotropy, which is dominated by the red central galaxies. In addition, the latter is noticeably more aligned with their group than the blue ones. In contrast to the observations, we find a strong dependence of the anisotropy on the central galaxy with mass, probably associated with the inability of observational methods to determine them. This result allows us to link the alignment to the process of halo assembly and the well-known dependence of halo anisotropy on mass. When we include the dark matter distribution in our analysis, we conclude that the galaxy alignment found in simulations (and observations) can be explained by a combination of physical processes at different scales: the central galaxy aligns with the dark matter halo it inhabits, and this, in turn, aligns with the surrounding structures at large scales.
Stability of interlinked neutron vortex and proton flux-tube arrays in a neutron star – III. Proton feedback
Authors: Thong K H , Melatos A , Drummond L V
Published: March 2023

The coupled, time-dependent Gross–Pitaevskii and Ginzburg–Landau equations are solved simultaneously in three dimensions to investigate the equilibrium state and far-from-equilibrium, spin-down dynamics of an interpenetrating neutron superfluid and proton type-II superconductor, as an idealized description of the outer core of a neutron star. The simulations generalize previous calculations without the time-dependent Ginzburg–Landau equation, where proton feedback is absent. If the angle θ between the rotation and magnetic axes does not equal zero, the equilibrium state consists of geometrically complicated neutron vortex and proton flux-tube tangles, as the topological defects pin to one another locally but align with different axes globally. During spin-down, new types of motion are observed. For θ = 0, entire vortices pair rectilinearly with flux tubes and move together while pinned. For θ ≠ 0, vortex segments pair with segments from one or more flux tubes, and the paired segments move together while pinned. The degree to which proton feedback impedes the deceleration of the crust is evaluated as a function of θ and the pinning strength, η. Key geometric properties of vortex-flux-tube tangles, such as filament length, mean curvature, and polarity are analysed. It is found that proton feedback smooths the deceleration of the crust, reduces the rotational glitch sizes, and stabilizes the vortex tangle dynamics. The dimensionless control parameters in the simulations are mutually ordered to match what is expected in a real neutron star, but their central values and dynamic ranges differ from reality by many orders of magnitude due to computational limitations.
Treatments and challenges in advanced prostate cancer
Authors: Gourdin Theodore , Velayati Arash
Published: March 2023

Purpose of review

This review is designed to highlight recent research examining treatment progress in advanced prostate cancer while identifying ongoing challenges to clinical outcomes.

Recent findings

Recent randomized trials suggest an overall survival advantage to treating some men with newly identified metastatic prostate cancer with a “triplet” of androgen deprivation therapy, docetaxel, and an androgen receptor axis-targeted agent. Questions remain about which men are best served by these combinations. Additional treatment success is being identified with prostate-specific membrane antigen positron emission tomography (PSMA)-radiopharmaceuticals, combinations involving targeted therapies, and novel manipulations of the androgen receptor axis. Challenges remain in selecting between available therapies, harnessing immune therapies, and treating tumors with emergent neuroendocrine differentiation.

An expanding number of therapeutics are becoming available for men with advanced prostate cancer improving outcomes but at the same time making treatment selection more demanding. Ongoing research will be required to continue to hone treatment paradigms.
Evolving systemic management of urothelial cancers
Authors: Tan Wei Shen , Tan Mae-Yen , Alhalabi Omar , Campbell Matthew T. , Kamat Ashish M. , Gao Jianjun
Published: March 2023

Purpose of review

Bladder cancer is the 12th most common cancer worldwide. Historically, the systemic management of urothelial carcinoma has been confined to platinum-based chemotherapy. In this review, we discuss the evolving landscape of systemic treatment for urothelial carcinoma.

Recent findings

Since 2016, when the Food and Drug Administration approved the first immune checkpoint inhibitor (CPI), programmed cell death 1 and programmed cell death ligand 1 inhibitors have been evaluated in the nonmuscle invasive bladder cancer, localized muscle invasive bladder cancer as well as advanced/metastatic bladder cancer settings. Newer approved treatments such as fibroblast growth factor receptor (FGFR) inhibitors and antibody–drug conjugates (ADCs) represent second-line and third-line options. These novel treatments are now being assessed in combination as well as with older traditional platinum-based chemotherapy.

Novel therapies continue to improve bladder cancer outcomes. Personalized approach with well validated biomarkers are important to predict response to therapy.