bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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 &lt; 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

ABSTRACT

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

Abstract
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

Abstract

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

Abstract
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

Abstract
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 &lt; 0.0001: PhenoAge, GrimAge, Zhang epigenetic mortality index; FDR q &lt; 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

SUMMARY
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

Abstract

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

Abstract

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

Abstract

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

ABSTRACTWe 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 &gt; 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

ABSTRACTObservations 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

ABSTRACTThe 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.