Functional genetic variants of the disulfidptosis-related INF2 gene predict survival of hepatitis B virus-related hepatocellular carcinoma.

Disulfidptosis is a novel form of programmed cell death involved in migration and invasion of cancer cells, but few studies investigated the roles of genetic variants in disulfidptosis-related genes in survival of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). We used Cox proportional hazards regression analyses, Kaplan-Meier curves and receiver operating characteristic curves to assess effects of genetic variants in 14 disulfidptosis-related genes on overall survival of 866 HBV-HCC patients. The Bayesian false discovery probability was used for multiple testing corrections. We also investigated biological mechanisms of the significant variants through expression quantitative trait loci analyses using the data from publicly available databases, luciferase reporter assays and differential expression analyses. As a result, we identified two independently functional single nucleotide polymorphisms (SNPs) (INF2 rs4072285 G > A and INF2 rs4444271 A > T) that predicted overall survival of HBV-HCC patients, with adjusted hazard ratios of 1.60 (95% CI = 1.22-2.11, P = 0.001) and 1.50 (95% CI = 1.80-1.90, P < 0.001), respectively, after multiple testing correction. Luciferase reporter assays indicated that both INF2 rs4072285 A and INF2 rs4444271 T alleles increased INF2 mRNA expression levels (P < 0.001) that were also higher in HCC tumor tissues than in adjacent normal tissues (P < 0.001); such elevated INF2 expression levels were associated with a poorer survival of HBV-HCC patients (P < 0.001) in the TCGA database. In summary, this study supported that INF2 rs4072285 and INF2 rs4444271 may be novel biomarkers for survival of HBV-HCC patients.

Genetic variants of m6A modification genes are associated with survival of HBV-related hepatocellular carcinoma.

N6-methyladenosine (m6A) is a dynamic and reversible modification process involving in a series of important biological and pathophysiological processes, including the progression of cancers. Herein, we aimed to assess the relationships of genetic variants in m6A modification genes with the survival of hepatitis B virus -related hepatocellular carcinoma (HBV-HCC). We performed a two-stage survival analysis to investigate the associations of 4425 single nucleotide polymorphisms (SNPs) in 36 m6A modification genes with the overall survival (OS) of HBV-HCC patients. Then, the identified SNPs were further used to functionally annotate. We identified that METTL3 rs1263790 (A > G) and ADARB1 rs57884102 (C > T) were significantly associated with the HBV-HCC OS (hazard ratios [HR] = 0.68, 95% confidence interval [CI] = 0.52-0.89, p = 0.004; and HR = 1.70, 95% CI = 1.33-2.18, p < 0.001, respectively). Combined analysis revealed that patients carrying more risk genotypes of two variants had a progressively poorer OS. Moreover, the expression quantitative trait loci (eQTL) analysis indicated that rs1263790 G allele decreased mRNA expression levels of METTL3 in 483 cell-cultured fibroblasts samples. And we found the mRNA expression levels of METTL3 and ADARB1 in HCC tissues were higher than in normal tissues, and the higher METTL3 and the lower ADARB1 were associated with poorer HCC OS. Our results demonstrated that two novel genetic variants (METTL3 rs1263790 and ADARB1 rs57884102) may be potential prognostic markers for HBV-HCC, but these results need larger different ethnic cohorts and functional experiments to validate in the future.

High-resolution myelin-water fraction and quantitative relaxation mapping using 3D ViSTa-MR fingerprinting.

PURPOSE: This study aims to develop a high-resolution whole-brain multi-parametric quantitative MRI approach for simultaneous mapping of myelin-water fraction (MWF), T1, T2, and proton-density (PD), all within a clinically feasible scan time. METHODS: We developed 3D visualization of short transverse relaxation time component (ViSTa)-MRF, which combined ViSTa technique with MR fingerprinting (MRF), to achieve high-fidelity whole-brain MWF and T1/T2/PD mapping on a clinical 3T scanner. To achieve fast acquisition and memory-efficient reconstruction, the ViSTa-MRF sequence leverages an optimized 3D tiny-golden-angle-shuffling spiral-projection acquisition and joint spatial-temporal subspace reconstruction with optimized preconditioning algorithm. With the proposed ViSTa-MRF approach, high-fidelity direct MWF mapping was achieved without a need for multicompartment fitting that could introduce bias and/or noise from additional assumptions or priors. RESULTS: The in vivo results demonstrate the effectiveness of the proposed acquisition and reconstruction framework to provide fast multi-parametric mapping with high SNR and good quality. The in vivo results of 1 mm- and 0.66 mm-isotropic resolution datasets indicate that the MWF values measured by the proposed method are consistent with standard ViSTa results that are 30× slower with lower SNR. Furthermore, we applied the proposed method to enable 5-min whole-brain 1 mm-iso assessment of MWF and T1/T2/PD mappings for infant brain development and for post-mortem brain samples. CONCLUSIONS: In this work, we have developed a 3D ViSTa-MRF technique that enables the acquisition of whole-brain MWF, quantitative T1, T2, and PD maps at 1 and 0.66 mm isotropic resolution in 5 and 15 min, respectively. This advancement allows for quantitative investigations of myelination changes in the brain.

DTI-MR fingerprinting for rapid high-resolution whole-brain T1 , T2 , proton density, ADC, and fractional anisotropy mapping.

PURPOSE: This study aims to develop a high-efficiency and high-resolution 3D imaging approach for simultaneous mapping of multiple key tissue parameters for routine brain imaging, including T1 , T2 , proton density (PD), ADC, and fractional anisotropy (FA). The proposed method is intended for pushing routine clinical brain imaging from weighted imaging to quantitative imaging and can also be particularly useful for diffusion-relaxometry studies, which typically suffer from lengthy acquisition time. METHODS: To address challenges associated with diffusion weighting, such as shot-to-shot phase variation and low SNR, we integrated several innovative data acquisition and reconstruction techniques. Specifically, we used M1-compensated diffusion gradients, cardiac gating, and navigators to mitigate phase variations caused by cardiac motion. We also introduced a data-driven pre-pulse gradient to cancel out eddy currents induced by diffusion gradients. Additionally, to enhance image quality within a limited acquisition time, we proposed a data-sharing joint reconstruction approach coupled with a corresponding sequence design. RESULTS: The phantom and in vivo studies indicated that the T1 and T2 values measured by the proposed method are consistent with a conventional MR fingerprinting sequence and the diffusion results (including diffusivity, ADC, and FA) are consistent with the spin-echo EPI DWI sequence. CONCLUSION: The proposed method can achieve whole-brain T1 , T2 , diffusivity, ADC, and FA maps at 1-mm isotropic resolution within 10 min, providing a powerful tool for investigating the microstructural properties of brain tissue, with potential applications in clinical and research settings.

Effects of berberine hydrochloride on antioxidant response and gut microflora in the Charybdis japonica infected with Aeromonas hydrophila.

This study used berberine hydrochloride to treat the Asian paddle crab, Charybdis japonica infected with the Gram-negative bacterium Aeromonas hydrophila at concentrations of 0, 100, 200 and 300 mg/L. The effect of berberine hydrochloride on the survival rate and gut microbiota of C. japonica was investigated. Berberine hydrochloride improved the stability of the intestinal flora, with an increase in the abundance of probiotic species and a decrease in the abundance of both pathogenic bacteria after treatment with high concentrations of berberine hydrochloride. Berberine hydrochloride altered peroxidase activity (POD), malondialdehyde (MDA), and lipid peroxidation (LPO) in the intestinal tract compared to the control. Berberine hydrochloride could modulate the energy released from the enzyme activities of hexokinase (HK), phosphofructokinase (PFK), and pyruvate kinase (PK) in the intestinal tract of C. japonica infected with A. hydrophila. Zona occludens 1 (ZO-1), Zinc finger E-box binding homeobox 1 (ZEB1), occludin and signal transducer, and activator of transcription5b (STAT5b) expression were also increased, which improved intestinal barrier function. The results of this study provide new insights into the role of berberine hydrochloride in intestinal immune mechanisms and oxidative stress in crustaceans.

Highly transparent Ce:Nd:YAG ceramic with good light conversion capacity for solar-pumped solid-state lasers.

Developing a high quality ceramic laser gain medium for solar directly pumped solid state lasers is essential, and yet the light conversion efficiency of the gain media for solar pumping remains a challenge. In this study, Ce and Nd ions, co-doped YAG transparent ceramics with theoretical transmittance and stable Ce3+ valent state were developed, and revealed that the absorbed visible light and light conversion efficiency in Ce,Nd:YAG ceramics were 3.98 times and 1.34 times higher than those in widely reported Cr,Nd:YAG ceramics, respectively. A concentration matching principle between Ce3+ and Nd3+ ions in YAG was established, and a higher Nd3+ ion doping concentration with a relatively low Ce3+ concentration was favorable to improve both the light conversion efficiency and emission intensity at 1064 nm of Ce,Nd:YAG ceramics. Energy transfer efficiency from Ce3+ to Nd3+ of the 0.3 at.%Ce,1.5at.%Nd:YAG ceramic reached as high as 61.71% at room temperature. Surprisingly, it was further promoted to 64.31% at a higher temperature of 473 K. More excited electrons at the upper energy level of Ce3+ ion under the high temperature accounted for this novel phenomenon. This study proposes a new design strategy of gain materials for solar directly pumped solid state lasers.

Gravitational Raman Scattering in Effective Field Theory: A Scalar Tidal Matching at O(G

We present a framework to compute amplitudes for the gravitational analog of the Raman process, a quasielastic scattering of waves off compact objects, in worldline effective field theory. As an example, we calculate third post-Minkowskian order [O(G^{3})], or two-loop, phase shifts for the scattering of a massless scalar field including all tidal effects and dissipation. Our calculation unveils two sources of the classical renormalization-group flow of dynamical Love numbers: a universal running independent of the nature of the compact object, and a running self-induced by tides. Restricting to the black hole case, we find that our effective field theory phase shifts agree exactly with those from general relativity, provided that the relevant static Love numbers are set to zero. In addition, we carry out a complete matching of the leading scalar dynamical Love number required to renormalize a universal short scale divergence in the S wave. Our results pave the way for systematic calculations of gravitational Raman scattering at higher post-Minkowskian orders.

Associations between modifiable risk factors and hepatocellular carcinoma: a trans-ancestry Mendelian randomization study.

BACKGROUND: Potentially modifiable risk factors for hepatocellular carcinoma (HCC) have been investigated in observational epidemiology studies in East Asian and European populations, whereas the causal associations of most of these risk factors remain unclear. METHODS: We collected genome-wide association summary statistics of 22 modifiable risk factors in East Asians and 33 risk factors in Europeans. Genetic summary statistics of HCC were sourced from the Biobank Japan study (1,866 cases and 195,745 controls) for East Asians, and the deCODE genetics study (406 cases and 49,302 controls) and the UK Biobank (168 cases and 372 016 controls) for Europeans. Two-sample Mendelian randomization (MR) analyses were performed independently for East Asian and European populations. RESULTS: In East Asians, genetically predicted alcohol frequency, ever drinkers, aspartate aminotransferase (AST), hypothyroidism, chronic hepatitis B, and chronic hepatitis C, metabolic dysfunction-associated steatotic liver disease (MASLD), and autoimmune hepatitis were significantly associated with an increased HCC risk (P < 0.05/22). Among European population, alanine transaminase, AST, MASLD, percent liver fat, and liver iron content were significantly associated with a higher risk of HCC (P < 0.05/33). The replication dataset and meta-analysis further confirmed these results. CONCLUSIONS: Although East Asian and European populations have different factors for HCC, their common modifiable risk factors AST and MASLD for HCC, offer valuable insights for targeted intervention strategies to mitigate society burden of HCC.

Effects of different concentrations and particle sizes of nanoplastics on gut microbiology, metabolism, and immunity in Chiromantes dehaani.

This study investigated the effects of nanoplastics (NPs) of varying particle sizes (75, 500, and 1000 nm) and concentrations (2.5 and 10 mg/L) on the gut health of Chiromantes dehaani. The experimental groups included a control (Cg0), and varying combinations of particle size and concentration. Our results showed that 75 nm NPs were more likely to enhance pathogenic bacterial growth than other sized NPs. Compared with CK, Low NPs concentrations (2.5 mg/L) raised total cholesterol (T-CHO) levels in the gut, while high concentrations significantly decreased both triglyceride (TG) and T-CHO levels (p < 0.05). The enzymatic activities of intestinal lipase and amylase were inhibited by NPs exposure, with greater inhibition at higher NPs concentrations. The 500 nm NPs exhibited a notably higher inhibitory effect than the 75 and 1000 nm NPs (P < 0.05). In terms of apoptosis, NPs exposure led to reduced mRNA expression of Bcl2 and increased expression of Caspase-3, Caspase-8, and Caspase-9, indicating an induction of apoptosis. This effect was more pronounced at higher NPs concentrations, with 75 nm NPs more likely to induce apoptosis in intestinal cells than 500 nm and 1000 nm NPs. Moreover, NPs triggered intestinal inflammatory responses, evidenced by the increased mRNA expression of TNF-ß, TNF-α, IL1ß, IL6, and IL8, and the decreased expression of IL10. High NPs concentrations were more likely to induce intestinal inflammation, with 500 nm NPs imparting the strongest effect. In summary, the study demonstrated that NPs, and particularly those at higher concentrations, disrupted the gut environment of C. dehaani by altering the microflora, reducing microbial diversity, inhibiting digestion and metabolism, inducing apoptosis, and triggering inflammation. Among the sizes of NPs tested, 500 nm NPs had the most significant adverse impact on digestion, metabolism, and inflammation, while 75 nm NPs most strongly induced apoptosis in C. dehaani's intestinal cells.

Genetic variants in m5C modification genes are associated with survival of patients with HBV-related hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with a high mortality rate. The 5-methylcytosine (m5C), a type of RNA modification, plays crucial regulatory roles in HCC carcinogenesis, metastasis, and prognosis. However, a few studies have investigated the effect of genetic variants in m5C modification genes on survival of patients with hepatitis B virus (HBV)-related HCC. In the present study, we evaluated associations between 144 SNPs in 15 m5C modification genes and overall survival (OS) in 866 patients with the HBV-related HCC. Expression quantitative trait loci (eQTL) analysis and differential expression analysis were conducted to investigate biological mechanisms. As a result, we identified that two SNPs (NSUN7 rs2437325 A > G and TRDMT1 rs34434809 G > C) were significantly associated with HBV-related HCC OS with adjusted allelic hazards ratios of 1.25 (95% confidence interval = 1.05-1.48 and P = 0.011) and 1.19 (1.02-1.38 and P = 0.027), respectively, with a trend of combined risk genotypes (Ptrend < 0.001). Moreover, the results of eQTL analyses showed that both NSUN7 rs2437325 G and TRDMT1 rs34434809 C alleles were associated with a reduced mRNA expression level in 208 normal liver tissues (P = 0.007 and P < 0.001, respectively). Taken together, genetic variants in the m5C modification genes may be potential prognostic biomarkers of HBV-related HCC after hepatectomy, likely through mediating the mRNA expression of corresponding genes.

Acute radiation skin injury in stage III-IV head and neck cancer: scale correlates and predictive model.

PURPOSE: Active radiation skin injury (ARSI) has the highest incidence of acute adverse reactions caused by radiotherapy (RT) in patients with head and neck cancer (HNC). This study aimed to screen risk factors that can facilitate the identification of HNC patients at high risk of ARSI. METHODS: Data from 255 stage III-IV HNC patients who underwent intensity-modulated radiation therapy (IMRT) were collected. The data from our medical records, including clinical characteristics and hematological indices before RT, were retrospectively collected and arranged. The Common Terminology Criteria for Adverse Events Criteria (CTCAE), Radiation Therapy Oncology Group Criteria (RTOG), World Health Organization Criteria (WHO), Oncology Nursing Society (ONS), Acute Radiation Dermatitis Graduation Scale, Douglas & Fowler and Radiation Dermatitis Severity Scale (RDSS) were used to assess ARSI. Of these, CTCAE was used for further analysis. Binary logistic regression analyses were used to identity risk factors. To establish the correction between each risk factor and the ARSI score, the odds ratio (OR) and 95% confidence interval (CI) were computed. RESULTS: The assessment results of the CTCAE with RTOG, WHO, ONS, Graduation Scale, Douglas & Fowler and RDSS have good consistency. After radiotherapy, 18.4% of patients had at least 3 (3 +) grade ARSI. Multivariate logistic regression analysis revealed that the KPS score, blood glucose level, white blood cell count, and plasma free thyroxine (FT4) concentration were independent risk factors for 3 + grade ARSI. A nomogram was constructed on the basis of these risk factors, which demonstrated good predictive power according to the area under the ROC curve (AUC). The satisfactory consistency and clinical efficacy of the nomogram were confirmed by calibration curves and decision curve analysis (DCA). CONCLUSION: A low KPS score, high blood glucose level, high white blood cell count, and high thyroid hormone prior to radiotherapy for stage III-IV HNC are independent risk factors for grade 3 + RSI.

Distinct regional vulnerability to Aß and iron accumulation in post mortem AD brains.

INTRODUCTION: The paramagnetic iron, diamagnetic amyloid beta (Aß) plaques and their interaction are crucial in Alzheimer's disease (AD) pathogenesis, complicating non-invasive magnetic resonance imaging for prodromal AD detection. METHODS: We used a state-of-the-art sub-voxel quantitative susceptibility mapping method to simultaneously measure Aß and iron levels in post mortem human brains, validated by histology. Further transcriptomic analysis using Allen Human Brain Atlas elucidated the underlying biological processes. RESULTS: Regional increased paramagnetic and diamagnetic susceptibility were observed in medial prefrontal, medial parietal, and para-hippocampal cortices associated with iron deposition (R = 0.836, p = 0.003) and Aß accumulation (R = 0.853, p = 0.002) in AD brains. Higher levels of gene expression relating to cell cycle, post-translational protein modifications, and cellular response to stress were observed. DISCUSSION: These findings provide quantitative insights into the variable vulnerability of cortical regions to higher levels of Aß aggregation, iron overload, and subsequent neurodegeneration, indicating changes preceding clinical symptoms. HIGHLIGHTS: The vulnerability of distinct brain regions to amyloid beta (Aß) and iron accumulation varies. Histological validation was performed on stained sections of ex-vivo human brains. Regional variations in susceptibility were linked to gene expression profiles. Iron and Aß levels in ex-vivo brains were simultaneously quantified.

The relationship between self-esteem and happiness of college students in China:A moderated mediation model.

The objective of the study is to explore the influence of self-esteem on the happiness levels of college students and the mediating roles of social avoidance and loneliness. 1021 college students between 18 and 24 years of age completed the Self-esteem Scale, General Well-being Scale, Social Avoidance and Distress Scale, UCLA Loneliness Scale and Interpersonal Trust Scale.And descriptive statistical analysis and correlation analysis, structural equation model analysis were conducted. The result turns out that Self-esteem negatively predicted the happiness levels of college students. Self-esteem indirectly predicted happiness through three paths: mediating the roles of social avoidance, mediating the roles of loneliness and the chain-mediated roles of social avoidance and loneliness in college students.Interpersonal Trust moderated the relationship between loneliness and happiness.The higher the self-esteem levels of the college students, the less happiness they experienced.

Biomimetic Charge-Neutral Anion Receptors for Reversible Binding and Release of Highly Hydrated Phosphate in Water.

Control of phosphate capture and release is vital in environmental, biological, and pharmaceutical contexts. However, the binding of trivalent phosphate (PO4 3-) in water is exceptionally difficult due to its high hydration energy. Based on the anion coordination chemistry of phosphate, in this study, four charge-neutral tripodal hexaurea receptors (L1-L4), which were equipped with morpholine and polyethylene glycol terminal groups to enhance their solubility in water, were synthesized to enable the pH-triggered phosphate binding and release in aqueous solutions. Encouragingly, the receptors were found to bind PO4 3- anion in a 1 : 1 ratio via hydrogen bonds in 100 % water solutions, with L1 exhibiting the highest binding constant (1.2×103 M-1). These represent the first neutral anion ligands to bind phosphate in 100 % water and demonstrate the potential for phosphate capture and release in water through pH-triggered mechanisms, mimicking native phosphate binding proteins. Furthermore, L1 can also bind multiple bioavailable phosphate species, which may serve as model systems for probing and modulating phosphate homeostasis in biological and biomedical researches.

NCAPD2 promotes breast cancer progression through E2F1 transcriptional regulation of CDK1.

Breast cancer (BC) is a serious threat to women's health worldwide. Non-SMC condensin I complex subunit D2 (NCAPD2) is a regulatory subunit of the coagulin I complex, which is mainly involved in chromosome coagulation and separation. The clinical significance, biological behavior, and potential molecular mechanism of NCAPD2 in BC were investigated in this study. We found that NCAPD2 was frequently overexpressed in BC, and it had clinical significance in predicting the prognosis of BC patients. Moreover, loss-of-function assays demonstrated that NCAPD2 knockdown restrained the progression of BC by inhibiting proliferation and migration and enhancing apoptosis in vitro. It was further confirmed that the downregulation of NCAPD2 inhibited tumor growth in vivo. NCAPD2 promoted the progression of BC through the extracellular signal-regulated kinase 5 (ERK5) signaling pathway. Additionally, NCAPD2 could transcriptionally activate CDK1 by interacting with E2F transcription factor 1 (E2F1) in MDA-MB-231 cells. Overexpression of CDK1 alleviated the inhibitory effects of NCAPD2 knockdown in BC cells. In summary, the NCAPD2/E2F1/CDK1 axis may play a role in promoting the progression of BC, which may provide a blueprint for molecular therapy.

Optimized three-dimensional ultrashort echo time: Magnetic resonance fingerprinting for myelin tissue fraction mapping.

Quantitative assessment of brain myelination has gained attention for both research and diagnosis of neurological diseases. However, conventional pulse sequences cannot directly acquire the myelin-proton signals due to its extremely short T2 and T2* values. To obtain the myelin-proton signals, dedicated short T2 acquisition techniques, such as ultrashort echo time (UTE) imaging, have been introduced. However, it remains challenging to isolate the myelin-proton signals from tissues with longer T2. In this article, we extended our previous two-dimensional ultrashort echo time magnetic resonance fingerprinting (UTE-MRF) with dual-echo acquisition to three dimensional (3D). Given a relatively low proton density (PD) of myelin-proton, we utilized Cramér-Rao Lower Bound to encode myelin-proton with the maximal SNR efficiency for optimizing the MR fingerprinting design, in order to improve the sensitivity of the sequence to myelin-proton. In addition, with a second echo of approximately 3 ms, myelin-water component can be also captured. A myelin-tissue (myelin-proton and myelin-water) fraction mapping can be thus calculated. The optimized 3D UTE-MRF with dual-echo acquisition is tested in simulations, physical phantom and in vivo studies of both healthy subjects and multiple sclerosis patients. The results suggest that the rapidly decayed myelin-proton and myelin-water signal can be depicted with UTE signals of our method at clinically relevant resolution (1.8 mm isotropic) in 15 min. With its good sensitivity to myelin loss in multiple sclerosis patients demonstrated, our method for the whole brain myelin-tissue fraction mapping in clinical friendly scan time has the potential for routine clinical imaging.

Both noise-floor and tissue compartment difference in diffusivity contribute to FA dependence on b-value in diffusion MRI.

Noninvasive diffusion magnetic resonance imaging (dMRI) has been widely employed in both clinical and research settings to investigate brain tissue microstructure. Despite the evidence that dMRI-derived fractional anisotropy (FA) correlates with white matter properties, the metric is not specific. Recent studies have reported that FA is dependent on the b-value, and its origin has primarily been attributed to either the influence of microstructure or the noise-floor effect. A systematic investigation into the inter-relationship of these two effects is however still lacking. This study aims to quantify contributions of the reported differences in intra- and extra-neurite diffusivity to the observed changes in FA, in addition to the noise in measurements. We used in-vivo and post-mortem human brain imaging, as well as numerical simulations and histological validation, for this purpose. Our investigations reveal that the percentage difference of FA between b-values (pdFA) has significant positive associations with neurite density index (NDI), which is derived from in-vivo neurite orientation dispersion and density imaging (NODDI), or Bielschowsky's silver impregnation (BIEL) staining sections of fixed post-mortem human brain samples. Furthermore, such an association is found to be varied with Signal-to-Noise Ratio (SNR) level, indicating a nonlinear interaction effect between tissue microstructure and noise. Finally, a multicompartment model simulation revealed that these findings can be driven by differing diffusivities of intra- and extra-neurite compartments in tissue, with the noise-floor further amplifying the effect. In conclusion, both the differences in intra- and extra-neurite diffusivity and noise-floor effects significantly contribute to the FA difference associated with the b-value.

Potentially functional genetic variants in RPS6KA4 and MAP2K5 in the MAPK signaling pathway predict HBV-related hepatocellular carcinoma survival.

Hepatocellular carcinoma (HCC) ranks the third leading cause of cancer deaths with a dismal 5-year survival rate. The mitogen-activated protein kinase (MAPK) signaling pathway is abnormally activated in HCC to promote growth and aggressive metastatic potential of cancer cells. Therefore, genetic variants in the MAPK signaling pathway may serve as potential predictors of Hepatitis B virus (HBV)-related HCC survival. In the present study, we performed a two-stage survival analysis to evaluate the associations between 10,912 single nucleotide polymorphisms (SNPs) in 79 MAPK signaling pathway genes and the overall survival (OS) of 866 HBV-related HCC patients, followed by functional annotation. In combined datasets, we identified two novel and potential functional SNPs (RPS6KA4 rs600377 T>G and MAP2K5 rs17300363 A>C) as prognostic factors for HBV-related HCC, with adjusted allelic hazards ratios of 1.24 (95% confidence interval [CI] = 1.05-1.46, p = 0.010) and 1.48 (1.15-1.91, p = 0.001), respectively. Furthermore, their combined risk genotypes also predicted a poor survival in a dose-response manner in the combined data set (Ptrend < 0.001). Additional functional analysis showed that RPS6KA4 rs600377 G and MAP2K5 rs17300363 C alleles were associated with elevated mRNA expression levels of the corresponding genes in normal tissues. These results provide new insights into the role of genetic variants in the MAPK signaling pathway genes in HBV-related HCC survival.

Rapid high-fidelity T 2 * mapping using single-shot overlapping-echo acquisition and deep learning reconstruction.

PURPOSE: To develop and evaluate a single-shot quantitative MRI technique called GRE-MOLED (gradient-echo multiple overlapping-echo detachment) for rapid T 2 * $$ {T}_2^{\ast } $$ mapping. METHODS: In GRE-MOLED, multiple echoes with different TEs are generated and captured in a single shot of the k-space through MOLED encoding and EPI readout. A deep neural network, trained by synthetic data, was employed for end-to-end parametric mapping from overlapping-echo signals. GRE-MOLED uses pure GRE acquisition with a single echo train to deliver T 2 * $$ {T}_2^{\ast } $$ maps less than 90 ms per slice. The self-registered B0 information modulated in image phase was utilized for distortion-corrected parametric mapping. The proposed method was evaluated in phantoms, healthy volunteers, and task-based FMRI experiments. RESULTS: The quantitative results of GRE-MOLED T 2 * $$ {T}_2^{\ast } $$ mapping demonstrated good agreement with those obtained from the multi-echo GRE method (Pearson's correlation coefficient = 0.991 and 0.973 for phantom and in vivo brains, respectively). High intrasubject repeatability (coefficient of variation <1.0%) were also achieved in scan-rescan test. Enabled by deep learning reconstruction, GRE-MOLED showed excellent robustness to geometric distortion, noise, and random subject motion. Compared to the conventional FMRI approach, GRE-MOLED also achieved a higher temporal SNR and BOLD sensitivity in task-based FMRI. CONCLUSION: GRE-MOLED is a new real-time technique for T 2 * $$ {T}_2^{\ast } $$ quantification with high efficiency and quality, and it has the potential to be a better quantitative BOLD detection method.

Vanishing of Black Hole Tidal Love Numbers from Scattering Amplitudes.

We extract the black hole (BH) static tidal deformability coefficients (Love numbers) and their spin-0 and spin-1 analogs by comparing on-shell amplitudes for fields to scatter off a spinning BH in the worldline effective field theory and in general relativity. We point out that the general relativity amplitudes due to tidal effects originate entirely from the BH potential region. Thus, they can be separated from gravitational nonlinearities in the wave region, whose proper treatment requires higher order effective field theory loop calculations. In particular, the elastic scattering in the near field approximation is produced exclusively by tidal effects. We find this contribution to vanish identically, which implies that the static Love numbers of Kerr BHs are zero for all types of perturbations. We also reproduce the known behavior of scalar Love numbers for higher-dimensional BHs. Our results are manifestly gauge invariant and coordinate independent, thereby providing a valuable consistency check for the commonly used off-shell methods.