Miracle-dz/UniFAR-FTUs huggingface dataset:
Hepatocellular Carcinoma With Portal Vein Tumor Thrombus Treated With Transarterial Chemoembolization and Sorafenib vs. 125Iodine Implantation

Background and Aims This study investigated the feasibility, safety, and efficacy of transarterial chemoembolization (TACE) combined with CT-guided 125iodine seed implantation for treatment of hepatocellular carcinoma (HCC) with first-branch portal vein tumor thrombosis (PVTT). Methods This prospective, controlled, multicenter study included HCC patients with Barcelona Clinic Liver Cancer stage C disease and PVTT in the right and/or left portal veins. Patients were treated with either TACE and sorafenib or TACE and CT-guided 125iodine seed implantation and regularly evaluated for clinical response and adverse events, with treatment termination resulting from declining clinical status, loss to follow-up, or death. Results This study demonstrated a significant between-group difference in median overall survival (OS); therefore, it was terminated early. A total of 123 patients were included in this study, with 52 patients in the TACE-sorafenib group and 71 patients in the TACE-125iodine group, without significant differences in baseline characteristics between groups. The median OS was 8.3 months (95% CI: 6.105–10.495) in the TACE-sorafenib group and 13.8 months (95% CI: 9.519–18.081) in the TACE-125iodine group. In a subgroup analysis of type IIa versus type IIb PVTT, the median OS was 17.5 months for type IIa and 7.1 months for IIb in the TACE-125iodine group. The median OS was 9.3 months for IIa and 4.0 months for IIb in the TACE-sorafenib group. Univariate and multivariate analyses confirmed that the PVTT type and treatment strategy were significant independent factors affecting OS. The objective response rates (ORR) for intrahepatic lesions and PVTT showed significant differences between groups. Most patients in both groups experienced minor adverse events related to TACE. The overall incidence of sorafenib-related adverse events or toxic effects was 90.4% in TACE-sorafenib group. In the TACE-125iodine group, the incidence of pneumothorax and minor hepatic subcapsular hemorrhage were 7.04% and 9.86%, respectively. Conclusions This study showed that TACE-125iodine treatment significantly enhanced survival of patients with HCC and type II PVTT, especially subtype IIa, with minimal adverse events. Clinical Trial Registration Chinese Clinical Trials Database, identifier ChiCTR-ONN-16007929.
Effects of Aging on the Structure and Expression of NMDA Receptors of Somatostatin Expressing Neurons in the Mouse Hippocampus

Changes in the physiology, neurochemistry and structure of neurons, particularly of their dendritic spines, are thought to be crucial players in age-related cognitive decline. One of the most studied brain structures affected by aging is the hippocampus, known to be involved in different essential cognitive processes. While the aging-associated quantitative changes in dendritic spines of hippocampal pyramidal cells have already been studied, the relationship between aging and the structural dynamics of hippocampal interneurons remains relatively unknown. Spines are not a frequent feature in cortical inhibitory neurons, but these postsynaptic structures are abundant in a subpopulation of somatostatin expressing interneurons, particularly in oriens-lacunosum moleculare (O-LM) cells in the hippocampal CA1. Previous studies from our laboratory have shown that the spines of these interneurons are highly plastic and influenced by NMDA receptor manipulation. Thus, in the present study, we have investigated the impact of aging on this interneuronal subpopulation. The analyses were performed in 3−, 9−, and 16-month-old GIN mice, a strain in which somatostatin positive interneurons express GFP. We studied the changes in the density of dendritic spines, en passant boutons, and the expression of NMDA receptors (GluN1 and GluN2B) using confocal microscopy and image analysis. We observed a significant decrease in dendritic spine density in 9-month-old animals when compared with 3-month-old animals. We also observed a decrease in the expression of the GluN2B subunit in O-LM cells, but not of that of GluN1, during aging. These results will constitute the basis for more advanced studies of the structure and connectivity of interneurons during aging and their contribution to cognitive decline.
A Combination of Biomarkers Predict Response to Immune Checkpoint Blockade Therapy in Non-Small Cell Lung Cancer

Immune checkpoint blockade (ICB) therapy has provided clinical benefits for patients with advanced non-small-cell lung cancer (NSCLC), but the majority still do not respond. Although a few biomarkers of ICB treatment response have been developed, the predictive power of these biomarkers showed substantial variation across datasets. Therefore, predicting response to ICB therapy remains a challenge. Here, we provided a concise combinatorial strategy for predicting ICB therapy response and constructed the ICB treatment signature (ITS) in lung cancer. The prediction performance of ITS has been validated in an independent ICB treatment cohort of NSCLC, where patients with higher ITS score were significantly associated with longer progression-free survival and better response. And ITS score was more powerful than traditional biomarkers, such as TMB and PD-L1, in predicting the ICB treatment response in NSCLC. In addition, ITS scores still had predictive effects in other cancer data sets, showing strong scalability and robustness. Further research showed that a high ITS score represented comprehensive immune activation characteristics including activated immune cell infiltration, increased mutation load, and TCR diversity. In conclusion, our practice suggested that the combination of biomarkers will lead to a better prediction of ICB treatment prognosis, and the ITS score will provide NSCLC patients with better ICB treatment decisions.
Brain Responses to Hypnotic Verbal Suggestions Predict Pain Modulation

Background: The effectiveness of hypnosis in reducing pain is well supported by the scientific literature. Hypnosis typically involves verbal suggestions but the mechanisms by which verbal contents are transformed into predictive signals to modulate perceptual processes remain unclear. We hypothesized that brain activity during verbal suggestions would predict the modulation of responses to acute nociceptive stimuli. Methods: Brain activity was measured using BOLD-fMRI in healthy participants while they listened to verbal suggestions of HYPERALGESIA, HYPOALGESIA, or NORMAL sensation (control) following a standardized hypnosis induction. Immediately after the suggestions, series of noxious electrical stimuli were administered to assess pain-related responses. Brain responses measured during the suggestions were then used to predict changes in pain-related responses using delayed regression analyses. Results: Listening to suggestions of HYPERALGESIA and HYPOALGESIA produced BOLD decreases (vs. control) in the parietal operculum (PO) and in the anterior midcingulate cortex (aMCC), and increases in the left parahippocampal gyrus (lPHG). Changes in activity in PO, aMCC and PHG during the suggestions predicted larger pain-evoked responses following the HYPERALGESIA suggestions in the anterior cingulate cortex (ACC) and the anterior insula (aINS), and smaller pain-evoked responses following the HYPOALGESIA suggestions in the ACC, aMCC, posterior insula (pINS) and thalamus. These changes in pain-evoked brain responses are consistent with the changes in pain perception reported by the participants in HYPERALGESIA and HYPOALGESIA, respectively. Conclusions: The fronto-parietal network (supracallosal ACC and PO) has been associated with self-regulation and perceived self-agency. Deactivation of these regions during suggestions is predictive of the modulation of brain responses to noxious stimuli in areas previously associated with pain perception and pain modulation. The response of the hippocampal complex may reflect its role in contextual learning, memory and pain anticipation/expectations induced by verbal suggestions of pain modulation. This study provides a basis to further explore the transformation of verbal suggestions into perceptual modulatory processes fundamental to hypnosis neurophenomenology. These findings are discussed in relation to predictive coding models.
Flow structures in spanwise rotating plane Poiseuille flow based on thermal analogy

Abstract The analogy between rotating shear flow and thermal convection suggests the existence of plumes, inertial waves and plume currents in plane Poiseuille flow under spanwise rotation. The existence of these flow structures is examined with the results of three-dimensional and two-dimensional three-component direct numerical simulations. The dynamics of plumes near the unstable side is embodied in a truncated exponential distribution of turbulent fluctuations. For large rotation numbers, inertial waves are identified near the stable side, and these can be used to explain the abnormal flow statistics, such as the large root-mean-square of the streamwise velocity fluctuation and the nearly negligible Reynolds shear stress. For small or medium rotation numbers, plumes generated from the unstable side form large-scale plume currents and the patterns of the plume currents show different capabilities in scalar transport.
Case Report: Abnormal ECG in a Patient With Acute Pancreatitis

Background: Both acute pancreatitis and acute myocardial infarction (AMI) are rapidly progressive and frequently fatal diseases that can be interrelated and lead to a vicious cycle for further problems. The concomitant occurrence of AMI and acute pancreatitis is rare but critical, and efficient diagnosis and treatment of such patients are challenging. Case Summary: We reported an uncommon case of abnormal ECG findings in a 63-year-old woman with acute pancreatitis. The patient exhibited increased biomarkers of myocardial injury, such as creatine kinase-MB (CK-MB) and troponin T, as well as ST segment elevation in inferior leads II, III, and aVF. Both of these have been previously observed in patients with acute abdomen in the absence of ST-segment elevation myocardial infarction (STEMI), including pancreatitis. In addition, lacking complaints of chest pain or tightness was also supportive of this idea. Echocardiography indicated abnormalities in the functioning of the left inferior posterior wall segments and decreased overall systolic function of the left ventricle with a 51% ejection fraction. Eventually, AMI was diagnosed after coronary computed tomography angiography (CCTA) showing critical stenosis of the right coronary artery and left anterior descending artery segments. The patient was urgently transferred to intensive care unit and was treated with anticoagulation, antiplatelet aggregation, lipid-lowering and other palliative drugs. Conclusion: Concomitant acute pancreatitis and AMI are often considered to be critical conditions with a poor prognosis. Therefore, it is important to rapidly identify this condition and consider transferring patients for multidisciplinary supportive care.
An Unfolded Protein Response Related Signature Could Robustly Predict Survival Outcomes and Closely Correlate With Response to Immunotherapy and Chemotherapy in Bladder Cancer

Background: The unfolded protein response (UPR) plays a significant role in maintaining protein hemostasis in tumor cells, which are crucial for tumor growth, invasion, and resistance to therapy. This study aimed to develop a UPR-related signature and explore its correlation with immunotherapy and chemotherapy in bladder cancer. Methods: The differentially expressed UPR-related genes were put into Lasso regression to screen out prognostic genes, which constituted the UPR signature, and were incorporated into multivariate Cox regression to generate risk scores. Subsequently, the predictive performance of this signature was estimated by receiver operating characteristic (ROC) curves. The CIBERSORTx, the maftool, and Gene set enrichment analysis (GSEA) were applied to explore infiltrated immune cells, tumor mutational burden (TMB), and enriched signaling pathways in both risk groups, respectively. Moreover, The Cancer Immunome Atlas (TCIA) and Genomics of Drug Sensitivity in Cancer (GDSC) databases were used to predict responses to chemotherapy and immunotherapy. Results: Twelve genes constituted the UPR-related signature. Patients with higher risk scores had worse overall survival (OS) in training and three validation sets. The UPR-related signature was closely correlated with clinicopathologic parameters and could serve as an independent prognostic factor. M0 macrophages showed a significantly infiltrated difference in both risk groups. TMB analysis showed that the risk score in the wild type and mutation type of FGFR3 was significantly different. GSEA indicated that the immune-, extracellular matrix-, replication and repair associated pathways belonged to the high risk group and metabolism-related signal pathways were enriched in the low risk group. Prediction of immunotherapy and chemotherapy revealed that patients in the high risk group might benefit from chemotherapy, but had a worse response to immunotherapy. Finally, we constructed a predictive model with age, stage, and UPR-related risk score, which had a robustly predictive performance and was validated in GEO datasets. Conclusion: We successfully constructed and validated a novel UPR-related signature in bladder cancer, which could robustly predict survival outcomes and closely correlate with the response to immunotherapy and chemotherapy in bladder cancer.
Susceptibilidade de espécies de plantas com potencial de fitorremediação do herbicida sulfentrazone

Among the new technologies, phytoremediation is considered as an option for the decontamination of areas that thave undergone intense herbicide applications. This work aimed to select species with potential to the phytoremediation of soils contaminated with the herbicide sulfentrazone. The tested species were Calopogonium mucunoides, hybrid Sorghum (Sorghum bicolor x Sorghum sudanense), Crotalaria breviflora, Crotalaria juncea, Canavalia ensiformis, Dolichos lablab, Stizolobium deeringianum e Stizolobium aterrimum. The experiment was conducted in a greenhouse, using 6 dm3 vases filled with soil samples collected at a depth of 20 cm. The experimental design was the randomized blocks in a factorial scheme of 8 x 5, with four repetitions, which were composed by the eight plant species, and five doses of sulfentrazone (0, 200, 400, 800 and 1,600g ha-1). We evaluated the phytotoxicity of the herbicide, plant height and dry weight of shoots and roots. The species showing the least symptoms of phytotoxicity and the highest rates of height and fresh and dry biomass were C. juncea, C. ensiformis and D. lablab, which were selected as tolerant to the herbicide sulfentrazone and with potential for phytoremediation.
Factors Affecting the Aluminum, Arsenic, Cadmium and Lead Concentrations in the Knee Joint Structures

Background: Toxic elements, such as aluminum (Al), arsenic (As), cadmium (Cd), and lead (Pb), are persistent environmental pollutants that can cause adverse effects on the health of exposed individuals. Bone is one of the primary target organs of accumulation and potential damage from toxic elements. Objectives: This study was performed to determine the Al, As, Cd, and Pb concentrations in the femoral cancellous bone, femoral cartilage, anterior cruciate ligament, meniscus, tibial cartilage, tibial cancellous bone and infrapatellar fat pad. Furthermore, the aim of this study was to explore the relationships between toxic element concentrations and related factors such as gender, age, place of residence, hypertension and diabetes, and to determine the correlations among these toxic elements in knee joint structures. Methods: The samples used this study were collected from 51 patients following total knee arthroplasty. The Al, As, Cd, and Pb concentrations were determined using inductively coupled plasma optic emission spectrometry. Results: Significant differences were found in the Al, As, Cd, and Pb concentrations among the knee joint structures. Cd concentration in the tibial cancellous bone in women was significantly higher than in men. Pb concentration in the infrapatellar fat pad of urban patients was significantly higher as compared to rural patients. Al concentrations in the femoral cancellous bone, femoral cartilage, anterior cruciate ligament, meniscus and tibial cartilage were significantly higher in patients living in urban areas than in rural areas. As concentration in the tibial cancellous bone of diabetic patients was significantly higher compared to non-diabetic patients. In addition, significant Spearman's positive correlations were found between Al and Pb in the knee joint structures. Conclusion: The obtained results of the investigated toxic elements may serve as a basis for establishing the reference values of Al, As, Cd, and Pb in the knee joint structures. The results reported in the study provides novel data regarding the relationships between the toxic element concentrations and gender, age, place of residence, hypertension and diabetes in the studied structures of knee joint. Furthermore, new interactions among these toxic elements were noted.
A Mixed-Method Evaluation of a Prison Anti-doping Intervention: The Hercules Prison Program

The Norwegian Offender Mental Health and Addiction study denotes the need for physical activity and anti-doping interventions in Norwegian prisons. We developed and evaluated the efficacy of such intervention—the Hercules prison program. The program combines theoretical anti-doping lessons with practical strength training. The study adopts a mixed-methods approach (pretest-posttest design) comprising a longitudinal survey, observation, informal conversations, and in-depth interviews. Survey respondents were 104 male prisoners aged 18–56 (M = 34.81, SD = 9.34) years from seven Norwegian prisons. Of these, 52 provided both baseline and posttest responses. Participants completed questionnaires including demographic, doping use, and psychophysical items/measures. At the end of the intervention, in-depth interviews were conducted with 11 of the survey respondents. The survey data were analyzed using descriptive statistics, as well as independent and paired samples t-tests. The qualitative data were analyzed using Interpretative Phenomenological Analysis. A total of 7.5% and 33.3% of participants were current and former AAS users respectively, whereas 86.1% personally knew at least one current or former AAS user. Consistent with our expectation, there were increases in self-rated physical strength (t = −4.1, p < 0.001, d = 0.46) and strength training self-efficacy (t = −8.33, p < 0.001, d = 1.36), and a decrease in moral disengagement in doping (t = −4.05, p < 0.001, d = 0.52) from baseline to posttest. These findings are supported by the qualitative data. Notable success factors are relationship-building, instructors' expertise and acceptability, and gatekeepers' navigation and co-creation. The program provides valuable evidence of the potential benefits of combining anti-doping education with practical strength training in doping prevention in correctional settings.
Immunometabolic Analysis of Mobiluncus mulieris and Eggerthella sp. Reveals Novel Insights Into Their Pathogenic Contributions to the Hallmarks of Bacterial Vaginosis

The cervicovaginal microbiome plays an important role in protecting women from dysbiosis and infection caused by pathogenic microorganisms. In healthy reproductive-age women the cervicovaginal microbiome is predominantly colonized by protective Lactobacillus spp. The loss of these protective bacteria leads to colonization of the cervicovaginal microenvironment by pathogenic microorganisms resulting in dysbiosis and bacterial vaginosis (BV). Mobiluncus mulieris and Eggerthella sp. are two of the many anaerobes that can contribute to BV, a condition associated with multiple adverse obstetric and gynecological outcomes. M. mulieris has been linked to high Nugent scores (relating to BV morphotypes) and preterm birth (PTB), whilst some bacterial members of the Eggerthellaceae family are highly prevalent in BV, and identified in ~85-95% of cases. The functional impact of M. mulieris and Eggerthella sp. in BV is still poorly understood. To determine the individual immunometabolic contributions of Eggerthella sp. and M. mulieris within the cervicovaginal microenvironment, we utilized our well-characterized human three-dimensional (3-D) cervical epithelial cell model in combination with multiplex immunoassays and global untargeted metabolomics approaches to identify key immune mediators and metabolites related to M. mulieris and Eggerthella sp. infections. We found that infection with M. mulieris significantly elevated multiple proinflammatory markers (IL-6, IL-8, TNF-α and MCP-1) and altered metabolites related to energy metabolism (nicotinamide and succinate) and oxidative stress (cysteinylglycine, cysteinylglycine disulfide and 2-hydroxygluatrate). Eggerthella sp. infection significantly elevated multiple sphingolipids and glycerolipids related to epithelial barrier function, and biogenic amines (putrescine and cadaverine) associated with elevated vaginal pH, vaginal amine odor and vaginal discharge. Our study elucidated that M. mulieris elevated multiple proinflammatory markers relating to PTB and STI acquisition, as well as altered energy metabolism and oxidative stress, whilst Eggerthella sp. upregulated multiple biogenic amines associated with the clinical diagnostic criteria of BV. Future studies are needed to evaluate how these bacteria interact with other BV-associated bacteria within the cervicovaginal microenvironment.
Living in a Fluctuating Environment Increases Tolerance to Marine Heatwaves in the Free-Living Coralline Alga Phymatolithon lusitanicum

Recently, increased attention is being paid to the importance of environmental history in species’ responses to climate-change related stressors, as more variable and heterogeneous environments are expected to select for higher levels of plasticity in species tolerance traits, compared to stable conditions. For example, organisms inhabiting environments with highly fluctuating thermal regimes might be less susceptible to the increasing frequency and intensity of marine heatwaves (MHWs). In this study, we assessed the metabolic and calcification responses of the rhodolith-bed forming Phymatolithon lusitanicum, from a coastal region that is strongly influenced by frequent changes between upwelling and downwelling conditions, to a simulated MHW scenario, with and without prior exposure to a moderate thermal stress. This allowed determining not only the influence of the species’ long-term thermal history on its resilience against MHWs, but also the rhodoliths capacity for short-term thermal stress memory and its importance during posterior MHW-exposure. Our findings indicate that the rhodoliths experienced negative impacts on daily net primary production (DNP) and calcification (DNC) during the MHW. The effect on the former was only temporary at the beginning of the MHW, while DNC was highly impacted, but exhibited a quick recovery after the event, suggesting a high resilience of the species. Furthermore, prior exposure to a moderate temperature increase, such as those occurring frequently in the natural habitat of the species, mitigated the effects of a subsequent MHW on DNP, while promoting a faster recovery of DNC after the event. Thus, our findings (1) support the hypothesis that benthic organisms living in nearshore habitats may benefit from the natural short-term temperature fluctuations in these environments with an increased resistance to MHW impacts and (2) provide first-time evidence for thermally induced stress memory in coralline algae.