bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential neural response to psychoanalytic intervention techniques during structural interviewing: A single-case analysis using EEG
Authors: Buchheim Anna , Kernberg Otto F. , Netzer Nikolaus , Buchheim Peter , Perchtold-Stefan Corinna , Sperner-Unterweger Barbara , Beckenbauer Fabian , Labek Karin 
Published: January 2023

BackgroundPrevious studies detected changes in the electroencephalographic (EEG) signal as an effect of psychoanalytic interventions. However, no study has investigated neural correlates of specific psychoanalytic interventions in the EEG power spectrum yet. In the present case study, we contrasted three types of interventions (clarification, confrontation, and interpretation) and a neutral control condition during a structural psychoanalytic interview conducted while EEG was recorded.MethodsA 27-year-old male patient diagnosed with major depressive disorder and borderline personality disorder with recurrent suicidal and self-injurious behavior underwent a structural interview while recording EEG. Two independent experts selected by consensus the characteristic episodes of the four conditions (clarification, confrontation, interpretation, and neutral control) within the interview, which were included in the EEG analyses. Fast Fourier transformation (FFT) was applied to subsegments of the intervention type to analyze the EEG power spectra. Alpha and beta power from central, frontal, and parietal sites were considered in linear mixed-effects models with segments as a random factor with maximum-likelihood estimates due to the lack of balance in the length of the interview segments.ResultsThe interventions “interpretation” and “confrontation” showed a significantly lower alpha power compared with the control condition in the central electrodes. In the frontal and parietal sites of the alpha power and all beta power sites, the omnibus tests (full model/model without intervention) and comparisons relative to control conditions showed no significant overall result or failed significance after alpha error correction.ConclusionIncisive interventions, such as confrontation with discrepancies and interpretation of unconscious intrapsychic conflicts, may have provoked temporary emotional lability, leading to a change in psychic processing akin to interference from external stimuli. This conclusion is consistent with the finding that interpretations, which are potentially the most concise interventions, had the strongest effects on alpha power. Using EEG during therapeutic psychoanalytic intervention techniques might be a helpful tool to evaluate differential responses to the psychotherapeutic process on a neural level. However, this single-case result has to be replicated in a larger sample and does not allow generalizations.
Efficacy of intra-arterial chemotherapy with sequential anti-PD-1 antibody in unresectable gastric cancer: A retrospective real-world study
Authors: Xiang Xiaosong , Guo Feilong , Li Guoli , Ma Long , Zhu Xi , Abdulla Zulpikar , Li Jiafei , Zhang Junling , Huang Mengli 
Published: January 2023

BackgroundThe prognosis of unresectable gastric cancer is poor, while the efficacy of anti-PD antibodies has not been evaluated.MethodsPatients with unresectable gastric cancer who received intra-arterial chemotherapy (IAC) with sequential anti-PD-1 antibody as induction therapy in Jinling Hospital were retrospectively analyzed. The primary outcome is R0 resection rate. The secondary outcomes include safety, conversion surgery rate, overall survival (OS) and progression free survival (PFS) after postoperative IAC and anti-PD-1 treatments. Meanwhile, Tumor immunity in the microenvironment (TIME) before and after IAC was comprehensively dissected with multiplex immunofluorescence in order to detect possible mechanisms favoring anti-PD-1 treatment response.ResultsBetween May 2019 and October 2020, 36 patients received at least one cycle of IAC with sequential anti-PD-1 antibody in our institution. The objective response was achieved in 28 patients (77.8%). Thirty patients (83.3%) successfully underwent conversion surgery, among which R0 resection was managed in 25/30 patients, and 23.3% (7/30) was assessed as pathological complete remission. During the median follow-up period of 19.7 months, patients who underwent R0 resection displayed superior OS (HR 0.14 [95% CI 0.04-0.50], P &lt; 0.0001) and PFS (HR 0.11 [0.03-0.44], P &lt; 0.0001) than those who did not. Grade 3 adverse events (AEs) were only encountered in 19.4% patients, no grade 4 AEs observed. In TIME analysis, the number of tertiary lymphoid structures (TLSs) (P = 0.004) were greatly induced by IAC, as well as CD8+ T cells (P = 0.011) and PD-1+ cells (P = 0.025). Meanwhile, Tumor associated macrophages shifted towards anti-tumor M1-like subtypes, with CD68+CD163+ M2-like subpopulation significantly decreased (P = 0.04).ConclusionPreoperative IAC with sequential anti-PD-1 antibody exhibited promising clinical benefit for unresectable gastric cancer with remarkable conversion rate and R0 resection rate, and also prolonged survival as postoperative regimen. TIME transformation induced by ICA might mediate the additive effect with the immune checkpoint inhibitor.
Association between early response of alpha-fetoprotein and treatment efficacy of systemic therapy for advanced hepatocellular carcinoma: A multicenter cohort study from China
Authors: Hou Gang , Liu Bo , Fan Zhong-Qi , Li Chao , Zhang Jian-Ping , Guo Yan-Hui , Zhang Ru-Yi , Zheng Yi , Zhu Hong , Wang Nan-Ya 
Published: January 2023

BackgroundAlpha-fetoprotein (AFP) is a well-identified biomarker in hepatocellular carcinoma (HCC). However, only limited AFP-related studies have evaluated its early response to systemic therapy. This study was performed with the aim of assessing the value of early AFP response in predicting overall survival (OS) and progression-free survival (PFS) in advanced HCC patients receiving systemic therapy.MethodsThis cohort study included HCC patients with baseline AFP ≥ 200 ng/ml and no prior treatment history. A &gt; 20% decline in the serum AFP level from baseline to the first follow-up (i.e., 4~6 weeks after treatment) was defined as an early AFP response. Patient demographic information, clinical characteristics, radiological response, and survival rates were compared between patients with early AFP response and patients without early AFP response. We further utilized multivariate Cox regression to seek characteristics related to OS and PFS.ResultsAmong 154 patients, 69 patients (44.8%) showed an early AFP response. The disease control rate (76.8 vs. 54.1%; P = 0.003) and objective response rate (38.4 vs. 11.8%; P = 0.001) were significantly higher in patients with an early AFP response. By performing multivariate analysis, early AFP response remained a prognostic factor for longer PFS (HR 0.546; 95% CI 0.371-0.804; P = 0.002) and longer OS (HR 0.529; 95% CI 0.335-0.834; P = 0.006).ConclusionAn early AFP response is correlated with longer overall survival and progression-free survival for advanced HCC patients receiving systemic therapy. Moreover, an early AFP response is an independent prognostic factor for longer OS and PFS.
Zoledronic acid induces ferroptosis by reducing ubiquinone and promoting HMOX1 expression in osteosarcoma cells
Authors: Ren Tianhao , Huang Ju , Sun Wei , Wang Guangze , Wu Yuwen , Jiang Zewei , Lv Yingshuai , Wu Guang , Cao Jiawei , Liu Min , Gu Haihua 
Published: January 2023

Aims: Ferroptosis plays important roles in tumorigenesis and cancer therapy. Zoledronic acid is known to inhibit the activity of farnesyl pyrophosphate synthase, a key enzyme in the mevalonate pathway. We examined whether zoledronic acid can inhibit the growth of osteosarcoma cells by inducing ferroptosis.Methods: Cell viability was analyzed by using CCK8 reagent and counting cells with trypan blue exclusion. Ferroptosis markers including lipid peroxide and PTGS2 expression were examined by flow cytometry, western blot, and quantitative PCR analyses. Cellular ubiquinone content was determined using high performance liquid chromatography. Ferrostatin-1 and RSL3 were used as the ferroptosis inhibitor and inducer respectively.Results: Zoledronic acid treatment decreased cell viability and promoted the increase in lipid peroxide content and PTGS2 expression. Addition of ferrostatin-1 reverted these effects of zoledronic acid on osteosarcoma cells, supporting a role of zoledronic acid in inducing ferroptosis. Mechanistically, zoledronic acid significantly decreased ubiquinone, a metabolite of the mevalonate pathway. Treating cells with exogenous ubiquinone prevented zoledronic acid-induced ferroptosis and decrease in the growth of osteosarcoma cells. In addition, zoledronic acid enhanced the expression of HMOX1, whereas knockdown of HMOX1 inhibited the zoledronic acid-induced increase in lipid peroxide level and decrease in cell growth. Finally, zoledronic acid together with RSL3 significantly enhanced the inhibitory effect on the growth of osteosarcoma cells.Conclusion: Our results indicate that zoledronic acid induces ferroptosis by decreasing ubiquinone content and promoting HMOX1 expression in osteosarcoma cells. Zoledronic acid together with ferroptosis inducer may be a promising new strategy for the treatment of osteosarcoma.
Successful establishment and five-year sustainability of a neonatal-specific antimicrobial stewardship program in a low middle-income country
Authors: Maalouf Faouzi I. , Saad Therese , Zakhour Ramia , Yunis Khalid 
Published: January 2023

Introduction: Antibiotic use varies substantially among neonatal intensive care units (NICUs) without any appreciable impact on outcomes. An increased use of antimicrobials has been reported in low-middle income countries. This raises the concern for potential overuse of antibiotics in a fragile patient population, thus increasing the rates of multidrug resistant organisms and affecting the developing microbiome. The presence of a neonatal-specific antimicrobial stewardship program can aid with the judicious use of antibiotics in the neonatal population and thus decrease the overuse of such medications.Methods: In this quality improvement project, we established and implemented a neonatal-specific antimicrobial stewardship program with the aim of reducing antimicrobial use in the neonatal intensive care units within a year of starting. Several interventions using a multidisciplinary approach included implementing standard algorithms, direct audit and feedback, and automated hard stops.Results: These series of interventions led to a 35% decrease in antimicrobial usage in the first 3 months and further decrease was seen with a median of 63% decline for a total of 5 years after project implementation. The use of the most commonly prescribed antibiotics, ampicillin and gentamicin, decreased by 63% and 79%, respectively. There was no evidence that this change in practice affected or jeopardized patient outcomes. Additionally, it showed sustainability and resilience despite the many challenges such as COVID-19 pandemic, political and financial unrest, and healthcare sector collapse.Discussion: This model-based and multidisciplinary low-cost approach can lead to marked improvement affecting neonatal outcomes and can be replicated in other similar centers.
The role played by ailanthone in inhibiting bone metastasis of breast cancer by regulating tumor-bone microenvironment through the RANKL-dependent pathway
Authors: Wang Yajun , Zhong Zeyuan , Ma Miao , Zhao Yannan , Zhang Chongjing , Qian Zhi , Wang Biyun 
Published: January 2023

Introduction: Bone metastasis of breast cancer (BC) is a process in which the disruption of the bone homeostatic microenvironment leads to an increase in osteoclast differentiation. Ailanthus altissima shows an inhibitory effect on osteoclast differentiation. Ailanthone (AIL) refers to a natural compound isolated from Ailanthus altissima, a Chinese herbal medicine, and has effective anti-tumor activity in numerous cell lines. Its impact on bone metastases for BC is yet unclear.Methods: We measured the effect of AIL on MDA-MB-231 cells by wound healing experiments, Transwell and colony formation experiment. Using the Tartrate-resistant Acid Phosphatase (TRAP) staining tests, filamentous (F-actin) staining and bone resorption test to detect the effect of AIL on the osteoclast cell differentiation of the Bone Marrow-derived Macrophages (BMMs), activated by the MDA-MB-231 cell Conditioned Medium (MDA-MB-231 CM) and the Receptor Activator of Nuclear factor-κB Ligand (RANKL),and to explore its possibility Mechanisms. In vivo experiments verified the effect of AIL on bone destruction in breast cancer bone metastasis model mice.Results:In vitro, AIL significantly decrease the proliferation, migration and infiltration abilities of MDA-MB-231 cells at a safe concentration, and also reduced the expression of genes and proteins involved in osteoclast formation in MDA-MB-231 cells. Osteoclast cell differentiation of the BMMs, activated by MDA-MB-231 CM and RANKL, were suppressed by AIL in the concentration-dependent manner. Additionally, it inhibits osteoclast-specific gene and protein expression. It was noted that AIL inhibited the expression of the osteoclast differentiation-related cytokines RANKL and interleukin-1β (IL-1β) that were secreted by the MDA-MB-231 cells after upregulating the Forkhead box protein 3 (FOXP3) expression. Furthermore, AIL also inhibits the expression of the Mitogen-Activated Protein Kinase (MAPK), Phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT), and Nuclear factor-κB Ligand (NF-κB) signaling pathways, which then suppresses the MDA-MB-231CM-induced development of Osteoclasts.Conclusion: Our study shows that AIL blocks osteoclast differentiation in the bone metastasis microenvironment by inhibiting cytokines secreted by BC cells, which may be a potential agent for the treatment of BC and its secondary bone metastasis.
An anoikis-based signature for predicting prognosis in hepatocellular carcinoma with machine learning
Authors: Guizhen Zhang , Weiwei Zhu , Yun Wang , Guangying Cui , Yize Zhang , Zujiang Yu 
Published: January 2023

Background: Hepatocellular carcinoma (HCC) is a common malignancy with high mortality worldwide. Despite advancements in diagnosis and treatment in recent years, there is still an urgent unmet need to explore the underlying mechanisms and novel prognostic markers. Anoikis has received considerable attention because of its involvement in the progression of human malignancies. However, the potential mechanism of anoikis-related genes (ANRGs) involvement in HCC progression remains unclear.Methods: We use comprehensive bioinformatics analyses to determine the expression profile of ANRGs and their prognostic implications in HCC. Next, a risk score model was established by least absolute shrinkage and selection operator (Lasso) Cox regression analysis. Then, the prognostic value of the risk score in HCC and its correlation with clinical characteristics of HCC patients were further explored. Additionally, machine learning was utilized to identify the outstanding ANRGs to the risk score. Finally, the protein expression of DAP3 was examined on a tissue microarray (TMA), and the potential mechanisms of DAP3 in HCC was explored.Results: ANRGs were dysregulated in HCC, with a low frequency of somatic mutations and associated with prognosis of HCC patients. Then, nine ANRGs were selected to construct a risk score signature based on the LASSO model. The signature presented a strong ability of risk stratification and prediction for overall survival in HCC patients.Additionally, high risk scores were closely correlated with unfavorable clinical features such as advanced pathological stage, poor histological differentiation and vascular invasion. Moreover, The XGBoost algorithm verified that DAP3 was an important risk score contributor. Further immunohistochemistry determined the elevated expression of DAP3 in HCC tissues compared with nontumor tissues. Finally, functional analyses showed that DAP3 may promote HCC progression through multiple cancer-related pathways and suppress immune infiltration.Conclusion: In conclusion, the anoikis-based signature can be utilized as a novel prognostic biomarker for HCC, and DAP3 may play an important role in the development and progression of HCC.
The importance of reminders and patient preferences to improve inhaler technique in older adults with COPD
Authors: Barnestein-Fonseca P. , Cotta-Luque VM. , Aguiar-Leiva VP. , Leiva-Fernández J. , Martos-Crespo Francisco , Leiva-Fernández F. 
Published: January 2023

Objectives: Medication non-adherence in patients with chronic obstructive pulmonary disease is common. The aim is to evaluate the efficacy of two interventions to improve the inhalation technique (IT) in patients with pulmonary disease is common. Also determine optimal IT reminder time and to test the role of preferences in the intervention selection.Method: 726 pulmonary disease in common patients (consecutive sampling) from two trials: 1) TECEPOC-study (patients’ preference trial/comprehensive cohort design) 2) TIEPOC-study (randomised controlled trial). Interventions: intervention-A (ad-hoc leaflet with instructions about correct IT according Spanish Respiratory Society), intervention B (intervention A+ individual training by instructors). Four visits were performed (baseline, 3, 6 and 12 months). Data on IT, sociodemographic and clinical characteristics, quality of life and respiratory drugs were recorded. Analysis under intention to treat principle. Multivariate analysis was conducted to measure the potential modifying factors of improvement in the IT along follow-up.Results: 660 patients (90.9%) did not perform a correct IT at baseline 89.75% with Handihaler, 86.95% with Turbuhaler, 84.75% with Accuhaler and 87.35% with pMDI. At 12 months, 221 patients 29.9% performed correctly the IT; a decrease in the slope of the curve (correct IT) was detected at 3 months follow-up. Intervention B was the most effective in both trials compared to control group or intervention A, regardless of preferences: 1) TECEPOC Study (preference trial): Intervention B versus control group, NNT = 3.22 (IC95%, 2.27–5.52); and versus Intervention A, NNT = 3.57 (CI95%, 2.41–6.8). Preferences improved 6.7% in the correct IT without statistical significance. 2) TIEPOC Study (randomized controlled trial): Intervention B versus control group, NNT = 1.74 (IC95%, 1.47–2.17), and versus intervention A, NNT = 3.33 (CI 95%, 2.43–5.55). No differences were measured between Intervention A and control group.Conclusion: Individual training significantly improves IT. Reminders every 3 months are recommended. Preferences do not influence the intervention effectiveness.
Dosimetric quantities and cell survival for spatially fractionated radiation therapy
Authors: Ahmed Mabroor , Bicher Sandra , Stewart Robert D. , Bartzsch Stefan , Schmid Thomas E. , Combs Stephanie E. , Meyer Juergen 
Published: January 2023

Purpose: Spatially Fractionated Radiation Therapy (SFRT) is characterized by large differences in peak and valley doses. Preclinical and clinical studies suggest that differences in biological mechanisms lead to differential normal tissue and tumor response compared to uniform irradiation. We hypothesize that to evaluate clinical effectiveness and understand fundamental biological mechanisms, radiobiological rather than physical dose quantities should be utilized for comparisons. The aim of this work is to determine whether Equivalent Uniform Dose (EUD) is a superior predictor of cell survival than absorbed dose.Methods: Absorbed dose parameters were compared to the Equivalent Uniform Dose to assess their predictive value for the relative effectiveness of uniform and SFRT with X-rays. A Bayesian bootstrap technique was utilized to model uncertainties in the biological fit parameters for a human fibroblast (MRC5) and two human tumor cell lines (LN18 and A549). Dose uncertainties were evaluated through measurements and error modeling of SFRT profiles. A dimensionless Relative Effectiveness Factor (REF) is proposed to quantify differences between uniform and SFRT irradiation.Results: For all cell lines, cell survival after SFRT matched uniform irradiation within the estimated uncertainties at equal values of the EUD. Average and peak dose showed poor correlation with in vitro cell survival. The proposed REF factor is dose dependent and suggests enhanced cell killing for both tumor cell lines (1.14 ± .08 for LN18, 1.32 ± .13 for A549 at 8 Gy EUD) for SFRT. Normal human fibroblasts showed reduced cell killing relative to uniform irradiation (.58 ± .06 for MRC5). Synthetically generated SFRT dose profiles revealed that EUD uncertainties are dominated by valley dose uncertainties, especially at high doses.Discussion: EUD is more predictive of cell survival than average or valley dose. Valley dose is close to equal to the EUD for values >10 Gy and has the advantage of being independent of uncertainties in biological parameters. The REF is a novel and useful metric to compare quantitative differences in SFRT and uniform irradiation.Conclusion: EUD is recommended for comparisons of SFRT and uniform irradiation. The results suggest an increase in survival of normal-human fibroblast cells and reduced survival for both tumor cell lines after SFRT relative to uniform irradiation.
Data-driven modeling of beam loss in the LHC
Authors: Krymova Ekaterina , Obozinski Guillaume , Schenk Michael , Coyle Loic , Pieloni Tatiana 
Published: January 2023

In the Large Hadron Collider, the beam losses are continuously measured for machine protection. By design, most of the particle losses occur in the collimation system, where the particles with high oscilla-tion amplitudes or large momentum error are scraped from the beams. The particle loss level is typically optimized manually by changing control parameters, among which are currents in the focusing and defocusing magnets. It is generally challenging to model and predict losses based only on the control parameters, due to the presence of various (non-linear) effects in the system, such as electron clouds, resonance effects, etc., and multiple sources of uncertainty. At the same time understanding the influence of control parameters on the losses is extremely important in order to improve the operation and performance, and future design of accelerators. Prior work [1] showed that modeling the losses as an instantaneous function of the control parameters does not generalize well to data from a different year, which is an indication that the leveraged statistical associations are not capturing the actual mechanisms which should be invariant from 1 year to the next. Given that this is most likely due to lagged effects, we propose to model the losses as a function of not only instantaneous but also previously observed control parameters as well as previous loss values. Using a standard reparameterization, we reformulate the model as a Kalman Filter (KF) which allows for a flexible and efficient estimation procedure. We consider two main variants: one with a scalar loss output, and a second one with a 4D output with loss, horizontal and vertical emittances, and aggregated heatload as components. The two models once learned can be run for a number of steps in the future, and the second model can forecast the evolution of quantities that are relevant to predicting the loss itself. Our results show that the proposed models trained on the beam loss data from 2017 are able to predict the losses on a time horizon of several minutes for the data of 2018 as well and successfully identify both local and global trends in the losses.