bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential immunomodulatory effects of epirubicin/cyclophosphamide and docetaxel in breast cancer patients
Authors: Wimmer Kerstin , Sachet Monika , Ramos Cristiano , Frantal Sophie , Birnleitner Hanna , Brostjan Christine , Exner Ruth , Filipits Martin , Bago-Horvath Zsuzsanna , Rudas Margaretha , Bartsch Rupert , Gnant Michael , Singer Christian F. , Balic Marija , Egle Daniel , Oehler Rudolf , Fitzal Florian 
Published: November 2023

Abstract
Background
Epirubicin/cyclophosphamide (EC) and docetaxel (D) are commonly used in a sequential regimen in the neoadjuvant treatment of early, high-risk or locally advanced breast cancer (BC). Novel approaches to increase the response rate combine this treatment with immunotherapies such as PD-1 inhibition. However, the expected stimulatory effect on lymphocytes may depend on the chemotherapy backbone. Therefore, we separately compared the immunomodulatory effects of EC and D in the setting of a randomized clinical trial.

Methods
Tumor and blood samples of 154 patients from the ABCSG-34 trial were available (76 patients received four cycles of EC followed by four cycles of D; 78 patients get the reverse treatment sequence). Tumor-infiltrating lymphocytes, circulating lymphocytes and 14 soluble immune mediators were determined at baseline and at drug change. Furthermore, six BC cell lines were treated with E, C or D and co-cultured with immune cells.

Results
Initial treatment with four cycles of EC reduced circulating B and T cells by 94% and 45%, respectively. In contrast, no comparable effects on lymphocytes were observed in patients treated with initial four cycles of D. Most immune mediators decreased under EC whereas D-treatment resulted in elevated levels of CXCL10, urokinase-type plasminogen activator (uPA) and its soluble receptor (suPAR). Accordingly, only the exposure of BC cell lines to D induced similar increases as compared to E. While treatment of BC cells with E was associated with cell shrinkage and apoptosis, D induced cell swelling and accumulation of cells in G2 phase.

Conclusion
The deleterious effect of EC on lymphocytes indicates strong immunosuppressive properties of this combination therapy. D, in contrast, has no effect on lymphocytes, but triggers the secretion of stimulatory proteins in vivo and in vitro, indicating a supportive effect on the immune system. Underlying differences in the induced cell death might be causal. These divergent immunomodulatory effects of epirubicin/cyclophosphamide and docetaxel should be considered when planning future combinations with immunotherapies in breast cancer.
Factors associated with pharmacological treatment in children with attention-deficit/hyperactivity disorders: a retrospective study of a series of 77 cases in a single third-level reference Centre in Apulia region
Authors: Amendola Simone , Fanizza Isabella , Scoditti Sara , De Rinaldis Marta , Trabacca Antonio 
Published: November 2023

Abstract
Background
The present study analysed data on children and adolescents with a diagnosis of attention-deficit/hyperactivity disorder (ADHD) who were referred to the ADHD reference centre of Scientific Institute IRCCS E. Medea (Brindisi, Italy) for ADHD pharmacotherapy initiation and monitoring overtime. The main aim of the study was to examine differences in pharmacological treatment status (i.e., treatment continuation vs discontinuation) between patients.

Methods
Seventy-seven children and adolescents (mean age at pharmacotherapy initiation = 9.5, standard deviation = 2.6) with ADHD received drugs treatment for ADHD at the reference center between January, 2013 and May, 2022. Demographic and clinical data were obtained from the Italian Registry for ADHD and medical records. Child Behavior Checklist (CBCL) available data were used.

Results
Pharmacological treatment status was examined for patients (n = 63) with at least 12 months of follow-up after the first pharmacological treatment for ADHD. After starting pharmacotherapy treatment, 77.8% (n = 49) patients were still on treatment whereas 22.2% (n = 14) discontinued it. No between group difference were observed in demographic and clinical data except for the intelligence quotient/intellectual disability and rule-breaking behavior (n = 40).

Conclusions
This study stressed the need of periodical assessments, monitoring difficulties with treatment and/or reasons for poor treatment compliance to provide individualized care.
Crusted scabies in a rabbit model: a severe skin disease or more?
Authors: Sharaf Mahmoud Shafeik , Othman Ahmad Ali , Abdel-Ghaffar Amira Elsayed , Ali Dareen Mohamed , Eid Mohamed Mahmoud 
Published: November 2023

Abstract
Background
Around 200–300 million people are estimated to be affected by scabies annually worldwide. However, the mechanisms by which this disease may affect the general condition of the host are not entirely clear. The aim of the present study was to evaluate the systemic changes that may accompany crusted scabies in both treated and non-treated experimental animals.

Methods
Male New Zealand rabbits were infected with Sarcoptes scabiei var. cuniculi and divided into the following three groups: control, ivermectin-treated, and fluralaner-treated. Several methods were used to evaluate the systemic changes, including histopathological examination of the liver, kidney, heart, and spleen, as well as the measurement of serum biochemical parameters and immunological parameters.

Results
Several definite structural and functional changes at the systemic level were revealed, as evidenced by the observed histopathological changes in the tissue sections of internal organs and the highly significant increases in markers of systemic inflammation, serum procalcitonin, and oxidative stress markers. Abnormalities in the liver and renal function results, as well as in the serum lipid profile, were also noted. Additionally, a disorganized immune response was noted, evidenced by a mixed type 1 and type 2 helper T cell response. Although there was notable clinical and parasitological cure in the ivermectin-treated group, the histopathological, biochemical, and immunological markers indicated incomplete resolution. In contrast, the fluralaner-treated group exhibited a nearly complete resolution of changes in these parameters.

Conclusions
We conclude that crusted scabies is a systemic syndrome that can affect several organs besides the skin. Inflammation, oxidative stress, and possibly bacterial infections, are all implicated as underlying mechanisms of tissue damage due to the disease. We recommend that fluralaner, a promising scabicidal agent, should be studied for possible human use, and especially for control programs.

Graphical Abstract
Adenosine triphosphate overrides the aversive effect of antifeedants and toxicants: a model alternative phagostimulant for sugar-based vector control tools
Authors: Lukenge Matthew , Ignell Rickard , Hill Sharon Rose 
Published: November 2023

Abstract
Background
Sugar, when used as the phagostimulant in attractive toxic bait control tools, limits the efficacy and selectivity of this technology. Thus, more potent and selective phagostimulants than sugar are required to improve this technology. The potency of adenosine triphosphate (ATP) as an alternative model phagostimulant was assessed to determine its capacity to override the aversive effects of select antifeedants and toxicants. How ATP and sucrose modulate the rate of toxicity in the yellow fever mosquito Aedes aegypti was also examined.

Methods
A no-choice feeding assay was used to investigate the phagostimulatory ability of ATP to override the aversive effects of structurally divergent antifeedant and toxicant compounds, and to modulate the rate of toxicity over 24 h. Binary combinations of antifeedant and toxicant compounds, at various concentrations, were similarly assessed for enhanced lethal potency. In comparison, no-choice open access and cotton wick feeding assays were used to determine the phagostimulatory role of sucrose in the ingestion of boric acid-laced diets. Dissections of the guts were performed to determine the diet destination as dependant on the phagostimulant.

Results
ATP is a potent phagostimulant that dose dependently overrides aversion to antifeedant and toxicant tastants. Feeding on antifeedant- or toxicant-laced diets that was induced by ATP selectively resulted in rapid knockdown (nicotine, lobeline and caffeine) or death (boric acid and propylene glycol), with a combination of the two lethal compounds inducing a synergistic effect at lower concentrations. ATP- and sucrose-induced feeding predominantly directed the antifeedant- or toxicant-laced meals to the midgut and the crop, respectively.

Conclusions
ATP is an efficacious alternative model phagostimulant to sucrose that overrides the aversive effects of antifeedants and toxicants, resulting in rapid toxic effects. Furthermore, this study demonstrates that variation in the rate of toxicity between ATP- and sugar-induced feeding is at least partly regulated by the differential feeding response, volume imbibed and the destination of the meals. Additional research is needed to identify structurally related, stable analogues of ATP due to the ephemeral nature of this molecule. For future applications, the workflow presented in this study may be used to evaluate such analogues for their suitability for use in attractive bait stations designed to target a broad range of haematophagous arthropods and prevent off-target species’ feeding.

Graphical Abstract
Genome sequence of a virulent and hypermucoviscous-like Klebsiella michiganensis clinical isolate
Authors: Alvarado-Delgado Alejandro , Rodríguez-Medina Nadia , Sánchez-Pérez Alejandro , Tamayo-Legorreta Elsa María , Cerón-Lopez Jackeline , Morfin-Otero Rayo , Garza-Ramos Ulises 
Published: November 2023

Abstract
Objectives
The hypermucoviscous-like phenotype has been described in Klebsiella pneumoniae species complex (KpSC) and was described as a contributor of increased virulence. This study described the characterization and whole-genome sequencing of an antibiotic susceptible and hypermucoviscous-like Klebsiella michiganensis 9273 clinical isolate.

Data description
Here, we report the genome sequence of a K. michiganensis clinical isolate obtained from a urinary tract infection exhibiting the hypermucoviscous-like phenotype. The draft genome sequence consisted of 145 contigs and ~ 6.6 Mb genome size. The annotation revealed 6648 coding DNA sequences and 56 tRNA genes. The strain belongs to the sequence type (ST) 50, and the OXY-1 beta-lactam resistance gene, aph(3′)-Ia gene for aminoglycoside resistance and multidrug efflux pumps were identified. The fyuA siderophore receptor of yersiniabactin siderophore was identified. Increased virulence was observed in Galleria mellonella larvae model and increased capsule production was determined by uronic acid quantification. The clinical implications of this phenotype are unknown, but the patient outcome might worsen compared to susceptible- or MDR-classical K. michiganensis isolates.
Computed tomography-based thermography (CTT) in microwave ablation: prediction of the heat ablation zone in the porcine liver
Authors: Kostyrko Bogdan , Rubarth Kerstin , Althoff Christian , Poch Franz Gerd Martin , Neizert Christina Ann , Zibell Miriam , Gebauer Bernhard , Lehmann Kai Siegfried , Niehues Stefan Markus , Mews Jürgen , Diekhoff Torsten , Pohlan Julian 
Published: November 2023

Abstract
Objectives
The aim of the study was to investigate computed tomography-based thermography (CTT) for ablation zone prediction in microwave ablation (MWA).

Methods
CTT was investigated during MWA in an in vivo porcine liver. For CTT, serial volume scans were acquired every 30 s during ablations and every 60 s immediately after MWA. After the procedure, contrast-enhanced computed tomography (CECT) was performed. After euthanasia, the liver was removed for sampling and further examination. Color-coded CTT maps were created for visualization of ablation zones, which were compared with both CECT and macroscopy. Average CT attenuation values in Hounsfield units (HU) were statistically correlated with temperatures using Spearman’s correlation coefficient. CTT was retrospectively evaluated in one patient who underwent radiofrequency ablation (RFA) treatment of renal cell carcinoma.

Results
A significant correlation between HU and temperature was found with r =  − 0.77 (95% confidence interval (CI), − 0.89 to − 0.57) and p < 0.001. Linear regression yielded a slope of − 1.96 HU/°C (95% CI, − 2.66 to − 1.26). Color-coded CTT maps provided superior visualization of ablation zones.

Conclusion
Our results show that CTT allows visualization of the ablation area and measurement of its size and is feasible in patients, encouraging further exploration in a clinical setting.

Critical relevance statement
CT-based thermography research software allows visualization of the ablation zone and is feasible in patients, encouraging further exploration in a clinical setting to assess risk reduction of local recurrence.

Graphical Abstract
Preoperative prediction of cholangiocyte phenotype hepatocellular carcinoma on contrast-enhanced MRI and the prognostic implication after hepatectomy
Authors: Chen Yidi , Chen Jie , Yang Chongtu , Wu Yuanan , Wei Hong , Duan Ting , Zhang Zhen , Long Liling , Jiang Hanyu , Song Bin 
Published: November 2023

AbstractBackgroundHepatocellular carcinoma (HCC) expressing cytokeratin (CK) 7 or CK19 has a cholangiocyte phenotype that stimulates HCC proliferation, metastasis, and sorafenib therapy resistance This study aims to noninvasively predict cholangiocyte phenotype-positive HCC and assess its prognosis after hepatectomy.MethodsBetween January 2010 and May 2022, preoperative contrast-enhanced MRI was performed on consecutive patients who underwent hepatectomy and had pathologically confirmed solitary HCC. Two abdominal radiologists separately assessed the MRI features. A predictive model for cholangiocyte phenotype HCC was created using logistic regression analysis and five-fold cross-validation. A receiver operating characteristic curve was used to calculate the model performance. Kaplan–Meier and log-rank methods were used to evaluate survival outcomes.ResultsIn total, 334 patients were included in this retrospective study. Four contrast-enhanced MRI features, including “rim arterial phase hyperenhancement” (OR = 5.9, 95% confidence interval [CI]: 2.9–12.0, 10 points), “nodule in nodule architecture” (OR = 3.5, 95% CI: 2.1–5.9, 7 points), “non-smooth tumor margin” (OR = 1.6, 95% CI: 0.8–2.9, 3 points), and “non-peripheral washout” (OR = 0.6, 95% CI: 0.3–1.0, − 3 points), were assigned to the cholangiocyte phenotype HCC prediction model. The area under the curves for the training and independent validation set were 0.76 and 0.73, respectively. Patients with model-predicted cholangiocyte phenotype HCC demonstrated lower rates of recurrence-free survival (RFS) and overall survival (OS) after hepatectomy, with an estimated median RFS and OS of 926 vs. 1565 days (p < 0.001) and 1504 vs. 2960 days (p < 0.001), respectively.ConclusionsContrast-enhanced MRI features can be used to predict cholangiocyte phenotype-positive HCC. Patients with pathologically confirmed or MRI model-predicted cholangiocyte phenotype HCC have a worse prognosis after hepatectomy.Critical relevance statementFour contrast-enhanced MRI features were significantly associated with cholangiocyte phenotype HCC and a worse prognosis following hepatectomy; these features may assist in predicting prognosis after surgery and improve personalized treatment decision-making.Key points• Four contrast-enhanced MRI features were significantly associated with cholangiocyte phenotype HCC.• A noninvasive cholangiocyte phenotype HCC predictive model was established based on MRI features.• Patients with cholangiocyte phenotype HCC demonstrated a worse prognosis following hepatic resection.Graphical Abstract
ADSC secretome constrains NK cell activity by attenuating IL-2-mediated JAK-STAT and AKT signaling pathway via upregulation of CIS and DUSP4
Authors: Ko Eunhee , Yoon Taejun , Lee Yoojin , Kim Jongsun , Park Yong-Beom 
Published: November 2023

Abstract
Background
Mesenchymal stem cells (MSCs) have immunomodulatory properties and therapeutic effects on autoimmune diseases through their secreted factors, referred to as the secretome. However, the specific key factors of the MSC secretome and their mechanisms of action in immune cells have not been fully determined. Most in vitro experiments are being performed using immune cells, but experiments using natural killer (NK) cells have been neglected, and a few studies using NK cells have shown discrepancies in results. NK cells are crucial elements of the immune system, and adjustment of their activity is essential for controlling various pathological conditions. The aim of this study was to elucidate the role of the adipose tissue-derived stem cell (ADSC) secretome on NK cell activity.

Methods
To obtain the ADSC secretome, we cultured ADSCs in medium and concentrated the culture medium using tangential flow filtration (TFF) capsules. We assessed NK cell viability and proliferation using CCK-8 and CFSE assays, respectively. We analyzed the effects of the ADSC secretome on NK cell activity and pathway-related proteins using a combination of flow cytometry, ELISA, cytotoxicity assay, CD107a assay, western blotting, and quantitative real-time PCR. To identify the composition of the ADSC secretome, we performed LC–MS/MS profiling and bioinformatics analysis. To elucidate the molecular mechanisms involved, we used mRNA sequencing to profile the transcriptional expression of human blood NK cells.

Results
The ADSC secretome was found to restrict IL-2-mediated effector function of NK cells while maintaining proliferative potency. This effect was achieved through the upregulation of the inhibitory receptor CD96, as well as downregulation of activating receptors and IL-2 receptor subunits IL-2Rα and IL-2Rγ. These changes were associated with attenuated JAK-STAT and AKT pathways in NK cells, which were achieved through the upregulation of cytokine-inducible SH2-containing protein (CIS, encoded by Cish) and dual specificity protein phosphatase 4 (DUSP4). Furthermore, proteomic analysis revealed twelve novel candidates associated with the immunomodulatory effects of MSCs.

Conclusions
Our findings reveal a detailed cellular outcome and regulatory mechanism of NK cell activity by the ADSC secretome and suggest a therapeutic tool for treating NK-mediated inflammatory and autoimmune diseases using the MSC secretome.
Sex-based differences in natural killer T cell-mediated protection against diet-induced steatohepatitis in Balb/c mice
Authors: Cuño-Gómiz Carlos , de Gregorio Estefanía , Tutusaus Anna , Rider Patricia , Andrés-Sánchez Nuria , Colell Anna , Morales Albert , Marí Montserrat 
Published: November 2023

Abstract
Background
Metabolic dysfunction-associated steatotic liver disease (MASLD) is prevalent in Western countries, evolving into metabolic dysfunction-associated steatohepatitis (MASH) with a sexual dimorphism. Fertile women exhibit lower MASLD risk than men, which diminishes post-menopause. While NKT-cell involvement in steatohepatitis is debated, discrepancies may stem from varied mouse strains used, predominantly C57BL6/J with Th1-dominant responses. Exploration of steatohepatitis, encompassing both genders, using Balb/c background, with Th2-dominant immune response, and CD1d-deficient mice in the Balb/c background (lacking Type I and Type II NKT cells) can clarify gender disparities and NKT-cell influence on MASH progression.

Methods
A high fat and choline-deficient (HFCD) diet was used in male and female mice, Balb/c mice or CD1d−/− mice in the Balb/c background that exhibit a Th2-dominant immune response. Liver fibrosis and inflammatory gene expression were measured by qPCR, and histology assessment. NKT cells, T cells, macrophages and neutrophils were assessed by flow cytometry.

Results
Female mice displayed milder steatohepatitis after 6 weeks of HFCD, showing reduced liver damage, inflammation, and fibrosis compared to males. Male Balb/c mice exhibited NKT-cell protection against steatohepatitis whereas CD1d−/− males on HFCD presented decreased hepatoprotection, increased liver fibrosis, inflammation, neutrophilic infiltration, and inflammatory macrophages. In contrast, the NKT-cell role was negligible in early steatohepatitis development in both female mice, as fibrosis and inflammation were similar despite augmented liver damage in CD1d−/− females. Relevant, hepatic type I NKT levels in female Balb/c mice were significantly lower than in male.

Conclusions
NKT cells exert a protective role against experimental steatohepatitis as HFCD-treated CD1d−/− males had more severe fibrosis and inflammation than male Balb/c mice. In females, the HFCD-induced hepatocellular damage and the immune response are less affected by NKT cells on early steatohepatitis progression, underscoring sex-specific NKT-cell influence in MASH development.
Coffee as a dietary strategy to prevent SARS-CoV-2 infection
Authors: Wu Chen-Shiou , Li Yi-Chuan , Peng Shin-Lei , Chen Chung-Yu , Chen Hsiao-Fan , Hsueh Po-Ren , Wang Wei-Jan , Liu Yen-Yi , Jiang Ciao-Ling , Chang Wei-Chao , Wang Shao-Chun , Hung Mien-Chie 
Published: November 2023

Abstract
Background
To date, most countries lifted the restriction requirement and coexisted with SARS-CoV-2. Thus, dietary behavior for preventing SARS-CoV-2 infection becomes an interesting issue on a daily basis. Coffee consumption is connected with reduced COVID-19 risk and correlated to COVID-19 severity. However, the mechanisms of coffee for the reduction of COVID-19 risk are still unclear.

Results
Here, we identified that coffee can inhibit multiple variants of the SARS-CoV-2 infection by restraining the binding of the SARS-CoV-2 spike protein to human angiotensin-converting enzyme 2 (ACE2), and reducing transmembrane serine protease 2 (TMPRSS2) and cathepsin L (CTSL) activity. Then, we used the method of "Here" (HRMS-exploring-recombination-examining) and found that isochlorogenic acid A, B, and C of coffee ingredients showed their potential to inhibit SARS-CoV-2 infection (inhibitory efficiency 43–54%). In addition, decaffeinated coffee still preserves inhibitory activity against SARS-CoV-2. Finally, in a human trial of 64 subjects, we identified that coffee consumption (approximately 1–2 cups/day) is sufficient to inhibit infection of multiple variants of SARS-CoV-2 entry, suggesting coffee could be a dietary strategy to prevent SARS-CoV2 infection.

Conclusions
This study verified moderate coffee consumption, including decaffeination, can provide a new guideline for the prevention of SARS-CoV-2. Based on the results, we also suggest a coffee-drinking plan for people to prevent infection in the post-COVID-19 era.