bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD8 T cells are dispensable for experimental autoimmune prostatitis induction and chronic pelvic pain development
Authors: Salazar Florencia C. , Martinez Maria S. , Paira Daniela A. , Chocobar Yair A. , Olivera Carolina , Godoy Gloria J. , Acosta-Rodriguez Eva V. , Rivero Virginia E. , Motrich Ruben D. 
Published: May 2024

IntroductionChronic Pelvic Pain Syndrome or Chronic Prostatitis (CPPS/CP) is the most prevalent urologic affliction among young adult men. It is a challenging condition to treat, which significantly decreases patient quality of life, mostly because of its still uncertain aetiology. In that regard, an autoimmune origin is a prominent supported theory. Indeed, studies in patients and in rodent models of Experimental Autoimmune Prostatitis (EAP) have provided compelling evidence suggesting a key role of CD4 Th1 cells in disease pathogenesis. However, the implication of other prominent effectors of the immune system, such as CD8 T cells, has yet to be studied.MethodsWe herein analyzed the induction of prostatitis and the development of chronic pelvic pain in EAP using CD8 T cell-deficient animals.ResultsWe found similarly elevated PA-specific immune responses, with high frequencies of specific IFNg+CD4+ and IL17+CD4+ T cells in prostate draining lymph nodes from PA-immunized either CD8 KO or wild type animals with respect to controls. Moreover, these peripheral immune responses were paralleled by the development of significant chronic pelvic pain, and accompanied by prostate histological lesions, characterized by hemorrhage, epithelial cell desquamation, marked periglandular leukocyte infiltration, and increased collagen deposition in both, PA-immunized CD8 KO and wild type animals. As expected, control animals did not develop prostate histological lesions.DiscussionOur results indicate that CD8 T cells do not play a major role in EAP pathogenesis and chronic pelvic pain development. Moreover, our results corroborate the previous notion that a CD4 Th1 associated immune response drives the induction of prostate tissue inflammation and the development of chronic pelvic pain.
Protein kinase CK2α is overexpressed in classical hodgkin lymphoma, regulates key signaling pathways, PD-L1 and may represent a new target for therapy
Authors: Ruggeri Edoardo , Frezzato Federica , Mouawad Nayla , Pizzi Marco , Scarmozzino Federico , Capasso Guido , Trimarco Valentina , Quotti Tubi Laura , Cellini Alessandro , Cavarretta Chiara Adele , Ruocco Valeria , Serafin Andrea , Angotzi Francesco , Danesin Nicolò , Manni Sabrina , Facco Monica , Piazza Francesco , Trentin Livio , Visentin Andrea 
Published: May 2024

IntroductionIn classical Hodgkin lymphoma (cHL), the survival of neoplastic cells is mediated by the activation of NF-κB, JAK/STAT and PI3K/Akt signaling pathways. CK2 is a highly conserved serine/threonine kinase, consisting of two catalytic (α) and two regulatory (β) subunits, which is involved in several cellular processes and both subunits were found overexpressed in solid tumors and hematologic malignancies.Methods and resultsBiochemical analyses and in vitro assays showed an impaired expression of CK2 subunits in cHL, with CK2α being overexpressed and a decreased expression of CK2β compared to normal B lymphocytes. Mechanistically, CK2β was found to be ubiquitinated in all HL cell lines and consequently degraded by the proteasome pathway. Furthermore, at basal condition STAT3, NF-kB and AKT are phosphorylated in CK2-related targets, resulting in constitutive pathways activation. The inhibition of CK2 with CX-4945/silmitasertib triggered the de-phosphorylation of NF-κB-S529, STAT3-S727, AKT-S129 and -S473, leading to cHL cell lines apoptosis. Moreover, CX-4945/silmitasertib was able to decrease the expression of the immuno-checkpoint CD274/PD-L1 but not of CD30, and to synergize with monomethyl auristatin E (MMAE), the microtubule inhibitor of brentuximab vedotin.ConclusionsOur data point out a pivotal role of CK2 in the survival and the activation of key signaling pathways in cHL. The skewed expression between CK2α and CK2β has never been reported in other lymphomas and might be specific for cHL. The effects of CK2 inhibition on PD-L1 expression and the synergistic combination of CX-4945/silmitasertib with MMAE pinpoints CK2 as a high-impact target for the development of new therapies for cHL
Effectiveness of different booster vaccine combinations against SARS-CoV-2 during a six-month follow-up in Mexico and Argentina
Authors: Garza-Silva Arnulfo , Rivera-Salinas Diego , Rivera-Cavazos Andrea , Fernández-Chau Iván Francisco , Cepeda-Medina Andrea Belinda , Morales-Rodríguez Devany Paola , Barco-Flores Irene Antonieta , Sanz-Sánchez Miguel Ángel , Acciardi Cecilia , Paez-Bo Graciela , Teixeira Mauro M. , Azzolini Elena , Pozzi Chiara , Rescigno Maria , Romero-Ibarguengoitia Maria Elena 
Published: May 2024

IntroductionGiven the limited number of patients in Latin America who have received a booster dose against the COVID-19, it remains crucial to comprehend the effectiveness of different vaccine combinations as boosters in real-world scenarios. This study aimed to assess the real-life efficacy of seven different vaccine schemes against COVID-19, including BNT162b2, ChAdOx1-S, Gam-COVID-Vac, and CoronaVac as primary schemes with either BNT162b2 or ChAdOx1-S as booster vaccines.MethodsIn this multicentric longitudinal observational study, participants from Mexico and Argentina were followed for infection and SARS-CoV-2 Spike 1–2 IgG antibodies during their primary vaccination course and for 185 days after the booster dose.ResultsA total of 491 patients were included, and the booster dose led to an overall increase in the humoral response for all groups. Patients who received BNT162b2 exhibited the highest antibody levels after the third dose, while those with primary Gam-COVID-Vac maintained a higher level of antibodies after six months. Infection both before vaccination and after the booster dose, and Gam-COVIDVac + BNT162b2 combination correlated with higher antibody titers.DiscussionThe sole predictor of infection in the six-month follow-up was a prior COVID-19 infection before the vaccination scheme, which decreased the risk of infection, and all booster vaccine combinations conveyed the same amount of protection.
Microfibrillar-associated protein 4 interaction with inflammation and clinical characteristics in neuropsychiatric systemic lupus erythematosus
Authors: Wegener Maria Alexandra Bandehkhoda , Möller Sören , Olesen Mads Nikolaj , Madsen Jonna Skov , Sorensen Grith Lykke , Voss Anne , Asgari Nasrin 
Published: May 2024

ObjectivesCentral nervous system (CNS) proteins such as neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are released into the body fluids following CNS injury. Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein. Recently we reported expression of MFAP4 in CNS and alteration of levels in patients with acute neuroinflammation. We aimed to determine the levels of MFAP4 in a predominantly population-based cohort of systemic lupus erythematosus (SLE) patients, including neuropsychiatric SLE (NPSLE), and to evaluate MFAP4 as a marker of inflammation.MethodsIn total 208 SLE patients, 44 of those with NPSLE, and 50 age- and sex-matched healthy controls (HC) were recruited. MFAP4 was measured using AlphaLISA immunoassay. NfL, GFAP and a panel of inflammatory mediators were measured using Simoa HD-1 digital ELISA or a Luminex 200 instrument.ResultsMFAP4 levels were elevated in patients with NPSLE compared to patients with non-NPSLE (p = 0.031), more prominent in NPSLE patients with CNS involvement (p = 0.017). NfL and GFAP were higher in the total SLE cohort (p &lt; 0.001, p &lt; 0.001, respectively) as well as NPSLE subgroup (p &lt; 0.001, p &lt; 0.001, respectively), and in the subgroup of NPSLE patients with CNS involvement (p &lt; 0.001, p &lt; 0.001), compared to HC. NfL and GFAP levels correlated positively with MFAP4 in the NPSLE as well as the non-NPSLE subgroup (ρ = 0.44, p = 0.003, ρ = 0.25, p = 0.004). VEGF was reduced in NPSLE patients compared to HC (p = 0.015). MMP-9 was elevated in NPSLE compared to non-NPSLE (p = 0.048). Inflammatory markers including IFN-α, IL-6, IL-10 and TNF-α, were elevated in the NPSLE group compared to HC (p &lt; 0.001, p = 0.0026, p = 0.042, p = 0.007, respectively). In NPSLE patients the levels of MFAP4 correlated with TNF-α (p = 0.016) and IL-17 (p = 0.0044) and with markers of blood brain barrier (BBB) disruption MMP-7 (p = 0.005) and VEGF (p &lt; 0.001). In NPSLE patients with CNS manifestations MMP-3 and VEGF correlated with MFAP4 (p = 0.011, p = 0.0004, respectively).ConclusionLevels of MFAP4 correlated with NfL, GFAP and proinflammatory cytokines and in NPSLE additionally with markers of BBB disruption, suggesting that MFAP4 is a marker of inflammation and vascular re-organization. Correlation of NfL and GFAP with MFAP4 may reflect CNS tissue damage.
Electronic mechanical braking system executive mechanism design, calculation, and modeling based on dynamic control
Authors: Wu Xinping , He Rongnian , Ge Han , Chen Mengyu 
Published: May 2024

Introduction: As science and technology develop, automobiles are moving toward intelligence and electrification and need better braking systems.Methods: To improve the braking system’s response speed and braking effect, a longitudinal dynamics control system for automobiles based on the electronic mechanical braking system was proposed, and the electronic mechanical braking system was improved through automatic disturbance rejection control.Results: The experimental results show that the time required for achieving the target clamping force in the electronic mechanical braking system using self-disturbance rejection control and proportional integral differential control is only 0.01 s, but there is an issue of excessive control in the proportional integral differential system between 0.12 s and 0.2 s, while the self-disturbance rejection controller does not have this problem. Meanwhile, regardless of the interference applied, the electronic mechanical braking system with automatic disturbance rejection control can ensure that the clamping force does not fluctuate. In the joint simulation experiment, the expected acceleration and actual acceleration can remain consistent, and if the expected braking force is 9000 N, then the actual braking force of the electronic mechanical brake (EMB) is also 9000 N.Discussion: The above results indicate that the vehicle longitudinal dynamics control system using the electronic mechanical braking system not only responds fast but also has a good braking effect, avoiding the problem of excessive control and improving the driving experience.
Validation of the antibacterial effect of topically applied tranexamic acid using in vitro and in vivo models
Authors: Benjumea Antonio , Díaz-Navarro Marta , Gago-Campos Ángela Sai , Visedo Andrés , Hafian Rama , Cercenado Emilia , Sánchez-Somolinos Mar , Muñoz Patricia , Vaquero Javier , Chana Francisco , Guembe María 
Published: May 2024

BackgroundSeveral studies have shown that tranexamic acid (TXA), an antifibrinolytic, reduces postoperative infection rates. Recent in vitro research showed that TXA alone and in combination with vancomycin and gentamicin had a synergistic effect against some staphylococcal strains. In the present study, this synergistic effect was validated in samples from patients with staphylococcal periprosthetic infection (PPI) and in an in vivo model.MethodsWe tested 19 clinical strains (5 Staphylococcus aureus and 14 coagulase-negative staphylococci [CoNS]) against 10 mg/ml TXA alone and in combination with serial dilutions of vancomycin and gentamicin. The standardized microtiter plate method was used. The minimal inhibitory concentration (MIC) were calculated using standard visualization of well turbidity. We also used an S. aureus (ATCC29213) murine subcranial PPI model to compare the synergistic effect of TXA and gentamicin with that of TXA or gentamicin alone after 4 days of monitoring. The mice were euthanized, and disks were removed for analysis of cfu/ml counts and cell viability rate. Biofilm structure of both in vitro and in vivo samples was also analyzed using scanning electron microscopy (SEM).ResultsWhen TXA was combined with vancomycin or gentamicin, the MIC decreased in 30% of the strains studied. According to species, the MIC50 for vancomycin and gentamicin alone and in combination with TXA against S. aureus strains was the same. This was also the case for CoNS with vancomycin and its corresponding combination, whereas with gentamicin and TXA, a reduction in MIC50 was observed (2 dilutions). In addition, in the in vivo model, the mean (SD) log cfu/ml and cell viability rate obtained from the implant was lower in the group of mice treated with TXA and gentamicin than in those treated only with TXA or gentamicin. SEM images also corroborated our findings in strains in which the MIC was reduced, as well as the in the mice implants, with the area occupied by biofilm being greater in samples treated only with gentamicin or TXA than in those treated with TXA+gentamicin.ConclusionWe confirm that combining TXA with vancomycin or gentamicin exerts a synergistic effect. However, this only occurs in selected strains.
Progression-free survival estimation of docetaxel-based second-line treatment for advanced non-small cell lung cancer: a pooled analysis from 18 randomized control trials
Authors: N Chaithra , Jain Anisha , C Sahana , Shreevatsa Bhargav , Rajendrasozhan Saravanan , Dharmashekar Chandan , Suresh Kuralayanapalya Puttahonnappa , Patil Sharanagouda S. , Singh Pranav , Vishwanath Prashant , Srinivasa Chandrashekar , Kollur Shiva Prasad , Shivamallu Chandan 
Published: May 2024

BackgroundLung cancer is the foremost cause of cancer-related death globally, with non-small cell lung cancer (NSCLC) accounting for 85–90% of cases. Targeted therapy is the most essential therapeutic option for NSCLC, other common treatments include radiation therapy, surgery, chemotherapy, and immunotherapy.ObjectiveOur study objective was to estimate whether progression-free survival (PFS) is an outcome of NSCLC extracted from 18 randomized control trials (RCTs) with docetaxel as experimental group and antineoplastic agent, kinase inhibitor, and monoclonal antibodies as a control group.MethodsWe selected relevant studies published between 2011 and 2022 using Google Scholar, PubMed, Scopus, Science Direct, and Cochrane Library. Advanced NSCLC, chemotherapy, RCT, docetaxel, and second-line treatment were the terms included in the search. A total of 9738 patients were evaluated from the 18 identified studies. We used the meta package of R Studio to perform the meta-analysis. Graphical funnel plots were used to evaluate publication bias visually.ResultsPatients who underwent docetaxel-based therapy had a considerably longer PFS than those who got antineoplastic agents, kinase inhibitors, or monoclonal antibodies-based treatment. Patients in the standard treatment arm had a slightly longer PFS than those in the experimental therapy arm in the overall meta-analysis.ConclusionDocetaxel outperformed monoclonal antibodies, antineoplastic agents, and kinase inhibitors in the second-line therapy of advanced NSCLC since PFS was extensively utilized.
Immunohistochemistry analysis of PSMA expression at prostatic biopsy in high-risk prostate cancer: potential implications for PSMA-PET patient selection
Authors: Droghetti Matteo , Bianchi Lorenzo , Presutti Massimiliano , Vetrone Luigia , Farolfi Andrea , Mei Riccardo , Giunchi Francesca , Degiovanni Alessio , Mottaran Angelo , Piazza Pietro , Cangemi Danilo , Castellucci Paolo , D’Errico Antonietta , Schiavina Riccardo , Brunocilla Eugenio , Fanti Stefano 
Published: May 2024

IntroductionProstate-specific membrane antigen (PSMA) is a transmembrane protein expressed by normal prostatic tissue. Therefore, molecular imaging targeting PSMA (PSMA-PET) has gained particular interest and diffusion for PCa staging and restaging. Several factors may affect PSMA-PET results, and many tools have been proposed to improve patient selection. Furthermore, PSMA expression is not homogeneous among different tissues and within the prostate itself. The aims of this study were to evaluate immunohistochemistry (IHC) features of prostate biopsy samples and to assess their correlation with whole-mount specimens and PSMA-PET parameters.MethodsWe included consecutive high-risk PCa patients who underwent PSMA-PET for staging proposal at our institution from January 2022 to December 2022. The PET parameters selected were SUVmax, total volume (TV), and total lesion activity (TL). Each patient underwent multiparametric MRI (mpMRI) and fusion-targeted prostate biopsy prior to surgery. IHC analyses were performed on the index lesion cores. IHC visual score (VS) (1, 2, 3) and visual pattern (VP) (membranous, cytoplasmic, and combined) and the percentage of PSMA-negative tumor areas (PSMA%neg) within biopsy cores were evaluated.ResultsForty-three patients who underwent robotic radical prostatectomy after PSMA-PET were available for analyses. Concordance between VS and VP at biopsy and final pathology showed a Cohen’s kappa coefficient of 0.39 and 0.38, respectively. Patients with PSMA%neg &lt;20% had a higher concordance in VS and VP (Cohen’s kappa 0.49 and 0.4, respectively). No difference emerged in terms of median PSMA-TV (p = 0.3) and PSMA-TL (p = 0.9) according to VS at biopsy, while median SUVmax was higher in patients with VS 3 (p = 0.04). Higher SUVmax was associated with membranous and combined VP expression (p = 0.008). No difference emerged between patients with PSMA%neg &lt;20% or PSMA%neg &gt;20% on biopsy cores in terms of SUVmax, PSMA-TL, and PSMA-TV (p = 0.5, p = 0.5, and p = 0.9 respectively).ConclusionsWe found a correlation between IHC VS and VP on targeted biopsy cores and SUVmax at PSMA-PET. However, the correlation between the IHC parameters of biopsy cores and final pathology was not as high as expected. Nevertheless, the presence of PSMA%neg &lt;20% seems to have a better concordance in terms of visual score.
MAGENTA: a Multinational patient survey assessing the Awareness, perceptions and unmet needs in GENetic Testing and counselling among patients with breAst cancer
Authors: Powell Sarah , Artigas Marta , Borovova Irina , Gadiya Poorva , Hsu Alice , Kaur Ranjit , Kidd Lisa , Rosenfeld Denise , Saeed Mai Mohamed , Scarelli Evelin , Youssef Magdy Waheeb 
Published: May 2024

ObjectiveGenetic testing and counselling are critical in assessing breast cancer risk and tailoring treatment strategies. However, several barriers hinder patients from opting for genetic testing/counselling, leading to fewer than one-third of patients undergoing testing and even fewer being offered counselling. A granular understanding of these barriers is essential in overcoming them.MethodsA multinational survey developed by patient authors was conducted in 9 countries, to identify the specific local/regional barriers. The survey question pathway was individualized, based on responses to prior questions. Percentage responses to a response option were calculated based on the total number of respondents to that question. Chi-square tests were used to assess the significance of the results, if applicable.ResultsThe final analysis set (FAS) included 1,176 respondents, with a subset of this responding to all questions. In the FAS, 63% of respondents had undergone testing. Among those who got tested, 70% were offered testing. Among untested respondents, only 40% were offered the test but eventually did not get tested. In the tested population, 44% received counselling, which was significantly higher than 7% (p&lt;0.00001) in the untested group. Among those reporting on awareness, 71% reported awareness level between ‘very low’ and ‘moderate’ prior to cancer diagnosis. Most respondents (71%) agreed that all breast cancer patients should undergo testing before treatment initiation. However, Asian patients were less likely to endorse this view compared to respondents from other regions (25% vs ≥50%; p&lt;0.00001). A higher proportion of tested respondents were ‘very willing’ to get their family members tested (44%) versus untested respondents (11%), with relatively higher willingness among Australian (77%) and Russian respondents (56%), the regional variation being statistically significant (p&lt;0.00001).ConclusionsCritical gaps remain in the access, awareness and perceived value of genetic testing and counselling, with regional variance or difference between the tested and untested groups. Most patients are not offered counselling, which may be associated with the low uptake of testing. Strategic action is needed to drive policy-shaping and improve access to testing and counselling, including raising patient awareness and improving patient experience for better treatment outcomes.
Neoadjuvant chemotherapy prior to radical cystectomy for non-muscle invasive bladder cancer: national trends and pathologic outcomes
Authors: Davis Kailey , Orf Jeffrey , Ballon-Landa Eric , Hamilton Zachary 
Published: May 2024

BackgroundThere is a sparsity of literature on treatment outcomes for patients with non-muscle invasive bladder cancer (NMIBC) who received neoadjuvant chemotherapy (NAC). We aim to analyze the outcomes associated with the use of NAC prior to radical cystectomy for NMIBC utilizing the National Cancer Database.Materials/MethodsThe National Cancer Database bladder dataset was evaluated for patients with NMIBC and known pT staging undergoing RC from 2006–2016. The primary outcome was the utilization of NAC. The secondary outcomes were pathologic down staging to pT0, positive surgical margins, 30-day readmission, and overall survival.ResultsThe proportion of patients receiving NAC prior to radical cystectomy for NMIBC increased from 8.6% in 2006 to 14.8% in 2016. Those who received NAC had significantly higher tumor stages (cT1 vs cTa/is) with 85.7% of patients receiving NAC presenting with cT1 as opposed to only 82% in those not receiving NAC (p &lt; 0.001). Similarly, there were significantly more patients who were cN+ in the NAC group as compared to those who did not receive NAC (5.5% vs. 1.1%, p &lt; 0.001). For patients who received NAC, the rate of downstaging to pT0 was 12.7% as compared to only 3.3% in patients who did not receive NAC (p &lt; 0.001). There was no significant difference comparing the rates of positive margins or 30-day readmissions between groups. On multivariable logistic regression for pathologic downstaging, NAC was significant (OR 4.1, p &lt; 0.05). There was no significant difference in overall survival between patients treated with or without NAC.ConclusionNAC prior to RC in patients with NMIBC has increased in recent years and correlates with tumor downstaging. Further research is requisite to identify patients who obtain the greatest benefit of NAC in the NMIBC setting.