bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypoxic glioblastoma-cell-derived extracellular vesicles impair cGAS-STING activity in macrophages
Authors: Tankov Stoyan , Petrovic Marija , Lecoultre Marc , Espinoza Felipe , El-Harane Nadia , Bes Viviane , Chliate Sylvie , Bedoya Darel Martinez , Jordan Olivier , Borchard Gerrit , Migliorini Denis , Dutoit Valérie , Walker Paul R. 
Published: February 2024

Abstract
Background
Solid tumors such as glioblastoma (GBM) exhibit hypoxic zones that are associated with poor prognosis and immunosuppression through multiple cell intrinsic mechanisms. However, release of extracellular vesicles (EVs) has the potential to transmit molecular cargos between cells. If hypoxic cancer cells use EVs to suppress functions of macrophages under adequate oxygenation, this could be an important underlying mechanism contributing to the immunosuppressive and immunologically cold tumor microenvironment of tumors such as GBM.

Methods
EVs were isolated by differential ultracentrifugation from GBM cell culture supernatant. EVs were thoroughly characterized by transmission and cryo-electron microscopy, nanoparticle tracking analysis (NTA), and EV marker expression by Western blot and fluorescent NTA. EV uptake by macrophage cells was observed using confocal microscopy. The transfer of miR-25/93 as an EV cargo to macrophages was confirmed by miRNA real-time qPCR. The impact of miR-25/93 on the polarization of recipient macrophages was shown by transcriptional analysis, cytokine secretion and functional assays using co-cultured T cells.

Results
We show that indirect effects of hypoxia can have immunosuppressive consequences through an EV and microRNA dependent mechanism active in both murine and human tumor and immune cells. Hypoxia enhanced EV release from GBM cells and upregulated expression of miR-25/93 both in cells and in EV cargos. Hypoxic GBM-derived EVs were taken up by macrophages and the miR-25/93 cargo was transferred, leading to impaired cGAS-STING pathway activation revealed by reduced type I IFN expression and secretion by macrophages. The EV-treated macrophages downregulated expression of M1 polarization-associated genes Cxcl9, Cxcl10 and Il12b, and had reduced capacity to attract activated T cells and to reactivate them to release IFN-γ, key components of an efficacious anti-tumor immune response.

Conclusions
Our findings suggest a mechanism by which immunosuppressive consequences of hypoxia mediated via miRNA-25/93 can be exported from hypoxic GBM cells to normoxic macrophages via EVs, thereby contributing to more widespread T-cell mediated immunosuppression in the tumor microenvironment.
Proteomic analysis of decellularized mice liver and kidney extracellular matrices
Authors: Diedrich Anna-Maria , Daneshgar Assal , Tang Peter , Klein Oliver , Mohr Annika , Onwuegbuchulam Olachi A. , von Rueden Sabine , Menck Kerstin , Bleckmann Annalen , Juratli Mazen A. , Becker Felix , Sauer Igor M. , Hillebrandt Karl H. , Pascher Andreas , Struecker Benjamin 
Published: February 2024

Abstract
Background
The extracellular matrix (ECM) is a three-dimensional network of proteins that encases and supports cells within a tissue and promotes physiological and pathological cellular differentiation and functionality. Understanding the complex composition of the ECM is essential to decrypt physiological processes as well as pathogenesis. In this context, the method of decellularization is a useful technique to eliminate cellular components from tissues while preserving the majority of the structural and functional integrity of the ECM.

Results
In this study, we employed a bottom-up proteomic approach to elucidate the intricate network of proteins in the decellularized extracellular matrices of murine liver and kidney tissues. This approach involved the use of a novel, perfusion-based decellularization protocol to generate acellular whole organ scaffolds. Proteomic analysis of decellularized mice liver and kidney ECM scaffolds revealed tissue-specific differences in matrisome composition, while we found a predominantly stable composition of the core matrisome, consisting of collagens, glycoproteins, and proteoglycans. Liver matrisome analysis revealed unique proteins such as collagen type VI alpha-6, fibrillin-2 or biglycan. In the kidney, specific ECM-regulators such as cathepsin z were detected.

Conclusion
The identification of distinct proteomic signatures provides insights into how different matrisome compositions might influence the biological properties of distinct tissues. This experimental workflow will help to further elucidate the proteomic landscape of decellularized extracellular matrix scaffolds of mice in order to decipher complex cell–matrix interactions and their contribution to a tissue-specific microenvironment.
Seroma control in axillary lymphadenectomy with Glubran 2® without drain. Multicenter, prospective, randomized, clinical trial. GALA-ND study (Glubran, Axillary Lymphadenectomy, Ambulatory, No Drain)
Authors: López Gordo Sandra , Ruiz-Edo Neus , Fernández-Planas Maria Teresa , Viscaya-Martín Sara , Serra-Serra Cristina ,   Breast Cancer Research Group, Buqueras Carmen , Recaj Mireia , Guerrero-López Raul , Blay-Aulina Lidia , Aparicio-Rodriguez Oscar , Cusiné Laura , Mira Xavier , Clos Montserrat , Alonso Immaculada , Cortés Prados Jairo , Espinoza Villalobos Sofía , Vallejo-Barnosell Elena , Espinoza-Villalobos A. S. , Jimenez Marta , Carrasquer-Puyal Aurora , Holub Priscila Giselle , Cases Baldo Maria José , Garcia de Castro R E. , Herrador Garcia Inmaculada , Esposito Emanuela , Garcia de Castro Rubio E. , Gonzalez Duaigues Marta Lourdes 
Published: February 2024

Abstract
Background
Seroma after breast cancer surgery is a frequent entity; therefore, different products have been described in literature with the aim to reduce it. The most studied ones have been the sealants products, being tested with aspirative drains. Symptomatic seroma represents the 19% after axillary lymphadenectomy without drains. The aim of this study is to analyze the effect of a sealant in the seroma control after axillary lymphadenectomy without drains and identify the risk factors related to symptomatic seroma.

Methods
This is a prospective, multicenter, international, and randomized clinical trial. Patients undergoing conservative surgery and axillary lymphadenectomy for breast cancer will be randomized to control group (lymphadenectomy without sealant) or interventional group (lymphadenectomy with sealant Glubran 2®). In any of the study groups, drains are placed. Patients who received neoadjuvant treatment are included. Measurements of the study outcomes will take place at baseline; at 7, 14, and 30 days post-surgery; and at 6–12 months. The primary outcome is symptomatic seroma. Secondary outcomes are seroma volume, morbidity, quality of life, and lymphedema.

Discussion
Several studies compare the use of sealant products in axillary lymphadenectomy but generally with drains. We would like to demonstrate that patients who underwent axillary lymphadenectomy could benefit from an axillary sealant without drains and reduce axillary discomfort while maintaining a good quality of life. Assessing the relationship between axillary volume, symptoms, and related risk factors can be of great help in the control of seroma in patients who received breast cancer surgery.

Trial registration
ClinicalTrials.gov, NCT05280353. Registration date 02 August 2022.
Ultrasound contrast agent assisted ultrasonography guidance percutaneous nephrostomy for non-hydronephrotic kidney
Authors: Jiao Weijie , Gong Xue , Sun Yuanyuan , Sang Lin , Ding Xiaoying , Yu Ming 
Published: February 2024

Abstract
Background
Given the limited success rate and considerable challenges associated with conventional ultrasonography (US) guidance for percutaneous nephrostomy (PCN) in non-hydronephrotic kidneys, this study proposed a solution with ultrasound contrast agent to enhance the success rate and mitigate the difficulties.

Materials and Methods
From January 2017 to August 2023, a total of thirteen patients diagnosed with non-hydronephrotic kidney were included in the study. Following routine ultrasonography examination, no significant dilatation of the renal collecting system was observed. US-guided percutaneous nephrostomy PCN was performed with the assistance of ultrasound contrast agent (UCA). The patients were subsequently monitored to assess the improvement of symptoms and postoperative recovery.

Results
The success rate was found to be 100% for all patients (13/13) and kidneys (20/20). The average volume of UCA solution used was 19 ± 6.7 mL (range, 11–35 mL), while the mean duration of the operation was 18.92 ± 8.96 min (range, 7–36 min). A majority of the patients (12/13) underwent a single puncture procedure. Throughout the follow-up period, no serious complications were observed, and surgery resulted in significant alleviation of symptoms in all patients.

Conclusion
The use of UCA-assisted US guidance PCN has been shown to be effective in achieving urinary diversion and alleviating associated clinical symptoms in non-hydronephrotic kidneys. In comparison to traditional methods, this approach demonstrates a high success rate and safety profile, while also offering a simplified operative procedure. Consequently, it presents a novel method and concept for managing non-hydronephrotic kidneys afflicted by urine leakage.
Isolation and characterization of coliphages from different water sources and their biocontrol application combined with electron beam irradiation for elimination of E. coli in domestic wastewater
Authors: Fathy Reham , Eid Amal S. , Hammad Ali A. , El-Nour Salwa A. Abou 
Published: February 2024

Abstract
Background
Antibiotic-resistant bacteria, including Escherichia coli (E. coli), are high-risk waterborne pathogens that pose a vital threat to the general public’s health. Therefore, this study aims to develop alternative and affordable treatment approaches. Coliphage treatment is an economically and environmentally sustainable method for eliminating pathogenic bacteria. A significant step toward improving germicidal effectiveness might be to combine coliphage with electron beam treatment.

Results
Twelve isolated E. coli were used as host bacteria. In addition, eleven coliphages were isolated and characterized to determine their suitable host range and lytic activities. Antibiotic resistance was tested to detect the most antimicrobial-resistant E. coli isolates. Results indicated that E. coli-2 and E. coli-10 were the most resistant bacterial isolates. Both somatic coliphage-3 (S3) and F-specific coliphage-3 (F3) were the most active lytic coliphages. Based on transmission electron microscope analysis, S3 was classified as a member of the Myoviridae family, while F3 belonged to the Leviviridae family. Genome types were detected; the S3 genome was a linear double-stranded DNA virus, while the F3 genome was a single-strand RNA virus. The adjustment of pH to 7 and temperature to 38 °C increased coliphage activity by 32.2% for S3 and 14% for F3. The optimum multiplicity of infection (MOI) for S3 was 1:1 and 2:1 for F3. From the one-step growth curve, both the latent periods of S3 and F3 were estimated to be 30 and 20 min, and the burst sizes showed 5.8 and 4.6 (PFU)/infected cells, respectively. The D10 values of the most two antimicrobial-resistant strains (E. coli-2 and E. coli-10) were calculated, showing nearly identical values (0.37 and 0.38 kGy), respectively. Both coliphages were used, either alone or in combination with electron beam irradiation (EBI), to eradicate the most multidrug-resistant E. coli in domestic wastewater. EBI reduced the counts of E. coli-2 and -10 by 59% and 65%, respectively. While the combination of coliphages and EBI completely eradicated these microbes.

Conclusions
Combination of each individual coliphage and EBI decreased the growth of E. coli in domestic wastewater to an undetectable level.

Graphical Abstract
Pembrolizumab-induced myocarditis with complete atrioventricular block and concomitant myositis in a metastatic bladder cancer patient: a case report and review of the literature
Authors: Saad R. , Ghaddar A. , Zeenny R. M. 
Published: February 2024

Abstract
Background
The cardiovascular system is among the least systems affected by immune-related adverse events. We report a rare life-threatening case of pembrolizumab-induced myocarditis with complete atrioventricular block and concomitant myositis in a metastatic bladder cancer patient.

Case presentation
An 82-year-old Caucasian female with invasive urothelial carcinoma, started on first-line pembrolizumab, was admitted four days after receiving her second dose for severe asthenia, diffuse muscle aches, neck pain, and lethargy. In the emergency department, she had several episodes of bradycardia reaching 40 beats per minute associated with general discomfort and fatigue. Electrocardiography showed a third-degree atrioventricular heart block, while the patient remained normotensive. Cardiac damage parameters were altered with elevated levels of creatine phosphokinase of 8930 U/L, suggestive of immune checkpoint inhibitor-induced myositis, and troponin T of 1.060 ng/mL. Transthoracic echocardiography showed a preserved ejection fraction. Pembrolizumab-induced myocarditis was suspected. Therefore, treatment was initiated with high-dose glucocorticoids for 5 days, followed by a long oral steroid taper. A pacemaker was also implanted. Treatment resulted in the resolution of heart block and a decrease in creatine phosphokinase to the normal range.

Conclusion
Life-threatening cardiac adverse events in the form of myocarditis may occur with pembrolizumab use, warranting vigilant cardiac monitoring. Troponin monitoring in high-risk patients, along with baseline echocardiography may help identify this complication promptly to prevent life-threatening consequences.
Phenotypically concordant distribution of pick bodies in aphasic versus behavioral dementias
Authors: Kawles Allegra , Keszycki Rachel , Minogue Grace , Zouridakis Antonia , Ayala Ivan , Gill Nathan , Macomber Alyssa , Lubbat Vivienne , Coventry Christina , Rogalski Emily , Weintraub Sandra , Mao Qinwen , Flanagan Margaret E. , Zhang Hui , Castellani Rudolph , Bigio Eileen H. , Mesulam M.-Marsel , Geula Changiz , Gefen Tamar 
Published: February 2024

AbstractPick’s disease (PiD) is a subtype of the tauopathy form of frontotemporal lobar degeneration (FTLD-tau) characterized by intraneuronal 3R-tau inclusions. PiD can underly various dementia syndromes, including primary progressive aphasia (PPA), characterized by an isolated and progressive impairment of language and left-predominant atrophy, and behavioral variant frontotemporal dementia (bvFTD), characterized by progressive dysfunction in personality and bilateral frontotemporal atrophy. In this study, we investigated the neocortical and hippocampal distributions of Pick bodies in bvFTD and PPA to establish clinicopathologic concordance between PiD and the salience of the aphasic versus behavioral phenotype. Eighteen right-handed cases with PiD as the primary pathologic diagnosis were identified from the Northwestern University Alzheimer’s Disease Research Center brain bank (bvFTD, N = 9; PPA, N = 9). Paraffin-embedded sections were stained immunohistochemically with AT8 to visualize Pick bodies, and unbiased stereological analysis was performed in up to six regions bilaterally [middle frontal gyrus (MFG), superior temporal gyrus (STG), inferior parietal lobule (IPL), anterior temporal lobe (ATL), dentate gyrus (DG) and CA1 of the hippocampus], and unilateral occipital cortex (OCC). In bvFTD, peak neocortical densities of Pick bodies were in the MFG, while the ATL was the most affected in PPA. Both the IPL and STG had greater leftward pathology in PPA, with the latter reaching significance (p < 0.01). In bvFTD, Pick body densities were significantly right-asymmetric in the STG (p < 0.05). Hippocampal burden was not clinicopathologically concordant, as both bvFTD and PPA cases demonstrated significant hippocampal pathology compared to neocortical densities (p < 0.0001). Inclusion-to-neuron analyses in a subset of PPA cases confirmed that neurons in the DG are disproportionately burdened with inclusions compared to neocortical areas. Overall, stereological quantitation suggests that the distribution of neocortical Pick body pathology is concordant with salient clinical features unique to PPA vs. bvFTD while raising intriguing questions about the selective vulnerability of the hippocampus to 3R-tauopathies.
Participation in cardiovascular screening consultations, the who, when and why - A cohort study on patients with rheumatoid arthritis
Authors: Karstensen Julie Katrine , Bremander Ann , Christensen Jeanette Reffstrup , Primdahl Jette 
Published: February 2024

Abstract
Background
In accordance with the EULAR recommendations, the Danish Hospital for Rheumatic Diseases have systematically invited patients with rheumatoid arthritis (RA) to cardiovascular (CV) risk assessment since 2011. Patients with high risk are invited to a follow-up screening after one year. To optimize the screening and tailor it to individual needs, information about who accepts vs. declines follow-up is needed. Thus, the aim of this study was to explore participation in systematic CV risk assessment among patients with RA. Furthermore, to explore differences between patients with low vs. high risk, and between patients with high risk who accept vs. decline follow-up.

Methods
Data from 2,222 outpatients with RA in the period 2011-2021 were retrieved, and of these 1,522 were under 75 years and eligible to be invited. To assess the 10-year risk for CV death, the modified Systematic Coronary Risk Evaluation (mSCORE), derived by multiplying the SCORE by 1.5, was used. Logistic regression analyses were used to explore differences in CV risk factors (triglycerides, HbA1c, lifestyle factors) and measures of disease impact (pain, fatigue, patient global assessment, HAQ, EQ-5D-5L) between patients with low vs. high risk. Differences between high risk patients who accepted vs. declined follow-up were analysed using Wilcoxon rank sum test and chi-squared test for groups.

Results
One thousand one hundred forty-nine received a CV screening invitation and 91 declined participation. Patients with high risk had significantly longer disease duration (OR; 95 CI) (1.017; 1.002-1.032), higher levels of triglycerides (1.834; 1.475-2.280), HbA1C (1.046; 1.020-1.070), pain (1.006; 1.001-1.012), and HAQ-score (1.305; 1.057-1.612) compared to patients with low risk and they more often declined follow-up (43% vs. 28%, p < 0.001). Those who declined a follow-up invitation were older (p = 0.016) and had shorter disease duration (p = 0.006) compared to those who accepted follow-up.

Conclusion
A first CV screening consultation was accepted by most patients with RA, while only every other patient with high to very high CV risk adhered to a follow-up screening consultation. Neither measures of disease impact nor lifestyle factors were associated with adherence. Further studies are needed to explore the patients' motivation, barriers and facilitators for adherence or non-adherence to a follow-up consultation.
Macrophage inclusions in cerebrospinal fluid following treatment initiation with antisense oligonucleotide therapies in motor neuron diseases
Authors: Vidovic Maximilian , Menschikowski Mario , Freigang Maren , Lapp Hanna Sophie , Günther René 
Published: February 2024

Abstract5q-associated spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS) are two distinct neurological disorders leading to degeneration of lower motor neurons. The antisense oligonucleotides (ASOs) nusinersen and tofersen are novel disease-modifying agents for these diseases, respectively. In the context of ASO treatment, the cytological characteristics and composition of cerebrospinal fluid (CSF) have recently garnered particular interest. This report presents a case series of CSF cytology findings in two patients with SMA and ALS revealing comparable unspecified macrophage inclusions following treatment initiation with nusinersen and tofersen. Yet, the presence of these “asophages” in the treatment course of two different ASOs is of unclear significance. While both treatments have been well tolerated, this phenomenon warrants attention, given the long-term nature of these treatments.
Immunoinformatic and molecular docking approaches: siRNA prediction to silence cell surface binding protein of monkeypox virus
Authors: Islam Rahatul , Shahriar Asif , Uddin Muhammad Ramiz , Fatema Nour 
Published: February 2024

Abstract
Background
Monkeypox virus (MPV), an endemic pathogen in Africa, shares clinical similarities with smallpox. Recent reports indicate a concerning increase in the number of MPV cases detected outside its endemic region, highlighting the emergence of a multi-country outbreak. Given the importance of the cell surface-binding protein E8L in facilitating viral attachment to host cells, this study aimed to identify potential small interfering RNAs (siRNAs) capable of silencing E8L and thereby serving as a basis for therapeutic development.

Results
siRNAs have emerged as promising candidates for genetic therapies and antiviral and antibacterial treatments. In this investigation, we employed computational assays, including GC content analysis, binding free energy assessment, folding properties evaluation, melting temperature determination, and siRNA efficacy prediction. Our comprehensive analysis identified five siRNAs with high potential for effectively silencing the cell surface-binding protein of the monkeypox virus. Among these siRNAs, molecular docking revealed that “S8” (Guide-UUAUGGAUCCAAUCACUUGAU, Passenger-CAAGUGAUUGGAUCCAUAAUC) demonstrated the strongest affinity with the human argonaute-2 protein.

Conclusions
The siRNA “S8” represents a promising therapeutic target for developing treatments against monkeypox virus infection by specifically silencing the cell surface-binding protein E8L. Our research lays the foundation for future endeavors in genome-level therapies. It can potentially create chemically produced RNA molecules as effective antiviral drugs targeting Monkeypox virus infection. These findings contribute to advancing therapeutic strategies and offer new avenues for combating the spread of MPV, particularly in regions affected by the multi-country outbreak.