bluuebunny/crossref_metadata_2025_split huggingface dataset:
Features of the microalga Raphidocelis subcapitata: physiology and applications
Authors: Machado Manuela D. , Soares Eduardo V. 
Published: February 2024

Abstract
The microalga Raphidocelis subcapitata was isolated from the Nitelva River (Norway) and subsequently deposited in the collection of the Norwegian Institute of Water Research as “Selenastrum capricornutum Printz”. This freshwater microalga, also known as Pseudokirchneriella subcapitata, acquired much of its notoriety due to its high sensitivity to different chemical species, which makes it recommended by different international organizations for the assessment of ecotoxicity. However, outside this scope, R. subcapitata continues to be little explored. This review aims to shed light on a microalga that, despite its popularity, continues to be an “illustrious” unknown in many ways. Therefore, R. subcapitata taxonomy, phylogeny, shape, size/biovolume, cell ultra-structure, and reproduction are reviewed. The nutritional and cultural conditions, chronological aging, and maintenance and preservation of the alga are summarized and critically discussed. Applications of R. subcapitata, such as its use in aquatic toxicology (ecotoxicity assessment and elucidation of adverse toxic outcome pathways) are presented. Furthermore, the latest advances in the use of this alga in biotechnology, namely in the bioremediation of effluents and the production of value-added biomolecules and biofuels, are highlighted. To end, a perspective regarding the future exploitation of R. subcapitata potentialities, in a modern concept of biorefinery, is outlined.

Graphical Abstract

Key points
• An overview of alga phylogeny and physiology is critically reviewed.
• Advances in alga nutrition, cultural conditions, and chronological aging are presented.
• Its use in aquatic toxicology and biotechnology is highlighted.
Dose–effect relationships in neuroendocrine tumour liver metastases treated with [166Ho]-radioembolization
Authors: Ramdhani K. , Beijer-Verduin J. , Ebbers S. C. , van Rooij R. , Smits M. L. J. , Bruijnen R. C. G. , de Jong H. W. A. M. , Lam M. G. E. H. , Braat A. J. A. T. 
Published: February 2024

Abstract
Purpose
Aim of this study was to investigate a dose-response relationship, dose-toxicity relationship, progression free survival (PFS) and overall survival (OS) in neuroendocrine tumour liver metastases (NELM) treated with holmium-166-microspheres radioembolization ([166Ho]-radioembolization).

Materials and methods
Single center, retrospective study included patients with NELM that received [166Ho]-radioembolization with post-treatment SPECT/CT and CECT or MRI imaging for 3 months follow-up. Post-treatment SPECT/CT was used to calculate tumour (Dt) and whole liver healthy tissue (Dh) absorbed dose. Clinical and laboratory toxicity was graded by Common Terminology Criteria for Adverse Events (CTCAE), version 5 at baseline and three-months follow-up. Response was determined according to RECIST 1.1. The tumour and healthy doses was correlated to lesion-based objective response and patient-based toxicity. Kaplan Meier analyses were performed for progression free survival (PFS) and overall survival (OS).

Results
Twenty-seven treatments in 25 patients were included, with a total of 114 tumours. Median follow-up was 14 months (3 – 82 months). Mean Dt in non-responders was 68 Gy versus 118 Gy in responders, p = 0.01. ROC analysis determined 86 Gy to have the highest sensitivity and specificity, resp. 83% and 81%. Achieving a Dt of ≥ 120 Gy provided the highest likelihood of response (90%) for obtaining response. Sixteen patients had grade 1–2 clinical toxicity and only one patient grade 3. No clear healthy liver dose-toxicity relationship was found. The median PFS was 15 months (95% CI [10.2;19.8]) and median OS was not reached.

Conclusion
This study confirms the safety and efficacy of [166Ho]-radioembolization in NELM in a real-world setting. A clear dose–response relationship was demonstrated and future studies should aim at a Dt of ≥ 120 Gy, being predictive of response. No dose-toxicity relationship could be established.
Peptoniphilus genitalis sp. nov. and Mobiluncus massiliensis sp. nov.: Novel Bacteria Isolated from the Vaginal Microbiome
Authors: Abou Chacra Linda , Bonnet Marion , Heredia Mégane , Haddad Gabriel , Armstrong Nicholas , Alibar Stéphane , Bretelle Florence , Fenollar Florence 
Published: February 2024

AbstractThe strains Marseille-Q7072T (= CSUR Q7072T = CECT 30604 T) and Marseille-Q7826T (= CSUR Q7826T = CECT 30727 T) were isolated from vaginal samples. As MALDI-TOF mass spectrometry failed to identify them, their genomes were directly sequenced to determine their taxogenomic identities. Both strains are anaerobic without any oxidase and catalase activity. C16:0 is the most abundant fatty acid for both strains. Strain Marseille-Q7072T is non-spore-forming, non-motile, Gram-stain-positive, and coccus-shaped, while strain Marseille-Q7826T is non-spore-forming, motile, Gram-stain-variable, and curved rod-shaped. The genomic comparison of the Marseille-Q7072T and Marseille-Q7826T strains showed that all digital DNA–DNA hybridisation (dDDH) and mean orthologous nucleotide identity (OrthoANI) values were below published species thresholds (70% and 95–96%, respectively) with other closely related species with standing in nomenclature. Thus, we conclude that both strains are new bacterial species. Strain Marseille-Q7072T is a new member of the Bacillota phylum, for which the name Peptoniphilus genitalis sp. nov. is proposed, while the Marseille-Q7826T strain is a new member of the Actinomycetota phylum, for which the name Mobiluncus massiliensis sp. nov. is proposed.
Die Modelltransferierbarkeit von KI in der digitalen Pathologie
Authors: Mayer Robin S. , Kinzler Maximilian N. , Stoll Alexandra K. , Gretser Steffen , Ziegler Paul K. , Saborowski Anna , Reis Henning , Vogel Arndt , Wild Peter J. , Flinner Nadine 
Published: February 2024

Zusammenfassung
Ziel der Arbeit
Künstliche Intelligenz hat das Potenzial, in der Pathologie weitreichende Fortschritte zu erzielen. Doch die tatsächliche Anwendung und Zertifizierung für die Praxis bleibt begrenzt, oft aufgrund von Herausforderungen bei der Transferierbarkeit von Modellen. In diesem Kontext untersuchen wir die Faktoren, die die Transferierbarkeit beeinflussen, und präsentieren Methoden, die dazu beitragen, die Nutzung von KI-Algorithmen in der Pathologie zu verbessern.

Material und Methoden
Mithilfe von Datensätzen aus 2 Instituten und dem öffentlich zugänglichen TCGA-MBIC-Datensatz (TCGA, The Cancer Genome Atlas) wurden Convolutional Neural Networks (CNN) und Vision Transformer (ViT) für Vorhersagen an Urothelgewebe (Karzinom- vs. Normalgewebe) und an intrahepatischen Cholangiokarzinomen (iCCA, „small vs. large duct“) trainiert. Veranschaulicht wird der Einfluss von Farbnormalisierung, Bildartefakten in Training und Anwendung sowie der NoisyEnsemble-Methode.

Ergebnisse
Wir konnten demonstrieren, dass Farbnormalisierung von Gewebeschnitten einen positiven Effekt auf die Interinstitutstransferierbarkeit von CNNs und ViTs hat (respektive +13 % und +10 %) und ViTs meist eine höhere Genauigkeit im externen Test erzielen (hier +1,5 %). Ebenso konnten wir zeigen, dass Artefakte in Testdaten die Vorhersagen von CNNs negativ beeinflusst und dass das Einbeziehen dieser Artefakte während des Trainings zu einer Verbesserung führt. Schließlich erhöhen NoisyEnsembles aus CNNs (besser als aus ViTs) auf verschiedenen Geweben und Fragestellungen die Transferierbarkeit (+7 % Blase, +15 % iCCA).

Diskussion
Wichtig ist vor allem, sich dem Problem der Transferierbarkeit bewusst zu sein: Gute Performance in der Entwicklung bedeutet nicht gute Performance in der Anwendung. Der Einbezug vieler bereits existierender Methoden zur Verbesserung der Transferierbarkeit, wie z. B. Farbnormalisierung und NoisyEnsemble, und deren Weiterentwicklung sind von großer Wichtigkeit.
Old for young kidney transplantation: a responsible option for our patients to reduce waiting time?
Authors: Zeuschner Philip , Mihm Janine , Sester Urban , Stöckle Michael , Friedersdorff Frank , Budde Klemens , Yakac Abdulbaki , Thomas Christian , Huber Johannes , Putz Juliane , Flegar Luka 
Published: February 2024

Abstract
Purpose
The Eurotransplant Senior program allocating grafts from donors ≥ 65 years to recipients aged ≥ 65 years has proven good results within the last 20 years. However, “old” grafts are also allocated to younger recipients < 65 years, and this outcome of “old for young” kidney transplantations (KT) still lacks detailed investigations.

Methods
All “old for young” KT performed at four tertiary referral centers were retrospectively compared including a recent follow-up, stratifying for “old for young” (donor ≥ 65 years to recipient < 65 years) vs. “very old for young” KT (donor ≥ 70 years to recipient < 65 years).

Results
Overall, 99 patients were included with 56 (56.6%) “old for young” and 43 (43.4%) “very old for young” KT. The median waiting time did not differ (60.7 vs. 45.8 months, respectively) at comparable living donation rates (57.1% vs. 44.2%) as well as intra- and postoperative results. At a median follow-up of 44 months (range 1; 133), the 3-year graft survival of 91% vs. 87% did not significantly vary. In subgroup analyses assessing living donation or donation after brain death (DBD) KT only, the graft survival was significantly longer for “old for young” KT within the living donation subgroup. In multivariate Cox regression analyses, the presence of panel-reactive antibodies was the only significant impact factor on graft survival (HR 8.32, p = 0.001).

Conclusion
This analysis clearly demonstrates the effectiveness of the "old for young" approach, enabling favorable perioperative results as well as comparable data of graft- and overall survival, while reducing waiting time for eligible patients.
PP2A and GSK3 act as modifiers of FUS-ALS by modulating mitochondrial transport
Authors: Tziortzouda Paraskevi , Steyaert Jolien , Scheveneels Wendy , Sicart Adria , Stoklund Dittlau Katarina , Barbosa Correia Adriana Margarida , Burg Thibaut , Pal Arun , Hermann Andreas , Van Damme Philip , Moens Thomas G. , Van Den Bosch Ludo 
Published: February 2024

AbstractAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease which currently lacks effective treatments. Mutations in the RNA-binding protein FUS are a common cause of familial ALS, accounting for around 4% of the cases. Understanding the mechanisms by which mutant FUS becomes toxic to neurons can provide insight into the pathogenesis of both familial and sporadic ALS. We have previously observed that overexpression of wild-type or ALS-mutant FUS in Drosophila motor neurons is toxic, which allowed us to screen for novel genetic modifiers of the disease. Using a genome-wide screening approach, we identified Protein Phosphatase 2A (PP2A) and Glycogen Synthase Kinase 3 (GSK3) as novel modifiers of FUS-ALS. Loss of function or pharmacological inhibition of either protein rescued FUS-associated lethality in Drosophila. Consistent with a conserved role in disease pathogenesis, pharmacological inhibition of both proteins rescued disease-relevant phenotypes, including mitochondrial trafficking defects and neuromuscular junction failure, in patient iPSC-derived spinal motor neurons (iPSC-sMNs). In FUS-ALS flies, mice, and human iPSC-sMNs, we observed reduced GSK3 inhibitory phosphorylation, suggesting that FUS dysfunction results in GSK3 hyperactivity. Furthermore, we found that PP2A acts upstream of GSK3, affecting its inhibitory phosphorylation. GSK3 has previously been linked to kinesin-1 hyperphosphorylation. We observed this in both flies and iPSC-sMNs, and we rescued this hyperphosphorylation by inhibiting GSK3 or PP2A. Moreover, increasing the level of kinesin-1 expression in our Drosophila model strongly rescued toxicity, confirming the relevance of kinesin-1 hyperphosphorylation. Our data provide in vivo evidence that PP2A and GSK3 are disease modifiers, and reveal an unexplored mechanistic link between PP2A, GSK3, and kinesin-1, that may be central to the pathogenesis of FUS-ALS and sporadic forms of the disease.
Long-term safety and tolerability of ambrisentan treatment for pediatric patients with pulmonary arterial hypertension: An open-label extension study
Authors: Ivy Dunbar , Beghetti Maurice , Juaneda-Simian Ernesto , Ravindranath Ramiya , Lukas Mary Ann , Machlitt-Northen Sandra , Scott Nicola , Narita Jun , Berger Rolf M. F. 
Published: February 2024

AbstractThis open-label, extension study assessed long-term safety, tolerability, and efficacy of ambrisentan in a pediatric population (age 8– < 18 years) with pulmonary arterial hypertension (PAH). Following completion of a 6-month, randomized study, participants entered the long-term extension at individualized ambrisentan dosages (2.5/5/7.5 or 10 mg/day). Safety assessments included adverse events (AEs), AEs of special interest, and serious AEs (SAEs); efficacy outcomes included 6-min walking distance (6MWD) and World Health Organization functional class (WHO FC). Thirty-eight of 41 (93%) randomized study participants entered the extension; 21 (55%) completed (reaching age 18 years). Most participants received concomitant phosphodiesterase-5 inhibitors (n = 25/38, 66%). Median ambrisentan exposure was 3.5 years. Most participants experienced ≥ 1 AE (n = 34/38, 89%), and 21 (55%) experienced SAEs, most commonly worsening PAH (n = 3/38, 8%), acute cardiac failure, pneumonia, or anemia (n = 2/38; 5% each); none considered ambrisentan-related. Seven participants (18%) died, with recorded reasons (MedDRA preferred term): cardiac failure (n = 2), PAH (n = 2), COVID-19 (n = 1), acute right ventricular failure (n = 1), and failure to thrive (n = 1); median time to death: 5.2 years. Anemia and hepatotoxicity AEs were generally mild to moderate and did not require ambrisentan dose adjustment. Assessed at study end in 29 participants (76%), mean 6MWD improved by 17% (standard deviation: 34.3%), and all (29/29, 100%) had improved or unchanged WHO FC. Conclusion: Long-term weight-based ambrisentan dosing, alone or combined with other PAH therapies in children with PAH aged 8– < 18 years, exhibited tolerability and clinical improvements consistent with prior randomized study results. Trial registration: NCT01342952, April 27, 2011.

What is Known:•The endothelin receptor antagonist, ambrisentan, is indicated for treatment of pulmonary arterial hypertension (PAH). Previous studies have shown similar efficacy and tolerability in pediatric patients as in adults.

What is New:• This open-label extension study assessed the long-term use of ambrisentan in pediatric patients (8–<18 years) with PAH, most of whom were also receiving recommended background PAH treatment. • Weight-based dosing of ambrisentan, given alone or in combination with other PAH therapies, was well tolerated with clinical improvements consistent with prior randomized study results.
Optimal sequence of LT for symptomatic BM in EGFR-mutant NSCLC: a comparative study of first-line EGFR-TKIs with/without upfront LT
Authors: Niu Lishui , Wu Honghua , Gao Ruihuan , Chen Liu , Wang Jiangtao , Duan Hexin , Long Yujiao , Xie Yi , Zhou Qin , Zhou Rongrong 
Published: February 2024

Abstract
Background
The third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) can penetrate blood–brain barrier and are effective for brain metastases (BMs). There is no consensus on the optimal sequence of local therapy (LT) and EGFR-TKIs for symptomatic BM patients because patients suffering neurological symptoms were not enrolled in most clinical trials.

Methods
Non-small cell lung cancer (NSCLC) patients with EGFR mutation (EGFRm) and symptomatic BM receiving first-line osimertinib and aumolertinib from two medical centers were collected. All participants were allocated into the third-generation EGFR-TKIs (TKIs) group and the upfront LT (uLT) plus third-generation EGFR-TKIs (TKIs + uLT) group. Demographic data, survival outcomes, treatment failure patterns, and adverse events were evaluated between the two groups. We also conducted subgroup analyses to explore the impact of BM number on survival outcomes.

Results
86 patients were enrolled, 44 in the TKIs group and 42 in the TKIs + uLT group. There were no significant differences in the short-term response between the groups. TKIs + uLT was associated with significantly longer overall survival (OS) (43 vs. 28 months; hazard ratio [HR], 0.36, 95% confidence interval [CI], 0.17–0.77; p = .011). No differences in progression-free survival (PFS), intracranial PFS (iPFS), failure patterns, or safety were observed. In subgroup analyses of oligo-BM patients, TKIs + uLT could prolong OS (43 vs. 31 months; HR 0.22; 95% CI 0.05–0.92; p = .015).

Conclusions
EGFRm NSCLC patients with symptomatic BM might benefit from uLT, particularly oligo-BM patients. However, larger prospective cohort studies should be carried out to confirm the responses of the TKIs + uLT scheme.
Tumor-to-stroma cd8+ t cells ratio combined with cancer-associated fibroblasts: an innovative approach to predicting lymph node metastases of cervical cancer
Authors: Guo Shuangshuang , Chen Peiyu , Yang Yang , Wei Wenfei , Pan YuHua , Zeng Fanke , Fan Liangsheng , Wang Wei 
Published: February 2024

Abstract
Purpose
Precise identification of lymph node metastases is vital for the management of cervical cancer. However, the existing diagnostic methods for lymph node metastases have certain drawbacks. In this study, we aim to explore the expression of cancer-associated fibroblasts (CAFs) and tumor-to-stroma CD8+ T cells ratio (CD8+ T cells T:S ratio) and its association with lymph node metastases of cervical cancer.

Methods
Hundred and ten cervical cancer tissues and 39 biopsy tissues from patients were investigated immunocytochemically for the expression of CAFs and CD8+ T cells. The statistical correlation analysis was carried out using the SPSS system.

Results
A strong and statistically significant negative correlation (r= − 0.690; P < 0.001) was observed between CAF density and CD8+ T cells T:S ratio. Not only were CAFs density and CD8+ T cells T:S ratio correlated with lymph node metastases respectively (P < 0.001), but the combination of them also significantly correlated with lymph node metastases (P < 0.001). Then, we constructed the combined diagnosis model (Logit (P) = − 4.446 + 0.300 × CAFs + 0.752 × CD8+ T cells T:S Ratio) of cervical cancer lymph node metastases. ROC curves analysis showed that the ROC curves areas for CAFs, CD8+ T cells T:S ratio, and a combination of both are 0.879, 0.747, and 0.951. Then, the prediction model was verified by biopsy specimens and consistent results were obtained.

Conclusions
The combination of CAF density and CD8+ T cells T:S ratio has a significant predictive value for lymph node metastases in patients with cervical cancer.
TEP RNA: a new frontier for early diagnosis of NSCLC
Authors: Wang Yuan , Dong Aiping , Jin Minhan , Li Shirong , Duan Yang 
Published: February 2024

Abstract
Background
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer (LC), which is the leading cause of tumor mortality. In recent years, compared with tissue biopsy, which is the diagnostic gold standard for tumor diagnosis, Liquid biopsy (LB) is considered to be a more minimally invasive, sensitive, and safer alternative or auxiliary diagnostic method. However, the current value of LB in early diagnosis of LC is not ideal, so it is particularly important to study the changes in blood composition during the process of tumorigenesis and find more sensitive biomarkers.

Purpose
Platelets are a type of abundant blood cells that carry a large amount of RNA. In the LC regulatory network, activated platelets play an important role in the process of tumorigenesis, development, and metastasis. In order to identify predictive liquid biopsy biomarkers for the diagnosis of NSCLC, we summarized the development and function of platelets, the interaction between platelets and tumors, the value of TEP RNA in diagnosis, prognosis, and treatment of NSCLC, and the method for detecting TEP RNA of NSCLC in this article.

Conclusion
The application of platelets in the diagnosis and treatment of NSCLC remains at a nascent stage. In addition to the drawbacks of low platelet count and complex experimental processes, the diagnostic accuracy of TEP RNA-seq for cancer in different populations still needs to be improved and validated. At present, a large number of studies have confirmed significant differences in the expression of TEP RNA in platelets between NSCLC patients and healthy individuals. Continuous exploration of the diagnostic value of TEP RNA in NSCLC is of utmost importance. The integration of NSCLC platelet-related markers with other NSCLC markers can improve current tumor diagnosis and prognostic evaluation systems, providing broad prospects in tumor screening, disease monitoring, and prognosis assessment.
Current look at the most promising proteomic and glycomic biomarkers of bladder cancer
Authors: Harsanyi Stefan , Kianickova Kristina , Katrlik Jaroslav , Danisovic Lubos , Ziaran Stanislav 
Published: February 2024

AbstractBackgroundBladder cancer (BC) belongs to the most frequent cancer types. The diagnostic process is still long and costly, with a high percentage of false-positive or -negative results. Due to the cost and lack of effectiveness, older methods need to be supplemented or replaced by a newer more reliable method. In this regard, proteins and glycoproteins pose high potential.MethodsWe performed an online search in PubMed/Medline, Scopus, and Web of Science databases to find relevant studies published in English up until May 2023. If applicable, we set the AUC threshold to 0.90 and sensitivity/specificity (SN/SP) to 90%.FindingsProtein and glycoprotein biomarkers are a demonstrably viable option in BC diagnostics. Cholinesterase shows promise in progression-free survival. BLCA-4, ORM-1 along with HTRA1 in the detection of BC. Matrix metallopeptidase 9 exhibits potential for stratification of muscle-invasive subtypes with high negative predictive value for aggressive phenotypes. Distinguishing non-muscle invasive subtypes benefits from Keratin 17. Neu5Gc-modified UMOD glycoproteins pose potential in BC diagnosis, while fibronectin, laminin-5, collagen type IV, and lamprey immunity protein in early detection of BC.