bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of elective neck dissection in T1 and T2 nasal cavity squamous cell carcinomas
Authors: Lill Claudia , Erovic Boban M. , Seemann Rudolf , Faisal Muhammad , Stelter Klaus , Gandler Bernd , Frommlet Florian , Strobl Andreas , Formanek Michael , Janik Stefan 
Published: November 2022

Abstract
Purpose
To evaluate the role of elective neck dissection (END) on oncological outcome in early-stage nasal cavity squamous cell carcinomas (SCCs).

Methods
In total, 87 patients with T1 (n = 59; 67.8%) and T2 (n = 28; 32.2%) SCCs were evaluated regarding performance of END, regional recurrences (RR) and its impact on cancer-specific survival (CSS). We further created a risk score based on T-classification, tumor subsite and grading to identify patients whom may benefit from END and calculated the corresponding numbers needed to treat (NNT) to prevent RR.

Results
Nine (10.3%) patients experienced RR of whom 3 (5.1%) were T1 and 6 (21.4%) T2 tumors (p = 0.042). All RR originated from moderately or poorly differentiated (G2–G3) SCCs of the nasal septum or vestibule. END was done in 15 (17.2%) patients and none of those experienced RR (p = 0.121). Onset of RR represented the worst prognostic factor for CSS (HR 23.3; p = 0.007) with a 5y-CSS of 44.4% vs. 97.3% (p < 0.001). RR occurred in none of the patients with no or low risk scores compared to 31.6% (6/19) in patients with high-risk scores (p = 0.006). Accordingly, three high-risk patients would need to undergo END (NNT 2.63) to prevent RR compared to a NNT of 8 for the whole cohort.

Conclusions
Although rare, occurrence of RR significantly deteriorates outcome in early stage nasal cavity SCCs, which could be effectively reduced by performance of END. The importance of END is currently underestimated and our proposed risk score helps identifying those patients who will benefit from END.
Surgical management of severe pancreatic fistula after pancreatoduodenectomy: a comparison of early versus late rescue pancreatectomy
Authors: Stoop Thomas F. , Fröberg Klara , Sparrelid Ernesto , Del Chiaro Marco , Ghorbani Poya 
Published: November 2022

Abstract
Background
Rescue pancreatectomy for postoperative pancreatic fistula (POPF) after pancreatoduodenectomy (PD) is associated with high mortality. However, in-depth literature is scarce and hard to interpret. This study aimed to evaluate the indications, timing and perioperative outcomes of rescue pancreatectomy for severe POPF after PD.

Methods
Retrospective single-centre study from all consecutive patients (2008–2020) with POPF-C after PD (ISGPS 2016 definition). Major morbidity and mortality during hospitalization or within 90 days after index surgery were evaluated. Time from index surgery to rescue pancreatectomy was dichotomized in early and late (≤ 11 versus > 11 days).

Results
From 1076 PDs performed, POPF-B/C occurred in 190 patients (17.7%) of whom 53 patients (4.9%) with POPF-C were included. Mortality after early rescue pancreatectomy did not differ significantly compared to late rescue pancreatectomy (13.6% versus 35.3%; p = 0.142). Timing of a rescue pancreatectomy did not change significantly during the study period: 11 (IQR, 8–14) (2008–2012) versus 14 (IQR, 7–33) (2013–2016) versus 8 days (IQR, 6–11) (2017–2020) (p = 0.140). Over time, the mortality in patients with POPF grade C decreased from 43.5% in 2008–2012 to 31.6% in 2013–2016 up to 0% in 2017–2020 (p = 0.014). However, mortality rates after rescue pancreatectomy did not differ significantly: 31.3% (2008–2012) versus 28.6% (2013–2016) versus 0% (2017–2020) (p = 0.104).

Conclusions
Rescue pancreatectomy for severe POPF is associated with high mortality, but an earlier timing might favourably influence the mortality. Hypothetically, this could be of value for pre-existent vulnerable patients. These findings must be carefully interpreted considering the sample sizes and differences among subgroups by patient selection.
Extranodal T- and NK-cell lymphomas
Authors: de Leval Laurence , Feldman Andrew L. , Pileri Stefano , Nakamura Shigeo , Gaulard Philippe 
Published: November 2022

AbstractNon-cutaneous extranodal NK/T cell lymphoproliferations constitute a heterogenous group of rare neoplasms, occurring primarily in the gastro-intestinal tract, nasal area, spleen, and liver. Their nomenclature refers to their usual clinical presentation and predilection for specific anatomic sites—i.e. extranodal NK/T-cell lymphoma, nasal-type, hepatosplenic T-cell lymphoma, primary intestinal T-cell lymphomas, indolent lymphoproliferative disorders of the gastrointestinal tract, and breast implant-associated anaplastic large cell lymphoma. Extranodal tissues may also be involved by T-cell leukemias, or other entities usually presenting as nodal diseases. Primary extranodal entities range from indolent to highly aggressive diseases. Here, we will review the clinicopathologic features of the pertinent entities including the recent advances in their molecular and genetic characterization, with an emphasis on the changes introduced in the 2022 International Consensus Classification of lymphoid neoplasms, and highlight the diagnostic criteria helpful to sort out the distinction with potential mimickers.
Real-world histopathological approach to malignancy of undefined primary origin (MUO) to diagnose cancers of unknown primary (CUPs)
Authors: Pisacane Alberto , Cascardi Eliano , Berrino Enrico , Polidori Alessio , Sarotto Ivana , Casorzo Laura , Panero Mara , Boccaccio Carla , Verginelli Federica , Benvenuti Silvia , Dellino Miriam , Comoglio Paolo , Montemurro Filippo , Geuna Elena , Marchiò Caterina , Sapino Anna 
Published: November 2022

AbstractThe aim of this study is to envisage a streamlined pathological workup to rule out CUPs in patients presenting with MUOs. Sixty-four MUOs were classified using standard histopathology. Clinical data, immunocytochemical markers, and results of molecular analysis were recorded. MUOs were histologically subdivided in clear-cut carcinomas (40 adenocarcinomas, 11 squamous, and 3 neuroendocrine carcinomas) and unclear-carcinoma features (5 undifferentiated and 5 sarcomatoid tumors). Cytohistology of 7/40 adenocarcinomas suggested an early metastatic cancer per se. In 33/40 adenocarcinomas, CK7/CK20 expression pattern, gender, and metastasis sites influenced tissue-specific marker selection. In 23/40 adenocarcinomas, a “putative-immunophenotype” of tissue of origin addressed clinical-diagnostic examinations, identifying 9 early metastatic cancers. Cell lineage markers were used to confirm squamous and neuroendocrine differentiation. Pan-cytokeratins were used to confirm the epithelial nature of poorly differentiated tumors, followed by tissue and cell lineage markers, which identified one melanoma. In total, 47/64 MUOs (73.4%) were confirmed CUP. Molecular analysis, feasible in 37/47 CUPs (78.7%), had no diagnostic impact. Twenty CUP patients, mainly with squamous carcinomas and adenocarcinomas with putative-gynecologic-immunophenotypes, presented with only lymph node metastases and had longer median time to progression and overall survival (< 0.001), compared with patients with other metastatic patterns. We propose a simplified histology-driven workup which could efficiently rule out CUPs and identify early metastatic cancer.
METTL3 promotes colorectal cancer metastasis by promoting the maturation of pri-microRNA-196b
Authors: Huang Lanlan , Liang Danlu , Zhang Yu , Chen Xiaoting , Chen Junxiong , Wen Chuangyu , Liu Huanliang , Yang Xiaorong , Yang Xiangling , Lin Shaoqiang 
Published: November 2022

Abstract
Purpose
Methyltransferase-like 3 (METTL3), a key member of the m6A methyltransferase complex, is upregulated in multiple human malignancies and plays a role in regulating tumor migration. This study aimed to reveal the underlying mechanism by which METTL3 in regulates the metastasis of colorectal cancer (CRC).

Methods
We compared METTL3 expression levels in CRC tumor tissues and adjacent nontumor tissues by immunohistochemistry (IHC). The functional roles of METTL3 in CRC were assessed by real-time cell migration assays, wound-healing assays and Transwell assays. miRNA sequencing (miRNA-seq), RNA-binding protein immunoprecipitation (RIP) assays and N6-methyladenosine immunoprecipitation (MeRIP) assays were performed to confirm the molecular mechanism underlying the involvement of METTL3 in CRC cell metastasis.

Results
We found that METTL3 was overexpressed in CRC tissues. METTL3 knockdown significantly inhibited CRC cell migration and invasion, while METTL3 overexpression had the opposite effects. Furthermore, we demonstrated that METTL3 regulates miR-196b expression via an N6-methyladenosine (m6A)-pri-miR-196b-dependent mechanism and thereby promotes CRC metastasis.

Conclusion
This study shows the important role of METTL3 in CRC metastasis and provides novel insight into m6A modification in CRC metastasis.
Combined effects of increased water temperature and cyanobacterial compounds exert heterogeneous effects on survival and ecological processes in key freshwater species
Authors: Adekolurejo Oloyede A. , Floyd Matthew , Dunn Alison M. , Kay Paul , Dean Andrew P. , Hassall Christopher 
Published: November 2022

AbstractClimate change is increasing water temperature and intensifying the incidence of cyanobacterial blooms worldwide. However, the combined effects of increased temperature and microcystin concentrations as co-stressors on survival and ecological processes in freshwater species are unclear. Here, using purified MC-LR and crude extract of toxigenic Microcystis aeruginosa, we tested the individual and combined effects of three water temperatures (15, 20, 25 °C) and a range of environmentally relevant concentrations of dissolved microcystin and crude extract (0.01–10 µg·L−1) on survival, growth inhibition, grazing and predation rates in three freshwater species: phytoplankton (Scenedesmus quadricauda), zooplankton (Daphnia pulex), and an invertebrate predator (Ischnura elegans). Purified MC-LR exerted a higher growth inhibitory effect on S. quadricauda compared to crude extract with the same concentration of MC-LR, while neither treatment affected its chlorophyll-a content or survival of D. pulex. Crude extract reduced grazing and survival of D. pulex and I. elegans, respectively. The combined effect of higher temperature and crude extract reduced I. elegans survival by 50%. Increased temperature reduced prey handing time in I. elegans by 49%, suggesting a higher predation rate. However, warming together with higher concentrations of crude extract jointly increased zooplankton grazing and reduced damselfly predation. Taken together, these results suggest crude extract, and not necessarily microcystin, can affect survival and productivity in freshwater species, although these effects may vary unevenly across trophic levels. Our findings highlight the importance of complex ecological mechanisms by which warming can exacerbate toxic effects of cyanobacterial bloom extracts on survival and functions among species in eutrophic freshwaters.
Habitat configurations shape the trophic and energetic dynamics of reef fishes in a tropical–temperate transition zone: implications under a warming future
Authors: Bosch Nestor E. , Pessarrodona Albert , Filbee-Dexter Karen , Tuya Fernando , Mulders Yannick , Bell Sahira , Langlois Tim , Wernberg Thomas 
Published: November 2022

AbstractUnderstanding the extent to which species’ traits mediate patterns of community assembly is key to predict the effect of natural and anthropogenic disturbances on ecosystem functioning. Here, we apply a trait-based community assembly framework to understand how four different habitat configurations (kelp forests, Sargassum spp. beds, hard corals, and turfs) shape the trophic and energetic dynamics of reef fish assemblages in a tropical–temperate transition zone. Specifically, we tested (i) the degree of trait divergence and convergence in each habitat, (ii) which traits explained variation in species’ abundances, and (iii) differences in standing biomass (kg ha−1), secondary productivity (kg ha−1 day−1) and turnover (% day−1). Fish assemblages in coral and kelp habitats displayed greater evidence of trait convergence, while turf and Sargassum spp. habitats displayed a higher degree of trait divergence, a pattern that was mostly driven by traits related to resource use and thermal affinity. This filtering effect had an imprint on the trophic and energetic dynamics of reef fishes, with turf habitats supporting higher fish biomass and productivity. However, these gains were strongly dependent on trophic guild, with herbivores/detritivores disproportionately contributing to among-habitat differences. Despite these perceived overall gains, turnover was decoupled for fishes that act as conduit of energy to higher trophic levels (i.e. microinvertivores), with coral habitats displaying higher rates of fish biomass replenishment than turf despite their lower productivity. This has important implications for biodiversity conservation and fisheries management, questioning the long-term sustainability of ecological processes and fisheries yields in increasingly altered marine habitats.
Möbius-Strip Topology of Expanded Porphyrins: A Minireview on EPR, ENDOR and DFT MO Studies
Authors: Möbius Klaus , Plato Martin , Savitsky Anton 
Published: November 2022

AbstractThe one-sided Möbius strip with its characteristic 180° twist in the loop has inspired philosophers, artists and scientists since hundreds of years and continues to do so. On the molecular level, only in the last 15 years have some groups succeeded in synthesizing new expanded porphyrin compounds large enough to adopt Möbius-strip topology and Möbius aromaticity, the first being Lechosław Latos-Grażyński and collaborators in Wroclaw (2007) and Atsuhiro Osuka and collaborators in Kyoto (2008). We report on new studies of expanded porphyrins with either Möbius topology or Hückel topology that were synthesized in these laboratories. In this minireview, we focus on recent continuous-wave and time-resolved EPR, ENDOR and DFT MO studies on open-shell states of di-p-benzi[28]hexaphyrin(1.1.1.1.1.1), specifically, on the ground-state radical cation doublet state (total electron spin S = 1/2) and the first excited triplet state (S = 1). The review is largely based on the results and discussions of two previous publications: Möbius et al. (Appl Magn Reson 47:757–780, 2016) and Ema et al. (J Phys Chem Lett 9:2685–2690, 2018). In the open-shell systems, besides the electron-nuclear hyperfine couplings also the zero-field interaction tensor turned out to be a viable sensor for electronic structure changes between Möbius and Hückel topologies. In the Outlook section, we address the cyclotides, a new class of natural circular mini-proteins, usually less than 100 amino acids long. They are distinguished by exceptional chemical and biological stability. This is due to topological constraints imposed by threefoil knot and Möbius-strip formation. As a result, their physical qualities are “topologically protected”. This makes them highly interesting for medical or agricultural applications, for example as novel active ingredients against autoimmune diseases, viral infections, or as agents against insect damage to crops.
Risk scores’ performance and their impact on operative decision-making in left-sided endocarditis: a cohort study
Authors: Fernández-Cisneros A. , Hernández-Meneses M. , Llopis J. , Sandoval E. , Pereda D. , Alcocer J. , Barriuso C. , Castellá M. , Ambrosioni J. , Pericàs J. M. , Vidal B. , Falces C. , Ibáñez C. , Perdomo J. , Rovira I. , García-de-la-María C. , Moreno A. , Almela M. , Perisinotti A. , Dahl A. , Castro P. , Miró J. M. , Quintana E. ,   Equip d’Endocarditis de l’Hospital Clínic de Barcelona
Published: November 2022

AbstractThe
accuracy of contemporary risk scores in predicting perioperative mortality in infective endocarditis (IE) remains controversial. The aim is to evaluate the performance of existent mortality risk scores for cardiovascular surgery in IE and the impact on operability at high-risk thresholds. A single-center retrospective review of adult patients diagnosed with acute left-sided IE undergoing surgery from May 2014 to August 2019 (n = 142) was done. Individualized risk calculation was obtained according to the available mortality risk scores: EuroScore I and II, PALSUSE, Risk-E, Costa, De Feo-Cotrufo, AEPEI, STS-risk, STS-IE, APORTEI, and ICE-PCS scores. A cross-validation analysis was performed on the score with the best area under the curve (AUC). The 30-day survival was 96.5% (95%CI 91–98%). The score with worse area under the curve (AUC = 0.6) was the STS-IE score, while the higher was for the RISK-E score (AUC = 0.89). The AUC of the majority of risk scores suggested acceptable performance; however, statistically significant differences in expected versus observed mortalities were common. The cross-validation analysis showed that a large number of survivors (> 75%) would not have been operated if arbitrary high-risk threshold estimates had been used to deny surgery. The observed mortality in our cohort is significantly lower than is predicted by contemporary risk scores. Despite the reasonable numeric performance of the analyzed scores, their utility in judging the operability of a given patient remains questionable, as demonstrated in the cross-validation analysis. Future guidelines may advise that denial of surgery should only follow a highly experienced Endocarditis Team evaluation.
Safety, tolerability, pharmacokinetics, and antitumour activity of oleclumab in Japanese patients with advanced solid malignancies: a phase I, open-label study
Authors: Kondo Shunsuke , Iwasa Satoru , Koyama Takafumi , Fujita Tomoko , Sugibayashi Ko , Murayama Kosho , Yamamoto Noboru 
Published: November 2022

Abstract
Background
Cluster of differentiation (CD) 73-targeted immunotherapy and CD73 inhibition may reduce adenosine production, which can augment the host and/or immunotherapy response to tumours. We aimed to assess the safety and tolerability, pharmacokinetics, and antitumour activity of oleclumab, an anti-CD73 monoclonal antibody, in adult Japanese patients with advanced solid malignancies resistant to standard therapy.

Methods
In this phase I, single-centre, open-label study, patients received oleclumab 1500 mg (Cohort 1) or 3000 mg (Cohort 2) intravenously every 2 weeks.

Results
In total, six patients were enrolled in the study (three in each cohort), and all six patients received the study treatment. The median patient age was 56.0 years and 4/6 were males. All patients (100%) reported adverse events (AEs) during the study; five (83.3%) patients reported AEs related to the study treatment. One (16.7%) patient reported a Grade 3 AE (neutrophil count decreased) that was not related to the study treatment. No AEs with an outcome of death were reported, and no patients reported AEs or serious AEs leading to oleclumab discontinuation/dose interruption. No dose-limiting toxicities were reported, and no patient discontinued due to an AE related to the study treatment. Oleclumab exposure increased dose proportionally. No patient achieved disease control at 8 weeks, and all six patients developed progressive disease.

Conclusions
Oleclumab was well tolerated in adult Japanese patients with advanced solid malignancies and no unexpected safety concerns were raised; oleclumab exposure increased with dose. Future studies on combination therapy with other agents are warranted.
Databases, Science Communication, and the Division of Epistemic Labour
Authors: Mößner Nicola 
Published: November 2022

AbstractThere are many ways in which biases can enter processes of scientific reasoning. One of these is what Ludwik Fleck has called a “harmony of illusions”. In this paper, Fleck’s ideas on the relevance of social mechanisms in epistemic processes and his detailed description of publication processes in science will be used as a starting point to investigate the connection between cognitive processes, social dynamics, and biases in this context.Despite its usefulness as a first step towards a more detailed analysis, Fleck’s account needs to be updated in order to take the developments of digital communication technologies of the 21st century into account. Taking a closer look at today’s practices of science communication shows that information and communication technologies (ICTs) play a major role here. By presenting a detailed case study concerning the database SCOPUS, the question will be investigated how such ICTs can influence the division of epistemic labour. The result will be that they potentially undermine the epistemic benefits of social dynamics in science communication due to their inherent tendency to reduce the diversity of scientific hypotheses and ideas.
Reconciling the Noema Debate
Authors: Hirvonen Ilpo 
Published: November 2022

AbstractOne of the key concepts of Edmund Husserl’s transcendental phenomenology is the noema. Husserl uses the concept to denote the aspect of what is intended in experience as it remains within the transcendental domain of inquiry after the phenomenological reduction. Despite such seeming simplicity, Husserl’s discussion of the noema is ambiguous to the extent that it has sparked a wide-ranging debate in the secondary literature. The gist of the dispute concerns the question about the relation between the noema and the object: whether the noema is content, ontologically distinct from the object, or the object itself just considered differently in philosophical reflection. In this paper, I propose an interpretation that aims to reconcile two opposing positions of this debate (the so-called West and East Coast interpretations). The impetus for the reconciliation stems from the fact that both interpretations seem to be correct while they also suffer from their own shortcomings. I propose the reconciliation by applying a distinction Husserl makes between two areas of phenomenological investigation, neutralized pure phenomenology and non-neutralized phenomenology of reason. Having clarified the distinction between them, I suggest that both competing interpretations can be partially correct when reserved for the aspect of the noema in either of the two areas of phenomenological investigation. Finally, I show how this proposal could aid in resolving issues in the recent discussion concerning Husserl’s noema and the internalism–externalism debate in philosophy of mind.
A systematic review of teaching and learning machine learning in K-12 education
Authors: Sanusi Ismaila Temitayo , Oyelere Solomon Sunday , Vartiainen Henriikka , Suhonen Jarkko , Tukiainen Markku 
Published: November 2022

AbstractThe increasing attention to Machine Learning (ML) in K-12 levels and studies exploring a different aspect of research on K-12 ML has necessitated the need to synthesize this existing research. This study systematically reviewed how research on ML teaching and learning in K-12 has fared, including the current area of focus, and the gaps that need to be addressed in the literature in future studies. We reviewed 43 conference and journal articles to analyze specific focus areas of ML learning and teaching in K-12 from four perspectives as derived from the data: curriculum development, technology development, pedagogical development, and teacher training/professional development. The findings of our study reveal that (a) additional ML resources are needed for kindergarten to middle school and informal settings, (b) further studies need to be conducted on how ML can be integrated into subject domains other than computing, (c) most of the studies focus on pedagogical development with a dearth of teacher professional development programs, and (d) more evidence of societal and ethical implications of ML should be considered in future research. While this study recognizes the present gaps and direction for future research, these findings provide insight for educators, practitioners, instructional designers, and researchers into K-12 ML research trends to advance the quality of the emerging field.