bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histone methyltransferase SUV420H1/KMT5B contributes to poor prognosis in hepatocellular carcinoma
Authors: Kato Hirotaka , Hayami Shinya , Ueno Masaki , Suzaki Norihiko , Nakamura Masashi , Yoshimura Tomohiro , Miyamoto Atsushi , Shigekawa Yoshinobu , Okada Ken‐Ichi , Miyazawa Motoki , Kitahata Yuji , Ehata Shogo , Hamamoto Ryuji , Yamaue Hiroki , Kawai Manabu 
Published: December 2023

AbstractHepatocellular carcinoma (HCC) has a high rate of recurrence and poor prognosis, even after curative surgery. Multikinase inhibitors have been applied for HCC patients, but their effect has been restricted. This study aims to clarify the clinical impact of SUV420H1/KMT5B, one of the methyltransferases for histone H4 at lysine 20, and elucidate the novel mechanisms of HCC progression. We retrospectively investigated SUV420H1 expression using HCC clinical tissue samples employing immunohistochemical analysis (n = 350). We then performed loss‐of‐function analysis of SUV420H1 with cell cycle analysis, migration assay, invasion assay and RNA sequence for Gene Ontology (GO) pathway analysis in vitro, and animal experiments with xenograft mice in vivo. The SUV420H1‐high‐score group (n = 154) had significantly poorer prognosis for both 5‐year overall and 2‐year/5‐year disease‐free survival than the SUV420H1‐low‐score group (n = 196) (p < 0.001 and p < 0.05, respectively). The SUV420H1‐high‐score group had pathologically larger tumor size, more tumors, poorer differentiation, and more positive vascular invasion than the SUV420H1‐low‐score group. Multivariate analysis demonstrated that SUV420H1 high score was the poorest independent factor for overall survival. SUV420H1 knockdown could suppress cell cycle from G1 to S phase and cell invasion. GO pathway analysis showed that SUV420H1 contributed to cell proliferation, cell invasion, and/or metastasis. Overexpression of SUV420H1 clinically contributed to poor prognosis in HCC, and the inhibition of SUV420H1 could repress tumor progression and invasion both in vitro and in vivo; thus, further analyses of SUV420H1 are necessary for the discovery of future molecularly targeted drugs.
Reflexive thematic analysis of a coaching‐based, holistic approach to child development
Authors: Sehajpal Khushi , McCrostie Claire , Charles Lucy , Hamill Arul , Terei Pio , Hamill James 
Published: December 2023

AbstractBackgroundThe F‐words Life Wheel (FWLW) approaches child development by hybridizing a holistic model in the F‐words for Child Development, and a coaching model in Occupational Performance Coaching, along with a life‐flow approach in the Kawa model. We report the impact of the FWLW as experienced by families.MethodsThis was a qualitative interview study of parents of children with developmental needs and experts in child development using reflexive thematic analysis.ResultsFrom 13 interviews, we developed three themes: 1) overwhelming, 2) power rebalance and 3) connectedness. The overwhelming theme addresses how life with developmental needs is challenging, engaging with the health and disability system is difficult and the focus on deficits can lead to a sense of being overwhelmed. The power rebalance theme addresses the transition from professionals calling the shots to giving agency to the child and family. Holistic goal setting empowers parents and children to direct and prioritize therapy, and helps shift from a deficit‐focused to a ‘can‐do’ attitude. The connectedness theme addresses the linkages between psychological health, physical health, the extended family and the planet as a whole.ConclusionsThe FWLW approach appears to be empowering and motivating for children and families.
Neurotropic virus infection and neurodegenerative diseases: Potential roles of autophagy pathway
Authors: Zhao Yu‐jia , Xu Kai‐fei , Shu Fu‐xing , Zhang Feng 
Published: December 2023

AbstractNeurodegenerative diseases (NDs) constitute a group of disorders characterized by the progressive deterioration of nervous system functionality. Currently, the precise etiological factors responsible for NDs remain incompletely elucidated, although it is probable that a combination of aging, genetic predisposition, and environmental stressors participate in this process. Accumulating evidence indicates that viral infections, especially neurotropic viruses, can contribute to the onset and progression of NDs. In this review, emerging evidence supporting the association between viral infection and NDs is summarized, and how the autophagy pathway mediated by viral infection can cause pathological aggregation of cellular proteins associated with various NDs is discussed. Furthermore, autophagy‐related genes (ARGs) involved in Herpes simplex virus (HSV‐1) infection and NDs are analyzed, and whether these genes could link HSV‐1 infection to NDs is discussed. Elucidating the mechanisms underlying NDs is critical for developing targeted therapeutic approaches that prevent the onset and slow the progression of NDs.
The characteristics of excitatory lineage differentiation and the developmental conservation in Reeler neocortex
Authors: Deng Huan‐Huan , Tong Shi‐Yuan , Shen Dan , Zhang Shu‐Qing , Fu Yinghui 
Published: December 2023

AbstractThe majority of neocortical projection neurons are generated indirectly from radial glial cells (RGCs) mediated by intermediate progenitor cells (IPCs) in mice. IPCs are thought to be a great breakthrough in the evolutionary expansion of the mammalian neocortex. However, the precise ratio of neuron production from IPCs and characteristics of RGC differentiation process are still unclear. Our study revealed that direct neurogenesis was seldom observed and increased slightly at late embryonic stage. Besides, we conducted retrovirus sparse labelling combined carboxyfluorescein diacetate succinimide ester (CFSE) and Tbr2‐CreER strain to reconstruct individual lineage tree in situ. The lineage trees simulated the output of RGCs at per round of division in sequence with high temporal, spatial and cellular resolution at P7. We then demonstrated that only 1.90% of neurons emanated from RGCs directly in mouse cerebral neocortex and 79.33% of RGCs contributed to the whole clones through IPCs. The contribution of indirect neurogenesis was underestimated previously because approximately a quarter of IPC‐derived neurons underwent apoptosis. Here, we also showed that abundant IPCs from first‐generation underwent self‐renewing division and generated four neurons ultimately. We confirmed that the intermediate proliferative progenitors expressed higher Cux2 characteristically at early embryonic stage. Finally, we validated that the characteristics of neurogenetic process in lineages and developmental fate of neurons were conserved in Reeler mice. This study contributes to further understanding of neurogenesis in neocortical development.
DNA image cytometry of bronchial washing as a diagnostic adjunct to radial endobronchial ultrasound‐guided sampling of peripheral lung lesions: A single center prospective study
Authors: Guo Cuiyan , Zhang Qi , Hu Yan , Huang Junfang , Wang Shixuan , Wang Guangfa 
Published: December 2023

AbstractObjectiveThe objective of this study is to study the adjunct role of combining DNA aneuploidy analysis with radial endobronchial ultrasound (R‐EBUS)‐guided sampling for diagnosis of peripheral lung lesions (PPLs).MethodA single‐center prospective study was conducted in patients undergoing R‐EBUS‐guided sampling for PPLs. DNA image cytometry (DNA‐ICM) was used to analyze DNA aneuploidy in bronchial washing from the bronchial segment of the PPL. Clinical information, R‐EBUS data, pathology, DNA‐ICM results, and follow‐up data were analyzed. Sensitivity, specificity, and predictive values for R‐EBUS‐guided sampling, DNA‐ICM, and the two methods combined were measured. Binary logistic regression was performed to determine influencing factors on diagnostic positivity rate. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff point for DNA‐ICM.ResultsA total of 101 patients were enrolled. Sixty‐four (63.4%) patients had confirmed malignant tumor, of whom 33 were confirmed by R‐EBUS‐guided sampling (biopsy and/or bronchial brush and wash cytology), and 31 by surgery or percutaneous lung biopsy. Thirty‐seven patients were finally considered to have benign lesions, based on clinical information and 1‐year follow‐up. The sensitivity for malignant disease was 51.6% by R‐EBUS, and specificity was 100%. DNA‐ICM had a sensitivity of 67.2% and a specificity of 86.5%. When combining the two methods, sensitivity increased to 78.1% and specificity was 86.5%. Lesion size and whether the R‐EBUS probe was located in the lesion were significantly associated with positivity rate of the combined methods. The optimal cutoff point for DNA‐ICM was 5c for max DNA content, and 1 for aneuploid cell count (sensitivity 67.2%, specificity 86.5%, accuracy 63.4%).ConclusionIn malignant PPLs, DNA‐ICM combined with R‐EBUS‐guided sampling can improve diagnostic positivity compared with either method alone.
Apocrine cystadenoma: A long‐standing apocrine hidrocystoma with an adenomatous proliferation
Authors: Connolly Deirdre M. , McGeehin Eleni L. , Lee Jason B. 
Published: December 2023

AbstractBackgroundApocrine cystadenoma is a rare, benign adenomatous cystic neoplasm, the pathogenesis of which is not fully understood. We sought to characterize the clinical, dermatoscopic, and histopathologic features of apocrine cystadenoma and its relationship to hidrocystoma.MethodsWe retrospectively analyzed cases of apocrine cystadenoma and hidrocystoma retrieved from the dermatopathology laboratory information system.ResultsOf the 350 cases apocrine cystic lesions, 13 cases of apocrine cystadenomas met the inclusion criteria. The age ranged from 20 to 84 years with an average of 64 years. They were long‐standing (duration 3–15 years), slow‐growing, large tumors usually found on the scalp. Dermatoscopy accentuated translucent light to dark blue color and prominent vessels that were present more at the periphery. All lesions were multilocular with columnar to cuboidal lining and decapitation secretion. A large portion of the lesion consisted of a simple nonproliferative epithelial lining, identical to that observed in apocrine hidrocystomas, while the proliferative adenomatous component made up a smaller portion with two patterns: (1) tubular proliferation, which either protruded into the cystic cavity or expanded outward peripherally, or (2) papillary projections, which were multiple layers thick with fibrovascular core, sometimes accompanied by tubular proliferation. Immunohistochemical stains showed strong staining for p40 and a sparse number of cells stained for Ki‐67 and p53.ConclusionsThe long duration of the lesion and the large areas of simple apocrine epithelial lining suggest that apocrine cystadenomas arise from long‐standing apocrine hidrocystomas. However, the retrospective nature of the study from a single institution is a limitation.
Cutaneous eccrine spiradenoma: Insights into cytomorphological features via fine needle aspiration biopsy and a comprehensive literature review
Authors: Shaker Nada , Vohra Poonam , Li Zaibo , Sangueza Omar P. , Abid Abdul 
Published: December 2023

Eccrine spiradenoma (ES) is an uncommon and benign adnexal tumour originating from sweat glands. The cytological examination of ES poses a diagnostic challenge, as it can be mistaken for various benign and malignant basaloid skin neoplasms. The cytomorphologic features of ES are infrequently documented in existing literature. This study seeks to present a thorough exploration of the cytomorphologic traits associated with ES, accompanied by an analysis of ancillary testing that contribute to the accurate identification of this entity in cytological specimens.Eccrine spiradenoma is infrequently encountered in fine needle aspiration (FNA) cytopathology, and the available literature on its cytomorphologic features is limited. The challenge arises from its similarity to other benign and malignant dermal basaloid neoplasms, emphasizing the critical role of clinicopathologic correlation and immunohistochemical staining in achieving a precise diagnosis.
Entwicklung der Patientencharakteristika und der Wirksamkeit der Biologika‐Therapie bei Patienten des Österreichischen Psoriasis‐Registers von 2004 bis 2022
Authors: Graier Thomas , Salmhofer Wolfgang , Jonak Constanze , Weger Wolfgang , Zikeli Claudia , Gruber Barbara , Sator Paul , Prillinger Knut , Mlynek Alexander , Schütz‐Bergmayr Martina , Richter Leo , Ratzinger Gudrun , Sassmann Christoph , Painsi Clemens , Häring Nina , Wippel‐Slupetzky Katharina , Skvara Hans , Trattner Hannes , Inzinger Martin , Bangert Christina , Ellersdorfer Christina , Falkensteiner Katharina , Sadoghi Birgit , Gruber‐Wackernagel Alexandra , Hofer Angelika , Legat Franz , Lange‐Asschenfeldt Bernhard , Schmuth Matthias , Vujic Igor , Hötzenecker Wolfram , Saxinger Werner , Müllegger Robert , Quehenberger Franz , Wolf Peter 
Published: December 2023

ZusammenfassungHintergrund und ZieleIn dieser Studie wurde untersucht, inwieweit die Einführung wirksamerer Medikamente in jüngster Zeit zu einer Verbesserung der Behandlungsergebnisse von Psoriasis‐Patienten im klinischen Alltag geführt hat.Patienten und MethodikEs wurden Patientencharakteristika und die Wirksamkeit der Therapie im ersten Behandlungsjahr bei Biologika‐naiven Patienten von 2004 bis heute analysiert, unabhängig von Therapiewechseln.ErgebnisseDie Daten von 2729 Patienten eigneten sich für die Analyse. Der Anteil der weiblichen Patienten stieg über die Jahre signifikant von 29,9% auf 36,2% (p < 0,028), während der Anteil der Patienten mit einer Psoriasis‐Arthritis von 36,6% auf 30,0% sank (p < 0,001). Außerdem nahm die Dauer der Psoriasis‐Erkrankung und der PASI‐Wert zu Beginn der Behandlung in Verlauf der Zeit signifikant ab. Die „letzte Beobachtung übernommen“ (LOCF)‐Analyse zeigte, dass das PASI‐90‐Ansprechen drei Monate nach Therapiebeginn von 18,9% auf 44,6% und 12 Monate nach Therapiebeginn von 32,9% auf 66,8% anstieg. Ebenso stiegen die PASI<3 Befunde von 33,2% auf 66,0% 3 Monate und von 41,9% auf 78,9% 12 Monate nach Behandlungsbeginn.SchlussfolgerungenDie kontinuierliche Einführung wirksamerer Biologika hat zu einer deutlichen Verbesserung des klinischen Ansprechens und der Patientenversorgung geführt. Dennoch erreicht auch heute noch, je nach gewähltem Endpunkt, jeder dritte bis fünfte Patient kein vollständig zufriedenstellendes Behandlungsergebnis (d.h. PASI 90 oder PASI ≤ 3).
Moderne Diagnostik und Therapie des Merkelzellkarzinoms
Authors: Weilandt Juliane , Peitsch Wiebke K. 
Published: December 2023

ZusammenfassungDas Merkelzellkarzinom (MCC) ist ein seltener, aggressiver Hauttumor mit epithelialer und neuroendokriner Differenzierung, dessen Inzidenz in den letzten Jahrzehnten deutlich zugenommen hat. Risikofaktoren sind fortgeschrittenes Lebensalter, heller Hauttyp, UV‐Exposition und Immunsuppression. Pathogenetisch wird ein durch das Merkelzell‐Polyomavirus (MCPyV) hervorgerufener Typ von einem UV‐induzierten Typ mit hoher Tumormutationslast unterschieden.Klinisch präsentiert sich das MCC als meist schmerzloser, schnell wachsender, rötlich‐violetter Tumor mit glänzender Oberfläche, der bevorzugt im Kopf‐Hals‐Bereich und an den distalen Extremitäten lokalisiert ist. Eine sichere Diagnose kann nur anhand histologischer und immunhistochemischer Merkmale gestellt werden. Bei Erstdiagnose weisen 20%–26% der Patienten lokoregionäre Metastasen und 8%–14% Fernmetastasen auf, weshalb eine Ausbreitungsdiagnostik unabdingbar ist. Bei fehlenden klinischen Hinweisen auf Metastasen wird eine Sentinel‐Lymphknotenbiopsie empfohlen.Wesentliche Säulen der Therapie sind die Operation, die adjuvante oder palliative Strahlentherapie und in fortgeschrittenen inoperablen Stadien die medikamentöse Tumortherapie. Die Einführung von Immuncheckpoint‐Inhibitoren führte zu einem Paradigmenwechsel, da sich hiermit ein wesentlich langfristigeres Ansprechen und bessere Überlebensraten als mit Chemotherapie erreichen lassen. Zur Therapie des metastasierten MCC ist in Deutschland der PD‐L1‐Inhibitor Avelumab zugelassen, aber auch die PD‐1‐Antikörper Pembrolizumab und Nivolumab werden mit Erfolg eingesetzt. Adjuvante und neoadjuvante Therapiekonzepte, Immunkombinationstherapien und zielgerichtete Therapien als Monotherapie oder in Kombination mit Immuncheckpoint‐Inhibitoren befinden sich in klinischer Prüfung.
VEXAS‐Syndrom, eine neu beschriebene autoinflammatorische Systemerkrankung mit dermatologischen Manifestationen
Authors: Baur Vera , Stoevesandt Johanna , Hueber Axel , Hüffmeier Ulrike , Kneitz Hermann , Morbach Henner , Schultz Erwin , Goebeler Matthias 
Published: December 2023

ZusammenfassungDas VEXAS‐Syndrom ist eine kürzlich erstbeschriebene autoinflammatorische Systemerkrankung, die auf einer erworbenen, somatischen Mutation des X‐chromosomal lokalisierten UBA1‐Gens, dem Schlüsselenzym des ersten Schritts der Ubiquitinierung, beruht. Das Akronym VEXAS steht für die Charakteristika Vacuoles, E1 enzyme, X‐linked, autoinflammatory und somatic. Die Erkrankung tritt im fortgeschrittenen Erwachsenenalter vorzugsweise bei Männern auf und ist insbesondere durch hämatologische, rheumatologische und dermatologische Symptome gekennzeichnet. Letztere umfassen unter anderem neutrophilenreiche, an das Sweet‐Syndrom erinnernde Läsionen, Erythema nodosum‐ und Pannikulitis‐artige Hauterscheinungen sowie rezidivierende Polychondritiden an Nase und Ohrmuscheln. Das Vorliegen zytoplasmatischer Vakuolen in myeloiden und erythroiden Vorläuferzellen des Knochenmarks ist charakteristisch. In bis zur Hälfte der Fälle ist das VEXAS‐Syndrom mit einem myelodysplastischen Syndrom vergesellschaftet. Dermatologen sollten das Krankheitsbild kennen, da Hauterscheinungen oft der erste Indikator für die Erkrankung sind. Eine molekulare Diagnostik ist essenziell für die Diagnosesicherung und die Risikostratifizierung betroffener Patienten. In dieser Arbeit geben wir einen Überblick über die Pathophysiologie, Diagnostik und Therapie des VEXAS‐Syndroms und illustrieren das klinische Spektrum anhand zweier eigener Fälle.
Considering species functional and phylogenetic rarity in the conservation of fish biodiversity
Authors: Lin Li , Liu Yang , Lin Hungdu , Kang Bin 
Published: December 2023

AbstractAimRare species make substantial contributions to coastal ecosystem functions. Functional rarity (FR) and phylogenetic rarity (PR) are important features for biodiversity conservation. This work aimed to discuss the necessity and reasonableness of conserving fish FR and PR in coastal seas.LocationChina.MethodsBy compiling historical fish investigation data, joint species distribution modelling (JSDM) was applied to model fish communities in coastal China Seas. Biogeographic patterns of FR and PR were explored, and the effectiveness of current MPA networks in terms of match/mismatch with the hotspots of rarity was assessed.ResultsA total of 44 functionally rare species and 22 phylogenetically rare species were identified. Six of these species were both functionally and phylogenetically rare, and only one was listed as endangered on the Red List of the International Union for Conservation of Nature (IUCN). Functional rarity hotspots covered 10.27% of the coastal areas, which geographically converged in the southern and eastern coast of Taiwan, the Yangtze River Estuary and the Yellow River Estuary. Phylogenetic rarity hotspots only covered 3.06% of the coastal areas, which were sporadically distributed in the coastal East China Sea, the Bohai Sea and the northern Yellow Sea. Current marine‐protected areas (MPAs) only represented 16.16% of the FR hotspots and 20.48% of the PR hotspots, indicating substantial mismatched areas between the MPAs and the hotspots of FR and PR.Main ConclusionsOnly considering threatened species in conservation practices will omit functionally and phylogenetically rare species because FR and PR are not necessarily correlated with species threat status on the IUCN Red List. Functional rarity hotspots do not necessarily overlap with PR hotspots, and current MPAs mismatch the majority of these areas. We therefore advocate that conservation prioritization and expansion of MPA networks should account for FR and PR both at the species and site levels.
Accounting for the topology of road networks to better explain human‐mediated dispersal in terrestrial landscapes
Authors: Rocabert Charles , Fenet Serge , Kaufmann Bernard , Gippet Jérôme M. W. 
Published: December 2023

Human trade and movements are central to biological invasions worldwide. Human activities not only transport species across biogeographical barriers, but also accelerate their post‐introduction spread in the landscape. Thus, by constraining human movements, the spatial structure of road networks might greatly affect the regional spread of invasive species. However, few invasion models have accounted for the topology of road networks so far, and its importance for explaining the regional distribution of invasive species remains mostly unexplored. To address this issue, we developed a spatially explicit and mechanistic human‐mediated dispersal model that accounts and tests for the influence of transport networks on the regional spread of invasive species. Using as a model the spread of the invasive ant Lasius neglectus in the middle Rhône valley (France), we show that accounting for the topology of road networks improves our ability to explain the current distribution of the invasive ant. In contrast, we found that using human population density as a proxy for the frequency of transport events decreases models' performance and might thus not be as appropriate as previously thought. Finally, by differentiating road networks into sub‐networks, we show that national and regional roads are more important than smaller roads for explaining spread patterns. Overall, our results demonstrate that the topology of transport networks can strongly bias regional invasion patterns and highlight the importance of better incorporating it into future invasion models. The mechanistic modelling approach developed in this study should help invasion scientists explore how human‐mediated dispersal and topography shape invasion dynamics in landscapes. Ultimately, our approach could be combined with demographic, natural dispersal and environmental suitability models to refine spread scenarios and improve invasive species monitoring and management at regional to national scales.Keywords: biological invasions, human‐mediated dispersal, road network, secondary spread, spatially explicit model, stochastic jump model