bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced medullary and extramedullary granulopoiesis sustain the inflammatory response in lupus nephritis
Authors: Zervopoulou Eleni , Grigoriou Maria , Doumas Stavros A , Yiannakou Danae , Pavlidis Pavlos , Gasparoni Gilles , Walter Jörn , Filia Anastasia , Gakiopoulou Harikleia , Banos Aggelos , Mitroulis Ioannis , Boumpas Dimitrios T 
Published: March 2024

ObjectivesIn SLE, deregulation of haematopoiesis is characterised by inflammatory priming and myeloid skewing of haematopoietic stem and progenitor cells (HSPCs). We sought to investigate the role of extramedullary haematopoiesis (EMH) as a key player for tissue injury in systemic autoimmune disorders.MethodsTranscriptomic analysis of bone marrow (BM)-derived HSPCs from patients with SLE and NZBW/F1 lupus-prone mice was performed in combination with DNA methylation profile. Trained immunity (TI) was induced through β-glucan administration to the NZBW/F1 lupus-prone model. Disease activity was assessed through lupus nephritis (LN) histological grading. Colony-forming unit assay and adoptive cell transfer were used to assess HSPCs functionalities.ResultsTranscriptomic analysis shows that splenic HSPCs carry a higher inflammatory potential compared with their BM counterparts. Further induction of TI, through β-glucan administration, exacerbates splenic EMH, accentuates myeloid skewing and worsens LN. Methylomic analysis of BM-derived HSPCs demonstrates myeloid skewing which is in part driven by epigenetic tinkering. Importantly, transcriptomic analysis of human SLE BM-derived HSPCs demonstrates similar findings to those observed in diseased mice.ConclusionsThese data support a key role of granulocytes derived from primed HSPCs both at medullary and extramedullary sites in the pathogenesis of LN. EMH and TI contribute to SLE by sustaining the systemic inflammatory response and increasing the risk for flare.
Enhanced supportive care in cancer centres: national cross-sectional survey
Authors: Caulfield Rachel Moya Helen , Selman Lucy E , Gibbins Jane , Forbes Karen , Chamberlain Charlotte 
Published: March 2024

Objectives‘Early’ specialist palliative care (SPC) has been shown to improve outcomes for patients with advanced cancer, yet patients are often referred late. ‘Enhanced supportive care’ (ESC) aims to facilitate earlier integrated supportive care for those with incurable cancer. This study aimed to explore clinicians’ understanding of ESC/SPC delivery through description of current service provision.MethodsThis national cross-sectional survey of 53 cancer centres had two parts. Part 1: Service details, was directed to lead ESC/SPC nurses or consultants about service configuration, and Part 2: Clinician understanding, targeting conceptual understanding of service aims including ESC/SPC teams and oncology consultants (n=262 surveys). Multiple-choice questions explored service provision, referral triggers and evidence of integration with oncology, with free-text responses. Quantitative results were analysed with Fischer’s exact test. Qualitative free text was line-by-line coded by two authors independently to derive themes.Results56% (30/53) of SPC and ESC teams and 14% (14/100) of oncologists responded. Those involved in ESC self-reported greater integration with oncology compared with non-ESC teams, for example, joint case discussions (64.3%, 9/14 vs 23.1%, 3/13, p=0.05), and timelier patient referral ((>6 months before death vs <6 months) (10/14 vs 4/13, p=0.06)). Qualitative themes described ambiguity in definitions of supportive and palliative terms and a perception of timelier identification of patients when ESC was involved.ConclusionProviders of ESC perceive greater integration with oncology and potentially timelier referral for patients compared with teams not delivering ESC. Terminology around SPC and ESC remains uncertain across England.
Patient stratification using plasma cytokines and their regulators in sepsis: relationship to outcomes, treatment effect and leucocyte transcriptomic subphenotypes
Authors: Antcliffe David Benjamin , Mi Yuxin , Santhakumaran Shalini , Burnham Katie L , Prevost A Toby , Ward Josie K , Marshall Timothy J , Bradley Claire , Al-Beidh Farah , Hutton Paula , McKechnie Stuart , Davenport Emma E , Hinds Charles J , O'Kane Cecilia M , McAuley Daniel Francis , Shankar-Hari Manu , Gordon Anthony C , Knight Julian C 
Published: March 2024

RationaleHeterogeneity of the host response within sepsis, acute respiratory distress syndrome (ARDS) and more widely critical illness, limits discovery and targeting of immunomodulatory therapies. Clustering approaches using clinical and circulating biomarkers have defined hyper-inflammatory and hypo-inflammatory subphenotypes in ARDS associated with differential treatment response. It is unknown if similar subphenotypes exist in sepsis populations where leucocyte transcriptomic-defined subphenotypes have been reported.ObjectivesWe investigated whether inflammatory clusters based on cytokine protein abundance were seen in sepsis, and the relationships with previously described transcriptomic subphenotypes.MethodsHierarchical cluster and latent class analysis were applied to an observational study (UK Genomic Advances in Sepsis (GAinS)) (n=124 patients) and two clinical trial datasets (VANISH, n=155 and LeoPARDS, n=484) in which the plasma protein abundance of 65, 21, 11 circulating cytokines, cytokine receptors and regulators were quantified. Clinical features, outcomes, response to trial treatments and assignment to transcriptomic subphenotypes were compared between inflammatory clusters.Measurements and main resultsWe identified two (UK GAinS, VANISH) or three (LeoPARDS) inflammatory clusters. A group with high levels of pro-inflammatory and anti-inflammatory cytokines was seen that was associated with worse organ dysfunction and survival. No interaction between inflammatory clusters and trial treatment response was found. We found variable overlap of inflammatory clusters and leucocyte transcriptomic subphenotypes.ConclusionsThese findings demonstrate that differences in response at the level of cytokine biology show clustering related to severity, but not treatment response, and may provide complementary information to transcriptomic sepsis subphenotypes.Trial registration numberISRCTN20769191,ISRCTN12776039.
Developmental changes in motor unit activity patterns: child-adult comparison using discrete motor unit analysis
Authors: Woods Stacey , McKiel Andrew , Herda Trent , Klentrou Panagiota , Holmes Michael , Gabriel David , Falk Bareket 
Published: March 2024

Using global surface electromyography (sEMG) and the sEMG threshold it has been suggested that children activate their type-II motor unit (MU) to a lesser extent compared with adults. However, when age-related differences in discrete MU activation are examined using sEMG decomposition this phenomenon is not observed. Furthermore, findings from these studies are inconsistent and conflicting. Therefore, the purpose of this study was to examine differences in discrete MU activation of the vastus lateralis (VL) between boys and men during moderate-intensity knee extensions. Seventeen boys and 20 men completed two laboratory sessions. Following a habituation session, maximal voluntary isometric knee extension (MVIC) torque was determined before completing trapezoidal contractions at 70% MVIC. sEMG of the VL was captured and mathematically decomposed into individual MU action potential trains. Motor unit action potential amplitude (MUAPamp), recruitment threshold (RT), and MU firing rates (MUFR) were calculated. We observed that MUAPamp–RT slope was steeper in men compared with boys ( p < 0.05) even after accounting for fat thickness and quadriceps muscle depth. The mean MUFR and y-intercept of the MUFR–RT relationship were significantly ( p < 0.001) lower in boys than in men. The slope of the MUFR–RT relationship tended to be steeper in men, but the differences did not reach statistical significance ( p = 0.056). Overall, our results suggest that neural strategies used to produce torque are different among boys and men. Such differences may be related, in part, to boys’ lower MUFR and lesser ability to activate their higher-threshold MUs. Although, other factors (e.g., muscle composition) likely also play a role.
The dynamical behavior of the capacitively coupled argon plasma driven by very high frequency
Authors: Yin Guiqin , Jiang Yongbo , Yuan Qianghua 
Published: March 2024

The dynamical behavior of the capacitively coupled Ar plasma driven by four frequencies (54, 80, 94 and 100[Formula: see text]MHz) at fixed pressure are simulated by the particle-in-cell/Monte-Carlo collisions (PIC/MCC) model based on the electromagnetic field. The magnetic field is generated by plasma current itself. The results show that the electron density, charge density, and electron temperature increase with the frequency increase when radio frequency (RF) power is 40[Formula: see text]W. The electron heating rate and argon ion heating rate near the sheath increase with the frequency increase. The high-energy electron density ([Formula: see text] [Formula: see text]eV) varies nonlinearly with the frequency increase. The high-energy electron density is highest at 80[Formula: see text]MHz among the four frequencies. The electron density, charge density, and high-energy electron density increase with RF power (30, 45, 60, and 75[Formula: see text]W) increase at 80[Formula: see text]MHz. The electron temperature decreases with RF power increase at 80[Formula: see text]MHz. The electron heating rate and argon ion heating rate near the sheath have no change with RF power increase at 80[Formula: see text]MHz. The electron energy probability distributions (EEPF) show that the number of high-energy electrons ([Formula: see text] [Formula: see text]eV) is highest at 80[Formula: see text]MHz. The reason may be the electron resonant heating that occurs in the plasma when the electron cyclotron frequency equals source frequency at 80[Formula: see text]MHz. The electron dynamics of capacitively coupled plasma is important for microelectronics etching and membrane deposition.
Hearty Mart: Democratizing Corporate Entrepreneurship
Authors: Ghura Amarpreet Singh , Abhishek  
Published: March 2024

Nadeem Jafri (Jafri), the founder of Hearty Mart Enterprise Private Limited (HMEPL), was based in Juhapura, Ahmedabad India. HMEPL catered to Hotel, Restaurant, and Café (HoReCa) segment. In 2017, Jafri started practicing corporate entrepreneurship at HMEPL with a dedicated team and later democratized the same for all employees of HMEPL. In the last quarter of 2022, HMEPL acquired four businesses and exercised organization restructuring which led to seven business entities with diverse backgrounds, were based in remote locations and had resource constraints when compared with HMEPL. Jafri wondered about a mechanism to successfully implement the innovation and entrepreneurship culture in the newly restructured entity HMEPL and across other seven businesses. The case provides an opportunity for students to step into the shoes of Jafri and plan a way to implement entrepreneurial and innovation culture in the newly restructured HMEPL and across other seven businesses. In doing so, students should take into consideration the data regarding the existing processes and teams at HMEPL that helped it to innovate, and make assumptions to analyze the feasibility of implementing entrepreneurial and innovation culture in newly restructured HMEPL and across seven other businesses. Nadeem Jafri (Jafri), the founder of Hearty Mart Enterprise Private Limited (HMEPL), was sitting in his Juhapura office in Ahmedabad on 18th July 2023 and reflecting on the integration of new business ventures within HMEPL. Jafri started HMEPL in Ahmedabad, India, and catered to Hotel, Restaurant, and Café (HoReCa) segment. In 2017, Jafri started practicing corporate entrepreneurship in HMEPL with the leadership team and later democratized the same for all the employees of HMEPL. In the last quarter of 2022, HMEPL acquired four businesses and post the acquisition, went through organizational restructuring leading to seven business units operating under HMEPL. Jafri was wondering about the mechanism to implement the innovation and corporate entrepreneurship culture in the newly restructured HMEPL and across the seven business units which had diverse businesses. Many questions remained unanswered during the early phase of implementing innovation and entrepreneurship culture in the newly restructured HMEPL and across the seven business units. He grappled with questions like, ‘do we need to implement corporate entrepreneurship in all the businesses or do a pilot in one of the business units,’ ‘are all the business units ready as each one of them is based in a remote location and is also facing resource constraints,’ and ‘will the employees agree?’ Despite such skepticism, Jafri had to share the way forward about the idea of implementing the innovation and corporate entrepreneurship culture in the next leadership meeting on the coming weekend. The business of HMEPL had gained momentum and had crossed pre-COVID levels by early June 2023. Jafri had to ensure that he made the right choices which ensured continued growth for HMEPL.
SPARC Stabilizes ApoE to Induce Cholesterol-Dependent Invasion and Sorafenib Resistance in Hepatocellular Carcinoma
Authors: Wan Shan , He Quan-Yao , Yang Yun , Liu Feng , Zhang Xue , Guo Xin , Niu Hui , Wang Yi , Liu Yi-Xuan , Ye Wen-Long , Li Xiu-Ming , ZhuanSun Xue-Mei , Sun Pu , He Xiao-Shun , Hu Guang , Breuhahn Kai , Zhao Hua , Wu Guo-Qiang , Wu Hua 
Published: March 2024

Abstract

Dysregulation of cholesterol homeostasis is implicated in the development and progression of hepatocellular carcinoma (HCC) that is characterized by intrahepatic and early extrahepatic metastases. A better understanding of the underlying mechanisms regulating cholesterol metabolism in HCC could help identify strategies to circumvent the aggressive phenotype. Here, we found that high expression of intracellular SPARC (secreted protein acidic and rich in cysteine) was significantly associated with elevated cholesterol levels and an enhanced invasive phenotype in HCC. SPARC potentiated cholesterol accumulation in HCC cells during tumor progression by stabilizing the ApoE protein. Mechanistically, SPARC competitively bound to ApoE, impairing its interaction with the E3 ligase tripartite motif containing 21 (TRIM21) and preventing its ubiquitylation and subsequent degradation. ApoE accumulation led to cholesterol enrichment in HCC cells, stimulating PI3K–AKT signaling and inducing epithelial–mesenchymal transition (EMT). Importantly, sorafenib-resistant HCC cells were characterized by increased expression of intracellular SPARC, elevated cholesterol levels, and enhanced invasive capacity. Inhibiting SPARC expression or reducing cholesterol levels enhanced the sensitivity of HCC cells to sorafenib treatment. Together, these findings unveil interplay between SPARC and cholesterol homeostasis. Targeting SPARC-triggered cholesterol-dependent oncogenic signaling is a potential therapeutic strategy for advanced HCC.

Significance:
Intracellular SPARC boosts cholesterol availability to fuel invasion and drug resistance in hepatocellular carcinoma, providing a rational approach to improve the treatment of advanced liver cancer.
Whole-Genome DNA Methylation Profiling of Intrahepatic Cholangiocarcinoma Reveals Prognostic Subtypes with Distinct Biological Drivers
Authors: Liao Haotian , Chen Xing , Wang Haichuan , Lin Youpei , Chen Lu , Yuan Kefei , Liao Mingheng , Jiang Hanyu , Peng Jiajie , Wu Zhenru , Huang Jiwei , Li Jiaxin , Zeng Yong 
Published: March 2024

Abstract

Intrahepatic cholangiocarcinoma (iCCA) is the second most prevalent primary liver cancer. Although the genetic characterization of iCCA has led to targeted therapies for treating tumors with FGFR2 alterations and IDH1/2 mutations, only a limited number of patients can benefit from these strategies. Epigenomic profiles have emerged as potential diagnostic and prognostic biomarkers for improving the treatment of cancers. In this study, we conducted whole-genome bisulfite sequencing on 331 iCCAs integrated with genetic, transcriptomic, and proteomic analyses, demonstrating the existence of four DNA methylation subtypes of iCCAs (S1–S4) that exhibited unique postoperative clinical outcomes. The S1 group was an IDH1/2 mutation–specific subtype with moderate survival. The S2 subtype was characterized by the lowest methylation level and the highest mutational burden among the four subtypes and displayed upregulation of a gene-expression pattern associated with cell cycle/DNA replication. The S3 group was distinguished by high interpatient heterogeneity of tumor immunity, a gene-expression pattern associated with carbohydrate metabolism, and an enrichment of KRAS alterations. Patients with the S2 and S3 subtypes had the shortest survival among the four subtypes. Tumors in the S4 subtype, which had the best prognosis, showed global methylation levels comparable to normal controls, increased FGFR2 fusions/BAP1 mutations, and the highest copy-number variant burdens. Further integrative and functional analyses identified GBP4 demethylation, which is highly prevalent in the S2 and S3 groups, as an epigenetic oncogenic factor that regulates iCCA proliferation, migration, and invasion. Together, this study identifies prognostic methylome alterations and epigenetic drivers in iCCA.

Significance:
Characterization of the DNA methylome of intrahepatic cholangiocarcinoma integrated with genomic, transcriptomic, and proteomic analyses uncovers molecular mechanisms affected by genome-wide DNA methylation alterations, providing a resource for identifying potential therapeutic targets.
Cell-free DNA Concentration as a Biomarker of Response and Recurrence in HER2-Negative Breast Cancer Receiving Neoadjuvant Chemotherapy
Authors: Magbanua Mark Jesus M. , Ahmed Ziad , Sayaman Rosalyn W. , Brown Swigart Lamorna , Hirst Gillian L. , Yau Christina , Wolf Denise M. , Li Wen , Delson Amy L. , Perlmutter Jane , Pohlmann Paula , Symmans W. Fraser , Yee Douglas , Hylton Nola M. , Esserman Laura J. , DeMichele Angela M. , Rugo Hope S. , van 't Veer Laura J. 
Published: March 2024

Abstract

Purpose:
We previously demonstrated the clinical significance of circulating tumor DNA (ctDNA) in patients with HER2-negative breast cancer receiving neoadjuvant chemotherapy (NAC). Here, we compared its predictive and prognostic value with cell-free DNA (cfDNA) concentration measured in the same samples from the same patients.

Experimental Design:
145 patients with hormone receptor (HR)-positive/HER2-negative and 138 triple-negative breast cancer (TNBC) with ctDNA data from a previous study were included in the analysis. Associations of serial cfDNA concentration with residual cancer burden (RCB) and distant recurrence-free survival (DRFS) were examined.

Results:
In TNBC, we observed a modest negative correlation between cfDNA concentration 3 weeks after treatment initiation and RCB, but none of the other timepoints showed significant correlation. In contrast, ctDNA was significantly positively correlated with RCB at all timepoints (all R &gt; 0.3 and P &lt; 0.05). In the HR-positive/HER2-negative group, cfDNA concentration did not associate with response to NAC, but survival analysis showed that high cfDNA shedders at pretreatment had a significantly worse DRFS than low shedders (hazard ratio, 2.12; P = 0.037). In TNBC, the difference in survival between high versus low cfDNA shedders at all timepoints was not statistically significant. In contrast, as previously reported, ctDNA at all timepoints was significantly correlated with DRFS in both subtypes.

Conclusions:
In TNBC, cfDNA concentrations during therapy were not strongly correlated with response or prognosis. In the HR-positive/HER2-negative group, pretreatment cfDNA concentration was prognostic for DRFS. Overall, the predictive and prognostic value of cfDNA concentration was more limited than that of ctDNA.
LLM-Assisted Data Augmentation for Chinese Dialogue-Level Dependency Parsing
Authors: Zhang Meishan , Jiang Gongyao , Liu Shuang , Chen Jing , Zhang Min 
Published: March 2024

Abstract
Dialogue-level dependency parsing, despite its growing academic interest, often encounters underperformance issues due to resource shortages. A potential solution to this challenge is data augmentation. In recent years, large language models (LLMs) have demonstrated strong capabilities in generation, which can facilitate data augmentation greatly. In this study, we focus on Chinese dialogue-level dependency parsing, presenting three simple and effective strategies with LLM to augment the original training instances, namely word-level, syntax-level, and discourse-level augmentations, respectively. These strategies enable LLMs to either preserve or modify dependency structures, thereby assuring accuracy while increasing the diversity of instances at different levels. We conduct experiments on the benchmark dataset released by Jiang et al. (2023) to validate our approach. Results show that our method can greatly boost the parsing performance in various settings, particularly in dependencies among elementary discourse units. Lastly, we provide in-depth analysis to show the key points of our data augmentation strategies.
Morphological and genetic diversification of pygmy and marbled newts, with the description of a new species from the wider Lisbon Peninsula (Triturus, Salamandridae)
Authors: Arntzen Jan W. 
Published: March 2024

Abstract
Iberian populations of large-bodied newts, with Triturus marmoratus in the north and T. pygmaeus in the south of the peninsula, were studied for external morphology, mitochondrial dna and for a panel of single nucleotide polymorphisms. This confirmed the species’ low level of interspecific hybridization and their parapatric, mosaic-like mutual range border across the peninsula. The genetic data also revealed substantial variation within T. pygmaeus, with narrow (0.43–35.2 km) clinal transitions in the very centre of Portugal. Similar clines were observed for body size and colouration pattern. Pygmy newts in the west of Portugal are larger, with a more striped (less reticulated) green dorso-lateral colouration pattern than those in the east and south of the country. The western group of populations is described as a new species, Triturus rudolfi sp. nov., on account of a long, ca. 2.5 Ma, independent evolutionary history and limited hybridization with its sister-species T. pygmaeus, suggesting selection against hybrid offspring. The range of the newly described species may be restricted to the wider Lisbon Peninsula, stretching northwards along the Atlantic coast to the river Vouga estuary. Inland, the range border may be set by the lower Tejo River, or by the currently wide area of agricultural land at either side of that river, that may accommodate a residual hybrid zone. The close contact between both pygmy newt species is effectively limited to a ca. 20 × 40 km area directly north of the town Entroncamento, where T. rudolfi sp. nov. is sandwiched in between T. marmoratus and the river Tejo.