bluuebunny/crossref_metadata_2025_split huggingface dataset:
TIGIT drives the immunosuppressive environment by downregulation of metalloproteinases MMP2 and MMP14 in perihilar cholangiocarcinoma
Authors: Heij Lara , Reichel Konrad , de Koning Willem , Bednarsch Jan , Tan Xiuxiang , Deierl Julia Campello , Groningen Marian Clahsen-van , Al-Masri Tarick , van Dam Ronald , Vallejo Juan Garcia , Ulmer Florian , Lang Sven , Luedde Tom , Rocha Flavio G. , Dahl Edgar , Jonigk Danny , Kuehne Mark , Sivakumar Shivan , Neumann Ulf 
Published: August 2023

AbstractBackgroundCheckpoint blockade in cholangiocarcinoma (CCA) is promising; however, little is known about the response to treatment in CCA subtypes. In this study, we investigated the spatial immune environment in combination with checkpoint expression in perihilar CCA (pCCA).Materials & MethodsThe levels of checkpoint molecules (PD-1, PD-L1, PD-L2, LAG-3, ICOS, TIGIT, TIM-3, and CTLA-4), macrophages (CD68), and T cells (CD4 and CD8) were assessed by multiplex immunofluorescence (mIF) in 50 patients. We investigated the transcriptomic profile using the NanoString Cancer Progression Panel, and validation was performed by mIF on tissue sections from 24 patients.ResultsThe expression of checkpoint molecules TIGIT, CTLA-4, and LAG-3 alone and in combination with other checkpoint molecules was more abundant in the Central Tumor (CT) and Invasive Margin (IM) than in peritumoral tissue (PT) (CD4 and CD8 TIGIT p<0.0001 for both CD4 and CD8 CTLA-4, p<0.0001 and p < 0.001, respectively, and CD8 LAG-3 p < 0.05). MMP2 and MMP14 were differentially expressed in patients with high TIGIT expression.ConclusionThe immune environment in pCCA is characterized by the expression of multiple checkpoints, demonstrating the complexity of ICI treatment. High TIGIT expression drives an immunosuppressive environment by modulating the extracellular matrix. Future clinical trials in pCCA could consider TIGIT as a therapeutically relevant target for (combination) treatment.
Transmission bottleneck size estimation fromde novoviral genetic variation
Authors: Shi Teresa , Harris Jeremy D. , Martin Michael A. , Koelle Katia 
Published: August 2023

AbstractSequencing of viral infections has become increasingly common over the last decade. Deep sequencing data in particular have proven useful in characterizing the roles that genetic drift and natural selection play in shaping within-host viral populations. They have also been used to estimate transmission bottleneck sizes from identified donor-recipient pairs. These bottleneck sizes quantify the number of viral particles that establish genetic lineages in the recipient host and are important to estimate due to their impact on viral evolution. Current approaches for estimating bottleneck sizes exclusively consider the subset of viral sites that are observed as polymorphic in the donor individual. However, allele frequencies can change dramatically over the course of an individual’s infection, such that sites that are polymorphic in the donor at the time of transmission may not be polymorphic in the donor at the time of sampling and allele frequencies at donor-polymorphic sites may change dramatically over the course of a recipient’s infection. Because of this, transmission bottleneck sizes estimated using allele frequencies observed at a donor’s polymorphic sites may be considerable underestimates of true bottleneck sizes. Here, we present a new statistical approach for instead estimating bottleneck sizes using patterns of viral genetic variation that arosede novowithin a recipient individual. Specifically, our approach makes use of the number of clonal viral variants observed in a transmission pair, defined as the number of viral sites that are monomorphic in both the donor and the recipient but carry different alleles. We first test our approach on a simulated dataset and then apply it to both influenza A virus sequence data and SARS-CoV-2 sequence data from identified transmission pairs. Our results confirm the existence of extremely tight transmission bottlenecks for these two respiratory viruses, using an approach that does not tend to underestimate transmission bottleneck sizes.
Testing the genomic link between intraspecific mating traits and interspecific mating barriers
Authors: Yusuf Leeban H , Pascoal Sonia , Moran Peter A , Bailey Nathan W 
Published: August 2023

AbstractDifferences in interspecific mating traits such as male sexual signals and female preferences often evolve quickly as initial barriers to gene flow between nascent lineages, and they may also strengthen such barriers during secondary contact via reinforcement. However, it is an open question whether loci contributing to intraspecific variation in sexual traits are co-opted during the formation and strengthening of mating barriers between species. To test this, we used a population genomics approach in natural populations of Australian cricket sister species that overlap in a contact zone:Teleogryllus oceanicusandTeleogryllus commodus.First, we identified loci associated with intraspecific variation inT. oceanicusmating signals, advertisement song and cuticular hydrocarbon (CHC) pheromones. We then separately identified candidate interspecific barrier loci between the species. Genes showing elevated allelic divergence between species were enriched for neurological functions, indicating potential behavioural rewiring. Only two CHC-associated genes overlapped with these interspecific barrier loci, and intraspecific CHC loci showed signatures of being under strong selective constraint between species. In contrast, 10 intraspecific song-associated genes showed high genetic differentiation betweenT. commodusandT. oceanicusand two had signals of high genomic divergence. Significant increased differentiation in sympatry supported a history of asymmetrical reinforcement driven primarily by divergence in sympatricT. commoduspopulations. The overall lack of shared loci in intra vs. inter-specific comparisons of mating trait and barrier loci is consistent with limited co-option of the genetic architecture of interspecific mating signals during establishment and maintenance of reproductive isolation.
Synergistic activity of rhamnolipid combined with linezolid against linezolid-resistantEnterococcus faecium
Authors: Chang Qingru , Chen Huinan , Li Yifan , Li Hai , Yang Zaixing , Zeng Jiankai , Zhang Ping , Gao Mingchun , Ge Junwei 
Published: August 2023

AbstractEnterococci resistance is increasing sharply, which poses a serious threat to public health. Rhamnolipids are a kind of amphiphilic compound used for its bioactivities, while the combination of nontraditional drugs to restore linezolid activity is an attractive strategy to treat infections caused by these pathogens. This study aimed to investigate the activity of linezolid in combination with the rhamnolipids againstEnterococcus faecium. Here, we determined that the rhamnolipids could enhance the efficacy of linezolid against enterococci infections by a checkerboard MIC assay, a time-kill assay, a combined disk test, anti-biofilm assay, molecular simulation dynamics, and mouse infection models. We identified that the combination of rhamnolipids and linezolid restored the linezolid sensitivity. Anti-biofilm experiments show that our new scheme can effectively inhibit biofilm generation. The mouse infection model demonstrated that the combination therapy significantly reduced the bacterial load in the feces, colons and kidneys following subcutaneous administration. This study showed that rhamnolipids could play a synergistic role with linezolid againstEnterococcus.Our combined agents could be appealing candidates for developing new combinatorial agents to restore antibiotic efficacy in the treatment of linezolid-resistantEnterococcusinfections.HighlightThe identification of a potential inhibitor of LRE, RLS could restore the antibacterial activity of LNZ.A rational mechanism of synergism between LNZ and RLS.;;L;;RLS in combination with LNZ promote the egress of pathogenicE. faeciumfrom the intestinal tract of mice to reduce its colonization, which has obvious synergistic effects.
ATG2A-mediated bridge-like lipid transport regulates lipid droplet accumulation
Authors: Korfhage Justin L. , Wan Neng , Elhan Helin , Kauffman Lisa , Pineda Mia , Fuller Devin M. , Thiam Abdou Rachid , Reinisch Karin M. , Melia Thomas J. 
Published: August 2023

AbstractATG2 proteins facilitate bulk lipid transport between membranes. ATG2 is an essential autophagy protein, but ATG2 also localizes to lipid droplets (LDs), and genetic depletion of ATG2 increases LD numbers while impairing fatty acid transport from LDs to mitochondria. How ATG2 supports LD homeostasis and whether lipid transport regulates this homeostasis remains unknown. Here we demonstrate that ATG2 is preferentially recruited to phospholipid monolayers such as those surrounding LDs rather than to phospholipid bilayers.In vitro, ATG2 can drive phospholipid transport from artificial LDs with rates that correlate with the binding affinities, such that phospholipids are moved much more efficiently when one of the ATG2-interacting structures is an artificial LD. ATG2 is thought to exhibit ‘bridge-like” lipid transport, with lipids flowing across the protein between membranes. We mutated key amino acids within the bridge to form a transport-dead ATG2 mutant (TD-ATG2A) which we show specifically blocks bridge-like, but not shuttle-like, lipid transportin vitro. TD-ATG2A still localizes to LDs, but is unable to rescue LD accumulation in ATG2 knockout cells. Thus, ATG2 has a natural affinity for, and an enhanced activity upon LD surfaces and uses bridge-like lipid transport to support LD dynamics in cells.
A chemical reaction network model of PURE
Authors: Jurado Zoila , Pandey Ayush , Murray Richard M. 
Published: August 2023

AbstractCell-free expression systems provide a method for rapid DNA circuit prototyping and functional protein synthesis. While crude extracts remain a black box with many components carrying out unknown reactions, the PURE system contains only the required transcription and translation components for protein production. All proteins and small molecules are at known concentrations, opening up the possibility of detailed modeling for reliable computational predictions. However, there is little to no experimental data supporting the expression of target proteins for detailed protein models PURE models. In this work, we build a chemical reaction network transcription model for PURE protein synthesis. We compare the transcription models using DNA encoding for the malachite-green aptamer (MGapt) to measure mRNA production. Furthermore, we expand the PURE detailed translation model for an arbitrary set of amino acids and length. Lastly, we combine the transcription and the expanded translation models to create a PURE protein synthesis model built purely from mass-action reactions. We use the combined model to capture the translation of a plasmid encoding MGapt and deGFP under a T7-promoter and a strong RBS. The model accurately predicts the MGapt mRNA production for the first two hours, the dynamics of deGFP expression, and the total protein production with an accuracy within 10 %.
Empirically investigating the organizational identity mechanism of empowering leadership affecting the innovation performance of knowledge workers
Authors: Wei Huafei , Chen Jun , Chudhery Muhammad Adnan Zahid , Fang Wenjie 
Published: August 2023

PurposeThe authors examined how the identification mechanism of the innovation performance of knowledge employees is affected by empowering leadership by influencing the organizational identification and the moderating effect of leaders on the role expectation of knowledge employees as an essential innovation subject.Design/methodology/approachThe authors employed a mixed-method research approach. The authors collected data from 378 knowledge employees and managers in 20 companies in China's Yangtze River Delta cities. The authors analyzed data using multiple regression analysis forecasting methods.FindingsThe authors found that there was an inverted U-shaped relationship between empowering leadership and the innovation performance of knowledge employees; organizational identity played a partial mediating role between empowering leadership and the innovation performance of knowledge employees; role expectation of leaders on the innovation behavior of employees regulated the relationship between the organizational identity and innovation performance of knowledge employees.Originality/valueThis study extends the literature on empowering leadership and innovation performance. This study empirically examines the mediating effect of organizational identity between empowering leadership and innovation performance. In addition, this study empirically examines how empowered leaders' expected innovation level moderates the association between organizational identity and innovation performance.
Punishing the pseudo‐opposition: Accountability under a minority government
Authors: HJERMITSLEV IDA B. 
Published: August 2023

AbstractMinority governments often rely on the legislative support of parties, which play an ambiguous role in politics: while they are formally part of the opposition, they are simultaneously committed to keeping the government in office and passing its bills. Are these support parties protected from the electoral cost of governing or do voters recognize their responsibility for policy outcomes and hold them accountable? I hypothesize that voters who are dissatisfied with government performance will have less sympathy towards and will be less likely to vote for support parties. Using Comparative Study of Electoral Systems data, I find consistent support for both hypotheses. Voters seem to recognize the connection between support parties and the government and have both an affective and an electoral response to it. While voters dislike support parties more than junior members when they are dissatisfied with government performance, they punish the two types of parties similarly at elections. Support parties are thus in no way exempt from the accountability mechanisms.
Association between depression and risk of type 2 diabetes and its sociodemographic factors modifications: A prospective cohort study in southwest China
Authors: Wu Yanli , Chen Min , Liu Tao , Zhou Jie , Wang Yiying , Yu Lisha , Zhang Ji , Tian Kunming 
Published: August 2023

AbstractBackgroundDepression may be associated with the risk of developing type 2 diabetes. The goal of this study was to explore the association of severe of depression with the risk of type 2 diabetes in adults in Guizhou, China.MethodsA 10‐year prospective cohort study of 7158 nondiabetes adults aged 18 years or older was conducted in Guizhou, southwest China from 2010 to 2020. The Patient Health Questionnaire‐9 (PHQ‐9) was used to measure the prevalence of depression. Cox proportional hazard models were used to estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) of depression and incident type 2 diabetes. A quantile regression (QR) analytical approach were applied to evaluate the associations of PHQ‐9 score with plasma glucose values.ResultsA total of 739 type 2 diabetes cases were identified during a median follow‐up of 6.59 years. The HR (95% CI) per 1‐SD increase for baseline PHQ‐9 score was 1.051 (1.021, 1.082) after multivariable adjustment. Compared with participants without depression, those with mild or more advanced depression had a higher risk of incident type 2 diabetes (HR:1.440 [95% CI, 1.095, 1.894]). Associations between depression with type 2 diabetes were suggested to be even stronger among women or participants aged ≥45 years (p < .05). There are significant positive associations of PHQ‐9 score with 2‐h oral glucose tolerance test blood glucose levels.ConclusionDepression significantly increased the risk of incident type 2 diabetes, especially in women, participants aged ≥45 years, Han ethnicity, and urban residents. These findings highlighted the importance and urgency of depression health care.
DYRK1B haploinsufficiency in a Holstein cattle with epilepsy
Authors: Jacinto Joana G. P. , Bolcato Marilena , Häfliger Irene M. , Oevermann Anna , Gentile Arcangelo , Drögemüller Cord 
Published: August 2023

AbstractIn this study, epilepsy with focal seizures progressing to generalized seizures was diagnosed in a 6‐month‐old Holstein heifer. The seizures were characterized by a brief pre‐ictal phase with depression and vocalization. During the ictal phase eyelid spasms, tongue contractions, nodding and abundant salivation were observed, rapidly followed by a convulsive phase with bilateral tonic, clonic or tonic–clonic activity and loss of consciousness. Finally, during the postictal phase the heifer was obtunded and disorientated, unable to perceive obstacles and hypermetric, and pressed its head against objects. In the inter‐seizure phase, the heifer was clinically normal. Neuropathology revealed axonal degeneration in the brainstem and diffuse astrocytic hypertrophic gliosis. Whole genome sequencing of the affected heifer identified a private heterozygous splice‐site variant in DYRK1B (NM_001081515.1: c.‐101‐1G>A), most likely resulting in haploinsufficiency owing to loss‐of‐function. This represents a report of a DYRK1B‐associated disease in cattle and adds DYRK1B to the candidate genes for epilepsy.
Investigation and analysis of ancient brick carvings of the Liuhe Pagoda in Hangzhou
Authors: Fang Xinxin , Xie Lina , Zhang Bingjian , Li Jiajia , Chen Weixiang 
Published: August 2023

AbstractThe Liuhe Pagoda in Hangzhou, China, has a large number of brick carvings from the Southern Song Dynasty (1152 ce), covering an area of 464 m2. However, the exquisite brick carvings in the Liuhe Pagoda have deteriorated due to natural weathering and a high‐humidity environment. Through laboratory analysis and on‐site nondestructive testing, the physical and chemical properties of the brick carvings of Liuhe Pagoda were investigated, and the weathering mechanism of the brick carvings was further analyzed. The brick carving of Liuhe Pagoda is composed of brick, white plastering and black coating. CaCO3 is the main component in white plastering, and the black coating on the top surface contains Chinese lacquer. The weathering products of the brick were analyzed and a trace of CaSO4.2H2O was found. In addition, the brick carvings with high water content have low Leeb hardness and severe weathering. Therefore, water and soluble salt are the main factors in weathering of the brick carvings of the Liuhe Pagoda.
XPO1 mutations identify early‐stage CLL characterized by shorter time to first treatment and enhanced BCR signalling
Authors: Moia Riccardo , Terzi di Bergamo Lodovico , Talotta Donatella , Bomben Riccardo , Forestieri Gabriela , Spina Valeria , Bruscaggin Alessio , Cosentino Chiara , Almasri Mohammad , Dondolin Riccardo , Bittolo Tamara , Zucchetto Antonella , Baldoni Stefano , Del Giudice Ilaria , Mauro Francesca Romana , Maffei Rossana , Chiarenza Annalisa , Tafuri Agostino , Laureana Roberta , Del Principe Maria Ilaria , Zaja Francesco , D'Arena Giovanni , Olivieri Jacopo , Rasi Silvia , Mahmoud Abdurraouf , Al Essa Wael , Awikeh Bassel , Kogila Sreekar , Bellia Matteo , Mouhssine Samir , Sportoletti Paolo , Marasca Roberto , Scarfò Lydia , Ghia Paolo , Gattei Valter , Foà Robin , Rossi Davide , Gaidano Gianluca 
Published: August 2023

SummaryHere we evaluated the epigenomic and transcriptomic profile of XPO1 mutant chronic lymphocytic leukaemia (CLL) and their clinical phenotype. By ATAC‐seq, chromatin regions that were more accessible in XPO1 mutated CLL were enriched of binding sites for transcription factors regulated by pathways emanating from the B‐cell receptor (BCR), including NF‐κB signalling, p38‐JNK and RAS‐RAF‐MEK‐ERK. XPO1 mutant CLL, consistent with the chromatin accessibility changes, were enriched with transcriptomic features associated with BCR and cytokine signalling. By combining epigenomic and transcriptomic data, MIR155HG, the host gene of miR‐155, and MYB, the transcription factor that positively regulates MIR155HG, were upregulated by RNA‐seq and their promoters were more accessible by ATAC‐seq. To evaluate the clinical impact of XPO1 mutations, we investigated a total of 957 early‐stage CLL subdivided into 3 independent cohorts (N = 276, N = 286 and N = 395). Next‐generation sequencing analysis identified XPO1 mutations as a novel predictor of shorter time to first treatment (TTFT) in all cohorts. Notably, XPO1 mutations maintained their prognostic value independent of the immunoglobulin heavy chain variable status and early‐stage prognostic models. These data suggest that XPO1 mutations, conceivably through increased miR‐155 levels, may enhance BCR signalling leading to higher proliferation and shorter TTFT in early‐stage CLL.
Public–private partnership, cost of debt and accounting conservatism
Authors: Deng Qu , Li Hezun , Yue Hong 
Published: August 2023

AbstractUsing a manually collected data set of Chinese publicly traded firms from 2010 to 2017, this study examines how public–private partnerships (PPP) affect the cost of debt and financial reporting. We argue that a firm gains political capital through a PPP and thus may access debt markets at a lower cost. Consistent with our expectation, we find that participants of PPP enjoy significantly lower bank loan interest rates than other firms. This is more pronounced for nonstate‐owned enterprises, for firms without politically connected CEOs, and for loans from state‐owned banks. However, these participants reduce their accounting conservatism, suggesting a substitution between financial reporting and political connections. Also, participating in PPP does not improve firms' financial performance. Thus, the lower interest rates are not justified by economic fundamentals or financial reporting quality. Overall, our study suggests that PPP distort state‐owned banks' lending decisions and lower accounting conservatism, highlighting the potential cost of PPP to society.
Service failure and service recovery: A hybrid review and research agenda
Authors: Sahaf Taiba Musadiq , Fazili Asif Iqbal 
Published: August 2023

AbstractIt is an opportune time to reflect on the progress of service failure and service recovery in the field of service marketing, specifically with a focus on perceived justice. Over the past three decades, justice theory has played a pivotal role in explaining these phenomena, prompting the need to evaluate its current standing and contributions. The study reviews the literature on service failure and recovery (SFR) using the hybrid review approach through an integration of bibliometric analysis and a framework‐based review (Theories–Characteristics–Contexts–Methods; Paul and Rosado‐Serrano, 2019, International Marketing Review, 36(6), 830–858). In the bibliometric overview, the publication trend and citation structure of articles dealing with perceived justice in SFR between 1990 and March 2022, the most prolific authors/sources as well as the most active institutions that contribute the most to this field of scientific inquiry have been analysed in detail. Following the performance analysis, the authors carry out scientific mapping that underscores the intellectual corpus as well as the emergent themes of the field. Using network analysis in visualization of similarities viewer software, service failure, service recovery and perceived justice in service failure and service recovery have been grouped into clusters based on co‐citation analysis and bibliographic coupling. The articles in the clusters are critically reviewed in terms of theories, contexts, characteristics and methods to not only synthesize the foundational knowledge in the field and propose avenues for future but also make recommendations for academia and industry. To add scientific rigour, the study uses Scientific Procedures and Rationales for Systematic Literature Reviews (Paul et al., 2021, International Journal of Consumer Studies, 45(4), O1–O16) protocol to guide review decisions in a bibliometric analysis.