bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrin αVβ6: Autoantigen and Driver of Epithelial Remodeling in Colon and Bile Ducts in Primary Sclerosing Cholangitis and Inflammatory Bowel Disease
Authors: Roth Dominik , Düll Miriam M , Horst Ludwig J , Lindemann Aylin , Malzer Xenia , Koop Kristina , Zundler Sebastian , Vetter Marcel , Jefremow André , Atreya Raja , Geppert Carol , Weidemann Sören , Waldner Maximilian J , Dietrich Peter , Günther Claudia , Munoz Luis E , Herrmann Martin , Scheffold Alexander , Neurath Markus F , Siebler Jürgen , Schramm Christoph , Kremer Andreas E , Leppkes Moritz 
Published: August 2024

Abstract

Background
Recently, autoantibodies directed against the epithelial adhesion protein integrin αVβ6 have been identified that are strongly associated with ulcerative colitis (UC). We aimed to elucidate whether anti-integrin αVβ6 (anti-αVβ6) is present in primary sclerosing cholangitis (PSC), its associated inflammatory bowel disease, or other cholestatic liver diseases and their persistence after proctocolectomy.

Methods
We detected anti-αVβ6 by an enzyme-linked immunosorbent assay in sera collected at 2 German tertiary centers, including healthy controls (N = 62), UC (N = 36), Crohn’s disease (CD, N = 65), PSC-inflammatory bowel diseases (IBD) (78 samples from N = 41 patients), PSC without IBD (PSC, 41 samples from N = 18 patients), primary biliary cholangitis (PBC, N = 24), autoimmune hepatitis (AIH, N = 32), secondary sclerosing cholangitis (SSC, N = 12), and metabolic dysfunction-associated steatotic liver disease (MASLD, N = 24). In addition, sera after proctocolectomy were studied (44 samples/N = 10 patients). Immunofluorescent analyses were performed in tissue samples from liver, large bile duct from surgical resections, and colon of PSC patients.

Results
Anti-αVβ6 occurred in 91% of UC, 17% of CD, 73% of PSC-IBD, 39% of PSC, 4% of PBC, 14% of AIH, and 0% of healthy controls, SSC, or MASLD. Integrin αVβ6 is selectively expressed in disease-associated epithelia of both bile duct and colon. Anti-αVβ6 levels correlate moderately with intestinal disease activity in PSC-IBD, but only weakly with biliary disease.

Conclusions
Anti-αVβ6 frequently occurs in patients suffering from PSC, especially in PSC-IBD. Anti-αVβ6 levels positively correlate to IBD activity in PSC-IBD, but may also occur in the absence of clinically manifest IBD in PSC.
Experimental evolution for improved postinfection survival selects for increased disease resistance inDrosophila melanogaster
Authors: Basu Aabeer , Tekade Kimaya , Singh Aparajita , Das Paresh Nath , Prasad Nagaraj Guru 
Published: August 2024

AbstractDisease resistance (defined as the host capacity to limit systemic infection intensity) and disease tolerance (defined as the host capacity to limit infection-induced damage) are 2 complementary defense strategies that help the hosts maximize their survival and fitness when infected with pathogens and parasites. In addition to the underlying physiological mechanisms, the existing theory postulates that these 2 strategies differ in terms of the conditions under which each strategy evolves in the host populations, their evolutionary dynamics, and the ecological and epidemiological consequences of their evolution. Here, we explored if one or both of these strategies evolve when host populations are subjected to selection for increased postinfection survival. We experimentally evolved Drosophila melanogaster populations, selecting for the flies that survived an infection with the entomopathogen Enterococcus faecalis. We found that the host populations evolved increased disease resistance in response to selection for increased survival. This was despite the physiological costs associated with increased resistance, the expression of which varied with the phase of infection. We did not find evidence of any change in disease tolerance in the evolved host populations.
Genetic Variability for Clonal Propagation of Acacia mearnsii
Authors: de Sá Larissa França , Lohmann Gabriele Taís , Bandeira Peres Fabiana Schmidt , Tambarussi Evandro Vagner 
Published: August 2024

Abstract
Plantations of Acacia mearnsii established from seeds often exhibit low levels of productivity due to significant differences in plant growth. Therefore, the aim of this study was to assess the genetic control associated with clonal propagation of A. mearnsii and use a selection index to quantify gains for traits related to vegetative propagation. Data collected from nurseries for 2 years included mini-cutting productivity per mini-stump (PD), percentage of adventitious rooting (ENR), and ramet productivity index (PI). For clone production traits, PD (r = 0.36) and PI (r = 0.24) demonstrated moderate repeatability, whereas ENR (r = 0.06) exhibited low repeatability. Tree height (H2 = 0.20), and diameter at breast height (H2 = 0.13) showed moderate and low heritability, respectively. Genotype selection for vegetative propagation supported by PI-generated selection gains of over 50%, suggesting the efficacy of using this criterion in early evaluation and selection of genotypes for nursery propagation. The additive selection index considering PI and Ht traits can be used for early selection of superior A. mearnsii genotypes, promoting estimated gains of up to 2.5%. Given the importance of these parameters, these findings provide crucial insights for A. mearnsii breeders, addressing a notable gap in the literature concerning these traits.
Study Implications: The moderate heritability of traits such as mini-cutting productivity, propagule productivity index (PI), height, and diameter at breast height, except for the percentage of adventitious rooting, which showed low heritability, suggests that these traits are influenced by genetic factors to a considerable extent. The study suggests that the selection of genotypes based on PI can significantly improve vegetative propagation outcomes, with potential selection gains of more than 50%. This indicates that nurseries can achieve higher productivity and efficiency by implementing genotype selection processes based on this criterion.
Saline-alkali stress affects the accumulation of proanthocyanidins and sesquiterpenoids via the MYB5-ANR/TPS31 cascades in the rose petals
Authors: Wang Qiao , Du Baoquan , Bai Yujing , Chen Yan , Li Feng , Du Jinzhe , Wu Xiuwen , Yan Liping , Bai Yue , Chai Guohua 
Published: August 2024

Abstract
Rose (Rosa rugosa) petals are rich in diverse secondary metabolites, which have important physiological functions as well as great economic values. Currently, it remains unclear how saline and/or alkaline stress(es) influence the accumulation of secondary metabolites in rose. In this study, we analyzed the transcriptome and metabolite profiles of rose petals under aline–alkali stress and uncovered the induction mechanism underlying major metabolites. Dramatic changes were observed in the expression of 1363 genes and the abundances of 196 metabolites in petals in response to saline–alkali stress. These differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) are mainly associated with flavonoid and terpenoid metabolism and the reconstruction of cell walls. Of them, TERPENE SYNTHASE 31 (TPS31) overexpression in tobacco leaves driven by its own promoter resulted in significant alterations in the levels of diverse terpenoids, which were differentially influenced by saline–alkali stress. An integrated analysis of metabolomic and transcriptomic data revealed a high correlation between the abundances of flavonoids/terpenoids and the expression of the transcription factor MYB5. MYB5 may orchestrate the biosynthesis of sesquiterpenoids and proanthocyanidins through direct regulation of TPS31 and ANR expression under aline–alkali stress. Our finding facilitates improving the bioactive substance accumulation of rose petals by metabolic engineering.
The circulation of methicillin-resistant Staphylococcus aureus between humans, horses and the environment at the equine clinic
Authors: Papouskova Aneta , Drabkova Zuzana , Brajerova Marie , Krutova Marcela , Cizek Alois , Tkadlec Jan 
Published: August 2024

Abstract

Objectives
We performed a retrospective analysis of MRSA isolates collected at the university equine clinic including clinical isolates from 2008 to 2021 and screening environmental, equine and personnel isolates from 2016.

Methods
Screening and clinical samples were cultured on Brilliance MRSA 2 and Columbia agar (Oxoid), respectively, with enrichment for environmental samples. Antimicrobial susceptibility was assessed by disc diffusion. All the isolates were characterized by spa typing. Eighteen selected isolates were subjected to WGS with subsequent wgMLST clonal analysis.

Results
Among 75 MRSA isolates, five spa types were identified, the majority (n = 67; 89.33%) was t011. All isolates were resistant to cefoxitin and ampicillin and carried the mecA gene. In addition, the isolates were resistant to tetracycline (n = 74; 98.67%), gentamicin (n = 70; 93.33%), enrofloxacin (n = 54; 72.00%), sulfamethoxazole-trimethoprim (n = 5; 6.67%) and lincomycin (n = 3; 4.00%) with corresponding genetic markers for the resistance detected in the sequenced isolates. All 18 sequenced isolates belonged to ST398, 16 carried SCCmec type IVa and two carried SCCmec type Vc (5C2&5). Further, isolates carried aur, hlgA, hlgB and hlgC virulence genes, and five isolates carried sak and scn genes, which are part of the immune evasion cluster. Close genetic relatedness was found between isolates from the staff of the clinic and clinical samples of horses.

Conclusions
Repeated introduction and long-term persistence of the equine LA-MRSA subclone (ST398-MRSA-IVa/Vc(5C2&5), t011) among the infected horses at the equine clinic with the colonization of personnel, and the environment contamination that might contribute to transmission were observed.
In silico analysis of polyphenols modulate bovine PPARγ to increase milk fat synthesis in dairy cattle via the MAPK signaling pathways
Authors: Safdar Muhammad , Hassan Faizul , Khan Muhammad Sajjad , Khan Aneeb Hassan , Junejo Yasmeen , Ozaslan Mehmet , Arain Muhammad Asif , Behan Atique Ahmed 
Published: August 2024

Abstract
This study investigates the potential phytochemicals that modulate bovine peroxisome proliferator-activated receptor gamma (PPARγ) and the mitogen-activated protein kinase (MAPK) pathways to enhance milk fat production in dairy animals. Bovine PPARγ, a key member of the nuclear hormone receptor superfamily, plays a vital role in regulating metabolic, cellular differentiation, apoptosis, and anti-inflammatory responses in livestock, while the MAPK pathway is contributory in cellular processes that impact milk fat synthesis. This approach involved an all-inclusive molecular docking analysis of 10,000 polyphenols to identify potential PPARγ ligands. From this extensive screening, top 10 compounds were selected that exhibited the highest binding affinities to bovine PPARγ. Particularly, curcumin sulfate, isoflavone, and quercetin emerged as the most promising candidates. These compounds demonstrated superior docking scores (−9.28 kcal/mol, −9.27 kcal/mol, and −7.31 kcal/mol, respectively) and lower RMSD values compared to the synthetic bovine PPARγ agonist, 2,4-thiazolidinedione (−4.12 kcal/mol), indicating a strong potential for modulating the receptor. Molecular dynamics simulations (MDS) further affirmed the stability of these polyphenols–bovine PPARγ complexes, suggesting their effective and sustained interactions. These polyphenols, known as fatty acid synthase inhibitors, are suggested to influence lipid metabolism pathways crucial to milk fat production, possibly through the downregulation of the MAPK pathway. The screened compounds showed favorable pharmacokinetic profiles, including nontoxicity, carcinogenicity, and high gastrointestinal absorption, positioning them as viable candidates for enhancing dairy cattle health and milk production. These findings may open new possibilities for the use of phytochemicals as feed additives in dairy animals, suggesting a novel approach to improve milk fat synthesis through the dual modulation of bovine PPARγ and MAPK pathways.
An improved understanding of pediatric chronic nonbacterial osteomyelitis pathophysiology informs current and future treatment
Authors: Roberts Eve , Charras Amandine , Hahn Gabriele , Hedrich Christian M 
Published: August 2024

Abstract
Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disease that primarily affects children and young people. It can cause significant pain, reduced function, bone swelling, and even (vertebral body) fractures. Because of a limited understanding of its pathophysiology, the treatment of CNO remains empiric and is based on relatively small case series, expert opinion, and personal experience. Several studies have linked pathological NOD-kike receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome activation and the resulting imbalance between pro- and anti-inflammatory cytokine expression with CNO. This agrees with elevated pro-inflammatory (mostly) monocyte-derived protein signatures in the blood of CNO patients that may be used as future diagnostic and/or prognostic biomarkers. Recently, rare variants in the P2RX7 gene, encoding for an ATP-dependent transmembrane channel, were linked with increased NLRP3 inflammasome assembly and prolonged monocyte/macrophage survival in CNO. Although the exact molecular mechanisms remain unclear, this will inform future target-directed and individualized treatment. This manuscript reviews most recent developments and their impact on diagnostic and therapeutic strategies in CNO.
Effect of temperature and humidity on insect DNA integrity evaluated by real-time PCR
Authors: Fowler Elizabeth V , Starkie Melissa L , Blacket Mark J , Mayer David G , Schutze Mark K 
Published: August 2024

Abstract
Insects collected in dry traps can degrade rapidly, especially in warm, humid environments where many biodiversity and biosecurity surveillance activities are undertaken. Degradation can severely impact diagnostics, as trap catches can become difficult to identify to species level using morphological characters or, of increasing importance, molecular approaches. This is especially problematic for biosecurity surveillance of exotic tephritid fruit flies, where diagnostics are heavily reliant on morphological characters. We tested the effects of differing temperature and humidity conditions on mock samples of tephritid fruit flies in a controlled environment and compared our results to field trap catches. DNA degradation was quantified using real-time PCR assays, including one assay newly developed and tested here. We observed a correlation between increasing DNA degradation and increasing temperature and humidity. The greatest DNA degradation occurred under combined high humidity (90% relative humidity) and constant high temperature (35 °C). Unexpectedly, fluctuating temperature did not have a significant impact on DNA. Other factors, such as trap design, time in the field, and rainfall, did not significantly correlate with DNA quality across the field samples tested. When plotted against mock samples, field samples clustered together, with no clear pattern or predictability regarding the quantity of DNA preserved, indicating other untested environmental variables may be at play. Predictably, increased exposure time was found to have a detrimental effect on DNA quality for all treatments. These findings will improve the delivery of surveillance activities through the implementation of shorter trap clearance timeframes and improved trap designs and procedures.
Difference in activated partial thromboplastin time values with two different reagents according to C-reactive protein values
Authors: Ishihara Yuya , Doi Hiroki , Sato Seiko , Ito Hiroyasu 
Published: August 2024

Abstract

Background
Activated partial thromboplastin time (APTT) is susceptible to reagent composition. This study aimed to investigate a large number of specimens and determine the cause of discrepancies.

Method
This study included 18,994 subjects who underwent coagulation tests at our hospital from May 2020 to December 2020. Measuring reagents included HemosIL SynthASil APTT (APTT-SS, Instrumentation Laboratory) and Coagpia APTT-N (APTT-N, Sekisui Medical).

Results
A total of 451 patients demonstrated APTT-N of &gt;39 seconds and an APTT-N/SS ratio of &gt;1.3. A C-reactive protein (CRP) level of ≥1.4 mg/L demonstrated a significant positive correlation, with a higher APTT-N/SS indicating higher CRP levels. All 28 subjects receiving no anticoagulants and who had remaining specimens underwent a cross-mixing test (CMT). Of them, 17 were suspected for lupus anticoagulant (LA) by both the waveform shape and the index of circulating anticoagulant (ICA) value, 6 by the ICA value, and 5 were difficult to determine.

Conclusion
This study revealed that the APTT-N prolongation correlated with CRP degree and the transient involvement of LA in CMT results due to CRP. This study indicated various reactivities depending on the assay reagents used. Further testing is warranted if LA is suspected, considering the patient’s background.
Analysis of HER2 expression changes from breast primary to brain metastases and the impact of HER2-low expression on overall survival
Authors: Pereslete Alyssa M , Hughes Melissa E , Martin Alyssa R , Files Janet , Nguyen Kyleen , Buckley Lauren , Patel Ashka , Moore Abigail , Winer Eric P , Dillon Deborah , Li Tianyu , Tolaney Sara M , Lin Nancy U , Sammons Sarah L 
Published: August 2024

Abstract

Background
There are limited data regarding HER2-low expression dynamics between matched primary tumors and brain metastases (BrMs) in breast cancer. HER2-low expression has emerged as a new therapeutic biomarker for highly active antibody-drug conjugates with emerging intracranial activity.

Methods
Patients with metastatic breast cancer and BrMs seen at an NCI-designated center between 2003 and 2023 were identified. HER2 expression was defined as HER2-positive (3+, 2+/ISH amplified), HER2-low (1+, 2+/ISH negative), or HER2–0 by ASCO-CAP guidelines. Estrogen receptor (ER) status was defined as ER ≥1%. Multivariate survival analyses by Cox proportional hazard models were determined from the time of BrM resection to death or last follow-up between the 3 subtypes, controlling for ER and age.

Results
Among 197 matched primary and resected BrMs, 81% exhibited HER2 expression in the brain: 61% HER2-positive, 20% HER2-low, and 19% HER2–0. Concordance was high in HER2-positive primary tumors with 100% retaining HER2 expression (97% retained HER2-positive expression and 2.7% switched to HER2-low). HER2–0 primaries frequently showed HER2 gain in BrMs to HER2-low (35%) or HER2-positive (5.4%) status. Among 48 HER2-low primary tumors, 52% were discordant for HER2 status in the brain with 21% testing HER2-positive and 31% testing HER2–0. In adjusted analyses, patients with HER2-positive BrMs had significantly lower death risk than patients with HER2-low BrMs (HR = 0.41, P = .0006); no difference was observed between HER2–0 and HER2-low.

Conclusions
In this retrospective analysis, HER2 expression is common in breast cancer BrMs, emphasizing the need for improved, noninvasive diagnostics. Patients with HER2-low and HER2–0 BrMs face inferior survival, presenting an unmet clinical need.
Ecology and conservation of cavity-nesting birds in the Neotropics: Recent advances, future directions, and contributions to ornithology
Authors: Bonaparte Eugenia Bianca , Cuatianquiz Lima Cecilia , Ferreira-Xavier Hipólito D , da Hora Jéssica S , Di Sallo Facundo G , López Fernando G , Cockle Kristina L , Núñez Montellano María Gabriela 
Published: August 2024

Abstract
About 35% of tree-cavity-nesting bird species inhabit the Neotropics, a region crucial to understanding their breeding ecology, conservation, and roles in social-ecological systems. Sixteen years ago, Cornelius et al. (2008) reviewed published knowledge and identified research priorities for Neotropical cavity-nesting birds. Advances since 2008 have not been synthesized and many remain excluded from dominant ornithology because of barriers that disproportionately affect people and ideas from the Global South. Here, we review recent advances in knowledge about Neotropical cavity-nesting birds, introduce the Special Feature series “Ecology and conservation of cavity nesters in the Neotropics,” and outline possible directions for future research. Research in the Neotropics has advanced knowledge of breeding biology, demonstrated that nest sites are limited and birds compete for cavities (mainly in humid forests), identified non-excavated cavities (formed by wood decay) as the main source of cavities and demonstrated the importance of understanding Indigenous and local community relationships to birds. With field studies across the Neotropics, the Special Feature series shows how environment, people’s common imaginaries, vegetation management, and behavior of avian excavators can interact to influence cavity availability, with ecological consequences for many cavity-using organisms. In the future, researchers should center ethno-knowledge and natural history to create an accurate list of cavity-nesting birds in the Neotropics, and integrate this knowledge into studies of population and community ecology. It is also important to study factors that influence cavity dynamics, especially using a social-ecological systems framework and especially in arid and semi-arid regions. We recommend expanding the concept of nest webs (ecological networks of cavity nesters) to incorporate additional cavity substrates (e.g., termitaria, cliffs), cavity alternatives (e.g., bulky enclosed stick nests of many Furnariidae), and cavity-using taxa beyond birds and mammals (e.g., social insects, snakes), which abound in the Neotropics but were not contemplated in the original nest web formulation. Translated versions of this article are available in Supplementary Material 1 (Spanish) and Supplementary Material 2 (Portuguese).
Assessment of safety culture in radiotherapy facilities using safety performance indicators
Authors: Sharma Smriti , Sivaramakrishnan Mahalakshmi , Tripathi Arti , Dixit Pramod Kumar , Krishnakumar Namitha , Sahani Ghanshyam , Dash Sharma Pankaj Kumar , Sharma Sunil Dutt 
Published: August 2024

Abstract
This paper describes the development of the Safety Performance Indicators (SPIs), the methodology for assessment of the safety culture of radiotherapy institutions using SPIs and common strengths and common areas for improvement. SPIs were categorized into eight sections which all together contain 23 attributes and each attribute has scoring criteria from 0 to 2 (in steps of 0.5). The maximum absolute cumulative score of SPIs was 46. A relative cumulative SPIs score of &gt;80% indicates an institution strong commitment towards safety while score &lt;50% indicates need for additional guidance to enhance safety culture. The assessment using SPIs was conducted for 17 radiotherapy institutions. The methodology of assessment includes interactive discussion, direct observations and document analysis. The relative cumulative SPIs score of seven institutions was found to be &gt;80% while it was found in the range of 67.0% to 80% for the remaining ten institutions. Institutions were communicated about the cumulative SPIs score, areas of strengths, and areas for improvement. SPIs were found to be a good tool for safety culture assessment and can be utilized by the radiotherapy institutes for self-assessment to identify the areas of improvement. Based on SPIs score, regulatory body can grade the institutions from a radiation safety compliance point of view.