bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endolysin NC5 improves early cloxacillin treatment in a mouse model of Streptococcus uberis mastitis
Authors: Vander Elst Niels , Bellemans Julie , Lavigne Rob , Briers Yves , Meyer Evelyne 
Published: January 2024

Abstract
Streptococcus uberis frequently causes bovine mastitis, an infectious udder disease with significant economic implications for dairy cows. Conventional antibiotics, such as cloxacillin, sometimes have limited success in eliminating S. uberis as a stand-alone therapy. To address this challenge, the study objective was to investigate the VersaTile engineered endolysin NC5 as a supplemental therapy to cloxacillin in a mouse model of bovine S. uberis mastitis. NC5 was previously selected based on its intracellular killing and biofilm eradicating activity. To deliver preclinical proof-of-concept of this supplemental strategy, lactating mice were intramammarily infected with a bovine S. uberis field isolate and subsequently treated with cloxacillin (30.0 μg) combined with either a low (23.5 μg) or high (235.0 μg) dose of NC5. An antibiotic monotherapy group, as well as placebo treatment, was included as controls. Two types of responders were identified: fast (n = 17), showing response after 4-h treatment, and slow (n = 10), exhibiting no clear response at 4 h post-treatment across all groups. The high-dose combination therapy in comparison with placebo treatment impacted the hallmarks of mastitis in the fast responders by reducing (i) the bacterial load 13,000-fold (4.11 ± 0.78 Δlog10; p < 0.001), (ii) neutrophil infiltration 5.7-fold (p > 0.05), and (iii) the key pro-inflammatory chemokine IL-8 13-fold (p < 0.01). These mastitis hallmarks typically followed a dose response dependent on the amount of endolysin added. The current in vivo study complements our in vitro data and provides preclinical proof-of-concept of NC5 as an adjunct to intramammary cloxacillin treatment.

Key points
• Engineered endolysin NC5 was preclinically evaluated as add-on to cloxacillin treatment.
• Two types of mice (slow and fast responding) were observed.
• The add-on treatment decreased bacterial load, neutrophil influx, and pro-inflammatory mediators.
Novel recombinant aminoacylase from Paraburkholderia monticola capable of N-acyl-amino acid synthesis
Authors: Haeger Gerrit , Jolmes Tristan , Oyen Sven , Jaeger Karl-Erich , Bongaerts Johannes , Schörken Ulrich , Siegert Petra 
Published: January 2024

Abstract
N-Acyl-amino acids can act as mild biobased surfactants, which are used, e.g., in baby shampoos. However, their chemical synthesis needs acyl chlorides and does not meet sustainability criteria. Thus, the identification of biocatalysts to develop greener synthesis routes is desirable. We describe a novel aminoacylase from Paraburkholderia monticola DSM 100849 (PmAcy) which was identified, cloned, and evaluated for its N-acyl-amino acid synthesis potential. Soluble protein was obtained by expression in lactose autoinduction medium and co-expression of molecular chaperones GroEL/S. Strep-tag affinity purification enriched the enzyme 16-fold and yielded 15 mg pure enzyme from 100 mL of culture. Biochemical characterization revealed that PmAcy possesses beneficial traits for industrial application like high temperature and pH-stability. A heat activation of PmAcy was observed upon incubation at temperatures up to 80 °C. Hydrolytic activity of PmAcy was detected with several N-acyl-amino acids as substrates and exhibited the highest conversion rate of 773 U/mg with N-lauroyl-L-alanine at 75 °C. The enzyme preferred long-chain acyl-amino-acids and displayed hardly any activity with acetyl-amino acids. PmAcy was also capable of N-acyl-amino acid synthesis with good conversion rates. The best synthesis results were obtained with the cationic L-amino acids L-arginine and L-lysine as well as with L-leucine and L-phenylalanine. Exemplarily, L-phenylalanine was acylated with fatty acids of chain lengths from C8 to C18 with conversion rates of up to 75%. N-lauroyl-L-phenylalanine was purified by precipitation, and the structure of the reaction product was verified by LC–MS and NMR.

Key points
• A novel aminoacylase from Paraburkholderia monticola was cloned, expressed in E. coli and purified.
• The enzyme PmAcy exhibits exceptional temperature and pH stability and a broad substrate spectrum.
• Synthesis of acyl amino acids was achieved in good yields.
Identification of acidic stress-responsive genes and acid tolerance engineering in Synechococcus elongatus PCC 7942
Authors: Zhang Jie , Sun Tao , Zhang Weiwen , Chen Lei 
Published: January 2024

Abstract
Cyanobacteria are excellent autotrophic photosynthetic chassis employed in synthetic biology, and previous studies have suggested that they have alkaline tolerance but low acid tolerance, significantly limiting their productivity as photosynthetic chassis and necessitating investigations into the acid stress resistance mechanism. In this study, differentially expressed genes were obtained by RNA sequencing-based comparative transcriptomic analysis under long-term acidic stress conditions and acidic shock treatment, in the model cyanobacterium Synechococcus elongatus PCC 7942. A pathway enrichment analysis revealed the upregulated and downregulated pathways during long-term acidic and shock stress treatment. The subsequent single gene knockout and phenotype analysis showed that under acidic stress conditions, the strains with chlL, chlN, pex, synpcc7942_2038, synpcc7942_1890, or synpcc7942_2547 knocked out grew worse than the wild type, suggesting their involvement in acid tolerance. This finding was further confirmed by introducing the corresponding genes back into the knockout mutant individually. Moreover, individual overexpression of the chlL and chlN genes in the wild type successfully improved the tolerance of S. elongatus PCC 7942 to acidic stress. This work successfully identified six genes involved in acidic stress responses, and overexpressing chIL or chIN individually successfully improved acid tolerance in S. elongatus PCC 7942, providing valuable information to better understand the acid resistance mechanism in S. elongatus PCC 7942 and novel insights into the robustness and tolerance engineering of cyanobacterial chassis.

Key points
• DEGs were identified by RNA-seq based transcriptomics analysis in response to acidic stress in S. elongatus PCC 7942.
• Six genes were identified to be involved in acid tolerance in S. elongatus PCC 7942.
• Overexpression of chIL or chIN individually successfully improved the acid tolerance of S. elongatus PCC 7942.
Community composition of phytopathogenic fungi significantly influences ectomycorrhizal fungal communities during subtropical forest succession
Authors: Chen Meirong , Yang Jiazhi , Xue Chunquan , Tu Tieyao , Su Zhiyao , Feng Hanhua , Shi Miaomiao , Zeng Gui , Zhang Dianxiang , Qian Xin 
Published: January 2024

Abstract
Ectomycorrhizal fungi (EMF) can form symbiotic relationships with plants, aiding in plant growth by providing access to nutrients and defense against phytopathogenic fungi. In this context, factors such as plant assemblages and soil properties can impact the interaction between EMF and phytopathogenic fungi in forest soil. However, there is little understanding of how these fungal interactions evolve as forests move through succession stages. In this study, we used high-throughput sequencing to investigate fungal communities in young, intermediate, and old subtropical forests. At the genus level, EMF communities were dominated by Sebacina, Russula, and Lactarius, while Mycena was the most abundant genus in pathogenic fungal communities. The relative abundances of EMF and phytopathogenic fungi in different stages showed no significant difference with the regulation of different factors. We discovered that interactions between phytopathogenic fungi and EMF maintained a dynamic balance under the influence of the differences in soil quality attributed to each forest successional stage. The community composition of phytopathogenic fungi is one of the strong drivers in shaping EMF communities over successions. In addition, the EMF diversity was significantly related to plant diversity, and these relationships varied among successional stages. Despite the regulation of various factors, the positive relationship between the diversity of phytopathogenic fungi and EMF remained unchanged. However, there is no significant difference in the ratio of the abundance of EMF and phytopathogenic fungi over the course of successions. These results will advance our understanding of the biodiversity–ecosystem functioning during forest succession.

Key points
•Community composition of both EMF and phytopathogenic fungi changed significantly over forest succession.
•Phytopathogenic fungi is a key driver in shaping EMF community.
•The effect of plant Shannon’s diversity on EMF communities changed during the forest aging process.
The effect of hospital caseload on perioperative mortality, morbidity and costs in bladder cancer patients undergoing radical cystectomy: results of the German nationwide inpatient data
Authors: Pyrgidis Nikolaos , Volz Yannic , Ebner Benedikt , Kazmierczak Philipp M. , Enzinger Benazir , Hermans Julian , Buchner Alexander , Stief Christian , Schulz Gerald Bastian 
Published: January 2024

Abstract
Objectives
To determine a data-based optimal annual radical cystectomy (RC) hospital volume threshold and evaluate its clinical significance regarding perioperative mortality, complications, length of hospital stay, and hospital revenues.

Material and methods
We used the German Nationwide inpatient Data, provided by the Research Data Center of the Federal Bureau of Statistics (2005–2020). 95,841 patients undergoing RC were included. Based on ROC analyses, the optimal RC threshold to reduce mortality, ileus, sepsis, transfusion, hospital stay, and costs is 54, 50, 44, 44, 71 and 76 cases/year, respectively. Therefore, we defined an optimal annual hospital threshold of 50 RCs/year, and we also used the threshold of 20 RCs/year proposed by the EAU guidelines to perform multiple patient-level analyses.

Results
28,291 (29.5%) patients were operated in low- (< 20 RC/year), 49,616 (51.8%) in intermediate- (20–49 RC/year), and 17,934 (18.7%) in high-volume (≥ 50 RC/year) centers. After adjusting for major risk factors, high-volume centers were associated with lower inpatient mortality (OR 0.72, 95% CI 0.64–0.8, p < 0.001), shorter length of hospital stay (2.7 days, 95% CI 2.4–2.9, p < 0.001) and lower costs (457 Euros, 95% CI 207–707, p < 0.001) compared to low-volume centers. Patients operated in low-volume centers developed more perioperative complications such as transfusion, sepsis, and ileus.

Conclusions
Centralization of RC not only improves inpatient morbidity and mortality but also reduces hospital stay and costs. We propose a threshold of 50 RCs/year for optimal outcomes.
Expression profiles of the lncRNA antisense GAS5-AS1 in colon biopsies from pediatric inflammatory bowel disease patients and its role in regulating sense transcript GAS5
Authors: Curci Debora , Franzin Martina , Zudeh Giulia , Bramuzzo Matteo , Lega Sara , Decorti Giuliana , Stocco Gabriele , Lucafò Marianna 
Published: January 2024

AbstractThe long non-coding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) level was demonstrated as involved in pediatric inflammatory bowel disease (IBD) pathogenesis. Since its antisense transcript GAS5-AS1 has never been investigated in IBD, this study aims to detect whether GAS5-AS1 and GAS5 levels are related to IBD clinical parameters and investigate their correlation in vitro. Twenty-six IBD pediatric patients were enrolled; paired inflamed and non-inflamed intestinal biopsies were collected. We evaluated GAS5 and GAS5-AS1 levels by real-time PCR. The role of GAS5 and GAS5-AS1 was assessed in vitro by transient silencing in THP1-derived macrophages. GAS5-AS1 and GAS5 levels were associated with patients’ clinical parameters; GAS5-AS1 expression was downregulated in inflamed tissues and inversely correlated with disease activity. A positive correlation between GAS5-AS1 and GAS5 levels was observed in non-inflamed biopsies. On THP1-derived macrophages, a reduced amount of both GAS5-AS1 and GAS5 was observed; accordingly, matrix metalloproteinase (MMP) 9 was increased. After GAS5-AS1 silencing, a downregulation of GAS5 was found, whereas no effect was detected on GAS5-AS1 after GAS5 silencing. Conclusion: This study provided for the first time new insights into the potential role of GAS5-AS1 in IBD. GAS5-AS1 modulates GAS5 levels in vitro and may serve as a potential IBD diagnostic biomarker.

What is Known:• GAS5 is involved in regulating intestinal MMP-2 and MMP-9 in pediatric patients with IBD;• GAS5-AS1 has never been investigated in the context of IBD;• GAS5-AS1 regulates the expression of GAS5, increasing its stability in tissues and in vitro cell models of cancer.

What is New:• GAS5-AS1 correlated with GAS5 and IBD clinical parameters;• GAS5-AS1 can modulate GAS5 levels in macrophages;• GAS5-AS1 may serve as potential IBD diagnostic biomarker.
Classification of anemia using Harris hawks optimization method and multivariate adaptive regression spline
Authors: Yagmur Nagihan , Dag İdiris , Temurtas Hasan 
Published: January 2024

AbstractData mining methods are important for the diagnosis and prediction of diseases. Early and accurate diagnosis of patients is vital for their treatment. Various methods have been used in the literature to classify anemia. However, due to the different characteristics of patient datasets, changes in dataset sizes, different parameter numbers and features, and different numbers of patient records, algorithm performances vary according to datasets. In this study, the Harris hawks algorithm (HHA) and the multivariate adaptive regression spline (MARS) were used to classify anemia based on blood data of 1732 patients from the Kaggle database of patients with and without anemia. Six different algorithms were proposed to determine the parameters of the linear anemia approximation, namely multilinear form HHA, multilinear quadratic form HHA, multilinear exponential form HHA, first-order MARS model, second-order MARS model, and the best performing MARS model. The performance of the six proposed algorithms has been analyzed and found to be better than the previous studies in the literature.
Psychometric properties of the Caregiver’s inventory neuropsychological diagnosis dementia (CINDD) in mild cognitive impairment and dementia
Authors: Cuoco Sofia , Blundo Carlo , Ricci Monica , Cappiello Arianna , Bisogno Rossella , Carotenuto Immacolata , Avallone Anna Rosa , Erro Roberto , Pellecchia Maria Teresa , Amboni Marianna , Barone Paolo , Picillo Marina 
Published: January 2024

Abstract
Objectives
The Caregiver’s Inventory Neuropsychological Diagnosis Dementia (CINDD) is an easy tool designed
to quantify cognitive, behavioural and functional deficits of patients with cognitive impairment. Aim of the present
study was to analyse the psychometric properties of the CINDD in Mild Cognitive Impairment (MCI) and Dementia
(D).

Design, setting and participants
The CINDD, composed by 9 sub-domains, was administered to fifty-six caregivers
of patients with different types of dementia (D) and 44 caregivers of patients with MCI. All patients underwent an
extensive neuropsychological assessment, the Neuropsychiatric Inventory (NPI) and functional autonomy scales.
The reliability, convergent construct validity and possible cut-off of CINND were measured by Cronbach’s alpha (α),
Pearson’s correlation and ROC analysis, respectively.

Results
The D and MCI patients differed only for age (p=0.006). The internal consistency of CINDD was high (α=
0.969). The α-value for each CINDD domain was considered acceptable, except the mood domain (α=0.209). The
CINDD total score correlated with cognitive screening tests; each domain of the CINDD correlated with the
corresponding score from either tests or NPI (p<0.05), except for visuo-spatial perception skills and apathy. A
screening cut-off equal to 59, can be used discriminate D from MCI (Sensitivity=0.70, Specificity=0.57).

Conclusion
The CINDD is a feasible, accurate and reliable tool for the assessment of cognitive and behavioural
difficulties in patients with different degree of cognitive impairment. It may be used to quantify and monitor
caregiver-reported ecological data in both clinical and research settings.
Development of a comprehensive and clinically applicable novel projection classification system for anterior communicating artery aneurysms
Authors: Orakdogen Metin , Mammadkhanli Orkhan , Chousein Baris , Simsek Osman 
Published: January 2024

AbstractVarious surgical and anatomical classifications have been proposed to date related to ACoA aneurysm projection. Nonetheless, a universally accepted classification system is yet to be established. This study is aimed at establishing a standardized classification system for ACoA aneurysms with utilization 3D technology and defining reference lines for their projections. The goal is to create a simple, understandable, surgically beneficial, and reliable classification system based on neurovascular structures in the region, including safe and hazardous zones. The radiologic data of 96 patients with ACoA aneurysm who were treated in our university hospital between 2012 and 2020 were retrospectively analyzed, and a planned classification scale was developed with the data obtained. The classification aimed to create 9 main projection groups in the sagittal plane: superior, inferior, anterior, and posterior in linear orientation, and anterosuperior, posterosuperior, anteroinferior, posteroinferior, and complex in quadrant orientation. The coronal and axial planes included medial, lateral, and midline classifications, resulting in a 3-dimensional classification system with 25 projections. Among the 96 patients, 32 had linear and 64 had quadrant projections. In the sagittal plane, the linear projection breakdown was as follows: superior (28%), inferior (6.25%), anterior (53%), and posterior (12.5%). For the quadrant projection, the distribution was as follows: anterosuperior (53%), posterosuperior (12.5%), anteroinferior (21.87%), posteroinferior (3.12%), and complex (9.37%). Overall, 35.4% aneurysms were anterosuperior, 17.7% anterior, 14.58% anteroinferior, 9.37% superior, 8.3% posterosuperior, 6.25% complex, 4.16% posterior, 2.08% posteroinferior, and 2.08% inferior projection. Our study proposes a projection classification that utilizes 3D technology for safe surgery based on neurovascular structures in the region and thus better reveals safe and hazardous zones, including three plans, three dimensions, and two orientations. The use of this classification system offers valuable guidance for daily practice in the treatment of ACoA aneurysms.
Towards a critical pedagogy of global citizenship: Breaking the silence as a trained dancer in post-apartheid South Africa
Authors: Esau Omar , Jones Danielle-Marie 
Published: January 2024

AbstractThis article reveals a reflective journey of a dancer through unpacking two performances experienced over the course of two years. It examines and navigates ways of decolonizing oppressive dominance and investigating the ramifications of indoctrination in dance. It depicts how a trained dancer evolved and became more conscious by breaking the “culture of silence” and changed in becoming a more critical reflective dancer in a post-apartheid South Africa. This project aligns itself with global citizenship education (GCE) as it re/imagines traditional forms of civic and citizenship education in a more critical and decolonial perspective. In writing this paper, we are reminded of “the myriad shifts of thinking, strategies and back-and-forth debating” with each other and can also see our “encounters as a dance” (Waghid in Dancing with doctoral encounters: Democratic education in motion, African Sun Media, 2015). In breaking the silence surrounding dance and its conservative elements, we question the technocratic practices and accepted norms in the performance arts and the dancing arena. How does a classical dancer redress the colonial past in a performance arts classroom? The significance of this paper lies in the argument that decolonization becomes an imperative within GCE if one is striving for social justice and intends to commit oneself to a more equitable society where crossing borders must be a seamless act.
Cell-free ascites from ovarian cancer patients induces Warburg metabolism and cell proliferation through TGFβ-ERK signaling
Authors: Szeőcs Dóra , Vida Beáta , Petővári Gábor , Póliska Szilárd , Janka Eszter , Sipos Adrienn , Uray Karen , Sebestyén Anna , Krasznai Zoárd , Bai Péter 
Published: January 2024

AbstractAscites plays a key role in supporting the metastatic potential of ovarian cancer cells. Shear stress and carry-over of cancer cells by ascites flow support carcinogenesis and metastasis formation. In addition, soluble factors may participate in the procarcinogenic effects of ascites in ovarian cancer. This study aimed to determine the biological effects of cell-free ascites on carcinogenesis in ovarian cancer cells. Cell-free ascites from ovarian cancer patients (ASC) non-selectively induced cell proliferation in multiple models of ovarian cancer and untransformed primary human dermal fibroblasts. Furthermore, ASC induced a Warburg-type rearrangement of cellular metabolism in A2780 ovarian cancer cells characterized by increases in cellular oxygen consumption and glycolytic flux; increases in glycolytic flux were dominant. ASC induced mitochondrial uncoupling and fundamentally reduced fatty acid oxidation. Ascites-elicited effects were uniform among ascites specimens. ASC-elicited transcriptomic changes in A2780 ovarian cancer cells included induction of the TGFβ-ERK/MEK pathway, which plays a key role in inducing cell proliferation and oncometabolism. ASC-induced gene expression changes, as well as the overexpression of members of the TGFβ signaling system, were associated with poor survival in ovarian cancer patients. We provided evidence that the activation of the autocrine/paracrine of TGFβ signaling system may be present in bladder urothelial carcinoma and stomach adenocarcinoma. Database analysis suggests that the TGFβ system may feed forward bladder urothelial carcinoma and stomach adenocarcinoma. Soluble components of ASC support the progression of ovarian cancer. These results suggest that reducing ascites production may play an essential role in the treatment of ovarian cancer by inhibiting the progression and reducing the severity of the disease.