bluuebunny/crossref_metadata_2025_split huggingface dataset:
Production of highly cytotoxic and low immunogenic L-asparaginase from Stenotrophomonas maltophilia EMCC2297
Authors: Abdelrazek Nada A. , Saleh Sarra E. , Raafat Marwa M. , Ali Amal E. , Aboulwafa Mohammad M. 
Published: May 2024

AbstractL-asparaginase is an important therapeutic enzyme that is frequently utilized in the chemotherapy regimens of adults as well as pediatric patients with acute lymphoblastic leukemia. However, a high rate of hypersensitivity with prolonged use has limited its utilization. Stenotrophomonas maltophilia (S. maltophilia) EMCC2297 isolate was reported as a novel and promising source for L- asparaginase. The present study aimed at the production, purification, and characterization of L- asparaginase from S. maltophilia EMCC2297 isolate. The microbial production of L-asparaginase by the test isolate could be increased by pre-exposure to chloramphenicol at 200 µg/ml concentration. S. maltophilia EMCC2297 L-asparaginase could be purified to homogeneity by ammonium sulphate precipitation and the purified form obtained by gel exclusion chromatography showed total activity of 96.4375 IU/ml and specific activity of 36.251 IU/mg protein. SDS-PAGE analysis revealed that the purified form of the enzyme is separated at an apparent molecular weight of 17 KDa. Michaelis-Menten constant analysis showed a Km value of 4.16 × 10− 2 M with L-asparagine as substrate and Vmax of 10.67 IU/ml. The antitumor activity of the purified enzyme was evaluated on different cell lines and revealed low IC50 of 2.2 IU/ml and 2.83 IU/ml for Hepatocellular cancer cell line (HepG-2), human leukemia cancer cell line (K-562), respectively whereas no cytotoxic effect could be detected on normal human lung fibroblast cells (MRC-5). However, mice treated with native L-asparaginase showed lower IgG titre compared to commercial L-asparaginase. This study highlights the promising characteristics of this enzyme making it a valuable candidate for further research and development to be an adduct in cancer chemotherapy.
Metagenomic nanopore sequencing for exploring the nature of antimicrobial metabolites of Bacillus haynesii
Authors: Eltokhy Mohamed A. , Saad Bishoy T. , Eltayeb Wafaa N. , Alshahrani Mohammad Y. , Radwan Sahar M R , Aboshanab Khaled M. , Ashour Mohamed S. E. 
Published: May 2024

AbstractMultidrug-resistant (MDR) pathogens are a rising global health worry that imposes an urgent need for the discovery of novel antibiotics particularly those of natural origin. In this context, we aimed to use the metagenomic nanopore sequence analysis of soil microbiota coupled with the conventional phenotypic screening and genomic analysis for identifying the antimicrobial metabolites produced by promising soil isolate(s). In this study, whole metagenome analysis of the soil sample(s) was performed using MinION™ (Oxford Nanopore Technologies). Aligning and analysis of sequences for probable secondary metabolite gene clusters were extracted and analyzed using the antiSMASH version 2 and DeepBGC. Results of the metagenomic analysis showed the most abundant taxa were Bifidobacterium, Burkholderia, and Nocardiaceae (99.21%, followed by Sphingomonadaceae (82.03%) and B. haynesii (34%). Phenotypic screening of the respective soil samples has resulted in a promising Bacillus isolate that exhibited broad-spectrum antibacterial activities against various MDR pathogens. It was identified using microscopical, cultural, and molecular methods as Bacillus (B.) haynesii isolate MZ922052. The secondary metabolite gene analysis revealed the conservation of seven biosynthetic gene clusters of antibacterial metabolites namely, siderophore lichenicidin VK21-A1/A2 (95% identity), lichenysin (100%), fengycin (53%), terpenes (100%), bacteriocin (100%), Lasso peptide (95%) and bacillibactin (53%). In conclusion, metagenomic nanopore sequence analysis of soil samples coupled with conventional screening helped identify B. haynesii isolate MZ922052 harboring seven biosynthetic gene clusters of promising antimicrobial metabolites. This is the first report for identifying the bacteriocin, lichenysin, and fengycin biosynthetic gene clusters in B. haynesii MZ922052.
First reported case in an Irish flock of MCF- like systemic necrotizing vasculitis in sheep associated with ovine herpesvirus 2
Authors: Sheehan Maresa , Pesavento Patricia A. , Campion Francis , Lynch John , McGettrick Shane , Toland Brian , Kennedy Aideen 
Published: May 2024

Abstract
Background
Ovine gammaherpesvirus 2 (OvHV-2) is the causative agent of sheep associated malignant catarrhal fever (MCF). As sheep are the adapted host for OvHV-2, it is generally presumed that infection is not associated with disease in this species. However, a recent case review combined in-situ hybridisation, PCR and histopathology and correlated the viral distribution with systemic necrotizing vasculitis and concluded OvHV-2 was the likely agent responsible for sporadic, MCF-like vascular disease in sheep.

Case presentation
Using similar methods this case study reports on the findings of the first reported cases in an Irish Flock of MCF- like systemic necrotizing vasculitis in sheep associated with OvHV-2. Sheep A, a 16-month-old Texel-cross hogget displayed signs of ill- thrift, Sheep B, a nine-month-old Belclare-cross lamb, was found dead having displayed no obvious symptoms. Both cases occurred on the same farm, however the animals were not related. Lymphohistiocytic vasculitis of various tissues was the predominant histopathological finding in both animals.

Conclusion
By combining histopathology, PCR and in-situ hybridisation results, MCF- like systemic necrotizing vasculitis associated with OvHV-2 has been diagnosed for the first time in an Irish flock.
Promotion of hair growth by a conditioned medium from human umbilical cord mesenchymal stem cells cultivated in a 3D scaffold of gelatin sponge
Authors: Ni Jintao , Ye Danyan , Zeng Weiping , Ma Siyi , Wang Zhixia , Kuang Yuping , Yang Lujun 
Published: May 2024

Abstract
Background
This study aims to investigate the effects of a conditioned medium (CM) from human umbilical cord mesenchymal stem cells (HuMSCs) cultivated in gelatin sponge (GS-HuMSCs-CM) on hair growth in a mouse model.

Methods
CM was collected from the HuMSCs cultivated in a monolayer or in a gelatin sponge. Vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), keratinocyte growth factor (KGF), and hepatocyte growth factor (HGF) levels in CMs were measured by enzyme-linked immunosorbent assays (ELISAs). A hair loss model by a C57 BL/6J mouse was prepared. The effects of GS-HuMSCs-CM and HuMSCs on hair regrowth in mice were investigated by intradermal injection in the depilated back skin with normal saline (NS) as the control. The time for hair regrowth and full covering in depilated areas was observed, and the hair growth was evaluated histologically and by grossly measuring hair length and diameter.

Results
Compared with monolayer cultured cells, the three-dimensional (3D) culture of HuMSCs in gelatin sponge drastically increased VEGF, IGF-1, KGF, and HGF production. GS-HuMSCs-CM and HuMSCs injection both promoted hair regeneration in mice, while GS-HuMSCs-CM presented more enhanced effects in hair length, hair diameter, and growth rate. GS-HuMSCs-CM significantly promoted angiogenesis in injected skin areas, which might also contribute to faster hair regrowth.

Conclusion
GS-HuMSCs-CM exerted significant effects on inducing hair growth and promoted skin angiogenesis in C57BL/6J mice.
Enhancement of work place comfort through the use of soft landscape
Authors: Ale Taiwo Ayomide , Ayeni Dorcas Aina , Adedayo Olatunde Folaranmi 
Published: May 2024

AbstractThe work environment has been shown to have a great influence on employees’ physical and mental state, as such employers try as much as possible to provide a comfortable working environment. However, recent studies have shown that the work environment is no longer as comfortable as it used to be due to heat gain from the increasing use of hard landscape features and neglect of soft landscape features in the work environment. This has resulted in stress causing both mild and severe health conditions for employees. Thus, this study aims to analyze the use of soft landscape in enhancing users' comfort with the view of reducing stress and health-related issues in the work environment. The paper adopted a mixed method using observation checklists, structured interviews, questionnaires, and case studies. A total of eighteen office complexes were selected to describe the existing situation as related to most office complexes and to also gain insight into the subject matter as already applied to life situations. Structured interviews and questionnaires were also conducted with occupants of the buildings and professionals to hear their perceptions and expectations of their work environment. Results showed that 20 percent of the offices give proper consideration to the use of soft landscapes in the work environment, and 40 percent give inconsiderable attention to soft landscapes while making use of them in small quantities solely for improving the aesthetical value of the building. In comparison, the remaining 40 percent do not consider landscape use as a means of improving comfort in the work environment. Findings also revealed that 80 percent of office buildings give major consideration to parking space using hard landscapes without a proper blend of soft landscapes after building design which hurts occupant comfort. The research concluded that the incorporation of soft landscape elements both within the building using recesses and protrusions and on the building walls through the use of exoskeleton and climbers while incorporating trees, shrubs, flowers, hedges and water around the building can have these required effects on employee’s comfort.
Non-infectious respiratory complications after allogeneic bone marrow transplantation: single center experience in Egypt
Authors: Motawea Mona M. , Samra Mohamed Abd Elmooti , Ganna Salwa Atef , Elshafey Basem Ibrahim 
Published: May 2024

Abstract
Background
Hematopoietic progenitor cells are infused intravenously, known as hematopoietic stem cell transplantation. The range of pulmonary problems after transplantation of hematopoietic stem cells varies significantly from infectious to non-infectious aetiologies.

Objectives
To study noninfectious respiratory complications in patients subjected to allogeneic bone marrow transplants.

Patients and methods
This retrospective study was carried out on 1000 patients with hematopoietic stem-cell transplantations. These patients were presented with respiratory symptoms suggestive of pulmonary complications following bone marrow transplant.

Result
The number of patients in this period was 1000 patients, and 247 of them had non-infectious pulmonary complications. Number and percent of bronchiolitis obliterans, diffuse alveolar hemorrhage, graft-versus-host disease (GVHD), pulmonary edema, Bronchiolitis obliterans with GVHD, Chemotherapy pneumonitis, Idiopathic pneumonia syndrome and Thoracic air leak syndrome to all number of cases were twenty-five (2.5%), sixteen (1.6%), eighty-one (8.1) sixty-four (25.9%), nineteen (1.9%), twenty-one (2.1%), thirteen (1.3%) and eight (0.8%) respectively, but number and percent of bronchiolitis obliterans, diffuse alveolar hemorrhage, GVHD, pulmonary edema, bronchiolitis obliterans with GVHD, chemotherapy-associated pneumonitis, Idiopathic pneumonia syndrome, and thoracic air leak syndrome to all complicated cases only were twenty-five (10.1%), sixteen (6.5%), eighty-one (32.8%), sixty-four (25.9 %), nineteen (7.7%), twenty-one (8.5 %), thirteen (5.3 %) and eight (3.2%) respectively.

Conclusions
Noninfectious respiratory complications included GVHD, pulmonary edema, bronchiolitis obliterans and diffuse alveolar hemorrhage bronchiolitis obliterans with GVHD, chemotherapy-associated pneumonitis, Idiopathic pneumonia syndrome, and thoracic air leak syndrome. Some of them occurred early, and some occurred late. The incidence of non-infectious respiratory complications is affected by increased patient age and female gender.
Associations of Plasma and Fecal Metabolites with Body Mass Index and Body Fat Distribution in Children
Authors: Hong Zhen , Zhou Kejun , Wei Yuanhuan , Ma Bingjie , Xie Guoxiang , Zhang Zheqing , Liang Jingjing 
Published: May 2024

Abstract

Context
Childhood obesity continues to be a critical public health concern with far-reaching implications for well-being.

Objective
This study aimed to investigate the association between metabolites in plasma and feces and indicators including body mass index (BMI), BMI for age Z score (BMIZ), and body fat distribution among children aged 6 to 9 years in China.

Methods
This cross-sectional study enrolled 424 healthy children, including 186 girls and 238 boys. Dual-energy X-ray absorptiometry was used to determine the body fat content and regional fat distribution. Plasma and fecal metabolites were analyzed using targeted metabolomic technologies.

Results
A total of 200 plasma metabolites and 212 fecal metabolites were accurately quantified via ultra-performance liquid chromatography coupled with tandem mass spectrometry. By using orthogonal projections to latent structures discriminant analysis and random forest model, we discovered that 9 plasma metabolites and 11 fecal metabolites were associated with different weight statuses. After adjusting for potential covariates and false discovery rate correction, multiple linear regression analyses revealed that plasma metabolites (fumaric acid, glycine, l-glutamine, methylmalonic acid, and succinic acid) and fecal metabolites (protocatechuic acid) were negatively associated (β −1.373 to −.016, pFDR &lt; 0.001-0.031; β −1.008 to −.071, pFDR 0.005-0.033), while plasma metabolites (isovaleric acid, isovalerylcarnitine, l-glutamic acid, and pyroglutamic acid) and fecal metabolites (3-aminoisobutanoic acid, butyric acid, N-acetylneuraminic acid, octanoylcarnitine, oleoylcarnitine, palmitoylcarnitine, stearoylcarnitine, taurochenodesoxycholic acid, and taurodeoxycholic acid) exhibited positive associations with BMI, BMIZ, and body fat distribution (β .023-2.396, pFDR &lt; 0.001; β .014-1.736, pFDR &lt; 0.001-0.049).

Conclusion
Plasma and fecal metabolites such as glutamine may serve as potential therapeutic targets for the development of obesity.
N-terminal Pro-B-Type Natriuretic Peptide and Risk for Diabetes Mellitus and Metabolic Syndrome
Authors: Nicoli Charles D , Long D Leann , Plante Timothy B , Judd Suzanne E , McClure Leslie A , Carson April P , Cushman Mary 
Published: May 2024

Abstract

Context
Natriuretic peptide concentrations are inversely associated with risk of diabetes mellitus and may be protective from metabolic dysfunction.

Objective
We studied associations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) with incident diabetes, metabolic syndrome (MetS), and MetS components.

Methods
A total of 2899 participants with baseline (2003-2007) and follow-up (2013-2016) examinations and baseline NT-proBNP measurement in the REasons for Geographic And Racial Differences in Stroke study. Logistic regression models were fitted to incident MetS, MetS components, and diabetes; covariates included demographics, risk and laboratory factors. Incident diabetes was defined as fasting glucose ≥126 mg/dL, random glucose ≥200 mg/dL, or use of insulin or hypoglycemic drugs at follow-up but not baseline. Incident MetS was defined as participants with ≥3 harmonized criteria at follow-up and &lt;3 at baseline.

Results
A total of 310 participants (2364 at risk) developed diabetes and 361 (2059 at risk) developed MetS over a mean 9.4 years of follow-up. NT-proBNP was inversely associated with odds of incident diabetes (fully adjusted OR per SD higher log NT-proBNP 0.80, 95% CI 0.69-0.93) and MetS in the highest vs lowest quartile only (fully adjusted OR 0.59, 95% CI 0.37-0.92); the linear association with incident MetS was not statistically significant. NT-proBNP was inversely associated with incident dysglycemia in all models (fully adjusted OR per SD log NT-proBNP 0.65, 95% CI 0.53-0.79), but not with other MetS components. Effect modification by sex, race, age, or body mass index was not observed.

Conclusion
NT-proBNP was inversely associated with odds of diabetes, MetS, and the MetS dysglycemia component. The metabolic implications of B-type natriuretic peptides appear important for glycemic homeostasis.
Residual Axillary Metastases in Node-Positive Breast Cancer Patients After Neoadjuvant Treatment: A Register-Based Study
Authors: Munck Frederikke , Jensen Maj-Britt , Vejborg Ilse , Gerlach Maria K. , Maraldo Maja V. , Kroman Niels T. , Tvedskov Tove H. F. 
Published: May 2024

Abstract
Background
Lymph node (LN) metastasis after neoadjuvant chemotherapy (NACT) generally warrants axillary lymph node dissection, which opposes guidelines of upfront surgery in many cases. We investigated the risk of having additional metastases in the axilla when the LNs removed by targeted axillary dissection (TAD) harbored metastases after NACT. We aimed to identify subgroups suitable for de-escalated axillary treatment.

Methods
This register-based study used data from the Danish Breast Cancer Cooperative Group database. Data were analyzed with logistic regression models. The primary outcome was the metastatic burden in non-TAD LNs in patients with positive TAD LNs after NACT.

Results
Among 383 patients, < 66.6% positive TAD LNs (adjusted odds ratio [OR] 0.34, 95% confidence interval [CI] 0.17–0.62), only isolated tumor cells (ITCs) [OR 0.11, 95% CI < 0.01–0.82], and breast pathological complete response (pCR) [OR 0.07, 95% CI < 0.01–0.56] were associated with a low risk of having more than three positive non-TAD LNs. In 315 patients with fewer than three positive non-TAD LNs, the proportion of positive TAD LNs (OR 0.45, 95% CI 0.27–0.76 for 33.3–66.6% vs. > 66.6%), size of the TAD LN metastasis (OR 0.14, 95% CI 0.04–0.54 for ITC vs. macrometastasis), tumor size at diagnosis (OR 0.30, 95% CI 0.15–0.64 for 20–49 mm vs. ≥ 50 mm) and breast pCR (OR 0.38, 95% CI 0.15–0.96) were associated with residual LN metastases in the axilla.

Conclusions
Breast pCR or ITC only in TAD LNs can, with reasonable certainty, preclude more than three positive non-TAD LNs. Additionally, patients with only ITCs in the TAD LN had a low risk of having any non-TAD LN metastases after NACT. De-escalated axillary treatment may be considered in both subgroups.
Enhancing the Efficacy of HIPEC Through Bromelain: A Preclinical Investigation in Appendiceal Cancer
Authors: Wajih Nadeem , Erali Richard A. , Forsythe Steven D. , Schaaf Cecilia R. , Shen Perry , Levine Edward A. , Soker Shay , Morris David L. , Votanopoulos Konstantinos I. 
Published: May 2024

Abstract
Introduction
Appendiceal cancer (AC) excessive mucin production is a barrier to heated intraperitoneal chemotherapy (HIPEC) drug delivery. Bromelain is a pineapple stem extract with mucolytic properties. We explored bromelain treatment effects against mucinous AC in a patient-derived tumor organoid (PTO) model and an AC cell line.

Patients and Methods
PTOs were fabricated from tumor specimens obtained from patients with AC undergoing cytoreductive surgery with HIPEC. PTOs underwent HIPEC treatment with bromelain, cisplatin, and mitomycin C (MMC) at 37 °C and 42 °C with and without bromelain pretreatment.

Results
From October 2020 to May 2023, 16 specimens were collected from 13 patients with low-grade (12/16, 75%) and high-grade AC (4/16, 25%). The mucin-depleting effects of bromelain were most significant in combination with N-acetylcysteine (NAC) compared with bromelain (47% versus 10%, p = 0.0009) or NAC alone (47% versus 12.8%, p = 0.0027). Bromelain demonstrated > 31% organoid viability reduction at 60 min (p < 0.001) and > 66% in 48 h (p < 0.0001). Pretreatment with bromelain increased cytotoxicity of both cisplatin and MMC HIPEC conditions by 31.6% (p = 0.0001) and 35.5% (p = 0.0001), respectively. Ki67, CK20, and MUC2 expression decreased after bromelain treatment; while increased caspase 3/7 activity and decreased Bcl-2 (p = 0.009) and Bcl-xL (p = 0.01) suggest induction of apoptosis pathways. Furthermore, autophagy proteins LC3A/B I (p < 0.03) and II (p < 0.031) were increased; while ATG7 (p < 0.01), ATG 12 (p < 0.04), and Becline 1(p < 0.03), expression decreased in bromelain-treated PTOs.

Conclusions
Bromelain demonstrates cytotoxicity and mucolytic activity against appendiceal cancer organoids. As a pretreatment agent, it potentiates the cytotoxicity of multiple HIPEC regimens, potentially mediated through programmed cell death and autophagy.
Phytochemical content and antioxidant capacity of ethyl acetate extracts from fifteen Orthosiphon aristatus leaves genotypes
Authors: BOVANI RAISADIBA PUTRI , LIWANDA NOVIAN , BATUBARA IRMANIDA , AMBARSARI LAKSMI , NURCHOLIS WARAS 
Published: May 2024

Abstract. Bovani RP, Liwanda N, Batubara I, Ambarsari L, Nurcholis W. 2024. Phytochemical content and antioxidant capacity of ethyl acetate extracts from fifteen Orthosiphon aristatus leaves genotypes. Biodiversitas 25: 763-769. Orthosiphon aristatus (Blume) Miq., also known as kumis kucing in Indonesia, is a medicinal plant belonging to the Lamiaceae family that contains various phytochemical compounds with antioxidant properties. This study investigated the phenolic content, flavonoid, rosmarinic acid, sinensetin, and antioxidant capacity of 15 genotypes of O. aristatus ethyl acetate extracts. Therefore, 15 genotypes were analyzed using quercetin as the standard for Total Phenolic Content (TPC) using a colorimetric method with gallic acid and Total Flavonoid Content (TFC). Sinensentin and rosmarinic acid were measured by High-Performance Liquid Chromatography (HPLC). Antioxidant capacity was determined using Trolox as a standard antioxidant by 2-Diphenyl Picrylhydrazyl (DPPH) and Ferric Reducing Antioxidant Power (FRAP) assays. The results revealed a diverse range of phytochemical compounds, with total phenolic content ranging from 3.39 to 13.80 mg GAE/g DW, total flavonoid content from 0.20 to 1.43 mg QE/g DW, rosmarinic acid from 0.02 to 0.19 mg/g DW, and sinensetin from 1.61 to 21.67 mg/g DW. Furthermore, the antioxidant assays demonstrated varying degrees of efficacy, with DPPH ranging from 2.09 to 13.98 ?mol TE/g DW and FRAP from 0.07 to 2.96 ?mol TE/g DW. Genotypes A10, A11, and A12 exhibited superior phytochemical contents and antioxidant capacities, highlighting their potential as valuable sources of medicinal compounds.