bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repeat kidney biopsy findings of lupus nephritis patients in clinical remission treated with Mycophenolate associated with Belimumab or Mycophenolate plus standard of care therapy. A “post-hoc” analysis of participants in the BLISS-LN and open label extension study belonging to a single center
Authors: Malvar Ana , Alberton Valeria , Recalde Cecilia , Heguilen Ricardo 
Published: September 2023

Background Lupus nephritis affects 40 to 70% of Systemic Lupus Erythematous(SLE) patients increasing their morbi-mortality; therefore, successful treatments are required to improve outcomes. Research Design and Study Sample In this paper 20 patients who participated in the BLISS LN trial at a single center (OMI) in Argentina were studied. All the patients continued Mycophenolate (MMF) treatment when the trial was finished and until a second biopsy was performed to determine the withdrawal of the immunosuppression according to the achieved clinical and histological response. Ten patients treated with MMF + Placebo versus 10 receiving MMF + Belimumab, were compared evaluating the complete clinical (CCR) and complete histological response (CHR) and the flares in each group. Results All the patients in the Belimumab group showed a CCR and 7 in the Placebo one; CHR was found in 9 and 5 patients of the Belimumab and Placebo group, respectively. None of the patients in the Belimumab group flared meanwhile two of the Placebo one did it. Conclusions Although the number of patients is insufficient to be able to draw unquestionable conclusions, adding Belimumab to the standard of care treatment with MMF would seem to increase the possibility of achieving a CCR, CHR, and a lower rate of relapses during treatment and long follow-up.
Branch retinal vein occlusion in a case of recalcitrant diffuse anterior scleritis treated with tofacitinib
Authors: Manoharan Anitha , Atmakur Harshita , Dutta Majumder Parthopratim , Biswas Jyotirmay 
Published: September 2023

AbstractA 47-year-old woman with hypertension and rheumatoid arthritis presented with non-necrotizing scleritis in both eyes. Despite a course of oral corticosteroids, she continued to experience persistent symptoms. A rheumatologist was consulted and initiated treatment with tofacitinib, a JAK/STAT inhibitor. Treatment with tofacitinib and oral corticosteroids resulted in an improvement in the scleritis in both eyes. However, a fundus examination of her left eye revealed a superior-temporal branch retinal vein occlusion. Given the growing concern regarding the increased risk of thromboembolic events with tofacitinib therapy, it is essential to consider the risk of retinal vascular occlusions when starting tofacitinib therapy, particularly in patients with underlying systemic comorbidities.
Antifungal screening of selenium nanoparticles biosynthesized by microcystin-producing Desmonostoc alborizicum
Authors: Nowruzi Bahareh , Jalil Bilal Saad , Metcalf James S 
Published: September 2023

AbstractMetal nanoparticles exhibit excellent antifungal abilities and are seen as a good substitute for controlling different kinds of fungi. Of all known taxa, cyanobacteria have received significant consideration as nanobiofactories, as a result of the cellular assimilation of heavy metals from the environment. The cellular bioactive enzymes, polysaccharides and pigments can be used as reducers and coatings during biosynthesis. The probability of the antifungal activity of selenium nanoparticles (SeNPs) to prevent plant fungi that can affect humans was evaluated and a toxic Iranian cyanobacterial strain of Desmonostoc alborizicum was used to study the biotechnology of SeNP synthesis for the first time. Characterization of nanoparticles with a UV-Vis spectrophotometer showed the formation of SeNPs in the range of 271–275 nm with the appearance of an orange color. Morphological examination of nanoparticles with Transmission Electron Microscopy (TEM), revealed the spherical shape of nanoparticles. The results of X-Ray Diffraction (XRD) showed 7 peaks and a hexagonal structure of average crystal size equal to 58.8 nm. The dispersion index of SeNPs was reported as 0.635, which indicated the homogeneity of the nanoparticle droplet size. The zeta potential of the nanoparticles was + 22.7. Fourier-transform infrared spectroscopy (FTIR) analysis exhibited a sharp and intense peak located at the wave number of 404 cm− 1, related to the SeNPs synthesized in this research. The results of the antifungal activity of SeNPs showed among the investigated fungi, Pythium ultimum had the highest resistance to SeNPs (14.66 ± 0.52 µg/ml), while Alternaria alternata showed the highest sensitivity (9.66 ± 0.51 µg/ml) (p < 0.05). To the best of our knowledge this is the first report concerning the characterization and antifungal screening of SeNPs biosynthesized by Iranian cyanobacteria, which could be used as effective candidates in medical applications.
Prognosis of Midkine and AT1R expression in resectable head and neck squamous cell carcinoma
Authors: Chiu Tai-Jan , Chen Chang-Han , Chen Yi-Ju , Wee Yinshen , Wang Ching-Shuen , Luo Sheng‑Dean 
Published: September 2023

Abstract
Background
Research studies have demonstrated that Midkine (MDK) can influence the expression and activity of Renin-angiotensin system (RAS) components. Angiotensin II is involved in tumor growth and angiogenesis in different cancers. We previously observed Angiotensin II receptor blockers (ARBs) improve the survival rates of patients with oral cancers. These findings have prompted us to investigate whether MDK can influence the RAS pathway, mainly through its association with angiotensin II type 1 receptor (AT1R), which contributes to the observed poor prognosis in head and neck squamous cell carcinoma (HNSCC) patients.

Methods
MDK and AT1R expressions were examined in 150 HNSCC patients post-operation by immunohistochemical staining between 1 January 2010 and 31 December 2016. We tested the over-expression and silencing of MDK to evaluate the AT1R expression and functional biological assays in HNSCC cell lines HSC-3 and SAS.

Results
Positive expression of MDK is correlated with positive AT1R expression. MDK predicted poor NSCC patients’ survival. Silencing MDK could suppress AT1R and pAKT expression and reduce the growth, migration, and invasion of HNSCC cells. ARB also inhibits MDK stimulating HNSCC cell proliferation. Overexpression of MDK could upregulate AT1R and pAKT.

Conclusions
MDK is an independent prognostic factor of HNSCC post-operation, and AT1R regulates HNSCC cell growth, invasion, and migration. Positive MDK and AT1R expressions are highly correlated. Mechanistically, the interaction between MDK and AT1R is crucial for MDK-mediated cell viability, and inhibiting AT1R can effectively counteract or abolish these effects. Furthermore, MDK exerts a regulatory role in the expression of AT1R, as well as in the growth and motility of HNSCC cells. These findings highlight the involvement of the interaction between MDK, AT1R, and the pAkt signaling pathways in HNSCC cell viability growth.
Synergistic effect of YOD1 and USP21 on the Hippo signaling pathway
Authors: Park Sang-Soo , Baek Kwang-Hyun 
Published: September 2023

Abstract
Background
Deubiquitinating enzymes (DUBs) comprise a family of proteases responsible for cleaving the peptide or isopeptide bond between ubiquitin and its substrate proteins. Ubiquitin is essential for regulating diverse cellular functions by attaching to target proteins. The Hippo signaling pathway plays a crucial role in controlling tissue size, cell proliferation, and apoptosis. In a previous study, we discovered that YOD1 regulates the Hippo signaling pathway by deubiquitinating the neural precursor cell expressed developmentally down-regulated protein 4 (NEDD4), an E3 ligase of large tumor suppressor kinase 1 (LATS1). Here, our aim was to investigate potential substrates of YOD1 implicated in the Hippo signaling pathway.

Methods
We employed various bioinformatics tools (BioGRID, STRING, and Cytoscape) to identify novel potential substrates of YOD1. Furthermore, we used western blotting, co-immunoprecipitation (co-IP), glutathione S-transferase (GST) pull-down, immunocytochemistry (ICC) assays to investigate cellular interactions. To evaluate cell proliferation, we performed cell counting kit-8 (CCK-8), wound healing, colony forming, and flow cytometry assays using A549, HEK293T, and HeLa cells. Additionally, we assessed the expression levels of YAP and p-YAP in A549, HEK293T, and HeLa cells through western blotting.

Results
Our investigations revealed that YOD1 interacts with ubiquitin-specific proteases 21 (USP21), a DUB involved in the Hippo signaling pathway, and deubiquitinates the microtubule-affinity regulating kinase (MARK). Intriguingly, YOD1 and USP21 mutually deubiquitinate each other; while YOD1 regulates the protein stability of USP21, USP21 does not exert a regulatory effect on YOD1. Moreover, we observed the synergistic effect of YOD1 and USP21 on cell proliferation through the modulation of the Hippo signaling pathway.

Conclusions
Our study revealed multiple cellular interactions between YOD1 and USP21. Moreover, our findings suggest that the combined activities of YOD1 and USP21 synergistically influence cell proliferation in A549 cells by regulating the Hippo signaling pathway.
Blood-spinal cord barrier disruption in degenerative cervical myelopathy
Authors: Kim Hyun Woo , Yong Hu , Shea Graham Ka Hon 
Published: September 2023

AbstractDegenerative cervical myelopathy (DCM) is the most prevalent cause of spinal cord dysfunction in the aging population. Significant neurological deficits may result from a delayed diagnosis as well as inadequate neurological recovery following surgical decompression. Here, we review the pathophysiology of DCM with an emphasis on how blood-spinal cord barrier (BSCB) disruption is a critical yet neglected pathological feature affecting prognosis. In patients suffering from DCM, compromise of the BSCB is evidenced by elevated cerebrospinal fluid (CSF) to serum protein ratios and abnormal contrast-enhancement upon magnetic resonance imaging (MRI). In animal model correlates, there is histological evidence of increased extravasation of tissue dyes and serum contents, and pathological changes to the neurovascular unit. BSCB dysfunction is the likely culprit for ischemia–reperfusion injury following surgical decompression, which can result in devastating neurological sequelae. As there are currently no therapeutic approaches specifically targeting BSCB reconstitution, we conclude the review by discussing potential interventions harnessed for this purpose.
Fragment merging approach for design, synthesis, and biological assessment of urea/acetyl hydrazide clubbed thienopyrimidine derivatives as GSK-3β inhibitors
Authors: Saleh Joseph S. , Abd El Hadi Soha R. , Ibrahim Hany S. , Elrazaz Eman Z. , Abouzid Khaled A. M. 
Published: September 2023

AbstractNew thienopyrimidine derivatives were designed and synthesized as GSK-3β inhibitors based on the structure of active binding site of GSK-3β enzyme. In this study, compounds 6b and 6a were found to be moderate GSK-3β inhibitors with IC50s 10.2 and 17.3 μM, respectively. Molecular docking study was carried out by docking the targeted compounds in the binding site of the GSK-3β enzyme using the MOE program. Moreover, ADME study was performed to predict certain pharmacokinetic properties. The results showed that all synthesized compounds may not be able to penetrate the blood brain barrier; so, the chances of CNS side effects are predicted to be low. CYP1D6 is predicted to be inhibited by compounds (5a, 5d, 6a, 9a and 9b), So drug-drug interactions are expected upon administration of these compounds.
Graphical Abstract
Optimisation of culture conditions for gesho (Rhamnus prinoides.L) callus differentiation using Artificial Neural Network-Genetic Algorithm (ANN-GA) Techniques
Authors: Dejene Minilu , Palanivel Hemalatha , Senthamarai Heeravathi , Varadharajan Venkatramanan , Prabhu S. Venkatesa , Yeshitila Alazar , Benor Solomon , Shah Shipra 
Published: September 2023

AbstractGesho (Rhamnus prinoides) is a medicinal plant with antioxidant and anti-inflammatory activities commonly used in the ethnomedicinal systems of Africa. Using a three-layer neural network, four culture conditions viz., concentration of agar, duration of light exposure, temperature of culture, and relative humidity were used to calculate the callus differentiation rate of gesho. With the ability to quickly identify optimal solutions using high-speed computers, synthetic neural networks have emerged as a rapid, reliable, and accurate fitting technique. They also have the self-directed learning capability that is essential for accurate prediction. The network's final architecture for four selected variables and its performance has been confirmed with high correlation coefficient (R2, 0.9984) between the predicted and actual outputs and the root-mean-square error of 0.0249, were developed after ten-fold cross validation as the training function. In vitro research had been conducted using the genetic algorithm’s suggestions for the optimal culture conditions. The outcomes demonstrated that the actual gesho differentiation rate was 93.87%, which was just 1.86% lesser than the genetic algorithm's predicted value. The projected induced differentiation rate was 87.62%, the actual value was 84.79%, and the predicted value was 2.83% higher than Response Surface Methods optimisation. The environment for the growth of plant tissue can be accurately and efficiently optimised using a genetic algorithm and an artificial neural network. Further biological investigations will presumably utilise this technology.
Clinical implications of aberrant PD-1 expression for acute leukemia prognosis
Authors: Ruan Yanjie , Wang Jiyu , Zhang Qiuye , Wang Huiping , Li Cong , Xu Xuanxuan , Zhai Zhimin 
Published: September 2023

Abstract
Background
Acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) are the most common types of leukemia in adults with an overall poor prognosis. PD-1 alone or combined with other immune checkpoint blockade is a promising research direction for the treatment of acute leukemia (AL) patients. However, clinical Implications of aberrant PD-1 expression in peripheral CD4+ and CD8+ T lymphocytes of AML and ALL patients in assessing the prognosis of diseases, remains inconclusive.

Methods
In the present study, we used flow cytometry to evaluate PD-1 expression on the surface of CD4+ and CD8+ T lymphocytes in the peripheral circulation of AML and ALL patients and its clinical significance. A total of 53 AML patients, 44 ALL patients and 28 healthy controls were enrolled in this study and peripheral blood specimens were detected by flow cytometry.

Results
Our results indicated that percentages of CD4+ PD1+ and CD8+ PD1+ T lymphocytes in newly diagnosed and non-remission groups were significantly higher than healthy control both in AML and ALL patients. The high level of CD4+ PD1+ and CD8+ PD1+ T lymphocytes were respectively poor prognostic indicators of AML patients and ALL patients but had no significant correlation with most common clinical risks.

Conclusions
Our findings show that aberrant PD-1 expression correlates with the prognosis of AL patient and may thus serve as poor prognostic indicators. Immunotherapy using PD-1 inhibitors may be a promising strategy for AML and ALL patients with peripheral circulating CD4+ PD1+ and CD8+ PD1+ T lymphocytes positively expressed, respectively.
Implications of vitamin D for flesh quality of grass carp (Ctenopharyngodon idella): antioxidant ability, nutritional value, sensory quality, and myofiber characteristics
Authors: Zhang Yao , Li Chaonan , Zhou Xiaoqiu , Jiang Weidan , Wu Pei , Liu Yang , Ren Hongmei , Zhang Lu , Mi Haifeng , Tang Jiayong , Zhang Ruinan , Feng Lin 
Published: September 2023

Abstract
Background
Muscle represents a unique and complex system with many components and comprises the major edible part of animals. Vitamin D is a critical nutrient for animals and is known to enhance calcium absorption and immune response. In recent years, dietary vitamin D supplementation in livestock has received increased attention due to biological responses including improving shear force in mammalian meat. However, the vitamin D acquisition and myofiber development processes in fish differ from those in mammals, and the effect of vitamin D on fish flesh quality is poorly understood. Here, the influence of dietary vitamin D on fillet quality, antioxidant ability, and myofiber development was examined in grass carp (Ctenopharyngodon idella).

Methods
A total of 540 healthy grass carp, with an initial average body weight of 257.24 ± 0.63 g, were allotted in 6 experimental groups with 3 replicates each, and respectively fed corresponding diets with 15.2, 364.3, 782.5, 1,167.9, 1,573.8, and 1,980.1 IU/kg vitamin D for 70 d.

Results
Supplementation with 1,167.9 IU/kg vitamin D significantly improved nutritional value and sensory quality of fillets, enhancing crude protein, free amino acid, lipid, and collagen contents; maintaining an ideal pH; and reducing lactate content, shear force, and cooking loss relative to respective values in the control (15.2 IU/kg) group. Average myofiber diameter and the frequency of myofibers > 50 μm in diameter increased under supplementation with 782.5–1,167.9 IU/kg vitamin D. Levels of oxidative damage biomarkers decreased, and the expression of antioxidant enzymes and nuclear factor erythroid 2-related factor 2 signaling molecules was upregulated in the 1,167.9 IU/kg vitamin D treatment compared to respective values in the control group. Furthermore, vitamin D supplementation activated cell differentiation by enhancing the expression of myogenic regulatory factors and myocyte enhancer factors compared to that in the control group. In addition, supplementation with 1,167.9 IU/kg vitamin D improved protein deposition associated with protein synthesis molecule (target of rapamycin) signaling and vitamin D receptor paralogs, along with inhibition of protein degradation (forkhead box protein 1) signaling.

Conclusions
Overall, the results demonstrated that vitamin D strengthened antioxidant ability and myofiber development, thereby enhancing nutritional value and sensory quality of fish flesh. These findings suggest that dietary vitamin D supplementation is conducive to the production of nutrient-rich, high quality aquaculture products.
A meme-based approach for knowledge mining, organization, and presentation of traditional Chinese settlement culture
Authors: Yang Simin , Yi Lina , Guan Hui , Li Yong 
Published: September 2023

Abstract
Traditional Chinese settlements are successful examples of harmonious coexistence between man and nature. Traditional Chinese settlement culture (TCSC) is the product of its inhabitants' adaptation to the natural and social environment and has national cultural originality and transmission. Core cultural elements of these being chosen to stay can be considered as memes. This study considers traditional Chinese settlement cultural memes (TCSCM) as a special kind of knowledge, and proposes a meme-based approach to mine, organize, and present traditional Chinese settlement cultural knowledge from a knowledge management perspective. This approach is composed of identifying memes, constructing the memes ontology, and the memes knowledge graph, mainly describing and establishing the memes identification index system, the ontology conceptual framework, and knowledge graph construction rules. In addition, the feasibility of the above work is verified by a case study of Jinggang Ancient town in Hunan province. This study provides new practical ideas for the authentic conservation and industrial construction of TCSC.
Research on the development methodology for clinical practice guidelines for organic integration of traditional Chinese and Western medicine
Authors: Jin Ying-Hui , Wang Yan-Ping , Xie Ying-Lan , Tian Gui-Hua , Zhang Xiao-Yu , Shi Nan-Nan , Yang Ke-Hu , Sun Xin , Chen Yao-Long , Wu Da-Rong , Guo Xin-Feng , Ge Long , Zhao Chen , Lu Cheng , Jiang Yin , Guo Jing , Yan Si-Yu , Wang Yong-Bo , Huang Qiao , Ren Xiang-Ying , Rao Ying-Yue , Wang Yun-Yun , Yuan Meng-Qian , Zeng Xian-Tao , Shang Hong-Cai 
Published: September 2023

AbstractIntegrated traditional Chinese medicine (TCM) and Western medicine (WM) is a new medical science grounded in the knowledge bases of both TCM and WM, which then forms a unique modern medical system in China. Integrated TCM and WM has a long history in China, and has made important achievements in the process of clinical diagnosis and treatment. However, the methodological defects in currently published clinical practice guidelines limit its development. The organic integration of TCM and WM is a deeper integration of TCM and WM. To realize the progression of "integration" to "organic integration", a targeted and standardized guideline development methodology is needed. Therefore, the purpose of this study is to establish a standardized development procedure for clinical practice guidelines for the organic integration of TCM and WM to promote the systematic integration of TCM and WM research results into clinical practice guidelines in order to achieve optimal results as the whole is greater than the sum of the parts.
Effects of bactericide–protease interactions on the protease-assisted soaking performance
Authors: Liu Hao , Pan Yahang , Shi Bi , Zeng Yunhang 
Published: September 2023

AbstractProtease-assisted soaking has received increasing attention in recent years. However, few reports have elaborated on the effect of bactericides, which are used to protect raw hides from microbial damage in the soaking process, on the performance of protease-assisted soaking. Here we investigate the effects of three bactericides, namely, 2-methyl-4-isothiazolin-3-one (MIT), sodium propyl 4-hydroxybenzoate (SPHB) and cetyl trimethyl ammonium bromide (CTAB), on the catalytic activity of protease. MIT and SPHB have little effect on the proteolytic activity, whilst CTAB has a negative effect. Fluorescence spectroscopy, synchronous fluorescence spectroscopy, molecular docking and molecular dynamics simulation were used to analyse the bactericide–protease interaction. The data reveal that MIT and SPHB are bound to the non-catalytic sites of protease, whilst CTAB affects the catalytic triad of protease. Furthermore, the protease and bactericides were used alone, simultaneously and sequentially in the soaking process, and their soaking performances were evaluated. The evaluation shows that the use of protease increases the microorganisms in the soaking float, and MIT exhibits the best bactericidal effect. The simultaneous use of protease and MIT effectively inhibits bacteria and scarcely affects the removal of unstructured proteins from hides and the attack on epidermis by protease. These findings contribute to a better understanding of the scientific use of protease with other auxiliaries in soaking.
Graphical Abstract