bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of three-dimensional scaffolds based on polyglycerol sebacate/ polycaprolactone/ gelatin in the presence of Nanohydroxyapatite in promoting chondrogenic differentiation of human adipose-derived mesenchymal stem cells
Authors: Talouki Pardis Yousefi , Tackallou Saeed Hesami , Shojaei Shahrokh , Benisi Soheila Zamanlui , Goodarzi Vahabodin 
Published: March 2023

Abstract
Background
Tissue engineering for cartilage regeneration has made great advances in recent years, although there are still challenges to overcome. This study aimed to evaluate the chondrogenic differentiation of human adipose-derived mesenchymal stem cells (hADSCs) on three-dimensional scaffolds based on polyglycerol sebacate (PGS) / polycaprolactone (PCL) / gelatin(Gel) in the presence of Nanohydroxyapatite (nHA).

Materials and methods
In this study, a series of nHA-nanocomposite scaffolds were fabricated using 100:0:0, 60:40:0, and 60:20:20 weight ratios of PGS to PCL: Gel copolymers through salt leaching method. The morphology and porosity of prepared samples was characterized by SEM and EDX mapping analysis. Also, the dynamic contact angle and PBS adsorption tests are used to identify the effect of copolymerization and nanoparticles on scaffolds' hydrophilicity. The hydrolytic degradation properties were also analyzed. Furthermore, cell viability and proliferation as well as cell adhesion are evaluated to find out the biocompatibility. To determine the potential ability of nHA-nanocomposite scaffolds in chondrogenic differentiation, RT-PCR assay was performed to monitor the expression of collagen II, aggrecan, and Sox9 genes as markers of cartilage differentiation.

Results
The nanocomposites had an elastic modulus within a range of 0.71–1.30 MPa and 0.65–0.43 MPa, in dry and wet states, respectively. The PGS/PCL sample showed a water contact angle of 72.44 ± 2.2°, while the hydrophilicity significantly improved by adding HA nanoparticles. It was found from the hydrolytic degradation study that HA incorporation can accelerate the degradation rate compared with PGS and PGS/PCL samples. Furthermore, the in vitro biocompatibility tests showed significant cell attachment, proliferation, and viability of adipose-derived mesenchymal stem cells (ADMSCs). RT-PCR also indicated a significant increase in collagen II, aggrecan and Sox9 mRNA levels.

Conclusions
Our findings demonstrated that these nanocomposite scaffolds promote the differentiation of hADSCs into chondrocytes possibly by the increase in mRNA levels of collagen II, aggrecan, and Sox9 as markers of chondrogenic differentiation. In conclusion, the addition of PCL, Gelatin, and HA into PGS is a practical approach to adjust the general features of PGS to prepare a promising scaffold for cartilage tissue engineering.

Graphical Abstract
Predicting miRNA-disease associations based on PPMI and attention network
Authors: Xie Xuping , Wang Yan , He Kai , Sheng Nan 
Published: March 2023

Abstract
Background
With the development of biotechnology and the accumulation of theories, many studies have found that microRNAs (miRNAs) play an important role in various diseases. Uncovering the potential associations between miRNAs and diseases is helpful to better understand the pathogenesis of complex diseases. However, traditional biological experiments are expensive and time-consuming. Therefore, it is necessary to develop more efficient computational methods for exploring underlying disease-related miRNAs.

Results
In this paper, we present a new computational method based on positive point-wise mutual information (PPMI) and attention network to predict miRNA-disease associations (MDAs), called PATMDA. Firstly, we construct the heterogeneous MDA network and multiple similarity networks of miRNAs and diseases. Secondly, we respectively perform random walk with restart and PPMI on different similarity network views to get multi-order proximity features and then obtain high-order proximity representations of miRNAs and diseases by applying the convolutional neural network to fuse the learned proximity features. Then, we design an attention network with neural aggregation to integrate the representations of a node and its heterogeneous neighbor nodes according to the MDA network. Finally, an inner product decoder is adopted to calculate the relationship scores between miRNAs and diseases.

Conclusions
PATMDA achieves superior performance over the six state-of-the-art methods with the area under the receiver operating characteristic curve of 0.933 and 0.946 on the HMDD v2.0 and HMDD v3.2 datasets, respectively. The case studies further demonstrate the validity of PATMDA for discovering novel disease-associated miRNAs.
Multidrug-resistant Aeromonas bacteria prevalence in Nile tilapia broodstock
Authors: Sherif Ahmed H. , Kassab Amina S. 
Published: March 2023

Abstract
Background
Aeromonas hydrophila is an opportunistic pathogen. Thus, it has received significant attention mainly in the fish sectors with high production scales. Nile tilapia broodstock confined in the environment of fish hatcheries can be stressed. Hence, they are vulnerable to A. hydrophila.

Results
Sequencing of the gyr B gene revealed the presence of 18 different A. hydrophila strains (kdy 10,620–10,637), which were deposited in the NCBI under accession numbers ON745861–ON745878. The median lethal doses of the isolates ranged from 2.62 × 104 to 3.02 × 106 CFU/mL. Antibiotic resistant genes, sulfonamide (sul1) and tetracycline (tetA) were found in the eighteen isolates. Approximately 83.3% of A. hydrophila strains were sensitive to ciprofloxacin and florfenicol. Further, eight A. hydrophila strains had high MDR indices at 0.27–0.45. All isolates presented with hemolysin activity. However, only 72.22% of them had proteolytic activity, and only 61.11% could form biofilms. Bacterial isolates harbored different pattern virulence genes, the heat-stable cytotonic enterotoxin (ast), cytotoxic enterotoxin (act), and hemolysin (hly) genes were the most prevalent. Also, a trial to inhibit bacterial growth was conducted using titanium dioxide nanoparticles (TiO2 NPs) with three sizes (13, 32, and 123 nm). If A. hydrophila strains with a high MDR index were tested against TiO2 NPs (20 µg/mL) for 1, 12, and 24 h, those with a small size had a greater bactericidal action than large ones. Bacterial strains were inhibited at different percentages in response to TiO2 NP treatment.

Conclusions
Nile tilapia broodstock, mortality is associated with different A. hydrophila strains, which harbored virulent and MDR genes. Furthermore, TiO2 NPs had bactericidal activity, thereby resulting in a considerable reduction in bacterial load.
Eubiotic effect of rifaximin is associated with decreasing abdominal pain in symptomatic uncomplicated diverticular disease: results from an observational cohort study
Authors: Ivashkin Vladimir , Shifrin Oleg , Maslennikov Roman , Poluektova Elena , Korolev Alexander , Kudryavtseva Anna , Krasnov George , Benuni Nona , Barbara Giovanni 
Published: March 2023

Abstract
Background
Rifaximin effectively treats symptomatic uncomplicated diverticular disease (SUDD) and has shown eubiotic potential (i.e., an increase in resident microbial elements with potential beneficial effects) in other diseases. This study investigated changes in the fecal microbiome of patients with SUDD after repeated monthly treatment with rifaximin and the association of these changes with the severity of abdominal pain.

Methods
This was a single-center, prospective, observational, uncontrolled cohort study. Patients received rifaximin 400 mg twice a day for 7 days per month for 6 months. Abdominal pain (assessed on a 4-point scale from 0 [no pain] to 3 [severe pain]) and fecal microbiome (assessed using 16 S rRNA gene sequencing) were assessed at inclusion (baseline) and 3 and 6 months. The Spearman’s rank test analyzed the relationship between changes in the gut microbiome and the severity of abdominal pain. A p-value ≤ 0.05 was considered statistically significant.

Results
Of the 23 patients enrolled, 12 patients completed the study and were included in the analysis. Baseline abdominal pain levels decreased significantly after 3 (p = 0.036) and 6 (p = 0.008) months of treatment with rifaximin. The abundance of Akkermansia in the fecal microbiome was significantly higher at 3 (p = 0.017) and 6 (p = 0.015) months versus baseline. The abundance of Ruminococcaceae (p = 0.034), Veillonellaceae (p = 0.028), and Dialister (p = 0.036) were significantly increased at 6 months versus baseline, whereas Anaerostipes (p = 0.049) was significantly decreased. The severity of abdominal pain was negatively correlated with the abundance of Akkermansia (r=-0.482; p = 0.003) and Ruminococcaceae (r=-0.371; p = 0.026) but not with Veillonellaceae, Dialister, or Anaerostipes. After 3 months of rifaximin, abdominal pain was significantly less in patients with Akkermansia in their fecal microbiome than in patients without Akkermansia (p = 0.022).

Conclusion
The eubiotic effect of rifaximin was associated with decreased abdominal pain in patients with SUDD.
Clinical-radiomics models based on plain X-rays for prediction of lung metastasis in patients with osteosarcoma
Authors: Yin Ping , Zhong Junwen , Liu Ying , Liu Tao , Sun Chao , Liu Xiaoming , Cui Jingjing , Chen Lei , Hong Nan 
Published: March 2023

Abstract
Objectives
Osteosarcoma (OS) is the most common primary malignant bone tumor in adolescents. Lung metastasis (LM) occurs in more than half of patients at different stages of the disease course, which is one of the important factors affecting the long-term survival of OS. To develop and validate machine learning radiomics model based on radiographic and clinical features that could predict LM in OS within 3 years.

Methods
486 patients (LM = 200, non-LM = 286) with histologically proven OS were retrospectively analyzed and divided into a training set (n = 389) and a validation set (n = 97). Radiographic features and risk factors (sex, age, tumor location, etc.) associated with LM of patients were evaluated. We built eight clinical-radiomics models (k-nearest neighbor [KNN], logistic regression [LR], support vector machine [SVM], random forest [RF], Decision Tree [DT], Gradient Boosting Decision Tree [GBDT], AdaBoost, and extreme gradient boosting [XGBoost]) and compared their performance. The area under the receiver operating characteristic curve (AUC) and accuracy (ACC) were used to evaluate different models.

Results
The radscore, ALP, and tumor size had significant differences between the LM and non-LM groups (tradscore = -5.829, χ2ALP = 97.137, tsize = -3.437, P < 0.01). Multivariable LR analyses showed that ALP was an important indicator for predicting LM of OS (odds ratio [OR] = 7.272, P < 0.001). Among the eight models, the SVM-based clinical-radiomics model had the best performance in the validation set (AUC = 0.807, ACC = 0.784).

Conclusion
The clinical-radiomics model had good performance in predicting LM in OS, which would be helpful in clinical decision-making.
Gastric ulcer and duodenitis associated with coinfection of human herpesvirus-8 and cytomegalovirus in a renal transplant recipient: a case report
Authors: Lee Sik , Kim Kyoung Min , Hwang Hong Pil , Hwang Jeong-Hwan 
Published: March 2023

Abstract
Background
The coinfection between cytomegalovirus (CMV) and either human herpesvirus‐6 (HHV‐6) or HHV-7 in renal transplant recipients is well known; however, there have been few reports of coinfection of CMV associated with HHV-8. This paper presents a first case of acute gastric ulcer and duodenitis associated with CMV and HHV‐8 coinfection after renal transplantation.

Case presentation
A 33-year-old male with a history of kidney transplantation was admitted to hospital because of postural epigastric pain. The recipient was CMV seropositive prior to transplantation and received trimethoprim-sulfamethoxazole without universal prophylaxis. Approximately 5 months after renal transplant, the recipient complained postural epigastric pain. An endoscopy revealed diffuse ulcerative lesions in the lower body and in the antrum of the stomach, as well as several erythematous mucosal lesions in the duodenum. Histopathologic examination identified CMV inclusions consistent with invasive CMV disease and immunohistochemical staining showed positive results for HHV-8 and CMV. No tumorous diseases such as Kaposi’s sarcoma were detected. After 3 weeks of intravenous ganciclovir treatment, we observed that serum CMV PCR remained within the normal range and clinical symptoms improved. A follow-up endoscopy performed 3 weeks later showed that the severity of the above mentioned lesions had improved.

Conclusions
We report the first case of a renal transplant recipient diagnosed with acute gastric ulcer and duodenitis associated with coinfection of CMV and HHV-8. Ganciclovir appears to be effective in diseases associated with coinfection of CMV and HHV-8.
Stability of sensor-based gait parameters reassessed after a period of one year in people with multiple sclerosis
Authors: Müller Roy , Hamacher Daniel , Keune Philipp M. , Oschmann Patrick 
Published: March 2023

AbstractBackgroundCurrently, there are several studies showing that wearable inertial sensors are highly sensitive in the detection of gait disturbances in people with multiple sclerosis (PwMS), showing excellent reliability within one or 7–14 days. However, it is not known how stable these gait parameters remain over a longer period of time. This is surprising, because many treatments last longer than two weeks. Thus, the purpose of the current study was to examine gait parameters obtained by means of wearable inertial sensors during a 6-min walk and to reassess these parameters after a period of one year.MethodsFifty PwMS (without a relapse or a recent change in the Expanded Disability Status Scale (EDSS) or treatment) and 20 healthy participants were examined at two assessment points (interval between assessments: 14.4 ± 6.6 months). At each assessment point, all participants had to complete a 6-min walking test, an observer-rater test (Berg Balance Scale, BBS) and a Timed-up and Go Test (TUG). To measure mean gait parameters (i.e. walking speed, stride length, stride time, the duration of the stance and swing phase and minimum toe-to-floor distance), as well as the intraindividual standard deviation of each mean gait parameter, wearable inertial sensors were utilized.ResultsWe found that even after one year all mean gait parameters showed excellent Intraclass Correlation Coefficients (ICC between 0.75 and 0.95) in PwMS. Looking at MS subgroups, the ICCs were slightly higher in MS subgroup 2 (EDSS 2.0–5.0) than those in MS subgroup 1 (EDSS 0.0–1.5) and healthy controls. Compared to the mean gait parameters, parameters of gait variability showed only good-to-fair ICC values in PwMS. Concerning BBS and TUG, the ICC values after one year were close to the ICC values of the measured mean gait parameters.ConclusionsDue to the excellent stability of mean gait parameters after one year, these sensor-based gait parameters can be identified as clinically relevant markers to evaluate treatment effects over a longer (several months) period of time in MS.
Successful mechanical thrombectomy in acute bilateral M1 middle cerebral artery occlusion: a case report and literature review
Authors: Li Zhiqiang , Wu Shuhui , Zhao Shuzhi , Li Ning , Ma Weibin , Jiang Guisheng , Liu Lingling , Jing Guoxian 
Published: March 2023

Abstract
Background
Acute bilateral occlusion of the middle cerebral artery (MCA) is a very rare condition, and most cases are accompanied by a poor prognosis. However, mechanical thrombectomy (MT) for bilateral MCA is challenging. Here, we report a case of acute unilateral MCA occlusion with sequential acute occlusion of the bilateral MCA during intravenous thrombolysis (IVT). We urgently performed bilateral MT of the MCA and effective recanalization.

Case presentation
The patient is a 73-year-old man who complained of a sudden adverse influence on speech and an inability to move his left limb for 2 h. He had a history of paroxysmal atrial fibrillation, but had never used any anticoagulants before. Head and neck computed tomography angiography (CTA) showed embolism in the right M1 MCA. During intravenous alteplase thrombolytic therapy, the patient suddenly became unconscious. Cerebral angiography showed occlusion of the M1 segment of the bilateral MCA in the patients. MT of the bilateral MCA was performed using a combination of a stent retriever and an aspiration catheter with mTici 3 revascularization. On the second day, the patient became conscious, although he had remaining symptoms of speech insufficiency and weakness of the left limb. The mRS score was 2 90 days after the operation.

Conclusions
Acute bilateral occlusion of the M1 segment of the MCA is extremely rare and is accompanied by high morbidity and high mortality. Intravenous alteplase thrombolysis can increase the risk of atrial thrombus shedding in patients with atrial fibrillation, so patients with acute bilateral MCA occlusion in the M1 segment chose direct MT or bridging therapy, which remains controversial, and the sequence of MT remains to be discussed. Nevertheless, early endovascular treatment can decrease the morbidity and mortality of such patients.
Tolerability of concurrent external beam radiotherapy and [177Lu]Lu-PSMA-617 for node-positive prostate cancer in treatment naïve patients, phase I study (PROQURE-I trial)
Authors: van der Sar Esmée C. A. , Braat Arthur J. A. T. , van der Voort- van Zyp Jochem R. N. , van der Veen Betty S. , van Leeuwen Pim J. , de Vries-Huizing Daphne M. V. , Hendrikx Jeroen M. A. , Lam Marnix G. E. H. , Vogel Wouter V. 
Published: March 2023

Abstract
Background
Prostate cancer patients with locoregional lymph node disease at diagnosis (N1M0) still have a limited prognosis despite the improvements provided by aggressive curative intent multimodal locoregional external beam radiation therapy (EBRT) with systemic androgen deprivation therapy (ADT). Although some patients can be cured and the majority of patients have a long survival, the 5-year biochemical failure rate is currently 29–47%. [177Lu]Lu-PSMA-617 has shown impressive clinical and biochemical responses with low toxicity in salvage setting in metastatic castration-resistant prostate cancer. This study aims to explore the combination of standard EBRT and ADT complemented with a single administration of [177Lu]Lu-PSMA-617 in curative intent treatment for N1M0 prostate cancer. Hypothetically, this combined approach will enhance EBRT to better control macroscopic tumour localizations, and treat undetected microscopic disease locations inside and outside EBRT fields.

Methods
The PROQURE-I study is a multicenter prospective phase I study investigating standard of care treatment (7 weeks EBRT and 3 years ADT) complemented with one concurrent cycle (three, six, or nine GBq) of systemic [177Lu]Lu-PSMA-617 administered in week two of EBRT. A maximum of 18 patients with PSMA-positive N1M0 prostate cancer will be included. The tolerability of adding [177Lu]Lu-PSMA-617 will be evaluated using a Bayesian Optimal Interval (BOIN) dose-escalation design. The primary objective is to determine the maximum tolerated dose (MTD) of a single cycle [177Lu]Lu-PSMA-617 when given concurrent with EBRT + ADT, defined as the occurrence of Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 grade three or higher acute toxicity. Secondary objectives include: late toxicity at 6 months, dosimetric assessment, preliminary biochemical efficacy at 6 months, quality of life questionnaires, and pharmacokinetic modelling of [177Lu]Lu-PSMA-617.

Discussion
This is the first prospective study to combine EBRT and ADT with [177Lu]Lu-PSMA-617 in treatment naïve men with N1M0 prostate cancer, and thereby explores the novel application of [177Lu]Lu-PSMA-617 in curative intent treatment. It is considered likely that this study will confirm tolerability as the combined toxicity of these treatments is expected to be limited. Increased efficacy is considered likely since both individual treatments have proven high anti-tumour effect as mono-treatments.

Trial registration
ClinicalTrials, NCT05162573. Registered 7 October 2021.
Negative regulation of CD44st by miR-138-5p affects the invasive ability of breast cancer cells and patient prognosis after breast cancer surgery
Authors: Jian Fang Xin , Bao Peng Xiao , Li Wang Fu , Cui Yan Hai , Hong Hang Guan 
Published: March 2023

Abstract
Objective
To investigate how the negative regulation of CD44st by miR-138-5p affects the invasive ability of breast cancer cell lines and prognosis in postoperative breast cancer patients.

Methods
RT-PCR, qRT-PCR, and western blot assays were used to detect the expression of CD44s, CD44v6, and CD44st at both mRNA and protein levels. The expression of miR-138-5p in breast cancer cell lines was also evaluated. The binding ability of miR-138-5p to CD44st was determined via a dual-luciferase assay. The CD44 protein expression in breast cancer tissues was detected using immunohistochemistry. A Transwell assay was used to detect the invasive ability of tumor cells. The correlation between CD44st and miR-138-5p mRNA expression in breast cancer tissues was evaluated using qRT-PCR, and the relationship between clinicopathological features was statistically analyzed.

Results
CD44s and CD44v6 were highly expressed in MDAMB-231 cell line, while CD44st was highly expressed in MCF-7/Adr and Skbr-3 cells. None of the CD44 isoforms were expressed in MCF-7 cells. The miR-138-5p was highly expressed in MCF-7 cells, but not in MCF-7/Adr, Skbr-3, and MDAMB-231 cells. The dual-luciferase assay suggested that miR-138-5p could bind to wild-type CD44st 3'-UTR, miR-138-5p overexpression significantly inhibited the expression level of CD44 protein in MCF-7/Adr cells, and miR-138-5p + CD44st (3'-UTR)-treated MCF-7/Adr and Skbr-3 cells were significantly less invasive than those in the control group (P < 0.05). RT-PCR results for 80 postoperative breast cancer patients showed that the mRNA expression rate for CD44st was higher in cancer tissues than in paracancerous tissues, and the expression rate of miR-138-5p was higher in paracancerous tissues than in cancerous tissues (P < 0.01). In cancer tissues, CD44st was negatively correlated with miR-138-5p expression, with correlation coefficient r = -0.76 (Pearson’s correlation), coefficient of determination R2 = 0.573, F = 106.89, and P < 0.001. The median overall survival value for patients in the low miR-138-5p expression group was 40.39 months [95% confidence interval (CI): 35.59–45.18 months] and 56.30 months (95% CI: 54.38–58.21 months) for patients in the high-expression group, with a log rank (Mantel-Cox) of 13.120, one degree of freedom, and P < 0.001.

Conclusion
In breast cancer cell lines, miR-138-5p negatively regulated expression of CD44st and affected the invasive ability of tumor cells and patient prognosis after breast cancer surgery.