bluuebunny/crossref_metadata_2025_split huggingface dataset:
Macrophage activation syndrome as a presenting feature in juvenile systemic lupus erythematosus
Authors: Ramadoss Ishwarya , Rengabashyam Pirahalathan , Seetharaman Varadhan Mythili , Ponniah Subramanian Arul R 
Published: August 2024

Background Macrophage activation syndrome (MAS) is an acquired form of hemo phagocytic lymphohistiocytosis (HLH) and is usually associated with infections, autoimmune, auto inflammatory syndromes and malignancies. Case details A 14 year old girl presented with sub-acute onset of fever with lymphadenopathy, pancytopenia,high ferritin values and a falling erythrocyte sedimentation rate. She was evaluated with relevant laboratory tests that was suggestive of systemic Lupus erythematosus and associated macrophage activation syndrome She recovered with immunosuppressive therapy and other supportive care. Conclusion There is a need for a high index of suspicion of occult MAS and MAS in patients with systemic lupus erythematosus as it may be an initial presentation. Delay in diagnosis and initiation of treatment can lead to a higher mortality.
Naringenin alleviates bone cancer pain via NF-κB/uPA/PAR2 pathway in mice
Authors: Li Yaoyuan , Zheng Guangda , Tang Yiting , Chen Yupeng , Yang Mingzhu , Zheng Qiuhui , Bao Yanju 
Published: August 2024

Purpose This investigation aims to explore the protective role of Naringenin (Nar) in bone cancer pain (BCP) via TNF-α-mediated NF-κB/uPA/PAR2 pathway. Methods BCP model was manipulated by the injection of LL2 cells into femur of mice. The levels of TNF-α and uPA in bone tissue and serum were studied by ELISA. The expressions of PAR2, PKC-γ, PKA and TRPV1 were determined by qPCR and western blot. Levels of p-IKKβ, IKKβ, p-p65, p65 were determined by western blot. Levels of p-p65 and uPA in bone tissue were studied by immunohistochemistry. Behavior tests in this investigation included paw withdrawal latency (PWL) and the paw withdrawal threshold (PWT). Radiological analysis and micro-CT were used to study bone structure. The lesions of bone tissue were determined by HE staining. The Dorsal root ganglia (DRG) isolated from mice were used to determine the level of PAR2 pathway. Results Naringenin improved the BCP-induced bone damage based on the increases of BV/TV, Conn. D, BMD and BMC and the decrease of bone destruction score. Naringenin repressed the reductions of PWT and PWL in BCP mice. Naringenin decreased the levels of PAR2, PKC-γ, PKA and TRPV1 of DRG and reduced the levels of p-IKKβ, p-p65, and uPA in serum and bone tissue in BCP. Importantly, naringenin suppressed the enhancement of TNF-α in serum and bone tissue in BCP mice. Conclusion Naringenin alleviated pain sensitization and bone damage of mice with BCP via TNF-α-mediated NF-κB/uPA/PAR2 pathway. We demonstrated a novel pathway for anti-BCP treatment with naringenin.
Diagnostic biomarkers in knee osteoarthritis: Based on bioinformatics and experimental verification in vivo and in vitro
Authors: Wen Yaqian , Zou Mengdi , Chen Chujie 
Published: August 2024

Background Knee osteoarthritis (KOA) is a multifactorial whole-joint disease with a high rate of disability. Considering the complexity of KOA, there is an urgent need to discover new molecular pathological markers and multi-target treatment strategies. Methods Two datasets, GSE51588 and GSE57218, were downloaded from the Gene Expression Omnibus database and screened for differentially expressed genes (DEGs) using the Gene Expression Omnibus 2R (GEO2R). Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of DEGs were performed. A protein-protein interaction (PPI) network was constructed and hub genes were identified using Molecular Complex Detection (MCODE). Receiver-operating characteristic curves (ROC) were plotted for the genes, and their prognostic values were evaluated. The expression levels of the hub genes in the monosodium iodoacetate (MIA)-induced KOA rat model and lipopolysaccharide (LPS)-stimulated C28/I2 cells were verified using reverse transcription quantitative real-time PCR (RT-qPCR). Results Overall, 33 DEGs were up-regulated and 6 DEGs were down-regulated in the two datasets. A total of 12 hub genes were identified, including COL15A1, THY1, COL1A1, COL5A1, CTHRC1, MXRA5, FN1, COL1A2, COL3A1, SPARC, COL8A1, and COL2A1, which all could be used as biomarkers to differentiate KOA samples from healthy controls. More importantly, we found that THY1, CTHRC1, SPARC, and COL8A1 were significantly upregulated in vivo and in vitro compared with the controls ( p < .01). Conclusions The expression levels of THY1, CTHRC1, SPARC, and COL8A1 were elevated and had good prognostic values as biomarkers in KOA.
Impairments of Human Dignity at the End of Life Quantitatively Assessed by Health Care Professionals: A Pilot Study From Germany
Authors: Derler Florian , Mielke Emilia L. 
Published: August 2024

Background Empirical investigations on health care professionals’ (HCPs) perception of dignity have already spotted common themes in preserving dignity in end-of-life care. However, heterogenic assessment results of varying HCP groups exist. This pilot study wants to provide further evidence on HCPs’ rating of dignity-impairing aspects based on a patient-centered concept, especially regarding different underlying job profiles and other professional characteristics. Methods In a quantitative study design, the rating of dignity-impairing factors in end-of-life care via an adapted version of the Patient Dignity Inventory (aPDI) was assessed. Participants of the relevant professional groups were recruited via convenience sampling from a region of Germany. Results From the final sample of participants, 229 questionnaires were analyzed. The overall importance of each dignity-impairing aspect in end-of-life care was considered to be very high by all different HCP groups. Nonetheless, ratings differed between professions: nursing staff had the highest ratings of importance compared to both physicians and individuals with multiple occupations. Participants with previous knowledge in bioethics also rated some aspects as more important compared to those without this feature. Conclusion With the findings of this investigation, an insight of how professionals rate impairments of dignity at the end of life based on a patient-centered concept is given. Thus, a link between empirical research and medical ethics is added. Potential normative implications for HCPs in practice of a dignified care can be derived, consisting of actively addressing social topics as well as further stressing ethics as a fundamental subject in the training and continuing education.
DNA Methylation Effects on Van der Woude Syndrome Phenotypic Variability
Authors: Seaberg Amanda , Awotoye Waheed , Qian Fang , Machado-Paula Ligiane A. , Dunlay Lindsey , Butali Azeez , Murray Jeff , Moreno-Uribe Lina , Petrin Aline L. 
Published: August 2024

Objective Van der Woude Syndrome (VWS) presents with combinations of lip pits (LP) and cleft lip and/or cleft palate (CL/P, CPO). VWS phenotypic heterogeneity even amongst relatives, suggests that epigenetic factors may act as modifiers. IRF6, causal for 70% of VWS cases, and TP63 interact in a regulatory loop coordinating epithelial proliferation and differentiation in palatogenesis. We hypothesize that differential DNA methylation within IRF6 and TP63 regulatory regions underlie VWS phenotypic discordance. Methods DNA methylation of CpG sites in IRF6 and TP63 promoters and in an IRF6 enhancer element was compared amongst blood or saliva DNA samples of 78 unrelated cases. Analyses were done separately for blood and saliva, within each sex and in combination, and to address cleft type (CL/P ± LP vs. CPO ± LP) and phenotypic severity (any cleft + LP vs. any cleft only). Results For cleft type, blood samples showed higher IRF6 and TP63 promoter methylation on males with CPO ± LP compared to CL/P ± LP and on individuals with CPO ± LP compared to those with CL/P ± LP, respectively. Saliva samples showed higher IRF6 enhancer methylation on individuals with CPO ± LP compared to CL/P ± LP and contrary to above, lower TP63 promoter methylation on CPO ± LP compared to CL/P ± LP. For phenotypic severity, blood samples showed no differences; however, saliva samples showed higher IRF6 promoter methylation in individuals with any cleft + LP compared to those without lip pits. Conclusion We observed differential methylation in IRF6 and TP63 regulatory regions associated with cleft type and phenotypic severity, indicating that epigenetic changes in IRF6 and TP63 can contribute to phenotypic heterogeneity in VWS.
Assessing the impact of aprepitant on response to dose-intensive cyclophosphamide, etoposide, and cisplatin (DICEP)
Authors: Thai Kevin , Jupp Jennifer , Dersch-Mills Deonne , Ghosh Sunita , Shafey Mona , Fong Leanne 
Published: August 2024

Background Despite evidence demonstrating the effectiveness of aprepitant for chemotherapy-induced nausea and vomiting (CINV), its use in stem cell transplant settings across Canada is not standard. While pharmacokinetic data exists, the clinical significance of cytochrome P450 3A4 (CYP 3A4) inhibition of cyclophosphamide by aprepitant is unclear. Reduced activation of cyclophosphamide may reduce the effectiveness of dose-intensive cyclophosphamide, etoposide, and cisplatin (DICEP). Objectives To compare response rates to DICEP in patients with Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL) in the presence and absence of aprepitant. Methods A retrospective review of patients who received full-dose DICEP for relapsed/refractory HL or DLBCL between June 1995 and September 2018 at the Foothills Medical Centre (FMC) in Calgary, Alberta, Canada was conducted. Descriptive statistics were used to assess response rate, as defined by the 2007 International Working Group response criteria. Results Of the 218 patients included in this study, 87.6% of patients in the control group and 88.5% of patients in the aprepitant group responded to DICEP (difference 0.025 [95% CI, −0.066 to 0.114], p = 0.827). Univariate analyses for age, sex, type of cancer, stage of cancer, number of prior relapses, and relapse status were not significant. No significant differences were observed for secondary outcomes. Conclusion Response rates to DICEP in relapsed/refractory HL and DLBCL patients were similar regardless of aprepitant use. Considering these results and the effectiveness of aprepitant in CINV, its addition to standard antiemetic therapy in patients receiving DICEP should be given strong consideration in the transplant setting.
Bilateral Congenital Pelvic Arteriovenous Malformation: A Case Report and Review of Literature
Authors: Viglione Margherita , Discalzi Andrea , Mistretta Francesco , Mancini Andrea , Nardelli Floriana , Bergui Mauro 
Published: August 2024

Purpose: Through a paradigmatic case and a systematic literature review, we present various endovascular strategies for treating pelvic paravesical arteriovenous vascular malformations (AVMs), with a focus on the efficacy of accessing the shunt point through direct puncture of the venous collector. Case Report: A 42-year-old male with nonspecific pelvic pain underwent a computed tomography (CT) scan, which revealed bilateral pelvic AVMs characterized by a network of arteriolar afferents originating from the internal iliac arteries and the inferior mesenteric artery, draining into 2 interconnected giant venous sacs in the bilateral paravesical space. The malformation was classified as type II according to the Cho classification. Following an unsuccessful attempt at transarterial embolization, we devised a plan for bilateral transvenous embolization in 2 separate sessions. Venous access was achieved through percutaneous transperineal ultrasound-guided puncture of the dominant outflow venous sac. A microcatheter was then placed directly into the shunt point, where sclerosant and embolic agents were specifically delivered. Follow-up imaging showed complete obliteration of both pelvic AVMs. Conclusions: Effective hemostasis of pelvic paravesical AVMs can be achieved by targeting the shunt point from the aneurysmal dominant outflow vein, potentially through direct percutaneous puncture. Clinical Impact This study aims to demonstrate the effectiveness of a transvenous approach in cases of embolization of pelvic paravesical arteriovenous vascular malformations (AVMs). The key to successful treatment lies in occluding the shunt point within the aneurysmal dominant outflow vein’s wall, which can be reached transvenously and potentially through direct percutaneous puncture. Although arterial occlusion can be performed additionally, it should not be performed alone due to its higher risk of AVM persistence/recurrence.
Perioperative pathways for children with neurodevelopmental conditions and behaviours that challenge: An evaluation of parent experiences for service improvement
Authors: Ong Natalie , Ahuja Hema , de Lima Jonathan , Tomsic Gail , Garg Pankaj , Silove Natalie , Henao Urrego Bobbi , Weatherall Andrew 
Published: August 2024

Previous research shows that children and young people with neurodevelopmental conditions experience greater challenges accessing care in hospitals and having their health needs met. Aim: To elicit experiences of parents of children with neurodevelopmental conditions using a new perioperative pathway. Method: Parents of children accessing an adapted perioperative clinical pathway in a tertiary children’s hospital between July 2019 and December 2020 were invited to participate. A mixed method study was conducted comprising a short survey questionnaire followed by telephonic interviews. Results: From 67 postal surveys sent out, 20 were completed. Six out of 20 parents participated in phone interviews and one parent submitted written prose. Parents were positive about their experiences. Six themes emerged: Negative past experiences (highlighting the need for adapted perioperative pathways); Reasonable adjustments (improving child and parent’s hospital journey); Facilitating communication, convenience and collaboration; Parent’s satisfaction and relief; Barriers to overcome and Areas in need of improvement were discussed. Conclusion: Parents of children with neurodevelopmental conditions report great satisfaction and relief from their experiences of a more efficient, streamlined and stress-free way for their child to have tests or procedures done. Parents report improved communication, convenience and collaboration with staff resulted in timely, safe and high-quality care.
Contribution of intrapulmonary shunt to the pathogenesis of profound hypoxaemia in viral infection: a mechanistic discussion with an illustrative case
Authors: Lyne Tom , Camporota Luigi , Montgomery Hugh 
Published: August 2024

Background: The formation of anastomoses between the pulmonary arteries and pulmonary veins, or the pulmonary and the bronchial circulation, is part of normal foetal lung development. They persist in approximately 30% of adults at rest, and open in almost all adults during exertion. Blood flowing through these anastomoses bypasses the alveolar surface and increases in such shunting can thus cause hypoxaemia. This is now known to contribute to the pathogenesis of hypoxaemia in COVID-19 disease. We here provide evidence to support a similar role in influenza A infection. Illustrative case presentation: We describe a case of influenza A infection associated with severe hypoxaemia, poorly responsive to supplemental oxygen and which worsened following the application of continuous positive airway pressure (CPAP), despite the presence of a normal physical examination, chest radiograph and echocardiogram. This combination suggests a significant intrapulmonary (extra-alveolar) shunt as a cause of the severe hypoxaemia. The shunt fraction was estimated to be approximately 57%. Discussion and conclusion: Intrapulmonary vascular shunts can contribute substantially to hypoxaemia in viral infection. Seeking to understand the pathogenesis of observed hypoxaemia can help guide respiratory therapy. Mechanistic research may suggest novel therapeutic targets which could assist in avoiding intubation and mechanical ventilatory support.
Xanthine Oxidase Inhibitory Activity of Some Vietnamese Remedies Used to Treat Bi Syndrome in Traditional Medicine
Authors: Duong Duc Phan Nguyen , Tran Chen Van , Chung My-Duyen Thi , Nguyen Bay Thi , Nguyen Triet Thanh 
Published: August 2024

Background Hyperuricemia is a metabolic disorder caused by abnormalities in purine metabolism that increase serum uric acid. Some traditional medicine remedies have been proven to cause hypouricemia by inhibiting xanthine oxidase. In Vietnam, some remedies that eliminate wind, cold, and dampness have been used to treat gouty arthritis, but there is still a lack of scientific evidence regarding the underlying biological mechanisms involved. This study aimed to assess the xanthine oxidase inhibitory activity in vitro and the hypouricemic effects of several Vietnamese remedies used to treat Bi syndrome in traditional medicine. Methods The chosen remedies that met our criteria were successively extracted with 70% ethanol. A preliminary investigation of the chemical composition of the extracts was performed by common chemical reactions. The in vitro xanthine oxidase inhibitory activity of the extracts was investigated using the procedure of Noro et al (1983). Acute toxicology and hypouricemic effect of the remedy that showed the highest xanthine oxidase inhibitory activity were investigated in vivo using a potassium oxonate-induced hyperuricemic mouse model. Results Five remedies that met the criteria were chosen. Phytochemical screening of all the extracts revealed the presence of flavonoids, saponins, alkaloids, tannins, and carbohydrates. The Bai nghiem phuong 2 extract did not show xanthine oxidase inhibitory activity whereas the Thang Tri Te Thap extract, which exhibited the highest inhibitory xanthine oxidase activity with an IC50 value of 48.33 ± 0.41 µg/mL, was selected for the subsequent in vivo experiments. The Thang Tri Te Thap extract did not cause acute toxicity, with a Dmax of 31.67 g/kg. At doses of 1.5 g/kg and 3 g/kg, Thang Tri Te Thap significantly reduced the serum uric acid concentration by 59.84 ± 5.79% and 65.01 ± 12.73%, respectively (p < 0.05). Conclusions Thang Tri Te Thap showed xanthine oxidase inhibitory activity in vitro and hypouricemic effects in vivo.
Automated machine learning models for nonalcoholic fatty liver disease assessed by controlled attenuation parameter from the NHANES 2017–2020
Authors: Liu Lihe , Lin Jiaxi , Liu Lu , Gao Jingwen , Xu Guoting , Yin Minyue , Liu Xiaolin , Wu Airong , Zhu Jinzhou 
Published: August 2024

Background Nonalcoholic fatty liver disease (NAFLD) is recognized as one of the most common chronic liver diseases worldwide. This study aims to assess the efficacy of automated machine learning (AutoML) in the identification of NAFLD using a population-based cross-sectional database. Methods All data, including laboratory examinations, anthropometric measurements, and demographic variables, were obtained from the National Health and Nutrition Examination Survey (NHANES). NAFLD was defined by controlled attenuation parameter (CAP) in liver transient ultrasound elastography. The least absolute shrinkage and selection operator (LASSO) regression analysis was employed for feature selection. Six algorithms were utilized on the H2O-automated machine learning platform: Gradient Boosting Machine (GBM), Distributed Random Forest (DRF), Extremely Randomized Trees (XRT), Generalized Linear Model (GLM), eXtreme Gradient Boosting (XGBoost), and Deep Learning (DL). These algorithms were selected for their diverse strengths, including their ability to handle complex, non-linear relationships, provide high predictive accuracy, and ensure interpretability. The models were evaluated by area under receiver operating characteristic curves (AUC) and interpreted by the calibration curve, the decision curve analysis, variable importance plot, SHapley Additive exPlanation plot, partial dependence plots, and local interpretable model agnostic explanation plot. Results A total of 4177 participants (non-NAFLD 3167 vs NAFLD 1010) were included to develop and validate the AutoML models. The model developed by XGBoost performed better than other models in AutoML, achieving an AUC of 0.859, an accuracy of 0.795, a sensitivity of 0.773, and a specificity of 0.802 on the validation set. Conclusions We developed an XGBoost model to better evaluate the presence of NAFLD. Based on the XGBoost model, we created an R Shiny web-based application named Shiny NAFLD ( http://39.101.122.171:3838/App2/ ). This application demonstrates the potential of AutoML in clinical research and practice, offering a promising tool for the real-world identification of NAFLD.
Anterior Cruciate Ligament Ruptures in Russian Premier League Soccer Players During the 2010 to 2021/2022 Competitive Seasons: The Epidemiology and Details of Return to Sports
Authors: Bezuglov Eduard , Malyakin Georgiy , Emanov Anton , Baranova Irina , Stepanov Igor , Goncharov Evgeniy , Shoshorina Maria , Izmailov Sergey , Morgans Ryland 
Published: August 2024

Background: There are limited data on the epidemiology of anterior cruciate ligament (ACL) ruptures in elite adult soccer players, especially in the Russian Premier League (RPL). There is an increased risk of injury due to a combination of additional risk factors such as playing in extremely high and low temperatures, frequent long flights, and regular play on natural and artificial surfaces. Purpose: To study the epidemiology of ACL ruptures and determine the patterns associated with their occurrence in RPL soccer players. Study Design: Descriptive epidemiology study. Methods: All ACL ruptures requiring surgery sustained by players competing in the RPL across 12 competitive seasons between 2010 and 2022 were analyzed. All required data were collected from media analysis and confirmed by club doctors. Results: A total of 85 players sustained 100 injuries during 12 competitive seasons. A total of 96.5% of players returned to competitive play. The injury incidence in RPL and during participation of RPL teams in European Cups were 0.4760 and 0.5622 per 1000 playing hours, respectively. When analyzing the outcomes of the primary ACL surgery (a total of 76 operations), the following data were obtained: in 11 cases (14.5%), there was a reinjury on the ipsilateral knee joint and in 4 cases (5.3%) on the contralateral knee joint. The mean return–to-play time after all operations was 284 ± 116 days. The time of return to play after primary reconstruction was 289 ± 136 days, 278 ± 91 days after reconstruction on the contralateral knee and 271 ± 51.5 days after the first ACL revision reconstruction on the ipsilateral knee joints. Conclusion: RPL ACL injury epidemiology is similar to that in the other leagues from around the world, although there are factors that can potentially influence the number of these injuries.