bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics of dexmedetomidine in anaesthetized horses following repeated subcutaneous administration and intravenous constant rate infusion
Authors: Di Cesare Federica , Rabbogliatti Vanessa , Draghi Susanna , Amari Martina , Brioschi Federica Alessandra , Villa Roberto , Ravasio Giuliano , Cagnardi Petra 
Published: December 2023

Abstract
Background
The inclusion of dexmedetomidine (DEX) within a balanced general anaesthesia protocol is effective in improving the clinical outcome and recovery quality of anaesthesia in horses. This study aimed to determine the pharmacokinetic profile of DEX following repeated subcutaneous (SC) administration at 2 µg/kg every 60 min till the end of the procedure in comparison to intravenous constant rate infusion (CRI) at 1 µg/kg/h in anaesthetized horses undergoing diagnostic procedures up to the end of the diagnostic procedure.

Results
In the CRI and SC groups DEX maximum concentrations (Cmax) were 0.83 ± 0.27 ng/mL and 1.14 ± 0.71 ng/mL, respectively, reached at a time (Tmax) of 57.0 ± 13.4 min and 105.5 ± 29.9 min. Mean residence time to the last measurable concentration (MRTlast) was 11.7 ± 6.2 and 55.8 ± 19.7 min for the CRI group and SC groups, respectively. The apparent elimination half-life was 18.0 ± 10.0 min in the CRI group and 94.8 ± 69.8 min for the SC group, whereas the area under the curve (AUC0-last) resulted 67.7 ± 29.3 and 83.2 ± 60.5 min*ng/mL for CRI and SC group, respectively. Clearance was 16.26 ± 8.07 mL/min/kg for the CRI group. No signs of adverse effects were recorded in both groups.

Conclusions
The pharmacokinetic profile of DEX following repeated SC administration in anaesthetized horses was comparable to intravenous CRI administration during the intranaesthetic period and beneficial during the recovery phase from general anaesthesia. The SC route could be considered as an alternative to CRI for improving the recovery quality of equine patients undergoing general anaesthesia.
Efficient de novo production of bioactive cordycepin by Aspergillus oryzae using a food-grade expression platform
Authors: Jeennor Sukanya , Anantayanon Jutamas , Panchanawaporn Sarocha , Chutrakul Chanikul , Vongsangnak Wanwipa , Laoteng Kobkul 
Published: December 2023

Abstract
Background
Cordycepin (3′-deoxyadenosine) is an important bioactive compound in medical and healthcare markets. The drawbacks of commercial cordycepin production using Cordyceps spp. include long cultivation periods and low cordycepin yields. To overcome these limitations and meet the increasing market demand, the efficient production of cordycepin by the GRAS-status Aspergillus oryzae strain using a synthetic biology approach was developed in this study.

Results
An engineered strain of A. oryzae capable of cordycepin production was successfully constructed by overexpressing two metabolic genes (cns1 and cns2) involved in cordycepin biosynthesis under the control of constitutive promoters. Investigation of the flexibility of carbon utilization for cordycepin production by the engineered A. oryzae strain revealed that it was able to utilize C6-, C5-, and C12-sugars as carbon sources, with glucose being the best carbon source for cordycepin production. High cordycepin productivity (564.64 ± 9.59 mg/L/d) was acquired by optimizing the submerged fermentation conditions.

Conclusions
This study demonstrates a powerful production platform for bioactive cordycepin production by A. oryzae using a synthetic biology approach. An efficient and cost-effective fermentation process for cordycepin production using an engineered strain was established, offering a powerful alternative source for further upscaling.
The emerging role of glycolysis and immune evasion in gastric cancer
Authors: Zheng Shanshan , Li Huaizhi , Li Yaqi , Chen Xu , Shen Junyu , Chen Menglin , Zhang Cancan , Wu Jian , Sun Qingmin 
Published: December 2023

AbstractGastric cancer (GC) is the fifth most common malignancy and the third leading cause of cancer-related deaths worldwide. Similar to other types of tumors, GC cells undergo metabolic reprogramming and switch to a “predominantly glycolytic” metabolic pattern to promote its survival and metastasis, also known as “the Warburg effect”, which is characterized by enhanced glucose uptake and lactate production. A large number of studies have shown that targeting cancer cells to enhanced glycolysis is a promising strategy, that can make cancer cells more susceptible to other conventional treatment methods of treatment, including chemotherapy, radiotherapy and immunotherapy, and so on. Therefore, this review summarizes the metabolic characteristics of glycolysis in GC cells and focuses on how abnormal lactate concentration can lead to immunosuppression through its effects on the differentiation, metabolism, and function of infiltrating immune cells, and how targeting this phenomenon may be a potential strategy to improve the therapeutic efficacy of GC.
Exploiting autophagy balance in T and NK cells as a new strategy to implement adoptive cell therapies
Authors: Giansanti Manuela , Theinert Tobias , Boeing Sarah Katharina , Haas Dorothee , Schlegel Paul-Gerhardt , Vacca Paola , Nazio Francesca , Caruana Ignazio 
Published: December 2023

AbstractAutophagy is an essential cellular homeostasis pathway initiated by multiple stimuli ranging from nutrient deprivation to viral infection, playing a key role in human health and disease. At present, a growing number of evidence suggests a role of autophagy as a primitive innate immune form of defense for eukaryotic cells, interacting with components of innate immune signaling pathways and regulating thymic selection, antigen presentation, cytokine production and T/NK cell homeostasis. In cancer, autophagy is intimately involved in the immunological control of tumor progression and response to therapy. However, very little is known about the role and impact of autophagy in T and NK cells, the main players in the active fight against infections and tumors. Important questions are emerging: what role does autophagy play on T/NK cells? Could its modulation lead to any advantages? Could specific targeting of autophagy on tumor cells (blocking) and T/NK cells (activation) be a new intervention strategy? In this review, we debate preclinical studies that have identified autophagy as a key regulator of immune responses by modulating the functions of different immune cells and discuss the redundancy or diversity among the subpopulations of both T and NK cells in physiologic context and in cancer.
Establishment and validation of early prediction model for hypertriglyceridemic severe acute pancreatitis
Authors: Shuanglian Yi , Huiling Zeng , Xunting Lin , Yifang Deng , Yufen Lin , Shanshan Xie , Lijuan Si , Yunpeng Liu 
Published: December 2023

Abstract
Background
The prevalence of hypertriglyceridaemia-induced acute pancreatitis (HTG-AP) is increasing due to improvements in living standards and dietary changes. However, currently, there is no clinical multifactor scoring system specific to HTG-AP. This study aimed to screen the predictors of HTG-SAP and combine several indicators to establish and validate a visual model for the early prediction of HTG-SAP.

Methods
The clinical data of 266 patients with HTG-SAP were analysed. Patients were classified into severe (N = 42) and non-severe (N = 224) groups according to the Atlanta classification criteria. Several statistical analyses, including one-way analysis, least absolute shrinkage with selection operator (LASSO) regression model, and binary logistic regression analysis, were used to evaluate the data.

Results
The univariate analysis showed that several factors showed no statistically significant differences, including the number of episodes of pancreatitis, abdominal pain score, and several blood diagnostic markers, such as lactate dehydrogenase (LDH), serum calcium (Ca2+), C-reactive protein (CRP), and the incidence of pleural effusion, between the two groups (P < 0.000). LASSO regression analysis identified six candidate predictors: CRP, LDH, Ca2+, procalcitonin (PCT), ascites, and Balthazar computed tomography grade. Binary logistic regression multivariate analysis showed that CRP, LDH, Ca2+, and ascites were independent predictors of HTG-SAP, and the area under the curve (AUC) values were 0.886, 0.893, 0.872, and 0.850, respectively. The AUC of the newly established HTG-SAP model was 0.960 (95% confidence interval: 0.936–0.983), which was higher than that of the bedside index for severity in acute pancreatitis (BISAP) score, modified CT severity index, Ranson score, and Japanese severity score (JSS) CT grade (AUC: 0.794, 0.796, 0.894 and 0.764, respectively). The differences were significant (P < 0.01), except for the JSS prognostic indicators (P = 0.130). The Hosmer–Lemeshow test showed that the predictive results of the model were highly consistent with the actual situation (P > 0.05). The decision curve analysis plot suggested that clinical intervention can benefit patients when the model predicts that they are at risk for developing HTG-SAP.

Conclusions
CRP, LDH, Ca2+, and ascites are independent predictors of HTG-SAP. The prediction model constructed based on these indicators has a high accuracy, sensitivity, consistency, and practicability in predicting HTG-SAP.
Dual peptides-modified cationic liposomes for enhanced Lung cancer gene therapy by a gap junction regulating strategy
Authors: Zhao Ziyu , Wang Wenhao , Wang Guanlin , Huang Zhengwei , Zhou Liping , Lin Li , Ou Yueling , Huang Wanzhen , Zhang Xuejuan , Wu Chuanbin , Tao Liang , Wang Qin 
Published: December 2023

Abstract
Background
Gene therapy for lung cancer has emerged as a novel tumor-combating strategy for its superior tumor specificity, low systematical toxicity and huge clinical translation potential. Especially, the applications of microRNA shed led on effective tumor ablation by directly interfering with the crucial gene expression, making it one of the most promising gene therapy agents. However, for lung cancer therapy, the microRNA treatment confronted three bottlenecks, the poor tumor tissue penetration effect, the insufficient lung drug accumulation and unsatisfied gene transfection efficiency. To address these issues, an inhalable RGD-TAT dual peptides-modified cationic liposomes loaded with microRNA miR-34a and gap junction (GJ) regulation agent all-trans retinoic acid (ATRA) was proposed, which was further engineered into dry powder inhalers (DPIs).

Results
Equipped with a rough particle surface and appropriate aerodynamic size, the proposed RGD-TAT-CLPs/ARTA@miR-34a DPIs were expected to deposit into the deep lung and reach lung tumor lesions guided by targeting peptide RGD. Assisted by cellular transmembrane peptides TAT, the RGD-TAT-CLPs/ARTA@miR-34a was proven to be effectively internalized by cancer cells, enhancing gene transfection efficiency. Then, the GJ between tumor cells was upregulated by ARTA, facilitating the intercellular transport of miR-34a and boosting the gene expression in the deep tumor.

Conclusion
Overall, the proposed RGD-TAT-CLPs/ARTA@miR-34a DPIs could enhance tumor tissue penetration, elevate lung drug accumulation and boost gene transfection efficiency, breaking the three bottlenecks to enhancing tumor elimination in vitro and in vivo. We believe that the proposed RGD-TAT-CLPs/ARTA@miR-34a DPIs could serve as a promising pulmonary gene delivery platform for multiple lung local disease treatments.
The epitranscriptome of high-grade gliomas: a promising therapeutic target with implications from the tumor microenvironment to endogenous retroviruses
Authors: Ramsoomair Christian K. , Ceccarelli Michele , Heiss John D. , Shah Ashish H. 
Published: December 2023

AbstractGlioblastoma (GBM) comprises 45.6% of all primary malignant brain cancers and is one of the most common and aggressive intracranial tumors in adults. Intratumoral heterogeneity with a wide range of proteomic, genetic, and epigenetic dysregulation contributes to treatment resistance and poor prognosis, thus demanding novel therapeutic approaches. To date, numerous clinical trials have been developed to target the proteome and epigenome of high-grade gliomas with promising results. However, studying RNA modifications, or RNA epitranscriptomics, is a new frontier within neuro-oncology. RNA epitranscriptomics was discovered in the 1970s, but in the last decade, the extent of modification of mRNA and various non-coding RNAs has emerged and been implicated in transposable element activation and many other oncogenic processes within the tumor microenvironment. This review provides background information and discusses the therapeutic potential of agents modulating epitranscriptomics in high-grade gliomas. A particular emphasis will be placed on how combination therapies that include immune agents targeting hERV-mediated viral mimicry could improve the treatment of GBM.
Lateralized response of skull bone marrow via osteopontin signaling in mice after ischemia reperfusion
Authors: Xu Chaoran , Zhang Qia , Zhang Yi , Chen Huaijun , Tang Tianchi , Wang Junjie , Xia Siqi , Chen Gao , Zhang Jianmin 
Published: December 2023

AbstractSkull bone marrow is thought to be an immune tissue closely associated with the central nervous system (CNS). Recent studies have focused on the role of skull bone marrow in central nervous system disorders. In this study, we performed single-cell RNA sequencing on ipsilateral and contralateral skull bone marrow cells after experimental stroke and then performed flow cytometry and analysis of cytokine expression. Skull marrow showed lateralization in response to stroke. Lateralization is demonstrated primarily by the proliferation and differentiation of myeloid and lymphoid lineage cells in the skull bone marrow adjacent to the ischemic region, with an increased proportion of neutrophils compared to monocytes. Analysis of chemokines in the skull revealed marked differences in chemotactic signals between the ipsilateral and contralateral skull, whereas sympathetic signals innervating the skull did not affect cranial bone marrow lateralization. Osteopontin (OPN) is involved in region-specific activation of the skull marrow that promotes inflammation in the meninges, and inhibition of OPN expression improves neurological function.
Graphical Abstract
Research priorities in HIV, aging and rehabilitation: building on a framework with the Canada-International HIV and Rehabilitation Research Collaborative
Authors: O’Brien Kelly K. , Ibáñez-Carrasco Francisco , Birtwell Kelly , Donald Graeme , Brown Darren A. , Eaton Andrew D. , Kasadha Bakita , Stanmore Emma , St. Clair-Sullivan Natalie , Townsend Liam , Vera Jaime H. , Solomon Patricia 
Published: December 2023

Abstract
Background
In 2016, the Canada-International HIV and Rehabilitation Research Collaborative established a framework of research priorities in HIV, aging and rehabilitation. Our aim was to review and identify any new emerging priorities from the perspectives of people living with HIV, clinicians, researchers, and representatives from community organizations.

Methods
We conducted a multi-stakeholder international consultation with people living with HIV, researchers, clinicians and representatives of community-based organizations. Stakeholders convened for a one-day Forum in Manchester, United Kingdom (UK) to discuss research priorities via a web-based questionnaire and facilitated discussions. We analyzed data using conventional content analytical techniques and mapped emerging priorities onto the foundational framework.

Results
Thirty-five stakeholders from the UK(n = 29), Canada(n = 5) and Ireland(n = 1) attended the Forum, representing persons living with HIV or representatives from community-based organizations(n = 12;34%), researchers or academics(n = 10;28%), service providers(n = 6;17%), clinicians(n = 4;11%); and trainees(n = 4;11%). Five priorities mapped onto the Framework of Research Priorities across three content areas: A–Episodic Health and Disability Aging with HIV (disability, frailty, social participation), B-Rehabilitation Interventions for Healthy Aging across the Lifespan (role, implementation and impact of digital and web-based rehabilitation interventions) and C–Outcome Measurement in HIV and Aging (digital and web-based rehabilitation health technology to measure physical activity). Stakeholders indicated methodological considerations for implementing digital and web-based rehabilitation interventions into research and practice and the importance of knowledge transfer and exchange among the broader community.

Conclusion
Results highlight the sustained importance of the Framework of Research Priorities and provide further depth and areas of inquiry related to digital and web-based rehabilitation interventions and technology aging with HIV.
Novel sternoclavicular hook plate for the treatment of posterior sternoclavicular dislocation: a retrospective study
Authors: Xin Hanlong , Wang Xingui , Zhang Shaohua , Lin Lie , Chen Haixiao , Hong Huaxing 
Published: December 2023

Abstract
Background
Controversies regarding the optimal internal fixation method for posterior sternoclavicular dislocation (SCD) exist. Therefore, this study aimed to investigate the clinical efficacy of a new type of sternoclavicular hook plate for treating posterior SCD.

Methods
Eleven patients (eight men and three women) with posterior SCD who underwent treatment with the new sternoclavicular hook plate from June 2011 to January 2022 were retrospectively analyzed. The patients’ ages ranged from 33 to 71 years (54.91 ± 13.58 years). Operation time, blood loss, length of hospital stay, and postoperative complications were recorded. Postoperative joint reduction and healing were evaluated using radiography and computed tomography. The Constant–Murley and Rockwood sternoclavicular joint scores were used to evaluate the functional recovery of the affected limb 12 months after surgery.

Results
All 11 patients were followed up for 12–24 months (18.00 ± 3.74 months). All incisions healed by first intention. The healing time ranged from 9 to 13 days (10.82 ± 1.54 days), and the joint healing time was 3–4 months (3.55 ± 0.52 months). The operation time was 45–75 min (59.55 ± 11.06 min), intraoperative blood loss was 22–58 mL (39.91 ± 11.07 mL), and the length of hospitalization was 6–14 days (9.91 ± 3.27 days). There were no complications such as infections, internal fixation failure, or nerve injury. The Constant–Murley score was 93.64 ± 9.01 at 12 months postoperatively. The Rockwood score was 13.36 ± 1.86, of which nine cases were excellent, one case was good, and one case was fair.

Conclusion
The novel sternoclavicular hook plate is effective for the treatment of posterior SCD. This novel device can facilitate early joint functional exercises and good functional recovery.
Circadian rhythm-associated lncRNA RP11-414H17.5 as a key therapeutic target in osteosarcoma affects the tumor immune microenvironment and enhances malignancy
Authors: Huang Liangkun , Liang Wanting , Cai Wenxiang , Peng Hao 
Published: December 2023

Abstract
Background
It has previously been proven that circadian rhythm disruption is associated with the incidence and deterioration of several tumors, which potentially leads to increased tumor susceptibility and a worse prognosis for tumor-bearing patients. However, their potential role in osteosarcoma has yet to be sufficiently investigated.

Methods
Transcriptomic and clinical data of 84 osteosarcoma samples and 70 normal bone tissue samples were obtained from the TARGET and GTEx databases, circadian rhythm-related genes were obtained from Genecards, and circadian rhythm-related lncRNAs (CRLs) were obtained by Pearson correlation analysis, differential expression analysis, and protein–protein interaction (PPI) analysis. COX regression and LASSO regression were performed on the CRLs in order to construct a circadian rhythm-related prognostic prediction signature (CRPS). CRPS reliability was verified by Kaplan–Meier (KM), principal component analysis (PCA), nomogram, and receiver operating characteristic (ROC) curve. CRPS effects on the immune microenvironment of osteosarcoma were explored by enrichment analysis and immune infiltration analysis, and the effect of critical gene RP11-414H17.5 on osteosarcoma was experimentally verified.

Result
CRPS consisting of three CRLs was constructed and its area under the curve (AUC) values predicted that osteosarcoma prognosis reached 0.892 in the training group and 0.843 in the test group, with a p value of < 0.05 for the KM curve and stable performance across different clinical subgroups. PCA analysis found that CRPS could significantly distinguish between different risk subgroups, and exhibited excellent performance in the prediction of the immune microenvironment. The experiment verified that RP11-414H17.5 can promote metastasis and inhibit apoptosis of osteosarcoma cells.

Conclusion
The study revealed that circadian rhythm plays a crucial role in osteosarcoma progression and identified the impact of the key gene RP11-414H17.5 on osteosarcoma, which provides novel insights into osteosarcoma diagnosis and therapy.
Pneumothorax with liposuction, awareness of rare complication: a case report
Authors: Alwadai Abdulelah , Gaber Mustafa , Alammar Alwaleed Khalid , Alsaedan Abdullah M. , Eldaib Jamal 
Published: December 2023

Abstract
Background
Liposuction is the most commonly performed procedure in aesthetic plastic surgery worldwide, the complications and morbidity are under evaluated. Pneumothorax is thought to be a rare complication after liposuction but the exact rate still unknown.

Case presentation
We presented to you a 45-year-old Arabian female with history of hypertension underwent lipoabdominoplasty, back liposuction and gluteal lipofilling. On the first postoperative day, the patient was complaining of chest pain accompanied with tachypnea and tachycardia, oxygen saturation was maintained on room air. Upon chest auscultation, diminished air entry was markedly noted on her left side, immediate chest x-ray and electrocardiogram (ECG) was done, which showed unremarkable x-ray and ECG shows sinus tachycardia. Computed tomography (CT) carried out and showed left side pneumothorax. An urgent thoracic surgery consultation was done and chest tube was inserted. The patient reported immediate improvement of her symptoms and the vital signs retain to normal range. On day 3, air leak stopped, chest tube was clipped by thoracic surgery, and the chest tube was removed 24 h later. The patient had a relatively smooth recovery with no other complications.

Conclusion
Pneumothorax have possibility to happen with liposuction, awareness of possible risk factors should detect by plastic surgeon, to manage earlier as soon as possible.
Extramedullary hematopoiesis in ribs and severe pulmonary hypertension disease following intermediate beta-thalassemia: a case report
Authors: Takaldani Ali Hossein Samadi , Javanshir Nima , Honardoost Helia , Negaresh Mohammad 
Published: December 2023

Abstract
Background
Thalassemia is a type of congenital hemoglobinopathy that falls into the category of hemolytic anemias. Extramedullary hematopoiesis is a complication of this disease, which is a mechanism to compensate for chronic anemia in these patients, and imaging is the best diagnostic method.

Case report
In this report, a 36-year-old Caucasian female patient with intermediate beta thalassemia is presented who, at the time of referral, complained of exacerbated shortness of breath. Imaging showed diffuse expansion masses with soft tissue components in the ribs of both hemithoraxes, leading to the diagnosis of extramedullary hematopoiesis.

Conclusion
Extramedullary hematopoiesis in the ribs is an uncommon finding in patients with thalassemia and is a sign of the severity of the disease and a poor prognostic factor that might be preventable if blood transfusion begins at younger ages.