bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reactive oxygen species enhance rAAV transduction by promoting its escape from late endosomes
Authors: Huang Xiaoping , Wang Xiao , Ren Yanxuan , Gao Pingzhang , Xu Wentao , Xie Xiaolan , Diao Yong 
Published: January 2023

Abstract
Background
Recent seminal studies have revealed that endosomal reactive oxygen species (ROS) promote rather than inhibit viral infection. Some ROS generators, including shikonin and H2O2, have the potential to enhance recombinant adeno-associated virus (rAAV) transduction. However, the impact of ROS on rAAV intracellular trafficking remains unclear.

Methods
To understand the effects of ROS on the transduction of rAAV vectors, especially the rAAV subcellular distribution profiles, this study systematically explored the effect of ROS on each step of rAAV intracellular trafficking pathway using fluorescently-labeled rAAV and qPCR quantification determination.

Results
The results showed promoted in-vivo and in-vitro rAAV transduction by ROS exposure, regardless of vector serotype or cell type. ROS treatment directed rAAV intracellular trafficking towards a more productive pathway by upregulating the expression of cathepsins B and L, accelerating the rAAV transit in late endosomes, and increasing the rAAV nucleus entry.

Conclusions
These data support that ROS generative drugs, such as shikonin, have the potential to promote rAAV vector transduction by promoting rAAV’s escape from late endosomes, and enhancing its productive trafficking to the nucleus.
Effects of vitamin D deficiency on blood lipids and bone metabolism: a large cross-sectional study
Authors: Gu Peng , Pu Bin , Chen BaiHang , Zheng XiaoHui , Zeng ZhanPeng , Luo WeiDong 
Published: January 2023

AbstractTo investigate the relationship between serum high-density lipoprotein (HDL-C) and spinal bone mineral density (BMD) under different serum 25-hydroxyvitamin D (25 (OH) D) levels in adults over 40 years old and to explore its mechanism. We include participants over the age of 40 with data on HDL-C, 25 (OH) D, spinal BMD, and other variables in the National Health and Nutrition Examination Survey 2007–2010 in the analysis. A weighted multiple linear regression model was used to evaluate the association between serum HDL-C and spinal BMD in different gender, ages, and serum 25 (OH) D levels. A total of 3599 subjects aged ≥ 40 years old were included in this study. Univariate analysis of the complete correction model showed a negative correlation between serum HDL-C and spinal BMD. In the two subgroups of serum 25 (OH) D, we found that the higher the serum HDL-C in the female with serum 25 (OH) D < 75 nmol/L aged 40–59 years old, the lower the total spinal BMD, and a similar relationship was found in the lumbar spine. However, no similar relationship was found in all populations with serum 25 (OH) D ≥ 75 nmol/L and males with serum 25 (OH) D < 75 nmol/L. These results suggest that among Americans over the age of 40, the increase in serum HDL-C is related to decreased BMD of spine only in women aged 40–59 years with vitamin D insufficiency or deficiency.
Surgeon-modified fenestrated endograft for urgent an aortic arch aneurysm: case report
Authors: Gallicchio Vito , Barbarisi Danilo , Condò Flavia , Sciarrillo Rosaria , Flora Loris 
Published: January 2023

AbstractWe report the case of an endovascular repair of an aortic arch aneurysm by a surgeon-modified fenestrated endograft with a single fenestration in a high-risk patient unfit for open surgery. A patient of 84 years, chronic ischemic cardiopathic, suffering from prostate adenocarcinoma in chemotherapy treatment, came to our hospital for post-traumatic fracture of the right femur. During the hospitalization, the patient exhibited dysphonia and respiratory disorders for several days, therefore, the patient performed Computed Tomography Angiography (CTA) that found the presence of voluminous aneurysm of the aortic arch with a maximum diameter of about 74 mm. The patient was treated with a hybrid-staged procedure; in the first instance, with a carotid-carotid-succlavium bypass to preserve the cerebral and upper limb vascularization and then, the procedure was completed by implanting the surgeon-modified fenestrated endograft with stent delivery to the patient with a fenestration on the anonymous trunk. This surgeon-modified fenestrated endograft was created by modifying a standard endograft by a single fenestration following the three-dimensional reconstructions of the CTA images. The procedure was successfully completed and postoperative course was uneventful. Computed Tomography Angiography demonstrated the exclusion of the aneurysm, patency of the implanted endograft modules, and absence of signs of endoleaks and / or cerebral or medullary ischemic complications.
Case of left ventricular thrombus managed with thrombectomy with left ventricular reconstruction in a patient who had coronavirus disease 2019 infection
Authors: Suzuki Kenji , Sakamoto Shun-Ichiro , Hiromoto Atsushi , Motoji Yusuke , Amitani Ryosuke , Yamaguchi Takako , Ishii Yosuke 
Published: January 2023

Abstract
Background
Intracardiac thrombus is relatively rare in patients with coronavirus disease 2019 (COVID-19). However, if it occurs, thrombotic complications are likely to develop. In this case, we performed a successful thrombectomy on a patient who developed left ventricular thrombus after COVID-19 infection without complications.

Case presentation
A 52-year-old man sought medical care due to fever, dyspnea, and abnormalities in the taste and smell that persisted for 2 weeks. The patient was diagnosed with COVID-19 and was treated with remdesivir, baricitinib, and heparin. Three weeks after hospitalization, electrocardiogram revealed angina pectoris, and cardiac catherization showed left anterior descending coronary artery stenosis. In addition, global hypokinesis and a thrombus at the left ventricular apex were observed on echocardiography. Left ventricular reconstruction concomitant with coronary artery bypass grafting was performed. A thrombus in the left ventricle was resected via left apical ventriculotomy, and the bovine pericardium was covered and sutured on the infarction site to exclude it. The patient was extubated a day after surgery and was transferred to another hospital for recuperation after 20 days. He did not present with complications.

Conclusions
Thrombotic events could be prevented via thrombectomy with left ventricular reconstruction using an intraventricular patch to exclude the residual thrombus.
Recurrent aortic-arch pseudoaneurysm eroding into the left main bronchus following descending thoracic aortic stent repair
Authors: Duan Lijun , Lu Xiaoqian , Pan Ruonan , Cao Dianbo 
Published: January 2023

Abstract
Background
Behcet's disease is a form of systematic vasculitis that affects vessels of various sizes anywhere in the body. Aortic pseudoaneurysm is the most hazardous lesion in Behcet's disease and is associated with high mortality rate once rupture.

Case presentation
In this report, we presented a patient with a known history of Behcet's disease, whose recurrent aortic-arch pseudoaneurysm eroding into the left main bronchus was identified after a 4-year duration of thoracic endovascular aortic repair for thoracic descending aortic pseudoaneurysm ruptured into the left lung. Repeated thoracic endovascular aortic repair combined with the chimney stent effectively controlled massive hemoptysis under the life-threatening circumstance, and the patient was in good condition at the 7-year follow-up.

Conclusions
Thoracic endovascular aortic repair can be used as an effective and problem-solving treatment approach for thoracic aortic aneurysms eroded into the lung, even recurrent pseudoaneurysm after thoracic endovascular aortic repair in BD patients. Among the imaging methods assessing the technical success, outcome and complications, computed tomography angiography offers a fast, accessible and sensitive imaging modality.
Low preoperative serum fibrinogen level is associated with postoperative acute kidney injury in patients with in acute aortic dissection
Authors: Guan Xin-Liang , Li Lei , Jiang Wen-Jian , Gong Ming , Li Hai-Yang , Liu Yu-Yong , Wang Xiao-Long , Zhang Hong-Jia 
Published: January 2023

Abstract
Objective
Acute kidney injury (AKI) after cardiac surgery is associated with serious complication and high risk of mortality. The relationship between hemostatic system and the prognosis of patients with acute type A aortic dissection (ATAAD) has not been evaluated. The purpose of this study was to investigate the association between preoperative serum fibrinogen level and risk of postoperative AKI in patients with ATAAD.

Methods
A total of 172 consecutive patients undergoing urgent aortic arch surgery for ATAAD between April 2020 and December 2021 were identified from Beijing Anzhen Hospital aortic surgery database. The primary outcome was postoperative AKI as defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria. The univariate and multivariate logistic regression analysis were done to assess the independent predictors of risk for postoperative AKI. Receiver operating characteristic (ROC) curve was generated to evaluate the predictive probabilities of risk factors for AKI.

Results
In our study, 51.2% (88/172) patients developed postoperative AKI. Multivariate logistic regression analysis identified low preoperative serum fibrinogen level (OR, 1.492; 95% CI, 1.023 to 2.476; p = 0.021) and increased body mass index (BMI) (OR, 1.153; 95% CI, 1.003 to 1.327; p = 0.046) as independent predictors of postoperative AKI in patients with ATAAD. A mixed effect analysis of variance modeling revealed that obese patients with low preoperative serum fibrinogen level had higher incidence of postoperative AKI (p = 0.04). The ROC curve indicated that low preoperative serum fibrinogen level was a significant predictor of AKI [area under the curve (AUC), 0.771; p < 0.001].

Conclusions
Low preoperative serum fibrinogen level and obesity were associated with the risk of postoperative AKI in patients with ATAAD. These data suggested that low preoperative serum fibrinogen level was preferred marker for predicting the postoperative AKI, especially in obese patients with ATAAD.
The association between preoperative anemia, blood transfusion need, and postoperative complications in adult cardiac surgery, a single center contemporary experience
Authors: Mufti Hani , Alsharm Faisal , Bahawi Mohanad , Almazmumi Mohammed , Alshaikh Yazeed , Abushouk Amir , Algarni Abdullah , Jamalallail Sahal , Almohammadi Mohammed 
Published: January 2023

AbstractBackgroundThe impact of preoperative anemia on postcardiac surgery outcomes is an area of great debate. Although several large-scale studies have been conducted, they have demonstrated conflicting results. A limited number of studies have been conducted in the Middle East. The primary aim of this study was to investigate the association between preoperative anemia and the need for blood transfusions, as well as major postoperative complications.MethodsAdult patients who underwent cardiac surgery at King Faisal Cardiac Center in Jeddah between June 2016 and January 2020 were included in this retrospective cohort study. The study excluded patients with hereditary preoperative anemia. Among the variables studied were variables related to demographics, comorbidities, laboratory data, operation-related data, in-hospital complications, and mortality.ResultsThe mean preoperative hemoglobin (Hb) level was 13.2 g/dL (SD ± 1.8). The overall mortality rate was 4.6%. A lower preoperative Hb level (pvalue = 0.016), postoperative day 1 WBC count (p-value = 0.003), and prolonged cross clamp time (pvalue < 0.001) were significantly associated with mortality. A lower Hb level during the preoperative period or within the first three days of surgery was associated with a higher blood transfusion requirement. However, there was no significant association between blood transfusion and postoperative complications. A multivariate stepwise logistic regression model was developed and several pre and intra operative factors were predictive of the need PRBCs transfusion after cardiac surgery (which included: older age, female gender, lower pre-operative hemoglobin and longer cardio-pulmonary bypass time), with had a predictive accuracy of around ~ 86%.ConclusionBased on our single center study, patients with preoperative lower Hb levels are at higher risk of mortality. However, blood transfusion does not seem to increase the risk of postoperative complications. Optimal utilization of blood products is an important quality metric and identification of patients at higher risk of requiring PRBCs transfusion prior to cardiac surgery can help in implementing pre or intra operative strategies to minimize the need for transfusion.
Understanding patient and parent/caregiver perceptions on gene therapy in Gaucher disease: an international survey
Authors: Collin-Histed Tanya , Rosenberg Aviva , Hopman Noortje , Pacey Jessica 
Published: January 2023

Abstract
Background
Gaucher disease is a rare, autosomal recessive genetic disorder. It is caused by a lack of sufficient activity of the lysosomal enzyme known as glucocerebrosidase, which leads to an accumulation of glucocerebroside, a fatty substance, in the spleen, liver, bone marrow, and rarely, the lungs or central nervous system. While there are several treatments available for people with Type 1 Gaucher disease and the visceral aspects of Type 3 Gaucher disease, no cure is present for any type of Gaucher disease. Clinical trials are currently underway to investigate the safety and efficacy of gene therapy in Gaucher disease, which has the potential to become a new type of (curative) treatment in the future. Gene therapy is a relatively new therapeutic approach, and with the desire to keep the community informed about new treatment developments, the International Gaucher Alliance (IGA) set-up a Gaucher disease specific survey to gauge current perceptions. The survey aimed to benchmark understanding of, and the educational needs surrounding, gene therapy among the Gaucher disease community.

Body
An international, online survey was developed, comprising twelve questions ranging from multiple choice, Likert scale, single tick-box, ranking and open questions. The survey was developed following three patient and caregiver focus groups and underwent review from members of the IGA for readability and accuracy before going live to respondents. The survey was available for two months and shared to audiences via specific Gaucher community channels.

Conclusion
Over 100 patients and parents/caregivers from the Gaucher disease community completed the survey, including people living with Type 1 Gaucher disease (52.88%), people living with Type 3 Gaucher disease (3.85%), parents/caregivers of people living with Type 1, 2 or 3 Gaucher disease (39.42%), and other (3.85%) who were defined as parents of multiple people with Gaucher disease. The survey uncovered various commonalities in perception of gene therapy among all groups, with large knowledge gaps identified on the mode of action, the usefulness of gene therapy and overall understanding of the therapeutic area. This survey provides an overview of the type of information that could be valuable to the Gaucher disease community when developing educational materials.
The N6-methyladenosine METTL3 regulates tumorigenesis and glycolysis by mediating m6A methylation of the tumor suppressor LATS1 in breast cancer
Authors: Xu Youqin , Song Mu , Hong Ziyang , Chen Wancheng , Zhang Qianbing , Zhou Jianlong , Yang Chao , He Zilong , Yu Juanjuan , Peng Xiaolin , Zhu Qiuhong , Li Shaotian , Ji Kaiyuan , Liu Minfeng , Zuo Qiang 
Published: January 2023

Abstract
Background
Posttranscriptional modification of tumor-associated factors plays a pivotal role in breast cancer progression. However, the underlying mechanism remains unknown. M6A modifications in cancer cells are dynamic and reversible and have been found to impact tumor initiation and progression through various mechanisms. In this study, we explored the regulatory mechanism of breast cancer cell proliferation and metabolism through m6A methylation in the Hippo pathway.

Methods
A combination of MeRIP-seq, RNA-seq and metabolomics-seq was utilized to reveal a map of m6A modifications in breast cancer tissues and cells. We conducted RNA pull-down assays, RIP-qPCR, MeRIP-qPCR, and RNA stability analysis to identify the relationship between m6A proteins and LATS1 in m6A regulation in breast cancer cells. The expression and biological functions of m6A proteins were confirmed in breast cancer cells in vitro and in vivo. Furthermore, we investigated the phosphorylation levels and localization of YAP/TAZ to reveal that the activity of the Hippo pathway was affected by m6A regulation of LATS1 in breast cancer cells.

Results
We demonstrated that m6A regulation plays an important role in proliferation and glycolytic metabolism in breast cancer through the Hippo pathway factor, LATS1. METTL3 was identified as the m6A writer, with YTHDF2 as the reader protein of LATS1 mRNA, which plays a positive role in promoting both tumorigenesis and glycolysis in breast cancer. High levels of m6A modification were induced by METTL3 in LATS1 mRNA. YTHDF2 identified m6A sites in LATS1 mRNA and reduced its stability. Knockout of the protein expression of METTL3 or YTHDF2 increased the expression of LATS1 mRNA and suppressed breast cancer tumorigenesis by activating YAP/TAZ in the Hippo pathway.

Conclusions
In summary, we discovered that the METTL3-LATS1-YTHDF2 pathway plays an important role in the progression of breast cancer by activating YAP/TAZ in the Hippo pathway.
A signature based on glycosyltransferase genes provides a promising tool for the prediction of prognosis and immunotherapy responsiveness in ovarian cancer
Authors: Xu Xuyao , Wu Yue , Jia Genmei , Zhu Qiaoying , Li Dake , Xie Kaipeng 
Published: January 2023

AbstractBackgroundOvarian cancer (OC) is the most fatal gynaecological malignancy and has a poor prognosis. Glycosylation, the biosynthetic process that depends on specific glycosyltransferases (GTs), has recently attracted increasing importance due to the vital role it plays in cancer. In this study, we aimed to determine whether OC patients could be stratified by glycosyltransferase gene profiles to better predict the prognosis and efficiency of immune checkpoint blockade therapies (ICBs).MethodsWe retrieved transcriptome data across 420 OC and 88 normal tissue samples using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, respectively. An external validation dataset containing 185 OC samples was downloaded from the Gene Expression Omnibus (GEO) database. Knockdown and pathway prediction of B4GALT5 were conducted to investigate the function and mechanism of B4GALT5 in OC proliferation, migration and invasion.ResultsA total of 50 differentially expressed GT genes were identified between OC and normal ovarian tissues. Two clusters were stratified by operating consensus clustering, but no significant prognostic value was observed. By applying the least absolute shrinkage and selection operator (LASSO) Cox regression method, a 6-gene signature was built that classified OC patients in the TCGA cohort into a low- or high-risk group. Patients with high scores had a worse prognosis than those with low scores. This risk signature was further validated in an external GEO dataset. Furthermore, the risk score was an independent risk predictor, and a nomogram was created to improve the accuracy of prognostic classification. Notably, the low-risk OC patients exhibited a higher degree of antitumor immune cell infiltration and a superior response to ICBs. B4GALT5, one of six hub genes, was identified as a regulator of proliferation, migration and invasion in OC.ConclusionTaken together, we established a reliable GT-gene-based signature to predict prognosis, immune status and identify OC patients who would benefit from ICBs. GT genes might be a promising biomarker for OC progression and a potential therapeutic target for OC.
Oral transmucosal fentanyl citrate analgesia in prehospital trauma care: an observational cohort study
Authors: Pietsch Urs , Fischer Henning , Rüst Christoph Alexander , Hossfeld Björn , Grünenfelder Andreas , Wenzel Volker , Albrecht Roland 
Published: January 2023

Abstract
Background
Pain is one of the major prehospital symptoms in trauma patients and requires prompt management. Recent studies have reported insufficient analgesia after prehospital treatment in up to 43% of trauma patients, leaving significant room for improvement. Good evidence exists for prehospital use of oral transmucosal fentanyl citrate (OTFC) in the military setting. We hypothesized that the use of OTFC for trauma patients in remote and challenging environment is feasible, efficient, safe, and might be an alternative to nasal and intravenous applications.

Methods
This observational cohort study examined 177 patients who were treated with oral transmucosal fentanyl citrate by EMS providers in three ski and bike resorts in Switzerland. All EMS providers had previously been trained in administration of the drug and handling of potential adverse events.

Results
OTFC caused a statistically significant and clinically relevant decrease in the level of pain by a median of 3 (IQR 2 to 4) in NRS units (P < 0.0001). Multiple linear regression analysis showed a significant absolute reduction in pain, with no differences in all age groups and between genders. No major adverse events were observed.

Conclusions
Prehospital administration of OTFC is safe, easy, and efficient for extrication and transport across all age groups, gender, and types of injuries in alpine environments. Side effects were few and mild. This could provide a valuable alternative in trauma patients with severe pain, without the delay of inserting an intravenous line, especially in remote areas, where fast action and easy administration are important.
Prevalence of Crimean-Congo haemorrhagic fever in livestock following a confirmed human case in Lyantonde district, Uganda
Authors: Atim Stella A. , Niebel Marc , Ashraf Shirin , Vudriko Patrick , Odongo Steven , Balinandi Stephen , Aber Peace , Bameka Ronald , Ademun Anna R. , Masembe Charles , Tweyongyere Robert , Thomson Emma C. 
Published: January 2023

Abstract
Background
Crimean-Congo haemorrhagic fever (CCHF) is a tick-borne viral infection, characterized by haemorrhagic fever in humans and transient asymptomatic infection in animals. It is an emerging human health threat causing sporadic outbreaks in Uganda. We conducted a detailed outbreak investigation in the animal population following the death from CCHF of a 42-year-old male cattle trader in Lyantonde district, Uganda. This was to ascertain the extent of CCHF virus (CCHFV) circulation among cattle and goats and to identify affected farms and ongoing increased environmental risk for future human infections.

Methods
We collected blood and tick samples from 117 cattle and 93 goats, and tested these for anti-CCHFV antibodies and antigen using an enzyme-linked immunosorbent assay (ELISA), quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and target enrichment next generation sequencing.

Results
CCHFV-specific IgG antibodies were detected in 110/117 (94.0%) cattle and 83/93 (89.3%) goats. Animal seropositivity was independently associated with female animals (AOR = 9.42, P = 0.002), and animals reared under a pastoral animal production system (AOR = 6.02, P = 0.019] were more likely to be seropositive than tethered or communally grazed animals. CCHFV was detected by sequencing in Rhipicephalus appendiculatus ticks but not in domestic animals.

Conclusion
This investigation demonstrated very high seroprevalence of CCHFV antibodies in both cattle and goats in farms associated with a human case of CCHF in Lyantonde. Therefore, building surveillance programs for CCHF around farms in this area and the Ugandan cattle corridor is indicated, in order to identify opportunities for case prevention and control.

Graphical Abstract