bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thromboembolic Events During Weightbearing vs Nonweightbearing Accelerated Rehabilitation Protocols for Complete Achilles Tendon Ruptures
Authors: Lee Conrad , Haarer Francesca , Titheradge Rachel , Iliopoulos Efthymios 
Published: June 2023

Background: Achilles tendon rupture can be treated nonoperatively with functional rehabilitation. However, prolonged immobilization has associated risk of venous thromboembolism (VTE). Early weightbearing may reduce VTE risk, and this was introduced to our rehabilitation protocol. We investigated the prevalence of symptomatic VTE events before and after the introduction of the early weightbearing protocol. Methods: Adults with ultrasonography-confirmed complete tendo-Achilles ruptures between January 2017 and June 2020 were included. Preprotocol, patients were instructed to not weightbear for 4 weeks. In 2018, immediate weightbearing was introduced to the treatment protocol. All patients in both cohorts were given low-molecular-weight heparin for 4 weeks. Patients with symptomatic VTE events were investigated with duplex ultrasonographic scan or chest computed tomography. Two independent anonymized examiners collected data from electronic records. Rates of symptomatic VTEs were compared. Results: A total of 296 patients were included. Sixty-nine patients were managed with the nonweightbearing protocol, and 227 patients were managed with the early-weightbearing protocol. Two patients in each group developed deep vein thrombosis and 1 developed pulmonary embolism in the early-weightbearing group. Rates of VTEs were lower in the early-weightbearing group (1.3% vs 2.9%) but did not reach statistical significance ( P = .33). Conclusion: In this cohort we found that symptomatic VTE after nonoperatively treated Achilles tendon rupture was uncommon. We did not demonstrate a reduction in symptomatic VTE between our early weightbearing and nonweightbearing rehabilitation protocols. We believe a larger study may help clarify whether early weightbearing is beneficial in VTE reduction. Level of Evidence: Level III, retrospective cohort study.
Intravital imaging of three different microvascular beds in SARS-CoV-2–infected mice
Authors: Castanheira Fernanda V. S. , Nguyen Rita , Willson Michelle , Davoli-Ferreira Marcela , David Bruna A. , Kelly Margaret M. , Lee Woo-Yong , Kratofil Rachel M. , Zhang Wen X. , Bui-Marinos Maxwell , Corcoran Jennifer A. , Kubes Paul 
Published: June 2023

Abstract
Severe acute respiratory syndrome coronavirus–2 (SARS-CoV-2) enters the respiratory tract, where it infects the alveoli epithelial lining. However, patients have sequelae that extend well beyond the alveoli into the pulmonary vasculature and, perhaps, beyond to the brain and other organs. Because of the dynamic events within blood vessels, histology does not report platelet and neutrophil behavior. Because of the rapid nontranscriptional response of these cells, neither single-cell RNA sequencing nor proteomics report robustly on their critical behaviors. We used intravital microscopy in level-3 containment to examine the pathogenesis of SARS-CoV-2 within 3 organs in mice expressing human angiotensin converting enzyme 2 (ACE-2) ubiquitously (CAG-AC-70) or on epithelium (K18-promoter). Using a neon-green SARS-CoV-2, we observed both the epithelium and endothelium infected in AC70 mice but only the epithelium in K18 mice. There were increased neutrophils in the microcirculation but not in the alveoli of the lungs of AC70 mice. Platelets formed large aggregates in the pulmonary capillaries. Despite only neurons being infected within the brain, profound neutrophil adhesion forming the nidus of large platelet aggregates were observed in the cerebral microcirculation, with many nonperfused microvessels. Neutrophils breached the brain endothelial layer associated with a significant disruption of the blood-brain-barrier. Despite ubiquitous ACE-2 expression, CAG-AC-70 mice had very small increases in blood cytokine, no increase in thrombin, no infected circulating cells, and no liver involvement suggesting limited systemic effects. In summary, our imaging of SARS-CoV-2–infected mice gave direct evidence that there is a significant perturbation locally in the lung and brain microcirculation induced by local viral infection leading to increased local inflammation and thrombosis in these organs.
Homocysteine promotes atherosclerosis through macrophage pyroptosis via endoplasmic reticulum stress and calcium disorder
Authors: Zhang Shan , Lv Ying , Luo Xing , Weng Xiuzhu , Qi Jinyu , Bai Xiaoxuan , Zhao Chen , Zeng Ming , Bao Xiaoyi , Dai Xinyu , Zhang Ying , Chen Yuwu , Liu Minghao , Hu Sining , Li Ji , Jia Haibo 
Published: June 2023

Abstract
Background
Elevated plasma homocysteine levels, known as hyperhomocysteinemia, have been identified as an independent risk factor for atherosclerosis and related cardiovascular diseases. Macrophage pyroptosis-mediated inflammation is crucial in the development of atherosclerosis, but the underlying mechanisms remain unclear.

Methods
A hyperhomocysteinemia atherosclerotic model with ApoE−/− mice fed with a high-methionine diet was constructed to investigate the role of plasma homocysteine in atherosclerosis. THP-1-derived macrophages were used to investigate the mechanisms by which Hcy regulates pyroptosis.

Results
We found that hyperhomocysteinemia resulted in larger atherosclerotic plaques and more secretion of inflammatory cytokines, while these effects were attenuated in Caspase-1 knockdown mice. Likewise, in vitro experiments demonstrated that treatment of macrophages with homocysteine resulted in NLRP3 inflammasome activation and pyroptosis, as evidenced by cleavage of Caspase-1, production of downstream IL-1β, elevation of lactate dehydrogenase activity, and extensive propidium iodide-positive staining of cells. These were all inhibited by Caspase-1 inhibitor. In addition, excessive generation of reactive oxygen species was associated with mitochondrial dysfunction, characterized by loss of mitochondrial membrane potential and ATP synthesis. Moreover, further experiments revealed that homocysteine induced endoplasmic reticulum stress, enhanced communication between the endoplasmic reticulum and mitochondria, and consequently contributed to calcium disorder. Furthermore, the endoplasmic reticulum stress inhibitor, 4PBA, the calcium chelator, BAPTA, and calcium channel inhibitor, 2-APB significantly improved macrophage pyroptosis.

Conclusion
Homocysteine accelerates atherosclerosis progression by enhancing macrophages pyroptosis via promoting endoplasmic reticulum stress, endoplasmic reticulum-mitochondria coupling, and disturbing of calcium disorder.
Improved intravenous lentiviral gene therapy based on endothelial-specific promoter-driven factor VIII expression for hemophilia A
Authors: Gong Jie , Yang Rui , Zhou Min , Chang Lung-Ji 
Published: June 2023

Abstract
Background
Hemophilia A (HA) is an X-linked monogenic disorder caused by deficiency of the factor VIII (FVIII) gene in the intrinsic coagulation cascade. The current protein replacement therapy (PRT) of HA has many limitations including short term effectiveness, high cost, and life-time treatment requirement. Gene therapy has become a promising treatment for HA. Orthotopic functional FVIII biosynthesis is critical to its coagulation activities.

Methods
To investigate targeted FVIII expression, we developed a series of advanced lentiviral vectors (LVs) carrying either a universal promoter (EF1α) or a variety of tissue-specific promoters, including endothelial-specific (VEC), endothelial and epithelial-specific (KDR), and megakaryocyte-specific (Gp and ITGA) promoters.

Results
To examine tissue specificity, the expression of a B-domain deleted human F8 (F8BDD) gene was tested in human endothelial and megakaryocytic cell lines. Functional assays demonstrated FVIII activities of LV-VEC-F8BDD and LV-ITGA-F8BDD in the therapeutic range in transduced endothelial and megakaryocytic cells, respectively. In F8 knockout mice (F8 KO mice, F8null mice), intravenous (iv) injection of LVs illustrated different degrees of phenotypic correction as well as anti-FVIII immune response for the different vectors. The iv delivery of LV-VEC-F8BDD and LV-Gp-F8BDD achieved 80% and 15% therapeutic FVIII activities over 180 days, respectively. Different from the other LV constructs, the LV-VEC-F8BDD displayed a low FVIII inhibitory response in the treated F8null mice.

Conclusions
The LV-VEC-F8BDD exhibited high LV packaging and delivery efficiencies, with endothelial specificity and low immunogenicity in the F8null mice, thus has a great potential for clinical applications.
Integrative multi-omics approach for identifying molecular signatures and pathways and deriving and validating molecular scores for COVID-19 severity and status
Authors: Lipman Danika , Safo Sandra E. , Chekouo Thierry 
Published: June 2023

Abstract
Background
There is still more to learn about the pathobiology of COVID-19. A multi-omic approach offers a holistic view to better understand the mechanisms of COVID-19. We used state-of-the-art statistical learning methods to integrate genomics, metabolomics, proteomics, and lipidomics data obtained from 123 patients experiencing COVID-19 or COVID-19-like symptoms for the purpose of identifying molecular signatures and corresponding pathways associated with the disease.

Results
We constructed and validated molecular scores and evaluated their utility beyond clinical factors known to impact disease status and severity. We identified inflammation- and immune response-related pathways, and other pathways, providing insights into possible consequences of the disease.

Conclusions
The molecular scores we derived were strongly associated with disease status and severity and can be used to identify individuals at a higher risk for developing severe disease. These findings have the potential to provide further, and needed, insights into why certain individuals develop worse outcomes.
Examining parent-of-origin effects on transcription and RNA methylation in mediating aggressive behavior in honey bees (Apis mellifera)
Authors: Bresnahan Sean T. , Lee Ellen , Clark Lindsay , Ma Rong , Markey Michael , Rangel Juliana , Grozinger Christina M. , Li-Byarlay Hongmei 
Published: June 2023

AbstractConflict between genes inherited from the mother (matrigenes) and the father (patrigenes) is predicted to arise during social interactions among offspring if these genes are not evenly distributed among offspring genotypes. This intragenomic conflict drives parent-specific transcription patterns in offspring resulting from parent-specific epigenetic modifications. Previous tests of the kinship theory of intragenomic conflict in honey bees (Apis mellifera) provided evidence in support of theoretical predictions for variation in worker reproduction, which is associated with extreme variation in morphology and behavior. However, more subtle behaviors – such as aggression – have not been extensively studied. Additionally, the canonical epigenetic mark (DNA methylation) associated with parent-specific transcription in plant and mammalian model species does not appear to play the same role as in honey bees, and thus the molecular mechanisms underlying intragenomic conflict in this species is an open area of investigation. Here, we examined the role of intragenomic conflict in shaping aggression in honey bee workers through a reciprocal cross design and Oxford Nanopore direct RNA sequencing. We attempted to probe the underlying regulatory basis of this conflict through analyses of parent-specific RNA m6A and alternative splicing patterns. We report evidence that intragenomic conflict occurs in the context of honey bee aggression, with increased paternal and maternal allele-biased transcription in aggressive compared to non-aggressive bees, and higher paternal allele-biased transcription overall. However, we found no evidence to suggest that RNA m6A or alternative splicing mediate intragenomic conflict in this species.
ROS accumulation-induced tapetal PCD timing changes leads to microspore abortion in cotton CMS lines
Authors: Zhang Jinlong , Zhang Li , Liang Dong , Yang Yujie , Geng Biao , Jing Panpan , Qu Yunfang , Huang Jinling 
Published: June 2023

Abstract
Background
Cytoplasmic male sterility (CMS) is the basis of heterosis exploitation. CMS has been used to hybrid production in cotton, but its molecular mechanism remains unclear. CMS is associated with advanced or delayed tapetal programmed cell death (PCD), and reactive oxygen species (ROS) may mediate this process. In this study, we obtained Jin A and Yamian A, two CMS lines with different cytoplasmic sources.

Results
Compared with maintainer Jin B, Jin A anthers showed advanced tapetal PCD with DNA fragmentation, producing excessive ROS which accumulated around the cell membrane, intercellular space and mitochondrial membrane. The activities of peroxidase (POD) and catalase (CAT) enzymes which can scavenge ROS were significantly decreased. However, Yamian A tapetal PCD was delayed with lower ROS content, and the activities of superoxide dismutase (SOD) and POD were higher than its maintainer. These differences in ROS scavenging enzyme activities may be caused by isoenzyme gene expressions. In addition, we found the excess ROS generated in Jin A mitochondria and ROS overflow from complex III might be the source in parallel with the reduction of ATP content.

Conclusion
ROS accumulation or abrogation were mainly caused by the joint action of ROS generation and scavenging enzyme activities transformation, which led to the abnormal progression of tapetal PCD, affected the development of microspores, and eventually contributed to male sterility. In Jin A, tapetal PCD in advance might be caused by mitochondrial ROS overproduction, accompanied by energy deficiency. The above studies will provide new insights into the cotton CMS and guide the follow-up research ideas.
Remimazolam-remifentanil causes less postoperative nausea and vomiting than remimazolam-alfentanil during hysteroscopy: a single-centre randomized controlled trial
Authors: Zhang Xiaoqiang , Li Shuang , Liu Jing 
Published: June 2023

Abstract
Background
Although the operation time of hysteroscopy is short, the incidence of postoperative nausea and vomiting is high. The aim of this study was to compare the incidence of postoperative nausea and vomiting in hysteroscopy when remimazolam is combined with remifentanil or alfentanil.

Methods
We conducted a randomized, controlled, double-blind trial. Patients undergoing hysteroscopy were recruited and randomly assigned to either the remimazolam-remifentanil (Group RR) or the remimazolam-alfentanil group (Group RA). All patients in the two groups were started with an induction dose of remimazolam besylate 0.2 mg/kg and then maintained with a dosage of 1.0 mg/kg/h. After induction with remimazolam besylate, in Group RR, remifentanil was infused using a target-controlled infusion system with a target concentration of 1.5 ng/ml and titrated throughout the procedure. In Group RA, infusion of alfentanil was started with an initial bolus dose of 20 µg/kg over 30 s and then maintained at an initial rate of 0.16 µg/kg/min. The primary observation outcome was the incidence rate of postoperative nausea and vomiting. The secondary observation outcomes were the time to awakening, the length of stay in the PACU, the total remimazolam dose and adverse effects, such as low SpO2, bradycardia, hypotension and body movement.

Results
A total of 204 patients were successfully included in this study. The incidence of postoperative nausea and vomiting in Group RR (2/102, 2.0%) was significantly lower than that in Group RA (12/102, 11.8%) (p < 0.05). There was no significant difference in the incidence of adverse events, such as low SpO2, bradycardia, hypotension and body movement, between Groups RR and RA (p > 0.05).

Conclusions
Remimazolam-remifentanil causes less postoperative nausea and vomiting than remimazolam-alfentanil in hysteroscopy.

Trial registration
Clinical trial registration number: ChiCTR2100044177. Full date of the first registration: 12/03/2021.
Risk factors for disease severity among children with Covid-19: a clinical prediction model
Authors: Ng David Chun-Ern , Liew Chuin-Hen , Tan Kah Kee , Chin Ling , Ting Grace Sieng Sing , Fadzilah Nur Fadzreena , Lim Hui Yi , Zailanalhuddin Nur Emylia , Tan Shir Fong , Affan Muhamad Akmal , Nasir Fatin Farihah Wan Ahmad , Subramaniam Thayasheri , Ali Marlindawati Mohd , Rashid Mohammad Faid Abd , Ong Song-Quan , Ch’ng Chin Chin 
Published: June 2023

Abstract
Background
Children account for a significant proportion of COVID-19 hospitalizations, but data on the predictors of disease severity in children are limited. We aimed to identify risk factors associated with moderate/severe COVID-19 and develop a nomogram for predicting children with moderate/severe COVID-19.

Methods
We identified children ≤ 12 years old hospitalized for COVID-19 across five hospitals in Negeri Sembilan, Malaysia, from 1 January 2021 to 31 December 2021 from the state’s pediatric COVID-19 case registration system. The primary outcome was the development of moderate/severe COVID-19 during hospitalization. Multivariate logistic regression was performed to identify independent risk factors for moderate/severe COVID-19. A nomogram was constructed to predict moderate/severe disease. The model performance was evaluated using the area under the curve (AUC), sensitivity, specificity, and accuracy.

Results
A total of 1,717 patients were included. After excluding the asymptomatic cases, 1,234 patients (1,023 mild cases and 211 moderate/severe cases) were used to develop the prediction model. Nine independent risk factors were identified, including the presence of at least one comorbidity, shortness of breath, vomiting, diarrhea, rash, seizures, temperature on arrival, chest recessions, and abnormal breath sounds. The nomogram’s sensitivity, specificity, accuracy, and AUC for predicting moderate/severe COVID-19 were 58·1%, 80·5%, 76·8%, and 0·86 (95% CI, 0·79 – 0·92) respectively.

Conclusion
Our nomogram, which incorporated readily available clinical parameters, would be useful to facilitate individualized clinical decisions.
Bacterial DNA metabolism analysis by metagenomic next-generation sequencing (mNGS) after treatment of bloodstream infection
Authors: Li Zhuo , Zhang Shiying , Liu Mengting , Ding Hongguang , Wen Yin , Zhu Huishan , Zeng Hongke 
Published: June 2023

Abstract
Background
With the advent of metagenomic next-generation sequencing (mNGS), the time of DNA metabolism can be explored after bacteria be killed. In this study, we applied mNGS in investigation of the clearance profile of circulating bacteria DNA.

Methods
All of the rabbits were injected with the inactivated Escherichia coli. Using mNGS, we analyzed serial samples of plasma collected from rabbits to detect clearance profile of circulating E. coli DNA.

Results
In this study, we found that the of E. coli DNA could still be detected 6 h after injecting killed bacteria. The clearance half-lives associated with the 2 phases are 0.37 and 1.81 h. We also explored there is no correlation between the disease severity with the E. coli DNA reads in circulation.

Conclusions
After the bacteria were completely killed, their DNA could still be detected in the blood circulation. The metabolism of bacterial DNA in the circulation had two phases: fast and slow phases, and there were no correlations between the level of bacteria reads with the severity of patients’ disease after the bacteria have been completely killed.
Relationship between SUVmax on 18F-FDG PET and PD-L1 expression in liver metastasis lesions after colon radical operation
Authors: Qiao Yan , Li Xiaomeng , Hu Yongquan , Guo Pu , Liu Hengchao , Sun Hong 
Published: June 2023

Abstract
Purpose
Our study was to investigate the correlation correlation between FDG uptake and PD-L1 expression of liver metastasis in patients with colon cancer, and to determine the value of FDG-PET in predicting PD-L1 expression in liver metastasis of colon cancer.

Methods
A total of 72 patients with confirmed liver metastasis of colon cancer were included in this retrospective study. The PD-L1 expression and immune cell infiltrating of tumors were determined through immunohistochemistry staining. The SUVmax of liver metastasis lesions were assessed using 18 F-FDG PET/CT. The correlation between PD-L1 expression and the clinicopathological were evaluated by the Cox proportional hazards model and the Kaplan-Meier survival analysis.

Results
PD-L1 expression was significantly correlated with FDG uptake (SUVmax), tumor size, differentiation, survival and cytotoxic T cells infiltration in liver metastasis of colon cancer (P < 0.05). And liver metastases with high counts of infiltrating cytotoxic T cells showed greater FDG uptake than those with low counts of infiltrating cytotoxic T cells. The SUVmax of liver metastases and the degree of differentiation of metastases were closely related to PD-L1 expression, and were independent risk factors.The combined assessment of SUVmax values and tthe degree of differentiation of metastase can help determine PD-L1 expression in liver metastasis of colon cancer.

Conclusions
FDG uptake in liver metastasis of colon cancer was positively correlated with the PD-L1 expression and the number of cytotoxic T cells infiltration. The joint evaluation of two parameters, SUVmax and degree of differentiation, can predict PD-L1 expression in liver metastases.
Analyze of factors and prognosis of eyes lost to follow-up in retinal vein occlusive disease patients receiving anti-vascular endothelial growth factor therapy
Authors: Huang Xiaoying , Zheng Minming , Lu Jiatao , Wang Xi , Zheng Zheng 
Published: June 2023

Abstract
Background
Patients with macular edema (ME) secondary to retinal vein occlusion (RVO) who received at least one intravitreal injection of anti-vascular endothelial growth factor therapy (VEGF) and lost to follow-up (LTFU) for more than six months were analyzed to investigate the factors contributing to the LTFU and the prognosis.

Method
This was a retrospective, single-center study to analyze the causes and prognosis of LTFU over six months in RVO-ME patients treated with intravitreal anti-VEGF injections at our institution from January 2019 to August 2022 and to collect patients’ baseline characteristics along with the number of injections before LTFU, primary disease, best corrected visual acuity (BCVA) before LTFU and after return visit, central macular thickness (CMT), months before LTFU and after LTFU, reasons for LTFU, and complications, to analyze the factors affecting visual outcome at a return visit.

Results
This study included 125 patients with LTFU; 103 remained LTFU after six months, and 22 returned after LTFU. The common reason for LTFU was “no improvement in vision” (34.4%), followed by “transport inconvenience” (22.4%), 16 patients (12.8%) were unwilling to visit the clinic, 15 patients (12.0%) had already elected to seek treatment elsewhere, 12 patients (9.6%) were not seen in time due to the 2019-nCov epidemic, and 11 patients (8.8%) cannot do it due to financial reasons. The number of injections before LTFU was a risk factor for LTFU (P < 0.05). LogMAR at the initial visit (P < 0.001), CMT at the initial visit (P < 0.05), CMT before the LTFU (P < 0.001), and CMT after the return visit (P < 0.05) were influential factors for logMAR at the return visit.

Conclusion
Most RVO-ME patients were LTFU after anti-VEGF therapy. Long-term LTFU is greatly detrimental to the visual quality of patients; thus, the management of RVO-ME patients in follow-up should be considered.