bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nigeria bee honey-enhanced adherence, neovascularisation and epithelisation of full-thickness skin autografts on distal extremities of dogs
Authors: Kodie Dorcas Oyueley , Oyetayo Noah Segun , Aina Oluwasanmi Olayinka , Eyarefe Oghenemega David 
Published: March 2022

Abstract
Background
Full thickness skin grafts (FTSGs), although ideal for resurfacing large defects of the distal extremities in veterinary patients, have a high failure rate due to issues of adherence, infection and inadequate revascularisation because of its thickness and high nutritional demand. This study investigated the effect of Nigeria bee honey on FTSG take at the distal extremities of dogs. The study was conducted on 6 adult male Nigerian indigenous dogs using 3 of the 4 limbs of each dog randomly divided into 3 treatment groups: Nigerian bee honey (HON group), platelet-rich plasma (PRP group) and normal saline (CON group). Full‐thickness skin wounds (3 cm × 1.5 cm) were created on the lateral aspect of the radioulnar or metatarsal areas and dressed till adequate granulation tissues formed. Donor skins harvested from the lateral thorax of each dog were sutured to the recipient bed following application of the assigned treatment, and evaluated grossly and histologically on days 0, 4, 7, 10, 14, 17, and 21.

Results
A higher percentage (4/6 representing 66.7%) of complete graft take was observed in the HON and PRP groups as compared to 3/6 (50%) in the CON group. The HON group had a greater percentage (5/6 representing 83.3%) of adhered grafts as compared to the PRP (4/6 representing 66.7%) and CON (3/6 representing 50%) groups at day 4. There was a significant decrease (p = 0.022) in percentage necrosis between the CON and HON/PRP groups on day 10, 14 and 17. The percentage open mesh area for the HON group was significantly lesser at day 4, 7 and 10 when compared with CON (p < 0.001) and at day 4 when compared with PRP (p = 0.001). At histology, graft neovascularisation score was highest in the HON group on days 4, 14 and 21.

Conclusion
Nigeria bee honey enhanced take of meshed full-thickness skin autografts by promoting adherence to the recipient bed, enhancing fibroblast proliferation and collagen laydown, and accelerating the rate of neovascularisation suggesting promising application as an alternative modality to enhance FTSG take.
Acute exacerbation of rheumatoid arthritis-associated interstitial lung disease: mortality and its prediction model
Authors: Hozumi Hironao , Kono Masato , Hasegawa Hirotsugu , Kato Shinpei , Inoue Yusuke , Suzuki Yuzo , Karayama Masato , Furuhashi Kazuki , Enomoto Noriyuki , Fujisawa Tomoyuki , Inui Naoki , Nakamura Yutaro , Yokomura Koshi , Nakamura Hidenori , Suda Takafumi 
Published: March 2022

Abstract
Background
Patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD), like those with idiopathic pulmonary fibrosis (IPF), might develop an unexpected acute exacerbation (AE)—a rapidly progressing and deadly respiratory decline. Although AE incidence and risk factors in RA-ILD patients are known, their post-AE clinical course remains unknown owing to the rarity of AE-RA-ILD. This multicentre retrospective study evaluated post-AE mortality and prognostic variables in AE-RA-ILD patients and created a mortality prediction model for AE-RA-ILD.

Methods
This research comprised 58 patients with AE-RA-ILD and 96 with AE-IPF (a control disease). Multivariate Cox regression analysis was performed to identify prognostic variables. A prediction model was created with recursive partitioning (decision tree).

Results
The post-AE 90-day mortality rate in the overall AE-RA-ILD group was 48.3%; percent predicted forced vital capacity within 12 months before AE onset (baseline %FVC) and PaO2/FiO2 ratio at AE onset (P/F at AE) were independent predictors of mortality. Post-AE 90-day mortality rates were 40.6% and 43.8%, respectively, in AE-RA-ILD and AE-IPF patients propensity score-matched for age, sex, baseline %FVC and P/F at AE (P = 1.0000). In AE-RA-ILD patients, C-indices of baseline %FVC and P/F at AE to predict post-AE 90-day mortality were 0.604 and 0.623, respectively. A decision tree model based on these prognostic factors classified AE-RA-ILD patients into mild, moderate and severe groups (post-AE 90-day mortality rates: 20.8%, 64.0% and 88.9%, respectively; P = 0.0002); the C-index improved to 0.775.

Conclusions
Post-AE mortality was high in AE-RA-ILD patients similar to AE-IPF patients. The discovered prognostic factors and our mortality prediction model may aid in the management of AE-RA-ILD patients.
Circ-ZEB1 promotes PIK3CA expression by silencing miR-199a-3p and affects the proliferation and apoptosis of hepatocellular carcinoma
Authors: Liu Weiwei , zheng Lu , Zhang Rongguiyi , Hou Ping , Wang Jiakun , Wu Linquan , Li Jing 
Published: March 2022

Abstract
Background
Although the prognostic outcomes of liver cancer (LC) cases have improved with the advancement in diagnostic technology and treatment methods, the transferability and recurrence of HCC and the 5-year and 10-year survival rates of patients have remained unsatisfactory. As a result, there is a need for more accurate diagnostic indicators that can detect liver cancer early, effectively improving the prognosis of patients. Whole-genome sequencing (WGS) revealed that circ-ZEB1 and PIK3CA are highly expressed in HCC tissues, whereas miR-199a-3p is significantly downregulated in HCC. Multiple databases search and biological analysis revealed that elevated expression of circ-ZEB1 and PIK3CA was related to poor prognosis of HCC. In vitro and in vivo studies revealed that upregulated levels of PIK3CA and circ-ZEB1 were closely associated with HCC proliferation and apoptosis. Based on these results, we believe that circ-ZEB1 and PIK3CA could be used as biomarkers to diagnose and treat patients with HCC. More importantly, circ-ZEB1 can promotes the expression of PIK3CA by silencing miR-199a-3p and affecting the progression of HCC.

Methods and results
Postoperative specimens from 56 patients with HCC who had not undergone chemotherapy from 2015 to 2018 were collected from the Department of Hepatobiliary Surgery, Second Affiliated Hospital of Nanchang University. WGS revealed differential expression of genes in HCC. Furthermore, RT-qPCR detected the expression of circ-ZEB1, miR-199a-3p, and PIK3CA in HCC tissues. MTT, EdU, and plate cloning experiments were conducted to detect cell proliferation, whereas flow cytometry analysis was used to detect apoptosis. FISH was used to co-localize circ-ZEB1 and miR-199a-3p, and biotin-coupled probe pull-down assay was used to detect the specific binding of circ-ZEB1 and miR-199a-3p. The dual-luciferase report assay detected the association of miR-199a-3p with PIK3CA. Western blotting was used to study the expression of PIK3CA protein. Circ-ZEB1 and PIK3CA were upregulated in HCC and predicted a poor prognosis. MiR-199a-3p showed low expression in HCC, whereas downregulation of circ-ZEB1 reduced HCC cell proliferation and promoted cell apoptosis. MiR-199a-3p blocked the effect of circ-ZEB1 on HCC. Circ-ZEB1 served as a biomarker of HCC. Circ-ZEB1 promoted the expression of PIK3CA by silencing miR-199a-3p to affect the progress of HCC.

Conclusions
Circ-ZEB1 promoted the expression of PIK3CA by depleting miR-199a-3p, thereby affecting HCC proliferation and apoptosis.
G6PC indicated poor prognosis in cervical cancer and promoted cervical carcinogenesis in vitro and in vivo
Authors: Zhu Kun , Deng Chunling , Du Pan , Liu Taorui , Piao Junjie , Piao Yingshi , Yang Meng , Chen Liyan 
Published: March 2022

Abstract
Background
The glucose-6-phosphatase catalytic subunit (G6PC) is a key enzyme that is involved in gluconeogenesis and glycogen decomposition during glycometabolism. Studies have shown that G6PC is abnormally expressed in various cancers and participates in the proliferation and metastasis of tumors. However, the role of G6PC in cervical cancer remains poorly established.

Methods
To analyze the expression of G6PC in cervical cancer tissues in patients by immunohistochemistry. Effects of G6PC deregulation on cervical cancer phenotype were determined using MTT, colony formation, transwell, and wound-healing assays. And constructed a nude mouse xenograft tumor model and CAM assay in vivo. The effect of G6PC on glycolysis in cervical cancer was also evaluated. Effect of G6PC on PI3K/AKT/mTOR pathway was detected by Western blot assay.

Results
In this study, G6PC expression was found to be upregulated in cervical cancer tissues, and this upregulated expression was associated with LN metastasis, clinical stage, recurrence, and disease-free survival and overall survival rates, indicating that G6PC could serve as a novel marker of early diagnosis in cervical cancer. G6PC promoted proliferation, invasion, epithelial mesenchymal transition (EMT) progression, and angiogenesis of cervical cancer cells. Mechanistically, G6PC activated PI3K/AKT/mTOR pathways. The PI3K/AKT pathway inhibitor, LY294002 could partially attenuate the effect.

Conclusions
G6PC plays a key role in the progression of cervical cancer, and overexpressed G6PC is closely related to patient LN metastasis, clinical stage, recurrence and shortened survival. G6PC promoted cervical cancer proliferation, invasion, migration, EMT progression, and angiogenesis, partially through activating the PI3K/AKT pathway. G6PC, as a metabolic gene, not only plays a role in metabolism, but also participates in the development of cervical cancer. Its complex metabolic and non metabolic effects may be a potential therapeutic target and worthy of further study.
Absence of the lectin-like domain of thrombomodulin reduces HSV-1 lethality of mice with increased microglia responses
Authors: Tsai Meng-Shan , Wang Li-Chiu , Wu Hua-Lin , Tzeng Shun-Fen , Conway Edward M. , Hsu Sheng-Min , Chen Shun-Hua 
Published: March 2022

Abstract
Background
Herpes simplex virus 1 (HSV-1) can induce fatal encephalitis. Cellular factors regulate the host immunity to affect the severity of HSV-1 encephalitis. Recent reports focus on the significance of thrombomodulin (TM), especially the domain 1, lectin-like domain (TM-LeD), which modulates the immune responses to bacterial infections and toxins and various diseases in murine models. Few studies have investigated the importance of TM-LeD in viral infections, which are also regulated by the host immunity.

Methods
In vivo studies comparing wild-type and TM-LeD knockout mice were performed to determine the role of TM-LeD on HSV-1 lethality. In vitro studies using brain microglia cultured from mice or a human microglia cell line to investigate whether and how TM-LeD affects microglia to reduce HSV-1 replication in brain neurons cultured from mice or in a human neuronal cell line.

Results
Absence of TM-LeD decreased the mortality, tissue viral loads, and brain neuron apoptosis of HSV-1-infected mice with increases in the number, proliferation, and phagocytic activity of brain microglia. Moreover, TM-LeD deficiency enhanced the phagocytic activity of brain microglia cultured from mice or of a human microglia cell line. Co-culture of mouse primary brain microglia and neurons or human microglia and neuronal cell lines revealed that TM-LeD deficiency augmented the capacity of microglia to reduce HSV-1 replication in neurons.

Conclusions
Overall, TM-LeD suppresses microglia responses to enhance HSV-1 infection.
Lifestyle changes, mental health, and health-related quality of life in children aged 6–7 years before and during the COVID-19 pandemic in South Germany
Authors: Kurz Deborah , Braig Stefanie , Genuneit Jon , Rothenbacher Dietrich 
Published: March 2022

Abstract
Background
The measures against the COVID-19 pandemic are challenging for children and parents, and detrimental effects on child health are suggested especially from lock-down measures and school closings.

Methods
We conducted a cross-sectional analysis using a population based longitudinal (birth-) cohort study (SPATZ study) conducted in the South of Germany. Data included all 6 or 7 year old children for whom a questionnaire was completed during first grade of school. Consequently, we were able to analyze children being in first grade before the first lockdown in Germany (≤ 15th March 2020), as well as children being in first grade during the pandemic (> 15th March 2020). We conducted descriptive statistics and estimated the associations between the two time periods, before and during the pandemic, and various outcomes of child health using multivariable adjusted linear or logistic regression modeling. The analysis was stratified by gender.

Results
Results among n = 362 children aged six or seven years showed substantially lower mean scores of health-related quality of life (difference in means: − 5.5, 95% confidence interval (CI) − 9.0, − 2.0), and higher mean scores in total emotional and behavioral difficulties (difference in means: 2.0, 95% CI 0.2, 3.8) in girls during vs. before the COVID-19 pandemic using multivariable linear regression modeling. In addition, weekly screen-time was increased in boys by 3.5 h (95% CI 0.6, 6.4). We did not find substantial differences in sleep quality, physical activity, and time spent with books, neither in boys nor in girls, however, the limited sample size has to be considered.

Conclusion
Child health (and behavior) of first grade school children is possibly impacted by the COVID-19 pandemic with adverse consequences possibly differing by gender.
Intravenous immunoglobulins improve live birth rate among women with underlying immune conditions and recurrent pregnancy loss: a systematic review and meta-analysis
Authors: Habets Denise H. J. , Pelzner Kim , Wieten Lotte , Spaanderman Marc E. A. , Villamor Eduardo , Al-Nasiry Salwan 
Published: March 2022

AbstractIntravenous immunoglobulin (IVIG) is increasingly used as a treatment for recurrent pregnancy loss (RPL) despite lack of clear evidence on efficacy. Recent data suggest IVIG might be more effective in a subgroup of women with an aberrant immunological profile. Therefore, a systematic review and meta-analysis of studies on the effectiveness of IVIG treatment on pregnancy outcome among women with RPL and underlying immunological conditions (e.g., elevated NK cell percentage, elevated Th1/Th2 ratio, diagnosis with autoimmune disorders) was conducted. Eight non-randomized controlled trials, including 478 women (intervention: 284; control: 194), met eligibility criteria. Meta-analysis showed that treatment with IVIG was associated with a two-fold increase in live birth rate (RR 1.98, 95% CI 1.44–2.73, P < 0.0001). The effect of IVIG was particularly marked in the subgroup of studies including patients based on presence of elevated (> 12%) NK-cell percentage (RR 2.32, 95% CI 1.77–3.02, P < 0.0001) and when starting intervention prior to or during cycle of conception (RR 4.47, 95% CI 1.53–13.05, P = 0.006). In conclusion, treatment with IVIG may improve live birth rate in women with RPL and underlying immune conditions. However, these results should be interpreted with caution as studies are limited by low number of participants and the non-randomized design, which represent seriously biases. Future randomized controlled trials in women with RPL and underlying immune conditions are needed before using IVIG in a clinical setting.
Glycyrrhiza uralensis attenuates TNF-α-induced muscle atrophy in myoblast cells through the Nrf2 and MAFbx signaling cascades
Authors: Choi Ji-Won , Choi Sang Yoon , Lee Hyun Hee L. , Yoo Guijae , Lee Sang-Hoon , Choi In-Wook , Cho Chi Heung , Hur Jinyoung 
Published: March 2022

AbstractMuscle atrophy is associated with chronic diseases, such as heart failure diabetes, and aging-related diseases. Glycyrrhiza uralensis (GU) extract is widely used in traditional medicine. However, no studies have evaluated the effects of GU on muscle atrophy. Thus, in this study, we assessed the effects of GU on prevention of muscle atrophy. GU reduced the levels of the TNF-α-induced muscle atrophy markers, muscle RING-finger protein-1(Murf-1) and muscle atrophy F-box (MAFbx), and upregulated myosin heavy chain expression (MyHC). It also reduced the phosphorylation of nuclear factor kappa B, and downregulated Smad3 proteins, which are involved in protein ubiquitination. When we examined whether GU exhibits antioxidant activities. GU suppressed TNF-α-induced muscle atrophy by increasing the translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), which regulates the expression of antioxidant factors such as heme oxygenase-1 (HO-1) as well as apoptosis-related factors, such as caspase-3/7. These results suggest that GU extract is potentially an important agent in the regulation of TNF-an induced muscle atrophy.
Distinct outcomes, ABL1 mutation profile, and transcriptome features between p190 and p210 transcripts in adult Philadelphia-positive acute lymphoblastic leukemia in the TKI era
Authors: Shi Ting , Xie Mixue , Chen Li , Yuan Wei , Wang Yungui , Huang Xin , Xie Wanzhuo , Meng Haitao , Lou Yinjun , Yu Wenjuan , Tong Hongyan , Ye Xiujin , Huang Jinyan , Jin Jie , Zhu Honghu 
Published: March 2022

Abstract
Background
The differential signaling and outcome of patients with p190 or p210 transcripts of BCR-ABL1 have been systematically investigated in chronic myeloid leukemia rather than in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL).

Methods
We analyzed the outcomes and ABL1 mutation profiles in 305 consecutive adult patients with Ph+ ALL treated with chemotherapy plus tyrosine kinase inhibitors. We also studied transcriptome features in two newly diagnosed patients with p190 and p210 using single-cell RNA sequencing (scRNA-seq).

Results
P190 and p210 were found in 199 (65%) and 106 (35%) patients, respectively. Compared to patients with p190, a higher white blood cell count (p = 0.05), platelet count (p = 0.047), BCR-ABL1 transcript level (p < 0.001), and lower bone marrow blasts (p = 0.003) were found in patients with p210. Patients with p210 had fewer types of ABL1 mutations (4 vs. 16) and a higher prevalence of T315I and E225K/V mutations (91.3% vs. 68.6%; p = 0.031). Patients with p210 had a similar complete remission rate (91.0% vs. 90.1%; p = 0.805) but a lower complete molecular remission rate at 1 month (9.9% vs. 22.0%; p = 0.031) compared with p190. Patients with p210 had lower 3-year overall survival (OS) and disease-free survival (DFS) rates than those with p190 (3-year DFS: 10.4% vs. 9.2%, p = 0.069, 3-year OS: 44.3% vs. 38.2%, p = 0.018, respectively). Multivariate analysis revealed that p210 was independently associated with worse OS [HR 1.692 (95% CI 1.009–2.838), p = 0.046]. Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) was associated with a better prognosis in patients with p210 (p < 0.0001). In addition, scRNA-seq data showed distinct molecular and cellular heterogeneity between bone marrow cells of the two transcripts.

Conclusions
Ph+ ALL patients with p190 and p210 had different clinical characteristics, outcomes, ABL1 mutation profiles, and transcriptome features. Allo-HSCT could improve the outcomes of patients with p210.
Graphic representation of the degree of historical-archaeological evidence: the 3D reconstruction of the “Baker’s House”
Authors: Cáceres-Criado Irene , García-Molina Diego Francisco , Mesas-Carrascosa Francisco-Javier , Triviño-Tarradas Paula 
Published: March 2022

Abstract
Over the years, the methodologies used for graphic representation in archaeology have evolved. The substantial change in representation was achieved with the use of computer software. Currently, 3D sketch scanning and photogrammetry are predominating tools used in this field. A new methodology, i.e., the use of the historical-archaeological evidence level scale, has entered this discipline to show the veracity of archaeological studies, as well as that of the vestiges found. The present study is focused on the virtual reconstruction of the ‘Baker’s House’ in the archaeological site of Torreparedones (Córdoba, Spain). The main aim of this study was to show and identify the veracity of the obtained reconstruction, through the use of the historical-archaeological evidence scale and the elaboration of a typological rank. The methodology used shows the evidence level employed by experts in the creation of virtual representations. The dissemination of the proposed historical-archaeological evidence scale entails the graphical identification of the veracity of reconstructions in this type of representations, always complying with the scientific quality criteria established by the Seville Letter.
Towards a biological definition of ARDS: are treatable traits the solution?
Authors: Bos Lieuwe D. J. , Laffey John G. , Ware Lorraine B. , Heijnen Nanon F. L. , Sinha Pratik , Patel Brijesh , Jabaudon Matthieu , Bastarache Julie A. , McAuley Daniel F. , Summers Charlotte , Calfee Carolyn S. , Shankar-Hari Manu 
Published: March 2022

AbstractThe pathophysiology of acute respiratory distress syndrome (ARDS) includes the accumulation of protein-rich pulmonary edema in the air spaces and interstitial areas of the lung, variable degrees of epithelial injury, variable degrees of endothelial barrier disruption, transmigration of leukocytes, alongside impaired fluid and ion clearance. These pathophysiological features are different between patients contributing to substantial biological heterogeneity. In this context, it is perhaps unsurprising that a wide range of pharmacological interventions targeting these pathophysiological processes have failed to improve patient outcomes. In this manuscript, our goal is to provide a narrative summary of the potential methods to capture the underlying biological heterogeneity of ARDS and discuss how this information could inform future ARDS redefinitions. We discuss what biological tests are available to identify patients with any of the following predominant biological patterns: (1) epithelial and/or endothelial injury, (2) protein rich pulmonary edema and (3) systemic or within lung inflammatory responses.