bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lgr4 Governs a Pro-Inflammatory Program in Macrophages to Antagonize Post-Infarction Cardiac Repair
Authors: Huang Chun-Kai , Dai Daopeng , Xie Hongyang , Zhu Zhengbin , Hu Jian , Su Min , Liu Mingyao , Lu Lin , Shen Weifeng , Ning Guang , Wang Jiqiu , Zhang Ruiyan , Yan Xiaoxiang 
Published: June 2020

Rationale:
Macrophages are critically involved in wound healing following myocardial infarction (MI). Lgr4, a member of LGR (leucine-rich repeat-containing G protein-coupled receptor) family, is emerging as a regulator of macrophage-associated immune responses. However, the contribution of Lgr4 to macrophage phenotype and function in the context of MI remains unclear.

Objective:
To determine the role of macrophage Lgr4 in MI and to dissect the underlying mechanisms.

Methods and Results:

During early inflammatory phase of MI, infarct macrophages rather than neutrophils expressed high level of Lgr4. Macrophage-specific Lgr4 knockout mice had no baseline cardiovascular defects but manifested improved heart function, modestly reduced infarct size, decreased early mortality due to cardiac rupture, and ameliorated adverse remodeling after MI. Improved outcomes in macrophage-specific Lgr4 knockout mice subjected to MI were associated with mitigated ischemic injury and optimal infarct healing, as determined by reduction of cardiac apoptosis in the peri-infarct zone, attenuation of local myocardial inflammatory response, decrease of matrix metalloproteinase expression in the infarct, enhancement of angiogenesis, myofibroblast proliferation, and collagen I deposition in reparative granulation tissue as well as formation of collagen-rich scar. More importantly, macrophage-specific Lgr4 knockout infarcts had reduced numbers of infiltrating leukocytes and inflammatory macrophages but harbored abundant reparative macrophage subsets. Lgr4-null infarct macrophages exhibited a less inflammatory transcriptional signature. These findings were further supported by transcriptomic profiling data showing repression of multiple pathways and broad-spectrum genes associated with proinflammatory responses in macrophage-specific Lgr4 knockout infarcts. Notably, we discovered that Lgr4-mediated functional phenotype programing in infarct macrophages was at least partly attributed to regulation of AP (activator protein)-1 activity. We further demonstrated that the synergistic effects of Lgr4 on AP-1 activation in inflammatory macrophages occurred via enhancing CREB (cAMP response element-binding protein)-mediated
c-Fos
,
Fosl1
, and
Fosb
transactivation.

Conclusions:
Together, our data highlight the significance of Lgr4 in governing proinflammatory phenotype of infarct macrophages and postinfarction repair.
Feasibility of In‐office Fine‐Needle Aspiration for Base of Tongue Tumors
Authors: Reeder Allison , Aulet Ricardo , Sajisevi Mirabelle , Brundage William 
Published: June 2020

We aim to demonstrate the feasibility of in‐office transcervical ultrasound (TCUS)–guided fine‐needle aspiration (FNA) of base of tongue (BOT) tumors in a single‐institution. Retrospective chart review was performed and 3 patients met criteria, with BOT tumors ≥3 cm. Two patients had no cervical adenopathy, while FNA of a cervical lymph node was inconclusive in patient 3. Two patients had multiple medical comorbidities rendering them high risk for general anesthesia, and 1 patient had a BOT tumor obscuring visualization of the glottis, which would have precluded intubation and potentially required tracheostomy to proceed. All patients underwent successful in‐office TCUS‐guided FNA, with results showing squamous cell carcinoma. There were no related complications. In‐office TCUS‐guided FNA can be used for diagnosis of BOT lesions that are evident on ultrasound. This is beneficial in cases where general anesthesia is considered high risk. Additionally, 1 patient safely continued anticoagulation, and another was able to avoid tracheostomy. This technique is cost‐effective as it avoids the expenses associated with operative intervention.
Olfactory and Gustatory Outcomes in COVID‐19: A Prospective Evaluation in Nonhospitalized Subjects
Authors: Paderno Alberto , Mattavelli Davide , Rampinelli Vittorio , Grammatica Alberto , Raffetti Elena , Tomasoni Michele , Gualtieri Tommaso , Taboni Stefano , Zorzi Silvia , Del Bon Francesca , Lombardi Davide , Deganello Alberto , Redaelli De Zinis Luca Oscar , Schreiber Alberto 
Published: June 2020

ObjectiveTo prospectively assess the rate and timing of recovery of olfactory (OD) and gustatory (GD) dysfunction in patients affected by COVID‐19.Study DesignCohort study.SettingPopulation‐based evaluation in a COVID‐19 high‐prevalence region.Subjects and MethodsWe analyzed the clinical course of OD and GD in a cohort of home‐quarantined SARS‐CoV‐2–positive patients from Northern Italy. Physicians administered a survey‐based questionnaire at recruitment (T0). During follow‐up, patients responded to online dedicated surveys modulated according to symptoms at T0.ResultsA total of 151 patients completed the follow‐up survey. OD and/or GD were observed in 83% and 89% of subjects, respectively. Resolution rates of OD and GD at 30 days from onset were 87% and 82%, respectively. Risk factors for late resolution were grade of dysfunction at onset (total vs partial), gender, and presence of nasal congestion. Three (2%) patients previously reporting complete resolution of symptoms complained of subsequent recurrence of OD and/or GD after a mean of 19 days from resolution of the previous episode.ConclusionCOVID‐19–related OD and GD had high rate of resolution in the first month from onset of symptoms. However, in 10% to 15% of patients, these symptoms showed only partial improvement after this period.
Development and verification of a personalized immune prognostic feature in breast cancer
Authors: Wang HongLei , Wu Li , Wang HongTao 
Published: June 2020

Immune-related genes have great potential as prognostic markers in many types of cancer. Therefore, we have attempted to develop immune-related gene markers to enhance the prognosis of breast cancer; 1159 samples of breast cancer gene expression data and clinical follow-up messages were downloaded from TCGA and GEO, which were classified into training set, test set, and validation set. In the training set, the gene pairs are established according to the relative expression levels between 320 immune genes, in which the prognosis-related gene pairs are screened, and Lasso is used for feature selection to screen the robust biomarkers. A prognostic model of immune gene correlation was set up and verified. Sixty-six IRGPs were obtained, and 17-IRGPs signature was established. 17-IRGPs signature is an independent prognostic indicator for BC patients, which can stratify the risk in the training set and testing series, and AUC of five years survival was greater than 0.7; 17-IRGPs signature had better classification performance in patients with advanced BC. In addition, we compared the prognostic characteristics of 17-IRGPs with four reported breast cancers and clinical stages; 17-IRGPs achieved the highest average C index (0.7, P < 0.05), and functional analysis found that the dysregulated immune environment may be the cause of the observed difference in survival between patient groups defined by our characteristics. 17-IRGPs signature was constructed as a newly developed prognostic indicator to calculate the survival of BC patients. Impact statement Breast cancer is among the highest prevalent malignant tumors worldwide with a low survival ratio. Immune-related genes have great potential as prognostic indicator in many types of tumors. Therefore, we have attempted to develop immune-related gene markers to enhance the prognosis of breast cancer. 17-IRGPs signature was constructed as a newly developed prognostic indicator to predict the survival of BC patients.
Changes in Bcl-2 members after ibrutinib or venetoclax uncover functional hierarchy in determining resistance to venetoclax in CLL
Authors: Haselager Marco V. , Kielbassa Karoline , ter Burg Johanna , Bax Danique J. C. , Fernandes Stacey M. , Borst Jannie , Tam Constantine , Forconi Francesco , Chiodin Giorgia , Brown Jennifer R. , Dubois Julie , Kater Arnon P. , Eldering Eric 
Published: June 2020

Abstract
Chronic lymphocytic leukemia (CLL) cells cycle between lymph node (LN) and peripheral blood (PB) and display major shifts in Bcl-2 family members between those compartments. Specifically, Bcl-XL and Mcl-1, which are not targeted by the Bcl-2 inhibitor venetoclax, are increased in the LN. Because ibrutinib forces CLL cells out of the LN, we hypothesized that ibrutinib may thereby affect expression of Bcl-XL and Mcl-1 and sensitize CLL cells to venetoclax. We investigated expression of Bcl-2 family members in patients under ibrutinib or venetoclax treatment, combined with dissecting functional interactions of Bcl-2 family members, in an in vitro model of venetoclax resistance. In the PB, recent LN emigrants had higher Bcl-XL and Mcl-1 expression than did cells immigrating back to the LN. Under ibrutinib treatment, this distinction collapsed; significantly, the pretreatment profile reappeared in patients who relapsed on ibrutinib. However, in response to venetoclax, Bcl-2 members displayed an early increase, underlining the different modes of action of these 2 drugs. Profiling by BH3 mimetics was performed in CLL cells fully resistant to venetoclax due to CD40-mediated induction of Bcl-XL, Mcl-1, and Bfl-1. Several dual or triple combinations of BH3 mimetics were highly synergistic in restoring killing of CLL cells. Lastly, we demonstrated that proapoptotic Bim interacts with antiapoptotic Bcl-2 members in a sequential manner: Bcl-2 &gt; Bcl-XL &gt; Mcl-1 &gt; Bfl-1. Combined, the data indicate that Bcl-XL is more important in venetoclax resistance than is Mcl-1 and provide biological rationale for potential synergy between ibrutinib and venetoclax.
Bimodal Whole-Mount Imaging of Tendon Using Confocal Microscopy and X-ray Micro-Computed Tomography
Authors: Marr Neil , Hopkinson Mark , Hibbert Andrew P. , Pitsillides Andrew A. , Thorpe Chavaunne T. 
Published: June 2020

Abstract
Background
Three-dimensional imaging modalities for optically dense connective tissues such as tendons are limited and typically have a single imaging methodological endpoint. Here, we have developed a bimodal procedure utilising fluorescence-based confocal microscopy and x-ray micro-computed tomography for the imaging of adult tendons to visualise and analyse extracellular sub-structure and cellular composition in small and large animal species.

Results
Using fluorescent immunolabelling and optical clearing, we visualised the expression of the novel cross-species marker of tendon basement membrane, laminin-α4 in 3D throughout whole rat Achilles tendons and equine superficial digital flexor tendon 5 mm segments. This revealed a complex network of laminin-α4 within the tendon core that predominantly localises to the interfascicular matrix compartment. Furthermore, we implemented a chemical drying process capable of creating contrast densities enabling visualisation and quantification of both fascicular and interfascicular matrix volume and thickness by x-ray micro-computed tomography. We also demonstrated that both modalities can be combined using reverse clarification of fluorescently labelled tissues prior to chemical drying to enable bimodal imaging of a single sample.

Conclusions
Whole-mount imaging of tendon allowed us to identify the presence of an extensive network of laminin-α4 within tendon, the complexity of which cannot be appreciated using traditional 2D imaging techniques. Creating contrast for x-ray micro-computed tomography imaging of tendon using chemical drying is not only simple and rapid, but also markedly improves on previously published methods. Combining these methods provides the ability to gain spatio-temporal information and quantify tendon substructures to elucidate the relationship between morphology and function.
Elevated vitreous Lipocalin-2 levels of patients with proliferative diabetic retinopathy
Authors: Wang Hui , Lou Hui , Li Yongrong , Ji Fengtao , Chen Wei , Lu Qianyi , Xu Guoxu 
Published: June 2020

Abstract
Background
Lipocalin-2 (LCN2) is a novel adipokine with potential roles in obesity, insulin resistance, and inflammation. This study aims to assess the concentrations of LCN2 and vascular endothelial growth factor (VEGF) expressed in the vitreous humors of patients with proliferative diabetic retinopathy (PDR).

Methods
The concentrations of LCN2 and VEGF were measured from the vitreous of 67 patients undergoing vitrectomy (20 controls and 47 PDR) via enzyme-linked immunosorbent assay (ELISA). Patients with non-ocular pathology that could elevate the LCN2 level in the vitreous were excluded. PDR activity and a history of panretinal photocoagulation were used for further grouping analysis.

Results
The vitreous concentration of LCN2 was statistically significantly higher in the PDR group compared to the control group (63,522 (30,009) pg/ml versus 1663 (1191) pg/ml, respectively; P < 0.001). VEGF level was also significantly higher in the PDR group than in the control group (1038 (1326) pg/ml versus 9 pg/ml, respectively; P < 0.001). The mean vitreous LCN2 and VEGF levels in active PDR patients were significantly higher than that of the inactive PDR patients. The mean LCN2 concentration in vitreous humor was significantly lower in the 28 PDR patients with a history of complete PRP (37,304 (16,651) pg/mL) in comparison with 19 PDR patients without preperformed panretinal photocoagulation or with preperformed incomplete panretinal photocoagulation (79,796 (24,391) pg/mL). A significant correlation between the vitreous LCN2 level and VEGF level was found in patients with PDR (R = 0.34; P = 0.019).

Conclusions
This report shows a significant increase of LCN2 in the vitreous fluid of patients with PDR and present a significant correlation between LCN2 and VEGF, suggesting LCN2 might be involved in the pathogenesis of PDR.
A comprehensive overview and qualitative analysis of government-led nutrition policies in Australian institutions
Authors: Rosewarne Emalie , Hoek Annet C. , Sacks Gary , Wolfenden Luke , Wu Jason , Reimers Jenny , Corben Kirstan , Moore Michael , Ni Mhurchu Cliona , Webster Jacqui 
Published: June 2020

Abstract
Background
Institutions are a recommended setting for dietary interventions and nutrition policies as these provide an opportunity to improve health by creating healthy food environments. In Australia, state and territory governments encourage or mandate institutions in their jurisdiction to adopt nutrition policies. However, no work has analysed the policy design across settings and jurisdictions. This study aimed to compare the design and components of government-led institutional nutrition policies between Australian states and territories, determine gaps in existing policies, and assess the potential for developing stronger, more comprehensive policies.

Methods
Government-led institutional nutrition policies, in schools, workplaces, health facilities and other public settings, were identified by searching health and education department websites for each Australian state and territory government. This was supplemented by data from other relevant stakeholder websites and from the Food Policy Index Australia website. A framework for monitoring and evaluating nutrition policies in publicly-funded institutions was used to extract data and a qualitative analysis of the design and content of institutional nutrition policies was performed. Comparative analyses between the jurisdictions and institution types were conducted, and policies were assessed for comprehensiveness.

Results
Twenty-seven institutional nutrition policies were identified across eight states and territories in Australia. Most policies in health facilities and public schools were mandatory, though most workplace policies were voluntary. Twenty-four included nutrient criteria, and 22 included guidelines for catering/fundraising/advertising. While most included implementation guides or tools and additional supporting resources, less than half included tools/timelines for monitoring and evaluation. The policy design, components and nutrient criteria varied between jurisdictions and institution types, though all were based on the Australian Dietary Guidelines.

Conclusions
Nutrition policies in institutions present an opportunity to create healthy eating environments and improve population health in Australia. However, the design of these policies, including lack of key components such as accountability mechanisms, and jurisdictional differences, may be a barrier to implementation and prevent the policies having their intended impact.
Incidental hepatic tuberculosis during planned resection of locally advanced ampullary carcinoma: a case report
Authors: Hoe Vee Chuan , Khairuddin Allim , Tan Jun Sam , Sharif Mohd Sharifudin , Azizan Nornazirah , Hayati Firdaus 
Published: June 2020

Abstract
Background
Tuberculosis (TB) is classified according to the site of disease as pulmonary or extrapulmonary. Extrapulmonary TB is less common than its counterpart in which it can be found anywhere in the body including the liver. Similar to ampullary carcinoma, TB liver can manifest with jaundice and deranged liver function tests, particularly in the obstructed biliary systems.

Case presentation
A 43-year-old gentleman with locally advanced ampullary carcinoma was noticed to have multiple suspicious liver nodules intraoperatively during curative ampulla resection. The surgery was then abandoned after a biopsy. The histology was consistent with chronic granulomatous inflammation. He was then subjected to a Whipple pancreaticoduodenectomy procedure after initiation of anti-tubercular treatment. He recovered well with no evidence of tumour recurrence and worsening TB.

Conclusions
A high index of suspicion and quick decision making can help to diagnose a possible extrapulmonary TB masquerading as a malignant disease in a patient with curative intention of ampullary carcinoma.
Superselective embolization for high-flow priapism refractory to medical and surgical treatments
Authors: Bi Yonghua , Yi Mengfei , Yu Zepeng , Han Xinwei , Ren Jianzhuang 
Published: June 2020

Abstract
Background
This study aimed to report long-term outcome of superselective embolization in patients with high-flow priapism refractory to medical and surgical treatments.

Methods
From August 2011 until July 2016, 14 patients with high-flow priapism refractory to local treatments were treated and their charts were retrospective reviewed. Clinical evaluation, color Doppler ultrasonography, arteriography and selective embolization were performed. Follow up was performed in all patients. Fourteen men (18–63 years old) were enrolled, with priapism duration of 14 h to 28 days. Internal pudendal arteries or glutaea inferior arteriae were successfully embolized with gelatin sponge particles, polyvinyl alcohol particles or microcoils.

Results
Pseudoaneurysm in right femoral artery was found in one case after intervention. The follow-up 1 week later showed that 13 patients were in good condition, the priapism diminished 1–7 days (mean 3.2 ± 0.5 days) after intervention, and 1 patient received second intervention. Mean follow-up was (range 10.8–69.6) months. One patient had recurrent priapism months after embolization and had his penis surgically removed for severe necrosis.

Conclusions
Superselective embolization is safe and effective in high-flow priapism refractory local treatments, with a good long-term prognosis.
Association between sleep disorder and quality of life in patients with type 2 diabetes: a cross-sectional study
Authors: Hashimoto Yoshitaka , Sakai Ryosuke , Ikeda Kenichiro , Fukui Michiaki 
Published: June 2020

Abstract
Background
We investigated the association between sleep symptoms, which cause sleep disorder, and quality of life (QoL) among people with type 2 diabetes (T2D).

Methods
In this cross-sectional study of 342 people with T2D, the Japan National Health and Wellness Survey (NHWS) database 2016 were used. We treated the respondents who reported experiencing any of the sleep symptoms as having sleep disorders. To examine health-related QoL (HRQoL), we used the physical component summary (PCS) and the mental component summary (MCS) from the 36-Item short-form and the EuroQol 5 Dimension (EQ-5D) survey instruments. Overall activity impairment was used for assessment of the effect on the individual’s ability to perform regular daily activities. We used t-test and one-way ANOVA test for comparison QoL scores between the participants with and without sleep disorders.

Results
66.4% of the participants with T2D reported having a sleep disorder. The PCS, MCS, EQ-5D, and overall activity impairment of people with sleep disorder was significantly poorer than those of the people without. Specific sleep symptoms, such as waking up to go to the bathroom, daytime sleepiness, and waking up too early (before the alarm clock), had high prevalence (35.4, 27.8 and 20.2%). The participants who experienced waking up to go to the bathroom or daytime sleepiness demonstrated significantly poorer QoL on all scores related to QoL, but those who experienced waking up too early only demonstrated significantly poorer QoL on the EQ-5D.

Conclusions
Two-thirds of people with T2D in this study suffer from sleep disorders. The people who experience waking up to go to the bathroom or daytime sleepiness had significantly poorer QoL than those without these symptoms. Thus, sleep disorders, especially the symptoms of waking up to go to the bathroom or daytime sleepiness, might be the treatment targets for QOL of people with T2DM.