bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toll-like receptor-agonist-based therapies for respiratory viral diseases: thinking outside the cell
Authors: Girkin Jason L.N. , Maltby Steven , Bartlett Nathan W. 
Published: May 2022

Respiratory virus infections initiate in the upper respiratory tract (URT). Innate immunity is critical for initial control of infection at this site, particularly in the absence of mucosal virus-neutralising antibodies. If the innate immune response is inadequate, infection can spread to the lower respiratory tract (LRT) causing community-acquired pneumonia (as exemplified by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/coronavirus disease 2019). Vaccines for respiratory viruses (influenza and SARS-CoV-2) leverage systemic adaptive immunity to protect from severe lung disease. However, the URT remains vulnerable to infection, enabling viral transmission and posing an ongoing risk of severe disease in populations that lack effective adaptive immunity.Innate immunity is triggered by host cell recognition of viral pathogen-associated molecular patternsviamolecular sensors such as Toll-like receptors (TLRs). Here we review the role of TLRs in respiratory viral infections and the potential of TLR-targeted treatments to enhance airway antiviral immunity to limit progression to severe LRT disease and reduce person-to-person viral transmission. By considering cellular localisation and antiviral mechanisms of action and treatment route/timing, we propose that cell surface TLR agonist therapies are a viable strategy for preventing respiratory viral diseases by providing immediate, durable pan-viral protection within the URT.
Pan-cancer analysis reveals RIPK2 predicts prognosis and promotes immune therapy resistance via triggering cytotoxic T lymphocytes dysfunction
Authors: Song Junquan , Yang Runyu , Wei Rongyuan , Du Yue , He Pengcheng , Liu Xiaowen 
Published: May 2022

Abstract
Background
Receptor-interacting protein kinase 2 (RIPK2, also known as RIP2) was reported to be associated with bacterial infections as well as inflammatory responses. However, the role of RIPK2 in prognosis and immunotherapy response is yet to be elucidated in human pan-cancer.

Methods
In this study, we investigated the expression, gene alteration landscape and prognostic value of RIPK2 in 33 cancers through various databases including Ualcan, cBioportal and Gene Expression Profiling Interactive Analysis 2 (GEPIA2). Then, the correlation between RIPK2 and immune infiltration, immune score, stromal score, and ESTIMATE score was investigated in the Cancer Genome Atlas (TCGA) and tumor immune estimation resource (TIMER) databases. Independent cohorts were utilized to explore the role of RIPK2 in tumor immunotherapy response. Furthermore, Gene set enrichment analysis (GSEA) was conducted to explore the mechanisms by which RIPK2 regulates immune therapy resistance. Single-cell RNA-seq datasets were used to analyze the expression level of RIPK2 on different immune cells. Moreover, CellMiner database was used to explore the relationship between RIPK2 expression with drug response.

Result
Compared with normal tissue, tumor tissue had a higher expression level of RIPK2 in various cancers. Survival analysis showed that high expression of RIPK2 associated with poor prognosis in numerous cancers. RIPK2 was found to promote a series of immune cell infiltration and B cells, macrophages, and neutrophils were significantly positively correlated with the expression of RIPK2. Moreover, RIPK2 affected immune score, stromal score and ESTIMATE score for a wide range of cancers. In the vast majority of 33 cancers, gene co-expression analysis showed that RIPK2 was positively correlated with the expression of immune checkpoint markers, such as PDCD1 (PD-1), CD274 (PD-L1), CTLA4 and TIGIT. RIPK2 aggravated cytotoxic T lymphocyte (CTL) dysfunction and related to the poor efficacy of immune checkpoint blockade in skin cutaneous melanoma (SKCM) and kidney renal clear cell carcinoma (KIRC). High expression of RIPK2 promoted innate immunotherapy resistance and adaptive immunotherapy resistance through IL-6/JAK/STAT3 signaling, interferon-gamma response, and interferon-alpha response pathway.

Conclusions
These results confirmed that RIPK2 could serve as a prognostic biomarker and promoted immune therapy resistance via triggering cytotoxic T lymphocytes dysfunction.
NDR1 increases NOTCH1 signaling activity by impairing Fbw7 mediated NICD degradation to enhance breast cancer stem cell properties
Authors: Wang Ling-Ling , Wan Xiao-Yun , Liu Chun-Qi , Zheng Fei-Meng 
Published: May 2022

Abstract
Background
The existence of breast cancer stem cells (BCSCs) causes tumor relapses, metastasis and resistance to conventional therapy in breast cancer. NDR1 kinase, a component of the Hippo pathway, plays important roles in multiple biological processes. However, its role in cancer stem cells has not been explored. The purpose of this study was to investigate the roles of NDR1 in modulating BCSCs.

Methods
The apoptosis was detected by Annexin V/Propidium Iodide staining and analyzed by flow cytometry. BCSCs were detected by CD24/44 or ALDEFLUOR staining and analyzed by flow cytometry. The proliferation ability of BCSCs was evaluated by sphere formation assay. The expression of interested proteins was detected by western blot analysis. The expression of HES-1 and c-MYC was detected by real-time PCR. Notch1 signaling activation was detected by luciferase reporter assay. Protein interaction was evaluated by immunoprecipitation. Protein degradation was evaluated by ubiquitination analysis. The clinical relevance of NDR1 was analyzed by Kaplan–Meier Plotter.

Results
NDR1 regulates apoptosis and drug resistance in breast cancer cells. The upregulation of NDR1 increases CD24low/CD44high or ALDEFLUORhigh population and sphere-forming ability in SUM149 and MCF-7 cells, while downregulation of NDR1 induces opposite effects. NDR1 increased the expression of the Notch1 intracellular domain (NICD) and activated the transcription of its downstream target (HES-1 and c-MYC). Critically, both suppression of Notch pathway activation by DAPT treatment or downregulation of Notch1 expression by shRNA reverses NDR1 enhanced BCSC properties. Mechanically, NDR1 interactes with both NICD or Fbw7 in a kinase activity-independent manner. NDR1 reduces the proteolytic turnover of NICD by competing with Fbw7 for NICD binding, thereby leading to Notch pathway activation. Furthermore, NDR1 might function as a hub to modulate IL-6, TNF-α or Wnt3a induced activation of Notch1 signaling pathway and enrichment of breast cancer stem cells. Moreover, we find that the elevation of NDR1 expression predictes poor survival (OS, RFS, DMFS and PPS) in breast cancer.

Conclusion
Our study revealed a novel function of NDR1 in regulating BCSC properties by activating the Notch pathway. These data might provide a potential strategy for eradicating BCSC to overcome tumor relapses, metastasis and drug resistance.
An Experimental Validation Study on Ferrofluid Evaporation
Authors: Yu Wenjuan , Li Decai , Niu Sifang 
Published: May 2022

AbstractThe current research on the evaporation of ferrofluids mainly focuses on the characterization of ultra-low vapor pressure ferrofluids in vacuum and the theoretical analysis of the evaporation process. Few studies have focused on the experimental validation of the proposed evaporation rate equations and on the comparison of the differences in ferrofluid evaporation. In this study, based on the Bolotov’s model, an evaporation rate equation is deduced from the experimental model. The experimental study included a comparison of the evaporation, magnetic particle volume fraction, temperature, height of the fluid surface from the outlet, and magnetic field of a kerosene-based ferrofluid and its base carrier liquid. The prepared sample was evaporated in a test tube, and the evaporation rate was calculated by measuring the weight loss of the sample. The experimental results show that the evaporation rate of the base carrier liquid is higher than that of the ferrofluid. The smaller the volume fraction of the magnetic particles, the greater the evaporation rate. The magnetic particles play a key role in preventing evaporation of the base liquid. The higher the temperature, the smaller the deviation of the evaporation rate from the predicted value. The evaporation rates obtained by the two control groups at the height of the fluid surface from the outlet were lower than the predict value. The magnetic field had a certain promotional effect on the evaporation of the ferrofluid. The experimental results were consistent with the results obtained using Bolotov’s model. This research validates Bolotov’s model and shows that the model is somewhat biased but still responds well to different variables.
Rotator cuff repair with single row technique provides satisfying clinical results despite consistent MRI retear rate
Authors: Vecchini Eugenio , Ricci Matteo , Elena Nicholas , Gasperotti Luca , Cochetti Andrea , Magnan Bruno 
Published: May 2022

Abstract
Background
The number of shoulder arthroscopies is steadily increasing to treat glenohumeral joint disorders, among which the rotator cuff tear is the most common. The prevalence of this condition ranges from 13% to 37% in the general population without considering the number of asymptomatic patients. The gold standard procedure for rotator cuff repair is still undefined. The purpose of this study is to evaluate a population who underwent a single row (SR) rotator cuff repair and correlate their clinical results with MRI findings.

Materials and methods
Sixty-seven consecutive rotator cuff procedures were retrospectively selected. All patients were diagnosed with a full-thickness rotator cuff tear and subsequently treated with an arthroscopic SR repair technique. Each patient was clinically assessed with the DASH questionnaire and the Constant–Murley Score to grade their satisfaction. Moreover, rotator cuff repair integrity was evaluated by MRI and graded using the Sugaya score.

Results
Mean follow-up was 19.5 ± 5.7 months. The mean Constant score was 82.8 ± 13.0 points, with 55 patients reporting excellent results. No patient scored less than 30 points, which could be deemed as unsatisfying. Meanwhile, on the DASH questionnaire, 6.1% of our patients rated their clinical outcome as unsatisfying, whereas 75.8% rated their outcome as excellent. Postoperative MRI classified 45 patients (83.3%) as either Sugaya type I, II, or III, whereas 9 patients (16.7%) presented a Sugaya type IV consistent with a full-thickness cuff retear. Of these nine patients, five (55.6%) and three (33.3%) reported excellent results for the Constant score and DASH questionnaire, respectively. The Mann–Whitney test reported that the retear group had worse scores than the intact repaired cuff group for pain (8.3 ± 5.0 versus 13.1 ± 3.4), Constant Score (68.8 ± 18.5 versus 83.1 ± 11.6), and DASH (66.2 ± 22.1 versus 44.2 ± 14.9). Still, range of motion (ROM) differences were not significant, except for better forward flexion in the intact group (p < 0.039).

Conclusions
Both groups with intact repaired and retorn cuffs showed improvement in their condition, but unexpectedly, there is no significant correlation between patient satisfaction and rotator cuff integrity.

Level of evidence
IV
Protective effects of dexmedetomidine in vital organ injury: crucial roles of autophagy
Authors: Zhao Shankun , Wu Weizhou , Lin Xuezheng , Shen Maolei , Yang Zhenyu , Yu Sicong , Luo Yu 
Published: May 2022

AbstractVital organ injury is one of the leading causes of global deaths. Accumulating studies have demonstrated that dexmedetomidine (DEX) has an outstanding protective effect on multiple organs for its antiinflammatory and antiapoptotic properties, while the underlying molecular mechanism is not clearly understood. Autophagy, an adaptive catabolic process, has been found to play a crucial role in the organ-protective effects of DEX. Herein, we present a first attempt to summarize all the evidence on the proposed roles of autophagy in the action of DEX protecting against vital organ injuries via a comprehensive review. We found that most of the relevant studies (17/24, 71%) demonstrated that the modulation of autophagy was inhibited under the treatment of DEX on vital organ injuries (e.g. brain, heart, kidney, and lung), but several studies suggested that the level of autophagy was dramatically increased after administration of DEX. Albeit not fully elucidated, the underlying mechanisms governing the roles of autophagy involve the antiapoptotic properties, inhibiting inflammatory response, removing damaged mitochondria, and reducing oxidative stress, which might be facilitated by the interaction with multiple associated genes (i.e., hypoxia inducible factor-1α, p62, caspase-3, heat shock 70 kDa protein, and microRNAs) and signaling cascades (i.e., mammalian target of rapamycin, nuclear factor-kappa B, and c-Jun N-terminal kinases pathway). The authors conclude that DEX hints at a promising strategy in the management of vital organ injuries, while autophagy is crucially involved in the protective effect of DEX.
A database for retrieving information on SARS-CoV-2 S protein mutations based on correlation network analysis
Authors: Ogata Yoshiyuki , Kitayama Ruri 
Published: May 2022

Abstract
Background
Over a million genomes and mutational analyses of SARS-CoV-2 are available in public databases, which reveal the phylogenetic tree of the virus. Although these data have enabled scientists to closely track the evolution and transmission dynamics of the virus at global and local scales, the Mu variant, recently identified in infections in South America, shows an unusual combination of mutations, and it is difficult to visualize these atypical characteristics in public databases based on a phylogenetic tree.

Results
The Vcorn SARS-CoV-2 database was constructed to provide information on COVID-19 infections and mutations in the S protein of the virus based on correlation network analysis. A correlation network was constructed using the recall index of one mutation to another mutation. The network includes several network modules in which nodes represent mutations and are tightly connected to each other. Individual network modules contain mutations of single variants, such as the alpha and delta variants. In the network constructed to emphasize mutations of the Mu variant using the database, the mutations were found to be located in multiple network modules, indicating that the mutations of the variant may have originated from multiple variants or be located at a basal position with a high frequency of mutation.

Conclusions
Vcorn SARS-CoV-2 provides information on COVID-19 and S protein mutations of SARS-CoV-2 via correlation network analysis. The network based on the analysis illustrates the unusual S protein mutations of the Mu variant. The database is freely available at http://www.plant.osakafu-u.ac.jp/~kagiana/vcorn/sarscov2/.
Survival-related genes are diversified across cancers but generally enriched in cancer hallmark pathways
Authors: Wang Po-Wen , Su Yi-Hsun , Chou Po-Hao , Huang Ming-Yueh , Chen Ting-Wen 
Published: May 2022

AbstractBackgroundPan-cancer studies have disclosed many commonalities and differences in mutations, copy number variations, and gene expression alterations among cancers. Some of these features are significantly associated with clinical outcomes, and many prognosis-predictive biomarkers or biosignatures have been proposed for specific cancer types. Here, we systematically explored the biological functions and the distribution of survival-related genes (SRGs) across cancers.ResultsWe carried out two different statistical survival models on the mRNA expression profiles in 33 cancer types from TCGA. We identified SRGs in each cancer type based on the Cox proportional hazards model and the log-rank test. We found a large difference in the number of SRGs among different cancer types, and most of the identified SRGs were specific to a particular cancer type. While these SRGs were unique to each cancer type, they were found mostly enriched in cancer hallmark pathways, e.g., cell proliferation, cell differentiation, DNA metabolism, and RNA metabolism. We also analyzed the association between cancer driver genes and SRGs and did not find significant over-representation amongst most cancers.ConclusionsIn summary, our work identified all the SRGs for 33 cancer types from TCGA. In addition, the pan-cancer analysis revealed the similarities and the differences in the biological functions of SRGs across cancers. Given the potential of SRGs in clinical utility, our results can serve as a resource for basic research and biotech applications.
Anemia and iron deficiency in patients with atrial fibrillation
Authors: Hanna-Rivero Nicole , Tu Samuel J. , Elliott Adrian D. , Pitman Bradley M. , Gallagher Celine , Lau Dennis H. , Sanders Prashanthan , Wong Christopher X. 
Published: May 2022

AbstractAtrial fibrillation (AF) is the most common cardiac tachyarrhythmia and has a rising global prevalence. Given the increasing burden of AF-related symptoms and complications, new approaches to management are required. Anemia and iron deficiency are common conditions in patients with AF. Furthermore, emerging evidence suggests that the presence of anemia may be associated with worse outcome in these patients. The role of anemia and iron deficiency has been extensively explored in other cardiovascular states, such as heart failure and ischemic heart disease. In particular, the role of iron repletion amongst patients with heart failure is now an established treatment modality. However, despite the strong bidirectional inter-relationship between AF and heart failure, the implications of anemia and iron-deficiency in AF have been scarcely studied. This area is of mechanistic and clinical relevance given the potential that treatment of these conditions may improve symptoms and prognosis in the increasing number of individuals with AF. In this review, we summarise the current published literature on anemia and iron deficiency in patients with AF. We discuss AF complications such as stroke, bleeding, and heart failure, in addition to AF-related symptoms such as exercise intolerance, and the potential impact of anemia and iron deficiency on these. Finally, we summarize current research gaps on anemia, iron deficiency, and AF, and underscore potential research directions.
Sporadic foveolar-type adenoma in gastric body/antrum junction with gastritis cystica profunda
Authors: Guan Jian , Li Zhuo , Shen Guihua , Huang Wenting 
Published: May 2022

Abstract
Background
Sporadic gastric foveolar-type adenomas are extremely rare and are usually small, flat or slightly raised lesions that occur in the oxyntic mucosa.

Case presentation
We reported here a case of a 70-year-old female with a sporadic gastric foveolar-type adenoma occurring in the mucosa at the junction of the gastric body/antrum. The adenoma was a protruding lesion of 2 × 1.8 cm sized, causing symptoms of upper gastrointestinal bleeding, and the basal and surrounding mucosa showed pseudopyloric gland metaplasia without atrophy, intestinal metaplasia, H. pylori infection, or active inflammation. It had somatic mutations in both APC and KRAS genes.

Conclusions
This is the first reported case of a large sporadic gastric foveolar-type adenoma that occurred in the mucosa of pseudopyloric gland metaplasia and with Gastritis Cystica Profunda, which modify our understanding of the morphological features and molecular underpinnings of this type of lesion.
Effect of individually tailored nutritional counselling on protein and energy intake among older people receiving home care at risk of or having malnutrition: a non-randomised intervention study
Authors: Kaipainen Tarja , Hartikainen Sirpa , Tiihonen Miia , Nykänen Irma 
Published: May 2022

Abstract
Background
With ageing, food intake may decrease and lead to an insufficient nutrient intake causing protein-energy malnutrition (PEM) which is associated with adverse health effects and increased mortality. The aim of this study was to investigate the effects of individually tailored dietary counseling focused on protein intake among home care clients with PEM or at risk of developing PEM. The secondary aim was to study the intake of energy and other nutrients.

Methods
This intervention study is part of the non-randomised population-based multidisciplinary Nutrition, Oral Health and Medication study (NutOrMed study). The intervention group comprised 112 and the control group 87 home care clients (≥75 years) with PEM or risk of PEM. PEM was defined by Mini Nutritional Assessment score < 24 and/or plasma albumin < 35 g/L. The nutrients intake was assessed from 24-hour dietary recall at the baseline and after the six-month intervention. The intervention consisted of an individually tailored dietary counseling; the persons were instructed to increase their food intake with protein and energy dense food items, the number of meals and consumption of protein-, energy- and nutrient-rich snacks for six months.

Results
After the six-month nutritional intervention, the mean change in protein intake increased 0.04 g/kgBW (95% CI 0.05 to 0.2), fibre 0.8 g (95% CI 0.2 to 4.3), vitamin D 8.5 μg (95% CI 0.7 to 4.4), E 0.6 mg (95% CI 0.4 to 2.2), B12 0.7 μg (95% CI 0.02 to 2.6), folate 8.7 μg (95% CI 1.5 to 46.5), iron 0.4 mg 95% CI 0.6 to 2.4), and zinc 0.5 mg (95% CI 0.6 to 2.2) in the intervention group compared with the control group. The proportion of those receiving less than 1.0 g/kg/BW protein decreased from 67 to 51% in the intervention group and from 84 to 76% in the control group. Among home care clients with a cognitive decline (MMSE< 18), protein intake increased in the intervention group by 0.2 g/kg/BW (p = 0.048) but there was no change in the control group.

Conclusion
An individual tailored nutritional intervention improves the intake of protein and other nutrients among vulnerable home care clients with PEM or its risk and in persons with cognitive decline.

Trial registration
ClinicalTrials.gov: NCT02214758. Date of trial registration: 12/08/2014.