bluuebunny/crossref_metadata_2025_split huggingface dataset:
YOD1 serves as a potential prognostic biomarker for pancreatic cancer
Authors: Zhang Zhishuo , Zhao Wenxia , Li Yiming , Li Yang , Cheng Hanzeng , Zheng Liyun , Sun Xiaoyu , Liu Hao , Shao Rongguang 
Published: May 2022

Abstract
Background
Ubiquitination is a basic post-translational modification of intracellular proteins and can be reversed enzymatically by DUBs (deubiquitinating enzymes). More than 90 DUBs have been identified. Among them, the deubiquitinating enzyme YOD1, a member of the ovarian tumor domain protease (OTUs) subfamily, is involved in the regulation of endoplasmic reticulum (ER)-related degradation pathways. In fact, it is reported that YOD1 is an important proliferation and metastasis-inducing gene, which can stimulate the characteristics of cancer stem cells and maintain circulating tumor cells (CTC). However, the expression level, prognostic effect and biological functional mechanism of YOD1 in pancreatic cancer are still unclear.

Results
In the GEO and TCGA databases, YOD1 mRNA expression is significantly up regulated in a variety of human pancreatic cancer tissues. Survival analysis showed that the up regulation of YOD1 can predict poor prognosis of pancreatic cancer. Cox analysis showed that high YOD1 expression is an independent prognostic factor of pancreatic cancer. ROC analysis shows that YOD1 has significant diagnostic value. The immunohistochemistry (IHC) results showed that the protein expression level of YOD1 in pancreatic cancer tissue was higher than that in neighboring non-pancreatic cancer tissues (P < 0.001). In addition, we found that YOD1 expression is negatively correlated with the infiltration level of CD8 + T cells, macrophages, neutrophils and dendritic cells (DC) in pancreatic cancer. The expression of YOD1 has a strong correlation with the different immune marker sets in PAAD. Co-expression network and functional enrichment analysis indicate that YOD1 may participate in the development of pancreatic cancer through cell adhesion molecules, p53, Hippo, TGF-β and other pathways. The experimental results of EDU, Transwell, Immunohistochemistry (IHC), Western blot and Flow Cytometry indicate that YOD1 is highly expressed in pancreatic cancer cells and pancreatic cancer tissues, and its overexpression can promote the proliferation and metastasis of pancreatic cancer cells and affect the immune microenvironment.

Conclusion
Our results indicate that YOD1 may be a useful biomarker for the prognosis of human pancreatic cancer, and it may also be a potential molecular target for the diagnosis and treatment of pancreatic cancer.
The unvirtuous cycle of discrimination affecting people with hepatitis B: a multi-country qualitative assessment of key-informant perspectives
Authors: Freeland Catherine , Mendola Lindsay , Cheng Vivian , Cohen Chari , Wallace Jack 
Published: May 2022

Abstract
Background
An estimated 296 million individuals live with chronic hepatitis B worldwide, most have not been diagnosed and remain at risk of liver disease and cancer. People with hepatitis B often face discrimination that denies them employment or education opportunities, results in unfair treatment at work or in school, limits their ability to emigrate to certain countries, and in some cases prohibits them from serving in the military. Discrimination specific to hepatitis B has not been widely documented within the literature. This study aims to investigate and describe hepatitis B related discrimination, document discrimination occurring around the globe, and provide initial recommendations for addressing discrimination using key informant interviews.

Methods
Purposive and snowball sampling were used to identify potential key informants for qualitative interview. Key informants identified as community health leaders, public health scientists, doctors, and researchers, many of whom were also living with hepatitis B. Using a semi-structured guide, participants were asked to describe their experience and any challenges for people living with hepatitis B including marginalization and its’ consequences. A codebook was used to guide the organization of data for analysis, and all transcripts N = 17 were double coded.

Results
The overarching themes identified from interviews demonstrate explicit experiences with discrimination of those directly affected, the psychological responses, and the negative health outcomes associated with the unvirtuous cycle of discrimination. All key informants reported on the substantial quality of life implications and often poorer health outcomes resulting from hepatitis B discrimination. Participants also identified the significant impact of hepatitis B discrimination occurring within a range of education-based services across several countries as well as military exclusion or removal if individuals are found to have hepatitis B.

Conclusion
Our data demonstrate that hepatitis B discrimination has a significant impact. Discrimination can occur at various points in life from education, to seeking employment, to marriage, to restrictions on entry, travel and stay in other countries. This study demonstrates the impact of discrimination and the need for future research that can lead to policy change and protections for people living with and impacted by hepatitis B.
Advances of nano drug delivery system for the theranostics of ischemic stroke
Authors: Lv Wei , Liu Yijiao , Li Shengnan , Lv Lingyan , Lu Hongdan , Xin Hongliang 
Published: May 2022

AbstractFrom the global perspective, stroke refers to a highly common cause of disability and death. Ischemic stroke (IS), attributed to blood vessel blockage, preventing the flow of blood to brain, acts as the most common form of stroke. Thus far, thrombolytic therapy is the only clinical treatment for IS with the approval from the FDA. Moreover, the physiology barrier complicates therapeutically and diagnostically related intervention development of IS. Accordingly, developing efficient and powerful curative approaches for IS diagnosis and treatment is urgently required. The advent of nanotechnology has brought dawn and hope to better curative and imaging forms for the management of IS. This work reviews the recent advances and challenges correlated with the nano drug delivery system for IS therapy and diagnosis. The overview of the current knowledge of the important molecular pathological mechanisms in cerebral ischemia and how the drugs cross the blood brain barrier will also be briefly summarized.Graphical Abstract
Targeted delivery of fat extract by platelet membrane-cloaked nanocarriers for the treatment of ischemic stroke
Authors: Wang Cheng , Yang Xuewei , Jiang Yixu , Qi Lin , Zhuge Deli , Xu Tongtong , Guo Yiyan , Deng Mingwu , Zhang Wenjie , Tian Dongyan , Yin Qingqing , Li Li , Zhang Zhijun , Wang Yongting , Yang Guo-Yuan , Chen Yijie , Tang Yaohui 
Published: May 2022

Abstract
Background
Our previous studies suggest that human fat extract (FE) contains a variety of angiogenic factors and may provide an alternative treatment option for stroke. However, the therapeutic effect is largely limited due to its short half-life, and inaccurate targeting.

Results
Herein, we leverage the targeting abilities of platelets (PLTs) to the lesion area of stroke and Arg-Gly-Asp (RGD) peptides to the angiogenic blood vessels to develop a biomimetic nanocarrier that capable of delivering FE precisely to treat stroke. The biomimetic nanocarriers are comprised of FE-encapsulated PLGA (poly(lactic-co-glycolic acid)) core enclosed by RGD peptides decorated plasma membrane of PLTs, namely RGD-PLT@PLGA-FE. We found that RGD-PLT@PLGA-FE not only targeted damaged and inflamed blood vessels but also achieved rapid accumulation in the lesion area of ischemic brain. In addition, RGD-PLT@PLGA-FE kept a sustained release behavior of FE at the lesion site, effectively increased its half-life and promoted angiogenesis and neurogenesis with delivering neurotrophic factors including BDNF, GDNF and bFGF to the brain, that ultimately resulted in blood flow increase and neurobehavioral recovery.

Conclusions
In conclusion, our study provides a new strategy to design a biomimetic system for FE delivery and it is a promising modality for stroke therapy.

Graphical Abstract
Natural antisense RNA Foxk1-AS promotes myogenic differentiation by inhibiting Foxk1 activity
Authors: Li Chun , Shen Hao , Liu Meng , Li Siguang , Luo Yuping 
Published: May 2022

Abstract
Background
Natural antisense RNAs are RNA molecules that are transcribed from the opposite strand of either protein-coding or non-protein coding genes and have the ability to regulate the expression of their sense gene or several related genes. However, the roles of natural antisense RNAs in the maintenance and myogenesis of muscle stem cells remain largely unexamined.

Methods
We analysed myoblast differentiation and regeneration by overexpression and knockdown of Foxk1-AS using lentivirus and adeno-associated virus infection in C2C12 cells and damaged muscle tissues. Muscle injury was induced by BaCl2 and the regeneration and repair of damaged muscle tissues was assessed by haematoxylin–eosin staining and quantitative real-time PCR. The expression of myogenic differentiation-related genes was verified via quantitative real-time PCR, Western blotting and immunofluorescence staining.

Results
We identified a novel natural antisense RNA, Foxk1-AS, which is transcribed from the opposite strand of Foxk1 DNA and completely incorporated in the 3′ UTR of Foxk1. Foxk1-AS targets Foxk1 and functions as a regulator of myogenesis. Overexpression of Foxk1-AS strongly inhibited the expression of Foxk1 in C2C12 cells and in tibialis anterior muscle tissue and promoted myoblast differentiation and the regeneration of muscle fibres damaged by BaCl2. Furthermore, overexpression of Foxk1-AS promoted the expression of Mef2c, which is an important transcription factor in the control of muscle gene expression and is negatively regulated by Foxk1.

Conclusion
The results indicated that Foxk1-AS represses Foxk1, thereby rescuing Mef2c activity and promoting myogenic differentiation of C2C12 cells and regeneration of damaged muscle fibres.
Transcriptomic datasets of cancer patients treated with immune-checkpoint inhibitors: a systematic review
Authors: Kovács Szonja Anna , Győrffy Balázs 
Published: May 2022

AbstractThe availability of immune-checkpoint inhibitors (ICI) in the last decade has resulted in a paradigm shift in certain areas of oncology. Patients can be treated either by a monotherapy of anti-CTLA-4 (tremelimumab or ipilimumab), anti-PD-1 (nivolumab or pembrolizumab), or anti-PD-L1 (avelumab or atezolizumab or durvalumab) or as combination therapy of anti-CTLA-4 and anti-PD-1. To maximize the clinical treatment benefit of cancer immunotherapy, the prediction of the actual immune response by the identification and application of clinically useful biomarkers will be required. Whole transcriptomic datasets of patients with ICI treatment could provide the basis for large-scale discovery and ranking of such potential biomarker candidates. In this review, we summarize currently available transcriptomic data from different biological sources (whole blood, fresh-frozen tissue, FFPE) obtained by different methods (microarray, RNA-Seq, RT-qPCR). We directly include only results from clinical trials and other investigations where an ICI treatment was administered. The available datasets are grouped based on the administered treatment and we also summarize the most important results in the individual cohorts. We discuss the limitations and shortcomings of the available datasets. Finally, a subset of animal studies is reviewed to provide an overview of potential in vivo ICI investigations. Our review can provide a swift reference for researchers aiming to find the most suitable study for their investigation, thus saving a significant amount of time.
Periappendiceal fluid collection on preoperative computed tomography can be an indication for interval appendectomy: a retrospective study
Authors: Kanaka Shintaro , Mizutani Satoshi , Yokoyama Yasuyuki , Matsutani Takeshi , Chihara Naoto , Katsuno Akira , Takata Hideyuki , Nakata Ryosuke , Mishima Keisuke , Wada Yudai , Shimizu Takao , Yamagiwa Ryo , Haruna Takahiro , Nakamura Yuka , Hamaguchi Akira , Taniai Nobuhiko , Yoshida Hiroshi 
Published: May 2022

Abstract
Background
The treatment strategies for acute appendicitis, such as emergency appendectomy (EA), interval appendectomy (IA), and repeating nonoperative management (NOM), are controversial. In this study, we examined the preoperative factors that can be used to distinguish which patients should undergo IA.

Methods
We retrospectively identified 902 patients who underwent surgery for appendicitis in our hospital from January 2010 to December 2021. Of these patients, 776 were included in this study. The patients were divided into two groups: those with a periappendiceal fluid collection (PAFC) on preoperative computed tomography (PAFC-positive group, n = 170) and those without a PAFC (PAFC-negative group, n = 606). In each group, we compared patients who underwent EA and IA.

Results
In the PAFC-positive group, patients who underwent EA had a significantly higher postoperative complication rate than those who underwent IA (40.5% vs. 24.0%, p = 0.037). In the multivariate analysis, only the presence of PAFC was significantly associated with an increased risk of postoperative complications (odds ratio, 7.11; 95% confidence interval, 2.73–18.60; p < 0.001). The presence of PAFC alone was not significantly associated with an increased risk of IA or NOM failure (odds ratio, 1.48; 95% confidence interval, 0.19–11.7; p = 0.71). The rate of neoplasia on pathologic examination was significantly higher in the PAFC-positive than PAFC-negative group (7.6% vs. 1.5%, p < 0.001); the rate of carcinoma was also higher in the PAFC-positive group (2.4% vs. 0.17%, p = 0.02).

Conclusions
The presence of PAFC on preoperative computed tomography was found to be a risk factor for postoperative complications but not IA or NOM failure. It was also correlated with neoplasia as the etiology of appendicitis. Therefore, PAFC positivity is useful as an indication for IA.
Quality of life following cardiac rehabilitation in cardiac surgery patients
Authors: Lourens Ernest Christian , Baker Robert Ashley , Krieg Bronwyn M. 
Published: May 2022

Abstract
Background
Undergoing cardiac surgery often result in perioperative loss of health-related quality of life (HRQOL). Although participation rates in Australia is low, cardiac rehabilitation (CR) has been demonstrated to improve patient HRQOL in cardiac patients. Literature is unclear regarding the role of CR and HRQOL in the cardiac surgery (CS) patient population.

Methods
A prospective non-randomised study was conducted on eligible cardiac surgery patients between December 2009 and March 2015. HRQOL was assessed using the Short Form 12 at baseline and post-operatively at 30 days and 180 days. CR participation was recorded and barriers to CR uptake was assessed using the Cardiac Rehabilitation Enrolment Obstacles (CREO) scale.

Results
At 180 days, 107 patients participated in CR and 111 did not participate in CR. A significant improvement from baseline mental and physical HRQOL was observed in both groups at 30 days and 180 days (p < 0.002). No significant difference between group characteristics or HRQOL was observed at any time. A trend of superior improvement in mental QOL was observed in the CR group. The study is limited by poor initial uptake (218/1772 of eligible) and may be underpowered to observe a clinical difference. A significant difference in CREO scores were observed between the two groups at 30 days (13 out of 16 questions, p < 0.001) and 180 days (11 out of 16 questions, p < 0.011).

Conclusion
Literature has shown that CR may improve numerous health outcomes in cardiac and CS patients, however CR uptake in Australia is low. Mental and Physical QOL is demonstrated to improve following CS, however further research is required to delineate the role of CR and QOL in CS patients. The CREO tool utilised in this study identified numerous potentially modifiable barriers to CR uptake. Specific strategies related to the survey are suggested to improve awareness, uptake, and adherence to CR, including advocacy of home-based and telehealth services.
Inhibitors of IFN gene stimulators (STING) improve intestinal ischemia–reperfusion-induced acute lung injury by activating AMPK signaling
Authors: Yang Mei , Ma Yu-Xia , Zhi Ying , Wang Hai-Bin , Zhao Li , Wang Peng-Sheng , Niu Jie-Ting 
Published: May 2022

Abstract
Background
Acute lung injury (ALI) caused by intestinal ischemia–reperfusion is a life-threatening disease. Interferon gene stimulator (STING) is a cytoplasmic DNA sensor that participates in the initiation of the inflammatory response. This study aims to establish whether C-176 (STING inhibitor) improves ALI under intestinal ischemia–reperfusion conditions.

Methods
To induce ALI, 72 male C57BL/6 mice were subjected to intestinal ischemia for 60 min and reperfusion for 3 h. Through intraperitoneal injection, C-176, a selective STING inhibitor, was injected 30 min before surgical treatment; meanwhile, compound C, an antagonist of adenosine monophosphate-activated protein kinase (AMPK), was administered 30 min after surgery. Based on immunofluorescence and Western blot assays, post-ALI assessments included lung water content (TLW), bronchoalveolar lavage fluid (BALF) protein, H&E staining, Masson staining, pulmonary pyroptosis [Gasdermin-D (GSDMD), cleaved caspase-1], and apoptosis (TUNEL, cleaved caspase-3).

Results
C-176 administration significantly attenuated intestinal ischemia–reperfusion-mediated ALI; this effect was reflected by exacerbated TLW and BALF protein, aggravated lung injury score, elevated degree of pulmonary fibrosis, increased TUNEL- and GSDMD-positive cells, and upregulated phospho-AMPK, cleaved caspase-1, cleaved caspase-3 and IFNβ mRNA expression. Moreover, C-176 increased phospho-AMPK under ALI conditions. Nonetheless, compound C partially reversed these beneficial effects.

Conclusion
C-176, a selective STING inhibitor, improves intestinal ischemia–reperfusion-mediated ALI, and its underlying mechanism may be associated with AMPK signal activation.
Heritable genomic diversity in breast cancer driver genes and associations with risk in a Chilean population
Authors: Morales-Pison Sebastian , Gonzalez-Hormazabal Patricio , Tapia Julio C. , Salas-Burgos Alexis , Ampuero Sandra , Gómez Fernando , Waugh Enrique , Reyes José Miguel , Jara Lilian 
Published: May 2022

Abstract
Background
Driver mutations are the genetic components responsible for tumor initiation and progression. These variants, which may be inherited, influence cancer risk and therefore underlie many familial cancers. The present study examines the potential association between SNPs in driver genes SF3B1 (rs4685), TBX3 (rs12366395, rs8853, and rs1061651) and MAP3K1 (rs72758040) and BC in BRCA1/2-negative Chilean families.

Methods
The SNPs were genotyped in 486 BC cases and 1258 controls by TaqMan Assay.

Results
Our data do not support an association between rs4685:C > T, rs8853:T > C, or rs1061651:T > C and BC risk. However, the rs12366395-G allele (A/G + G/G) was associated with risk in families with a strong history of BC (OR = 1.2 [95% CI 1.0–1.6] p = 0.02 and OR = 1.5 [95% CI 1.0–2.2] p = 0.02, respectively). Moreover, rs72758040-C was associated with increased risk in cases with a moderate-to-strong family history of BC (OR = 1.3 [95% CI 1.0–1.7] p = 0.02 and OR = 1.3 [95% CI 1.0–1.8] p = 0.03 respectively). Finally, risk was significantly higher in homozygous C/C cases from families with a moderate-to-strong BC history (OR = 1.8 [95% CI 1.0–3.1] p = 0.03 and OR = 1.9 [95% CI 1.1–3.4] p = 0.01, respectively). We also evaluated the combined impact of rs12366395-G and rs72758040-C. Familial BC risk increased in a dose-dependent manner with risk allele count, reflecting an additive effect (p-trend = 0.0002).

Conclusions
Our study suggests that germline variants in driver genes TBX3 (rs12366395) and MAP3K1 (rs72758040) may influence BC risk in BRCA1/2-negative Chilean families. Moreover, the presence of rs12366395-G and rs72758040-C could increase BC risk in a Chilean population.
Renal health benefits of sustainable diets in Japan: a review
Authors: Nagai Kei , Kosaka Shiho , Kawate Yuka , Itsubo Norihiro 
Published: May 2022

AbstractGlobal warming may reduce food production and force people to adopt dietary habits of inadequate quantity or quality. Such dietary habits could trigger chronic kidney disease through inappropriate nutrition or lifestyle diseases. Livestock farming and other types of food production are responsible for many greenhouse gases. These problems are being emphasized as a diet-environment-health trilemma to be addressed on a global scale, with various methods being proposed toward its resolution. Diets like plant-based and low-protein diets not only potentially prevent the progression of chronic kidney disease, but are also rational from an environmental preservation perspective. Evidence from Japan on resolutions for this trilemma is sparse, but one concrete proposal is the use of traditional Japanese diets like washoku, the Okinawa diet, and the traditional Buddhist diet. However, traditional Japanese diets also have several problems, such as excessive salt content and caloric deficiencies, and need to be modified and incorporated into the current lifestyle. The progression of chronic kidney disease needs to be prevented with appropriate dietary treatment and environmental friendly manner.
Causes and treatments of nasal obstruction in children and adolescents: a systematic literature review
Authors: Tanveer Muhammad Saad , Javed Mamoona , Tanveer Muhammad Hassan 
Published: May 2022

Abstract
Objective
To identify the causes and treatments of nasal obstruction in the paediatric population.

Methods
A systematic search of Medline and Embase was conducted to identify the relevant articles. A detailed inclusion and exclusion criterion was developed and implemented to screen the abstracts. Full texts of the selected studies were then assessed to establish their inclusion or exclusion in our review. All relevant data were extracted, and the results were summarised narratively.

Results
Fifty-nine studies met out inclusion-exclusion criteria and were included in this systematic review. All of these primary research studies were categorised into causes and treatments. Cleft lip and palate was the most reported cause of nasal obstruction among congenital causes. However, among the acquired causes, allergic rhinitis was the most reported. Twenty-one of 39 studies described treatments for allergic rhinitis, including perennial rhinitis, 9 for adenoid hypertrophy, 2 for the common cold, 5 for septal deviation, and 2 for chronic rhinosinusitis.

Conclusion
This systematic review provides good evidence regarding the causes and treatments of nasal obstruction. Allergic rhinitis is the most common cause of acquired nasal obstruction, and cetirizine, fexofenadine, fluticasone furoate nasal spray, and mometasone furoate monohydrate nasal are the commonly used treatments to alleviate the symptoms.