bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of healthy lifestyle score with all-cause mortality and life expectancy: a city-wide prospective cohort study of cancer survivors
Authors: Sun Ce , Li Ke , Xu Huan , Wang Xiangjun , Qin Pengzhe , Wang Suixiang , Liang Boheng , Xu Lin 
Published: July 2021

Abstract
Background
Adherence to a healthy lifestyle could reduce the cancer mortality in the western population. We conducted a city-wide prospective study in China investigating the association of a healthy lifestyle score with all-cause mortality and the life expectancy in cancer survivors.

Methods
This prospective cohort study included 46,120 surviving patients who were firstly diagnosed with cancer in Guangzhou. Five low-risk lifestyle factors including never smoking, never alcohol use, regular physical activity (≥ 2 h/week), sufficient sleep (≥ 6 h/day), and normal or high BMI (≥ 18.5 kg/m2) were assessed and a lifestyle score (0–5, a higher score indicates healthier lifestyle) was generated. Hazard ratios (HRs) of all-cause mortality and the life expectancy by levels of the lifestyle scores were estimated.

Results
Of 46,120 cancer survivors registered from 2010 to 2017, during an average follow-up of 4.3 years (200,285 person-years), 15,209 deaths were recorded. Adjusted HRs for mortality in cancer survivors with lifestyle score of 0–2, versus 5, were 2.59 (95% confidence interval (CI): 2.03–3.30) in women, 1.91 (95%CI 1.77–2.05) in men, 2.28 (95%CI 2.03–2.55) in those aged <65 years, and 1.90 (95%CI 1.75, 2.05) in those aged ≥ 65 years. Life expectancy at age 55 for those with a score of 0–2 and 5 was 53.4 and 57.1 months, respectively. We also found that cancer survivors with healthy lifestyle scores of 5 showed 59.9 months of life expectancy on average, which was longer than those with a score of 0–2.

Conclusion
Adopting a healthy lifestyle was associated with a substantially lower risk of all-cause mortality and longer life expectancy in cancer survivors. Our findings should be useful for health education and health promotion in primary care and clinical practice.
Small heterodimer partner (SHP) aggravates ER stress in Parkinson’s disease-linked LRRK2 mutant astrocyte by regulating XBP1 SUMOylation
Authors: Lee Jee Hoon , Han Ji-hye , Joe Eun-hye , Jou Ilo 
Published: July 2021

Abstract
Background
Endoplasmic reticulum (ER) stress is a common feature of Parkinson’s disease (PD), and several PD-related genes are responsible for ER dysfunction. Recent studies suggested LRRK2-G2019S, a pathogenic mutation in the PD-associated gene LRRK2, cause ER dysfunction, and could thereby contribute to the development of PD. It remains unclear, however, how mutant LRRK2 influence ER stress to control cellular outcome. In this study, we identified the mechanism by which LRRK2-G2019S accelerates ER stress and cell death in astrocytes.

Methods
To investigate changes in ER stress response genes, we treated LRRK2-wild type and LRRK2-G2019S astrocytes with tunicamycin, an ER stress-inducing agent, and performed gene expression profiling with microarrays. The XBP1 SUMOylation and PIAS1 ubiquitination were performed using immunoprecipitation assay. The effect of astrocyte to neuronal survival were assessed by astrocytes-neuron coculture and slice culture systems. To provide in vivo proof-of-concept of our approach, we measured ER stress response in mouse brain.

Results
Microarray gene expression profiling revealed that LRRK2-G2019S decreased signaling through XBP1, a key transcription factor of the ER stress response, while increasing the apoptotic ER stress response typified by PERK signaling. In LRRK2-G2019S astrocytes, the transcriptional activity of XBP1 was decreased by PIAS1-mediated SUMOylation. Intriguingly, LRRK2-GS stabilized PIAS1 by increasing the level of small heterodimer partner (SHP), a negative regulator of PIAS1 degradation, thereby promoting XBP1 SUMOylation. When SHP was depleted, XBP1 SUMOylation and cell death were reduced. In addition, we identified agents that can disrupt SHP-mediated XBP1 SUMOylation and may therefore have therapeutic activity in PD caused by the LRRK2-G2019S mutation.

Conclusion
Our findings reveal a novel regulatory mechanism involving XBP1 in LRRK2-G2019S mutant astrocytes, and highlight the importance of the SHP/PIAS1/XBP1 axis in PD models. These findings provide important insight into the basis of the correlation between mutant LRRK2 and pathophysiological ER stress in PD, and suggest a plausible model that explains this connection.
A review on gut microbiota: a central factor in the pathophysiology of obesity
Authors: Cunningham A. L. , Stephens J. W. , Harris D. A. 
Published: July 2021

AbstractObesity and its complications constitute a substantial burden. Considerable published research describes the novel relationships between obesity and gut microbiota communities. It is becoming evident that microbiota behave in a pivotal role in their ability to influence homeostatic mechanisms either to the benefit or detriment of host health, the extent of which is not fully understood. A greater understanding of the contribution of gut microbiota towards host pathophysiology is revealing new therapeutic avenues to tackle the global obesity epidemic. This review focuses on causal relationships and associations with obesity, proposed central mechanisms encouraging the development of obesity and promising prospective methods for microbiota manipulation.
Personalized medicine and allergen immunotherapy: the beginning of a new era?
Authors: Incorvaia Cristoforo , Ridolo Erminia , Bagnasco Diego , Scurati Silvia , Canonica Giorgio Walter 
Published: July 2021

AbstractThe concept of personalized medicine as a diagnostic and therapeutic approach tailored to the medical needs of each patient is currently revolutionizing all fields of medicine and in particular allergology. Allergen immunotherapy (AIT) meets the three main needs for precision medicine: identification of molecular mechanism of disease, diagnostic tools for the mechanism and treatment blocking the mechanism itself. AIT adapts to the spectrum of specific IgE of each individual subject, changing the course and natural history of the disease, so is a clear model of precision and personalized medicine. This first step before the prescription of AIT is to define the sensitization profile of the patient; after that, the healthcare professional has numerous levers for adapting the treatment to the physio-pathological mechanisms involved. AIT allows to adapt treatments to the profile of the patients, but also to the its preferences, to ensure optimal treatment efficacy, resulting in an agile and personalized approach, with the aim to ensure adherence to the treatment, which is usually quite low. AIT also broadens the field of possibilities for healthcare professionals and patients, by allowing to choose the galenic formulation according to patient preferences and on the basis of their clinical history, adapting the product composition to the patient’s sensitization profiles and the underlying biological mechanisms identified at the diagnostic stage, while guaranteeing quality of the prescribed product as the production of allergens and allergoids is today more regulated than in the past years. In the management of AIT, it is also possible to involve patients in decisions throughout their care pathway thanks to multiple services, offering personalized follow-up and support, to ensure the highest treatment efficacy levels, and recalling medication intake, medical appointments and prescription renewals.
Circ_001209 aggravates diabetic retinal vascular dysfunction through regulating miR-15b-5p/COL12A1
Authors: Wang Fang , Zhang Meixia 
Published: July 2021

Abstract
Objective
Diabetic retinopathy, a common complication of diabetes mellitus and a major cause of blindness. circRNAs spongs target miRNA and thus influencing mRNA expression in DR. We investigated the mechanism of circ_001209 in regulating diabetic retinal vascular dysfunction.

Methods
QRT-PCR analysis was performed to detect the expression of miR-15b-5p, COL12A1 and circ_001209 in human retinal vascular endothelial cells (HRVECs) under high glucose conditions. Western blot assay, wound healing assay, transwell assay and tube formation were used to explore the roles of circ_001209/miR-15b-5p/COL12A1 in retinal vascular dysfunction. Bioinformatics analysis and luciferase reporter, RNA-FISH, and overexpression assays were performed to reveal the mechanisms of the circ_001209/miR-15b-5p/COL12A1 interaction. TUNEL staining and H&E staining were used to evaluate the pathological changes in streptozotocin (STZ)-induced DR in rats.

Results
Downregulation of miR-15b-5p under HG conditions promoted proliferation, migration, and tube formation of HRVECs. QRT-PCR and western blot results revealed that miR-15b-5p affected the HRVECs function through targeting COL12A1. Under HG conditions, circ_001209, which acts as a sponge of miR-15b-5p, is upregulated. Besides, overexpression of circ_001209 can affect HRVEC function and aggravate retinal injury in diabetic rats.

Conclusion
Upregulation of circ_001209 contributes to vascular dysfunction in diabetic retinas through regulating miR-15b-5p and COL12A1, providing a potential treatment strategy for diabetic retinopathy.
Rare chondroblastoma of the 6th left rib, video-assisted thoracoscopy resected: one case report and literature review
Authors: Wu Yonghui , Guan Jiexia , Zhang Kai , Chen Huiguo , Wu Weibin , Zhang Jian 
Published: July 2021

Abstract
Introduction
Chondroblastoma is a rare, benign locally but aggressive bone tumor. It accounts for < 1% of primary bony tumors, and mostly arises from long bones; the rib chondroblastoma is especial rare. Due to its rarity, there are no definitive or standard treatment guidelines.

Case presentation
A case of a 24-year-old male with a chondroblastoma located on the 6th posterior left rib. Computed tomography (CT) demonstrated a rib tumor that was a well-defined oval lesion of 20 mm × 18 mm, with lytic bone destruction. The imaging first diagnosis was Langerhans cell histiocytosis (LCH), a giant cell tumor, or other type of neoplasm. The whole tumor and a part of partial rib were resected by video-assisted thoracoscopy surgery (VATS). Pathological and immunohistochemical (IHC) examination made a diagnosis of chondroblastoma. Compared with traditional open thoracic surgery, VATS can achieve the same effects and cause less injury to patient. No postoperative adjuvant therapy was given, and had followed up 23 months after surgery, there was no recurrence or metastasis.

Conclusion
Chondroblastoma has a risk of recurrence and metastasis, surgery plays an important role in the treatment of chondroblastoma, VATS can achieve the same outcome as traditional open thoracic surgery with less pain and lung function. Close follow-up is needed postoperative.
Case report of a 72-year-old man with diaphragmatic hernia and thoracic gastropericardial fistula after esophagectomy for 18 years
Authors: Xu Xinjian , Yan Zhaoyang , He Ming 
Published: July 2021

Abstract
Background
Both diaphragmatic hernia and thoracic gastropericardial fistula rarely occur simultaneously in patients with radical esophagectomy.

Case presentation
A 72-year-old man presented to our hospital with 1 day of nausea, vomiting and acute left chest pain. He had radical esophagectomy (Sweet approach) for esophageal cancer 18 years ago. Computed tomography (CT) of the chest revealed diaphragmatic hernias and air collection within the pericardial space. While an operation of diaphragmatic hernia repair was decisively performed to prevent further serious complications, unusually, a thoracic gastropericardial fistula was also found unusually.

Conclusion
Diaphragmatic hernia and thoracic gastropericardial fistula may occasionally coexist in patients with esophagectomy. Upper GI radiograph with a water-soluble contrast agent is a better diagnostic tool than CT in visualizing the fistula.
Life-sustaining treatment decisions in pediatric intensive care: an Italian survey on ethical concerns
Authors: Carnevale Franco A. , Giannini Alberto , Bonaldi Amabile , Bravi Elena , Cecchi Costanza , Pettenazzo Andrea , Amigoni Angela , Pulitanò Silvia Maria Modesta , Tosin Chiara , Biban Paolo 
Published: July 2021

Abstract
Objectives
To investigate how life-sustaining treatment (LST) decisions are made and identify problematic ethical concerns confronted by physicians and nurses in pediatric intensive care within Italy.

Methods
An 88-question online survey was created, based on a previous qualitative study conducted by this team. The survey was designed to identify how LST decisions were managed; contrasting actual practices with what participants think practices should be. Replies from physicians and nurses were compared, to identify potential inter-professional ethical tensions. The study also identified participants’ principal ethical concerns. Moreover, open-ended questions elicited qualitative perspectives on participants’ views. The survey was pilot-tested and refined before initiation of the study.

Results
31 physicians and 65 nurses participated in the study. Participants were recruited from pediatric intensive care units across five Italian cities; i.e., Florence, Milan, Padua, Rome, Verona. Statistically significant differences were identified for (a) virtually all questions contrasting actual practices with what participants think practices should be and (b) 14 questions contrasting physician replies with those of nurses. Physicians and nurses identified the absence of legislative standards for LST withdrawal as a highly problematic ethical concern. Physicians also identified bearing responsibility for LST decisions as a major concern. Qualitative descriptions further demonstrated that these Italian pediatric intensive care clinicians encounter significantly distressing ethical problems in their practice.

Conclusions
The results of this study highlight a need for the development of (a) strategies for improving team processes regarding LST decisions, so they can be better aligned with how clinicians think decisions should be made, and (b) Italian LST decision-making standards that can help ensure optimal ethical practices.
The seasonal dynamics and biting behavior of potential Anopheles vectors of Plasmodium knowlesi in Palawan, Philippines
Authors: Malijan Richard Paul B. , Mechan Frank , Braganza Jessie C. , Valle Kristelle Mae R. , Salazar Ferdinand V. , Torno Majhalia M. , Aure Wilfredo E. , Bacay Brian A. , Espino Fe Esperanza , Torr Stephen J. , Fornace Kimberly M. , Drakeley Chris , Ferguson Heather M. 
Published: July 2021

AbstractBackgroundA small number of human cases of the zoonotic malariaPlasmodium knowlesihave been reported in Palawan Island, the Philippines. Identification of potential vector species and their bionomics is crucial for understanding human exposure risk in this setting. Here, we combined longitudinal surveillance with a trap-evaluation study to address knowledge gaps about the ecology and potential for zoonotic spillover of this macaque malaria in Palawan Island.MethodsThe abundance, diversity and biting behavior of human-bitingAnophelesmosquitoes were assessed through monthly outdoor human landing catches (HLC) in three ecotypes representing different land use (forest edge, forest and agricultural area) across 8 months. Additionally, the host preference and biting activity of potentialAnophelesvectors were assessed through comparison of their abundance and capture time in traps baited with humans (HLC, human-baited electrocuting net—HEN) or macaques (monkey-baited trap—MBT, monkey-baited electrocuting net—MEN). All femaleAnophelesmosquitoes were tested for the presence ofPlasmodiumparasites by PCR.ResultsPreviously incriminated vectorsAnopheles balabacensisandAn. flavirostrisaccounted for > 95% of anophelines caught in longitudinal surveillance. However, human biting densities were relatively low (An. balabacensis: 0.34–1.20 per night,An. flavirostris: 0–2 bites per night). Biting densities ofAn. balabacensiswere highest in the forest edge, whileAn. flavirostriswas most abundant in the agricultural area.The abundance ofAn. balabacensisandAn. flavirostriswas significantly higher in HLC than in MBT. None of the 357 femaleAnophelesmosquitoes tested forPlasmodiuminfection were positive.ConclusionsThe relatively low density and lack of malaria infection inAnophelesmosquitoes sampled here indicates that exposure toP. knowlesiin this setting is considerably lower than in neighboring countries (i.e. Malaysia), where it is now the primary cause of malaria in humans. Although anophelines had lower abundance in MBTs than in HLCs,An. balabacensisandAn. flavirostriswere caught by both methods, suggesting they could act as bridge vectors between humans and macaques. These species bite primarily outdoors during the early evening, confirming that insecticide-treated nets are unlikely to provide protection againstP. knowlesivectors.Graphical abstract
Identifying the deceiver: the non-neoplastic mimickers of genital system neoplasms
Authors: Onder Omer , Karaosmanoglu Ali Devrim , Kraeft Jessica , Uysal Aycan , Karcaaltincaba Musturay , Akata Deniz , Ozmen Mustafa Nasuh , Hahn Peter F. 
Published: July 2021

AbstractTumors of the genital system are common and imaging is of crucial importance for their detection and diagnosis. Several non-neoplastic diseases may mimic these tumors and differential diagnosis may be difficult in certain cases. Misdiagnosing non-neoplastic diseases as tumor may prompt unnecessary medical treatment or surgical interventions. In this article, we aimed to present the imaging characteristics of non-neoplastic diseases of the male and female genital systems that may mimic neoplastic processes. Increasing awareness of the imaging specialists to these entities may have a severe positive impact on the management of these patients.
Stable trimer formation of spike protein from porcine epidemic diarrhea virus improves the efficiency of secretory production in silkworms and induces neutralizing antibodies in mice
Authors: Masuda Akitsu , Lee Jae Man , Miyata Takeshi , Ebihara Takeru , Kakino Kohei , Hino Masato , Fujita Ryosuke , Mon Hiroaki , Kusakabe Takahiro 
Published: July 2021

AbstractPorcine epidemic diarrhea virus (PEDV) is a highly infectious pathogen of watery diarrhea that causes serious economic loss to the swine industry worldwide. Especially because of the high mortality rate in neonatal piglets, a vaccine with less production cost and high protective effect against PEDV is desired. The intrinsically assembled homotrimer of spike (S) protein on the PEDV viral membrane contributing to the host cell entry is a target of vaccine development. In this study, we designed trimerized PEDV S protein for efficient production in the silkworm-baculovirus expression vector system (silkworm-BEVS) and evaluated its immunogenicity in the mouse. The genetic fusion of the trimeric motif improved the expression of S protein in silkworm-BEVS. A small-scale screening of silkworm strains to further improve the S protein productivity finally achieved the yield of about 2 mg from the 10 mL larval serum. Mouse immunization study demonstrated that the trimerized S protein could elicit strong humoral immunity, including the S protein-specific IgG in the serum. These sera contained neutralizing antibodies that can protect Vero cells from PEDV infection. These results demonstrated that silkworm-BEVS provides a platform for the production of trimeric S proteins, which are promising subunit vaccines against coronaviruses such as PEDV.
Metabolomic and transcriptomic profiling of adult mice and larval zebrafish leptin mutants reveal a common pattern of changes in metabolites and signaling pathways
Authors: Ding Yi , Haks Mariëlle C. , Forn-Cuní Gabriel , He Junling , Nowik Natalia , Harms Amy C. , Hankemeier Thomas , Eeza Muhamed N. H. , Matysik Jörg , Alia A. , Spaink Herman P. 
Published: July 2021

Abstract
Background
Leptin plays a critical role in the regulation of metabolic homeostasis. However, the molecular mechanism and cross talks between leptin and metabolic pathways leading to metabolic homeostasis across different species are not clear. This study aims to explore the effects of leptin in mice and zebrafish larvae by integration of metabolomics and transcriptomics. Different metabolomic approaches including mass spectrometry, nuclear magnetic resonance (NMR) and high-resolution magic-angle-spinning NMR spectrometry were used to investigate the metabolic changes caused by leptin deficiency in mutant ob/ob adult mice and lepb−/− zebrafish larvae. For transcriptome studies, deep RNA sequencing was used.

Results
Thirteen metabolites were identified as common biomarkers discriminating ob/ob mice and lepb−/− zebrafish larvae from their respective wild type controls: alanine, citrulline, ethanolamine, glutamine, glycine, histidine, isoleucine, leucine, methionine, phenylalanine, putrescine, serine and threonine. Moreover, we also observed that glucose and lipid levels were increased in lepb−/− zebrafish larvae compared to the lepb+/+ group. Deep sequencing showed that many genes involved in proteolysis and arachidonic acid metabolism were dysregulated in ob/ob mice heads and lepb mutant zebrafish larvae compared to their wild type controls, respectively.

Conclusions
Leptin deficiency leads to highly similar metabolic alterations in metabolites in both mice and zebrafish larvae. These metabolic changes show similar features as observed during progression of tuberculosis in human patients, mice and zebrafish larvae. In addition, by studying the transcriptome, we found similar changes in gene regulation related to proteolysis and arachidonic acid metabolism in these two different in vivo models.
Interaction between early in ovo stimulation of the gut microbiota and chicken host – splenic changes in gene expression and methylation
Authors: Dunislawska A. , Slawinska A. , Gryzinska M. , Siwek M. 
Published: July 2021

Abstract
Background
Epigenetic regulation of the gene expression results from interaction between the external environment and transcription of the genetic information encoded in DNA. Methylated CpG regions within the gene promoters lead to silencing of the gene expression in most cases. Factors contributing to epigenetic regulation include intestinal microbiota, which in chicken can be potently modified by in ovo stimulation. The main aim of this study was to determine global and specific methylation patterns of the spleen under the influence of host-microbiome interaction.

Results
Fertilized eggs of two genotypes: Ross 308 and Green-legged Partridgelike were in ovo stimulated on d 12 of incubation. The injected compounds were as follows: probiotic – Lactococcus lactis subsp. cremoris IBB477, prebiotic – galactooligosaccharides, and synbiotic – combination of both. Chickens were sacrificed on d 42 post-hatching. Spleen was collected, RNA and DNA were isolated and intended to gene expression, gene methylation and global methylation analysis. We have proved that negative regulation of gene expression after administration of bioactive substances in ovo might have epigenetic character. Epigenetic changes depend on the genotype and the substance administered in ovo.

Conclusion
Epigenetic nature of microbial reprogramming in poultry and extension of issues related to host-microbiome interaction is a new direction of this research.